ANP promotes HTR-8/SVneo cell invasion by upregulating protein kinase N 3 via autophagy inhibition.

Preeclampsia is a gestational disease characterized by two major pathological changes-shallow trophoblast invasion and impaired spiral artery remodeling. Atrial natriuretic peptide (ANP) is a kind of peptide hormone that regulates blood pressure, while the lack of active ANP participates in preeclampsia pathogenesis. However, the underlying mechanism of how ANP modulates trophoblasts function remains unclarified. Here, we performed isobaric tags for relative and absolute quantification (iTRAQ) in ANP-treated HTR-8/SVneo cells and identified Protein Kinase 3 (PKN3) as the downstream factor of ANP, which was downregulated in preeclamptic placenta. Chromatin immunoprecipitation analysis and luciferase assays showed that NFYA was one of the transcription factors for the PKN3 promoter, which was also regulated by ANP treatment in HTR-8/SVneo cells. Transmission electron microscopy and Western Blotting in HTR-8/SVneo cells indicated that ANP inhibited autophagy via AMPK-mTORC1 signaling, while excess autophagy was observed in preeclamptic placenta. The increased expression of PKN3 and enhanced cell invasion ability in HTR-8/SVneo cells induced by ANP could be abolished by autophagy activation or transfection with PKN3 shRNA or NFYA shRNA or NPR-A shRNA via regulating the invasion-related genes and the epithelial mesenchymal transition molecules. Our results demonstrated that ANP could enhance trophoblast invasion by upregulating PKN3 via NFYA promotion through autophagy inhibition in an AMPK/mTORC1 signaling-dependent manner.

The threaten of typhoons to the health of residents in inland areas: a study on the vulnerability of residents to death risk during typhoon "Lekima" : In Jinan, China.

BACKGROUND: Studies had suggested increased risk of death of residents was associated with typhoons, particularly coastal regions. However, these findings ignored the impact of inland typhoons on the health of residents, especially the indirect death risk caused by typhoons. This study aimed to investigate the acute death risk of residents during inland typhoon Lekima in Jinan, further identify vulnerable populations and areas. METHODS: We selected the daily death from 11 to 27th August 2019 in Jinan as case period, and conducted a time-stratified case-crossover design to match the contemporaneous data from 2016 to 2018 as control period. We used the generalized linear Poisson models to estimate the related effects of death risk during typhoon Lekima and lag days. RESULTS: During the Lekima typhoon month, there were 3,366 deaths occurred in Jinan. Compared to unexposed periods, the acute death risk of non-accidental diseases (especially circulatory diseases), female and the older adults increased significantly in the second week after the typhoon. The maximum significant effect of circulatory disease deaths, female and older adult deaths were appeared on lag9, lag9, and lag13 respectively. And the typhoon-associated RR were 1.19 (95%CI:1.05,1.34), 1.28 (95%CI:1.08,1.52), and 1.22 (95%CI:1.06,1.42) respectively. The acute death risk of residents living in TQ and CQ increased significantly on Lag2 and Lag6 after the typhoon, respectively, while those living in LX, LC, HY, JY, and SH occurred from Lag 8 to Lag 13 after the typhoon. LC lasted the longest days. CONCLUSIONS: Typhoons would increase the vulnerability of residents living in Jinan which mainly occurred from the seventh day after the typhoon. Residents suffering from non-accidental diseases (circulatory diseases), female and the older adults were more vulnerable. The vulnerability of TQ and CQ occurred on Lag2 and Lag6 after typhoon Lekima, respectively, and the other areas except ZQ and PY occurred from Lag 8 to Lag 13. LC lasted the longest duration. Our findings emphasized the importance of the emergency response, which would help policymakers to identify vulnerable regions and populations accurately during typhoons and formulate the emergency response plan.

Extreme cold weather and circulatory diseases of older adults: A time-stratified case-crossover study in jinan, China.

OBJECTIVES: We aimed to investigate the acute effect of extreme cold weather on circulatory disease mortality of older adults in Jinan, with individual and regional-scale characteristics as subgroup analyses to further identify vulnerable populations. METHODS: This study contained the death data of Jinan from 2011 to 2020 (Nov-Mar). A time-stratified case-crossover method was used to estimate the effects of extreme cold weather and lags 0-8 days, controlling for holiday and relative humidity. To evaluate the impact of different durations and thresholds of extreme cold weather, we considered 4 cold day and 12 cold wave definitions RESULTS: Our results showed an increase in circulatory disease deaths under several definitions. The number of older adults died of circulatory diseases totaled 92,119 during the study period. In the definitions of cold day, the maximum significant effect ranging from 1.08 (95% CI: 1.03,1.14) to 1.13 (95% CI: 1.04,1.24) and appeared on Lag5 or Lag6. In the definitions of cold wave, the maximum significant effect ranging from 1.07 (95% CI: 1.02, 1.12) to 1.14 (95% CI: 1.03, 1.25). The cold effect is mainly attributable to cold day rather than an added effect related to the duration. Our research confirmed that extreme cold weather had a stronger impact on women [maximum effects with an OR of 1.21 (95% CI: 1.08, 1.36) in P1, 1.19 (95% CI: 1.05, 1.36) in M12)], and the effect gradient increased with age. CONCLUSIONS: Our findings support the evidence on the impact of extreme cold weather on circulatory disease mortality and provide a basis for policymakers to select target groups to develop policies and reduce the public health burden.

Accuracy of dynamic navigation in implant surgery: A systematic review and meta-analysis.

OBJECTIVE: To assess the accuracy of dynamic computer-assisted implant surgery. MATERIALS AND METHODS: An electronic search up to March 2020 was conducted using PubMed, Embase, and the Cochrane Central Register of Controlled Trial to identify studies using dynamic navigation in implant surgery, and additional manual search was performed as well. Clinical trials and model studies were selected. The primary outcome was accuracy. A single-arm meta-analysis of continuous data was conducted. Meta-regression was utilized for comparison on study design, guidance method, jaw, and systems. RESULTS: Ten studies, four randomized controlled trials (RCT) and six prospective studies, met the inclusion criteria. A total of 1,298 drillings and implants were evaluated. The meta-analysis of the accuracy (five clinical trials and five model studies) revealed average global platform deviation, global apex deviation, and angular deviation were 1.02 mm, 95% CI (0.83, 1.21), 1.33 mm, 95% CI (0.98, 1.67), and 3.59°, 95% CI (2.09, 5.09). Meta-regression shown no difference between model studies and clinical trials (p = .295, 0.336, 0.185), drilling holes and implant (p = .36, 0.279, 0.695), maxilla and mandible (p = .875, 0.632, 0.281), and five different systems (p = .762, 0.342, 0.336). CONCLUSION: Accuracy of dynamic computer-aided implant surgery reaches a clinically acceptable range and has potential in clinical usage, but more patient-centered outcomes and socio-economic benefits should be reported.

Genetic association of polymorphism rs2230054 in CXCR2 gene with gout in Chinese Han male population.

Neutrophils are crucial in the process of gout flare and remission. The signal transduction pathway of chemokine plays a vital role in the chemotaxis and activation of neutrophils. CXCR2 gene knocked out can avoid the acute neutrophilic inflammation stimulated by monosodium urate (MSU) crystals in mice. To investigate the relationship among CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 polymorphisms with gout arthritis flare in the Chinese Han male population, a case-control study was carried out in 412 gout patients and 508 gout-free individuals. TaqMan probes fluorescence real-time polymerase chain reaction (PCR) was used to genotype CXCR1 rs2234671, CXCR2 rs1126579, and rs2230054 SNPs. There was a clear link between CXCR2 rs2230054 T included genotypic and T allelic frequencies and gout cases (c2 = 9.286, p = 0.002 by genotype, c2 = 8.639, p = 0.003 by allele), while no significant differences were observed between the gouty arthritis group and the control group in CXCR1 rs2234671 and CXCR2 rs1126579 genotypic and allelic frequencies. Multivariate logistic regression analysis showed that the T genotype included in rs2230054 can decrease the risk of gouty arthritis (adjusted OR = 0.47; 95% CI: 0.31-0.74) compared with the CC genotype. Our study might suggest that rs2230054 in CXCR2 is associated with susceptibility to gout in Chinese males.

Photochemical fabrication of 3D hierarchical Mn3O4/H-TiO2 composite films with excellent electrochemical capacitance performance.

We herein report a novel, energy-saving and environmentally benign photodeposition approach to fabricate a manganese oxide film on hydrogenated TiO2 (H-TiO2) nanotube arrays using a Mn(2+)-containing solution as a precursor. Mn(2+) ions are oxidized to Mn3O4 by the photogenerated holes during the photodeposition. The preferential growth of Mn3O4 on the nucleation sites leads to the formation of Mn3O4 nanorods on each H-TiO2 nanotube, forming a 3D hierarchical Mn3O4/H-TiO2 composite film. The as-fabricated 3D hierarchical Mn3O4/H-TiO2 composite film electrode delivers a high specific capacitance of 508 F g(-1) at a current of 0.7 A g(-1). The composite film electrode still shows a specific capacitance of 228 F g(-1) even at a high rate of 35.7 A g(-1), demonstrating its prominent rate capability. Remarkably, the composite film electrode shows no obvious capacitance decay after 10,000 charge/discharge cycles at a current density of 3.6 A g(-1), revealing its superior electrochemical cycling stability. The prominent pseudocapacitive performance of the composite film electrode can be attributed to its unique structure characteristics. The as-constructed energy-saving and environmentally benign photodeposition method can be used as a general and efficient route to prepare other composite materials with controlled morphologies and dimensions.

Phenome-wide association study (PheWAS) for detection of pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network.

Using a phenome-wide association study (PheWAS) approach, we comprehensively tested genetic variants for association with phenotypes available for 70,061 study participants in the Population Architecture using Genomics and Epidemiology (PAGE) network. Our aim was to better characterize the genetic architecture of complex traits and identify novel pleiotropic relationships. This PheWAS drew on five population-based studies representing four major racial/ethnic groups (European Americans (EA), African Americans (AA), Hispanics/Mexican-Americans, and Asian/Pacific Islanders) in PAGE, each site with measurements for multiple traits, associated laboratory measures, and intermediate biomarkers. A total of 83 single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) were genotyped across two or more PAGE study sites. Comprehensive tests of association, stratified by race/ethnicity, were performed, encompassing 4,706 phenotypes mapped to 105 phenotype-classes, and association results were compared across study sites. A total of 111 PheWAS results had significant associations for two or more PAGE study sites with consistent direction of effect with a significance threshold of p<0.01 for the same racial/ethnic group, SNP, and phenotype-class. Among results identified for SNPs previously associated with phenotypes such as lipid traits, type 2 diabetes, and body mass index, 52 replicated previously published genotype-phenotype associations, 26 represented phenotypes closely related to previously known genotype-phenotype associations, and 33 represented potentially novel genotype-phenotype associations with pleiotropic effects. The majority of the potentially novel results were for single PheWAS phenotype-classes, for example, for CDKN2A/B rs1333049 (previously associated with type 2 diabetes in EA) a PheWAS association was identified for hemoglobin levels in AA. Of note, however, GALNT2 rs2144300 (previously associated with high-density lipoprotein cholesterol levels in EA) had multiple potentially novel PheWAS associations, with hypertension related phenotypes in AA and with serum calcium levels and coronary artery disease phenotypes in EA. PheWAS identifies associations for hypothesis generation and exploration of the genetic architecture of complex traits.

[Advances of research on the mechanism of Down syndrome birth at advanced maternal age].

Down syndrome is caused by partial or complete triplication of genes located on chromosome 21. Its incidence increases dramatically with the age of women. Hypotheses proposed for this have included abnormal homologous recombination, defective spindle assembly, biological aging, reduction of cohesion complexes, endocrine disorders, oocyte selection model, and single nucleotide polymorphisms of genes that maintain chromosome stability, etc. A literature review is provided here.

Polymorphisms in the vitamin D receptor and risk of gout in Chinese Han male population.

Previous studies have showed that patients with gout showed lower serum 25(OH)D levels. As the specific receptor of vitamin D, VDR plays an important role in regulating immune system by combining with vitamin D. In this study, we investigated whether the functional VDR polymorphisms were associated with susceptibility to gout in Chinese Han male population. A total of 504 patients with gout and 523 gout-free controls were recruited from the Affiliated Hospital of the Medical College, Qingdao University. Genotyping of VDR rs11568820, rs2228570 and rs1544410 was performed by TaqMan allele discrimination assays. An association analysis was carried out using the χ(2) test. A genotype-phenotype analysis was also conducted. Our results showed that polymorphisms of rs11568820 and rs1544410 in VDR were associated with gout in Chinese Han male population. The A allele of both rs11568820 and rs1544410 was associated with the risk of gout [P = 0.012 OR 1.251, 95% CI (1.051-1.490); P = 0.006, OR 1.574, 95% CI (1.139-2.175)]. However, there was no statistic significance between rs2228570 and gout (P = 0.186). Our study suggested that the polymorphisms of VDR may be relevant host susceptibility factors for the development of gout in Chinese Han male population. However, further study should be done in a larger size sample and other ethic to test and verify our result.

Pharmacokinetic and pharmacodynamic evaluation study of etomidate: a randomized, open-label, 2-period crossover study in healthy Chinese subjects.

Etomidate is a sedative and hypnotic drug through intravenous administration that act on the central nervous system through GABA (Gamma-Amino Butyric Acid) receptors, which is widely used in anesthesia induction and maintenance and long-term sedation in severe patients. The study aimed to evaluate the pharmacokinetic and pharmacodynamic properties of two etomidate fat emulsions after administration through the intravenous infusion pump in healthy Chinese subjects. A randomized, open-label, 2-period crossover study was performed in 52 healthy subjects. The wash-out period was 7 days. Blood samples and pharmacodynamic index values were collected at the specified time points. Etomidate concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were analyzed using a non-compartment model method. Pharmacodynamic parameters were calculated using pharmacodynamic index values. The study also evaluated the safety of the etomidate. Both the pharmacokinetic parameters and pharmacodynamic parameters result of the test and reference formulation were very similar. The 90% confidence intervals (CI) of the geometric least-squares mean (GLSM) ratios of the test to reference formulation were 91.33-104.96% for the maximum plasma concentration (Cmax), 97.21-102.03% for the area under the plasma concentration time curve from time 0 to the time of the last measurable concentration (AUC0-t), and 97.22-102.33% for the area under the plasma concentration time curve from time 0 to infinity (AUC0-∞). Meanwhile, the 90% CI of the GLSM ratios of the test to reference formulation were 102.28-110.69% for the minimal BIS value (BISmin), 99.23-101.17% for the area under the BIS time curve from time 0-60 min after administration (BISAUC0-60 min), respectively. The 90% CI of these pharmacokinetic and pharmacodynamic parameters all fall in the accepted bioequivalence range of 80.00-125.00%. No serious adverse events occurred during the study. This study has shown that the etomidate fat emulsion test and reference formulation had similar pharmacokinetic and pharmacodynamic characteristics in vivo. The two formulations exhibited good safety and well-tolerance.Clinical trials registration number: http://www.chinadrugtrials.org.cn/index.html . # CTR20191836.

Do antibody CDR loops change conformation upon binding?

Antibodies have increasingly been developed as drugs with over 100 now licensed in the US or EU. During development, it is often necessary to increase or reduce the affinity of an antibody and rational attempts to do so rely on having a structure of the antibody-antigen complex often obtained by modeling. The antigen-binding site consists primarily of six loops known as complementarity-determining regions (CDRs), and an open question has been whether these loops change their conformation when they bind to an antigen. Existing surveys of antibody-antigen complex structures have only examined CDR conformational change in case studies or small-scale surveys. With an increasing number of antibodies where both free and complexed structures have been deposited in the Protein Data Bank, a large-scale survey of CDR conformational change during binding is now possible. To this end, we built a dataset, AbAgDb, that currently includes 177 antibodies with high-quality CDRs, each of which has at least one bound and one unbound structure. We analyzed the conformational change of the Cα backbone of each CDR upon binding and found that, in most cases, the CDRs (other than CDR-H3) show minimal movement, while 70.6% and 87% of CDR-H3s showed global Cα RMSD ≤ 1.0Å and ≤ 2.0Å, respectively. We also compared bound CDR conformations with the conformational space of unbound CDRs and found most of the bound conformations are included in the unbound conformational space. In future, our results will contribute to developing insights into antibodies and new methods for modeling and docking.

Financial development, technological innovation and urban-rural income gap: Time series evidence from China.

The main purpose of the paper is to investigate the relationship between technological innovation and income inequality for China based on the financial Kuznets curve (FKC) hypothesis. The study uses time-series data from 1985 to 2019. We employ the Johansen cointegration, ARDL model and VECM Granger causality techniques to analyze the links between the variables. We also use the DOLS, FMOLS and CCR mechanisms to estimate the long-run parameters. The paper finds that the FKC is valid for China's economy in the long run. Technological innovation positively affects the urban-rural income gap, while there is an inverted-U shaped between financial development and the urban-rural income gap. The relationship between financial development and the urban-rural income gap is bi-directional causality. Technological innovation and the urban-rural income gap cause each other. Empirical results suggest a twofold policy meaning: i) to further the financial system and ii) to eliminate the adverse impacts of technological innovations on income distribution.

Identification of LncRNA-miRNA-mRNA ceRNA network in hypoxia-induced HTR-8/SVneo cells for preeclampsia.

Preeclampsia (PE) is a common pregnancy complication, and placental hypoxia is one of its causes. We aimed to identify the transcriptional profile and construct a long non-coding RNAs (lncRNA)-centered competing endogenous RNAs (ceRNA) network in hypoxia-induced HTR8/SVneo cells. We used datasets from the GEO database to identify important pathways in PE. We performed microarray profiling and functional analysis to identify differentially expressed long non-coding RNAs (lncRNAs), differentially expressed profiles of microRNA (miRNAs), and differentially expressed profiles of messenger RNA (mRNAs) in hypoxia-induced HTR8/SVneo cells. The candidates were validated using quantitative reverse transcription polymerase chain reaction. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were performed to understand the functional significance of differentially expressed genes. Finally, we constructed an lncRNA-centered ceRNA network. Several hub genes were validated both in placentas from PE and normal pregnancy, and in hypoxia-induced HTR8/SVneo cells. The hypoxic response pathway was involved in the pathophysiology of PE. Subsequently, we identified 536 differentially expressed profiles of lncRNAs (183 upregulated and 353 downregulated), 46 differentially expressed profiles of miRNAs (35 upregulated and 11 downregulated), and 2782 differentially expressed profiles of mRNAs (DEmRNAs) (1031 upregulated and 1751 downregulated) in hypoxia-induced HTR8/SVneo cells. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed potential pathways affected by these genes, such as angiogenesis, the HIF-1 signaling pathway, and the PI3K-Akt signaling pathway. The ceRNA network comprised 35 lncRNAs, 11 miRNAs, 27 mRNAs, and 2 hub lncRNAs, which might play a vital role in placental functions and PE. Our results revealed the transcriptome profile and constructed an lncRNA-centered ceRNA network in hypoxia-induced HTR8/SVneo cells, thereby providing potential therapeutic targets for PE.

Quantifying the effects of cold waves on carbon monoxide poisoning: A time-stratified case-crossover study in Jinan, China.

Background: Previous studies have shown that carbon monoxide (CO) poisoning occurs mostly in winter and is associated with severe cold weather (e.g., ice storms, temperature drops). However, according to previous studies, the impact of low temperature on health has a delayed effect, and the existing research cannot fully reveal the delayed effect of cold waves on CO poisoning. Objectives: The purpose of this study is to analyze the temporal distribution of CO poisoning in Jinan and to explore the acute effect of cold waves on CO poisoning. Methods: We collected emergency call data for CO poisoning in Jinan from 2013 to 2020 and used a time-stratified case-crossover design combined with a conditional logistic regression model to evaluate the impact of the cold wave day and lag 0-8 days on CO poisoning. In addition, 10 definitions of a cold wave were considered to evaluate the impact of different temperature thresholds and durations. Results: During the study period, a total of 1,387 cases of CO poisoning in Jinan used the emergency call system, and more than 85% occurred in cold months. Our findings suggest that cold waves are associated with an increased risk of CO poisoning in Jinan. When P01, P05, and P10 (P01, P05, and P10 refer to the 1st, 5th, and 10th percentiles of the lowest temperature, respectively) were used as temperature thresholds for cold waves, the most significant effects (the maximum OR value, which refers to the risk of CO poisoning on cold wave days compared to other days) were 2.53 (95% CI:1.54, 4.16), 2.06 (95% CI:1.57, 2.7), and 1.49 (95% CI:1.27, 1.74), respectively. Conclusion: Cold waves are associated with an increased risk of CO poisoning, and the risk increases with lower temperature thresholds and longer cold wave durations. Cold wave warnings should be issued and corresponding protective policies should be formulated to reduce the potential risk of CO poisoning.

Nitidine chloride regulates cell function of bladder cancer in vitro through downregulating Lymphocyte antigen 75.

Nitidine chloride (NC) is effective on cancer in many tumors, but its effect on bladder cancer (BC) is unknown. We conducted cell function experiments to verify the antineoplastic effect of NC on BC cell lines (5637, T24, and UM-UC-3) in vitro. Then, mRNAs of NC-treated and NC-untreated BC cells were extracted for mRNA sequencing. Differentially expressed genes (DEGs), expression analysis, and drug molecular docking were conducted to discover the target gene of NC. Finally, functional enrichment was analyzed to explore the underlying mechanisms. NC dramatically inhibited proliferation, migration, and invasion, and it induced apoptosis and arrested the S and G2/M phases of BC cell lines. Lymphocyte antigen 75 (LY75) appeared to be the target of NC. LY75 was highly expressed and had the ability to distinguish BC tissue from non-cancerous tissue. Then, drug molecular docking confirmed the targeting relationship between NC and LY75. Gene enrichment analysis showed that the downregulated genes, after being treated with NC, were mainly enriched in pathways relevant to cell pathophysiological processes. NC inhibits BC cell proliferation, migration, and invasion, induces apoptosis, and arrests cell cycles by downregulating the expression of LY75. This study provides molecular and theoretical bases for NC treatment of BC.

Association between gout and polymorphisms in GCKR in male Han Chinese.

Several genome-wide association studies (GWASs) have reported associations between single nucleotide polymorphisms (SNPs) and uric acid concentrations or gout in a number of different ethnic populations. To clarify the global relevance of the previously identified SNPs in the development of the qualitative trait gout, in the present study, the associations between two SNPs in the glucokinase (hexokinase 4) regulator (GCKR) gene and gout were assessed in a male Chinese Han population. The study population comprised 476 male gout patients and 465 male controls. Multiple PCR was performed using time-of-flight mass spectrometry (MALDI-TOF MS) to identify genotypes. Two SNPs, rs780093 and rs780094, located in intronic regions of the GCKR gene were found to be significantly associated with the development of gout. Thus, the association between the two GCKR SNPs and gout was replicated in the male Han Chinese population investigated in the present study. Furthermore, GCKR was identified as a novel candidate gene associated with gout.

Lack of association of -607 C/A and -137 G/C polymorphisms in interleukin 18 gene with susceptibility to gout disease in Chinese Han male population.

To identify association of IL18-607 C/A and -137 G/C polymorphism with susceptibility to gout in Chinese Han male population, We evaluate the genetic contribution of the IL18-607 C/A and -137 G/C polymorphism in 202 gout male patients and 493 gout-free control of Chinese Han population by allele-specific polymerase chain reaction assay. Our results reveal no significant association between the polymorphisms -607C/A and -137G/C in IL18 with gout. Our study might suggest that -607 C/A and -137 G/C polymorphisms in the promoter of IL18 are not associated with susceptibility to gout and thus do not play a major role in the development of gout in the Chinese Han male population.

Spatiotemporal evolution characteristics of coordinated development of urbanization and ecological environment in eastern Russia-Perspectives from the 3D global trend and 2D plane analysis.

Under the background of "the Belt and Road" and "the economic corridor of China, Mongolia and Russia" initiatives, it has great value to study the temporal and spatial evolution characteristics of the coordinated development between the urbanization and ecological environment in eastern Russia (the Siberian Federal District and the Far East Federal District). In this paper, we studied the urbanization development level, eco-environment development level, and their coupling coordinated development degree during 2005-2018 in the eastern Russia from the perspectives of the 3D global trend and 2D plane analysis. First, combining with the Population-Economic-Sociology and Pressure-State-Response models, the urbanization development level and eco-environment development level were calculated by the comprehensive weighting method of entropy weight and variation coefficient for eastern Russia. Second, the coupling coordinated development degree of the urbanization development level and eco-environment development level was measured by the coupling coordination model for eastern Russia. Finally, the spatial differentiation of the urbanization development level, the eco-environment development level and their coupling coordinated development degree was performed respectively by the 3D global trend and 2D plane analysis using ArcGIS. The results are as following. First, the comprehensive urbanization development level of eastern Russia has increased from 2005 to 2018, and the economic urbanization is the main factor that affects the urbanization development in eastern Russia. The comprehensive eco-environment development level of eastern Russia has decreased from 2005 to 2018, and the eco-environment pressure is the main factor that affects the eco-environment development in eastern Russia. The coupling coordination degree of the urbanization development and eco-environment development has increased from 2005 to 2018. However, it is still in the uncoordinated stage. Second, from 2005 to 2018, the urbanization development level of the Siberian Federal District is higher than that of the Far East Federal District. The eco-environment development level of the Siberian Federal District is balanced to that of the Far East Federal District. The coupling coordination degree of the Siberian Federal District is higher than that of the Far East Federal District. Among the Siberian and Far East Federal Districts, most of the federal subjects belong to the uncoordinated stage of the urbanization development and the eco-environment development. Third, the urbanization development level, the eco-environment development level, and their coupling coordinated development level are all spatially imbalanced in the eastern Russia, which show the "High West, Low East" and "High Center, Low North and Low South" spatial pattern from the perspectives of the 3D global trend and 2D plane analysis. The areas with high levels are concentrated in the Novosibirsk Region, Altay Territory, Kemerovo Region, Krasnoyarsk Territory, and Irkutsk Region. The areas with low ones are mostly in the Republic of Altay and Chukotka Autonomous Area. Finally, we suggest policies and strategies that can boost the growth and development of the urbanization and the eco-environment in the Sino-Russian border areas.

Evolution characteristics of temporal and spatial pattern of Russian economic differences since the 21st century.

Under the background of "the Belt and Road" and "the economic corridor of China, Mongolia and Russia" initiatives, it is of great significance to study the temporal and spatial economic pattern in the Russian Federation. Based on the economic development difference index, regional economic grade index, global trend analysis tool and spatial autocorrelation model, this paper analyzes the temporal and spatial pattern evolution characteristics of Russian economic differences from 2002 to 2020. The results are as following. First, although the economic imbalance among various federal subjects has been decreasing, the economic polarization has been still severe between the prosperous developed regions and the stagnant backward regions during 2002-2020. Russia's economy shows a trend of changing from significant positive correlation in strong agglomeration space to positive correlation in weak agglomeration space, and then to random distribution. Second, there has been great differences of the economic development among various federal subjects. The economic grade of the Russian federal subjects presents a significant spatial differentiation pattern. The Russian Federation's economic resources are concentrated in the first-class federal subject (Moscow City), second-class federal subjects (Tumen Region, Moscow Region and Saint-Petersburg city) and a few third-class federal subjects (Yamalo-Nenetsky Autonomous Area, Khanty-Mansiysky Autonomous Area, Republic of Tatarstan, Krasnodar Territory, Sverdlovsk Region, etc). Third, the Russian Federation's economy presents "High Core, Low Periphery", "High West, Low East" and "High south, Low north" spatial differentiation pattern. The economic hot regions coincide with the high-class economic regions, which are mainly distributed in the contiguous areas of Ural Federal District and Volga Federal District, as well as the Moscow City, Moscow Region, Saint-Petersburg city, Krasnodar Territory and Rostov Region. The economic cold regions coincide with the low-class economic regions, which are mainly located in the Far East Federal District, the east of Siberian Federal District, the north of North West Federal District and the south of North-Caucasian Federal District. Finally, we suggest the recommendation for policy makers in Russia. And we propose the future research ideas.

Progesterone Attenuates SIRT1-Deficiency-Mediated Pre-Eclampsia.

Pre-eclampsia is a severe hypertensive disorder of pregnancy (HDP), mainly characterized by new-onset hypertension with proteinuria after 20-week gestation. Sirtuin1 (SIRT1), a class III histone deacetylase, is associated with the regulation of various pathophysiological processes, including inflammation, immune response, metabolism, and autophagy. However, the effect of SIRT1 in the pathogenesis of pre-eclampsia remains to be elucidated. In this study, we found that the expression of SIRT1 was relatively lower in the placentas and serum samples of pre-eclampsia patients. Typical pre-eclampsia-like symptoms, such as hypertension, proteinuria, fetal growth restriction, kidney injury, and a narrow placental labyrinth layer, were observed in SIRT1 knockdown (SIRT1+/-) mice. Of note, these performances could be improved after the intraperitoneal injection of SIRT1 agonist SRT2104. More importantly, we found that the efficacy of progesterone on attenuating symptoms of PE was profoundly better than that of metformin in SIRT1+/- mice. In addition, our results suggested that progesterone can promote the invasion and inhibit the apoptosis of trophoblasts. These data suggest that SIRT1 plays an important role in pre-eclampsia and that progesterone alleviates pre-eclampsia-like symptoms mediated by SIRT1 deficiency.