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Abstract Background Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. Methods This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. Results 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. Conclusion Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.

PurposeHashimoto’s thyroiditis (HT) is one of the most commonly encountered types of autoimmune thyroid disorders (AITDs), influenced by environmental factors, genetics, and the immune system. Previous research has shown a correlation between gut microbiota and HT, as well as the involvement of immune cells in its onset and progression. We aimed to investigate whether immune cells act as intermediaries in the causal relationship between gut microbiota and HT.MethodsIn this study, we conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the relationship between gut microbiota and HT using data from genome-wide association studies (GWAS) and the MiBioGen study. Subsequently, MR analyses were performed to investigate the interactions between 731 immune cells and gut microbiota. Additionally, an MR analysis was performed to examine the association between HT and these 731 immune cells, using a GWAS dataset that included 3,757 European subjects. This approach provided insights into the impact of 22 million genetic variants on 731 immune cell signatures.ResultsThere was a causal relationship between the increase in the number of 15 gut microbiota and HT. We observed that the genus Akkermansia, family Alcaligenaceae, family Desulfovibrionaceae, family Verrucomicrobiaceae, class Verrucomicrobiae, order Verrucomicrobiales, phylum Verrucomicrobia, class Alphaproteobacteria, order Desulfovibrionales, genus Ruminococcus torques group, genus Butyrivibrio, and genus Coprococcus3 were negatively correlated with HT. In addition, the genus Intestinimonas, genus Turicibacter, and genus Anaerostipes were positively correlated with HT. We identified EM CD4 + T cells as a mediator between the gut microbiota and HT.ConclusionIn conclusion, we presented causal associations between the EM CD4 + T cell-mediated gut microbiota and HT, as inferred from the MR findings derived from extensive aggregated GWAS data. Our research offers guidance and direction for treating and preventing HT.

Abstract Background Toll-like receptor 8 (TLR8) can recognize specific pathogen-associated molecular patterns and exert multiple immunological functions through activation of signaling cascades. However, the precise distribution and age-related alterations of TLR8 in the spleens of Bactrian camels have not yet been investigated. This study aimed to prepare a rabbit anti-Bactrian camel TLR8 polyclonal antibody and elucidate the distribution of TLR8 in the spleens of Bactrian camels at different age groups. The methodology involved the construction of the pET-28a-TLR8 recombinant plasmid, followed by the expression of TLR8 recombinant protein via prokaryotic expression. Subsequently, rabbits were immunized with the purified protein to prepare the TLR8 polyclonal antibody. Finally, twelve Alashan Bactrian camels were categorized into four groups: young (1–2 years), pubertal (3–5 years), middle-aged (6–16 years) and old (17–20 years). These camels received intravenous sodium pentobarbital (20 mg/kg) anesthesia and were exsanguinated to collect spleen samples. Immunohistochemical techniques were employed to observe and analyze the distribution patterns and age-related changes of TLR8 in the spleen. Results The results showed that the TLR8 recombinant protein was expressed in the form of inclusion body with a molecular weight of 52 kDa, and the optimal induction condition involved 0.3 mmol/L IPTG induction for 8 h. The prepared antibody yielded a titer of 1:32 000, and the antibody demonstrated specific binding to TLR8 recombinant protein. TLR8 positive cells exhibited a consistent distribution pattern in the spleen across different age groups of Bactrian camels, primarily scattered within the periarterial lymphatic sheath of the white pulp, marginal zone, and red pulp. The predominant cell type expressing TLR8 was macrophages, with expression also observed in neutrophils and dendritic cells. Statistical analysis revealed that there were significant differences in the distribution density of TLR8 positive cells among different spleen regions at the same age, with the red pulp, marginal zone, and white pulp showing a descending order (P

Summary: Disruption of circadian rhythms during fetal development may predispose mice to developing heart disease later in life. Here, we report that male, but not female, mice that had experienced chronic circadian disturbance (CCD) in utero were more susceptible to pathological cardiac remodeling compared with mice that had developed under normal intrauterine conditions. CCD-treated males showed ventricular chamber dilatation, enhanced myocardial fibrosis, decreased contractility, higher rates of induced tachyarrhythmia, and elevated expression of biomarkers for heart failure and myocardial remodeling. In utero CCD exposure also triggered sex-dependent changes in cardiac gene expression, including upregulation of the secretoglobin gene, Scgb1a1, in males. Importantly, cardiac overexpression of Scgb1a1 was sufficient to induce myocardial hypertrophy in otherwise naive male mice. Our findings reveal that in utero CCD exposure predisposes male mice to pathological remodeling of the heart later in life, likely as a consequence of SCGB1A1 upregulation.

AbstractBackground Bile acids play crucial roles in various metabolisms, as well as Lactobacillus in the intestine. But studies on their roles in acute coronary syndrome (ACS) are still insufficient. The aim of this study was to investigate their role and potential association with the severity of coronary lesions and the prognosis of ACS.Methods Three hundred and sixty ACS patients were selected. Detection of gut Lactobacillus levels was done through 16S rDNA sequence analysis. Evaluation of the extent of lesions was done using the SYNTAX (SS) score. Mediation analysis was used to assess the relationship between serum total bile acid (TBA), Lactobacillus, atherosclerotic lesions and prognosis of ACS.Results Logistic regressive analysis disclosed that serum TBA and Lactobacillus were independent predictors of coronary lesions (high vs. low SS: serum TBA adjusted odds ratio (aOR) = 0.8, 95% confidence interval (CI): 0.6–0.9, p

Abstract Background Sparassis crispa polysaccharides (SCPs) have multiple pharmacological activities. Fermentation characteristics of SCPs and its effects on the intestinal microbes in mice remain inconclusive. Results In this study, SCPs were fermented by the human feces and used to administer the Kunming mice to explore the fermentation characteristics of SCPs in the intestinal tract and the effects on the intestinal microbes in mice. Results from in vitro experiments revealed that SCPs were utilized by intestinal microbiota to produce short-chain fatty acids (SCFAs). The specific monosaccharide composition of SCPs determines which SCFAs are produced. Furthermore, the colon index and villi length of the SCPs-treated mice were significantly higher compared with the control group. In addition, SCPs exhibited beneficial effect on the relative abundance and diversity of dominant bacteria in the intestinal tract, such as increasing Bacteroidetes/Firmicutes ratio and up-regulating SCFA-producing bacteria, including Bacteroidales_S24-7_group, Alloprevotella, Alistipes, Bacteroides, Butyricimonas, Parabacteroides, Lachnospiraceae_NK4A136_group and Oscillibacter. SCPs increased the abundance of genes in carbohydrate, amino acid, and energy metabolism. Conclusion Our results indicate SCPs can improve the physiological indices of the colon in mice, which is likely to be associated with the increase in the relative abundance and diversity of SCFA-producing bacteria and SCFAs level produced by intestinal microbiota. Graphic abstract

Rhododendron micranthum Turcz., Rhododendron capitatum Maxim., Rhododendron dauricum L. and Rhododendron schlippenbachii Maxim. are four species of Rhododendron with the same geographical distribution, mainly distributed in the northeast of China and abundant in sources. This paper is the first comprehensive review on the chemical composition and pharmacological activities of these four species. The review, showed 323 compounds including terpenoids, flavonoids, coumarins, lignans, and volatile components were found in the four plants, and these four plants of Rhododendron not only had many chemical constituents of novel structures but also possessed extensive pharmacological effects, such as insecticide, analgesic, antibacterial, antitumor and so on. These research papers and literatures about the four plants were carried out using resources including classic books about Chinese herbal medicine, Flora Reipublicae Popularis Sinicae, and scientific databases including Web of Science, Sci-Finder, CNKI, Pubmed, etc. In recent years, our research group has engaged in the study of chemical composition and pharmacological activities of Rhododendron plants. The terpenes and volatile components isolated from Rhododendron plants contributed greatly to insecticidal activity. Therefore, it is of great significance to review researches of the four endemic resource-rich Rhododendron plants to help make full use of them especially on plant-derived insecticide. This comprehensive review will be significant for the discovery of new bioactive compounds from the above four endemic plants and will be informative for researchers seeking for new pharmacological activity of the four species.

Background: Several studies have demonstrated that using a higher dose of statin can easily induce liver injury and myopathy. Low-density lipoprotein cholesterol (LDL-C) is a well-established modifiable risk factor for cardiovascular disease; however, the large majority of Chinese patients cannot meet the target level of LDL-C recommended by the Chinese expert consensus. Evolocumab has been demonstrated to reduce LDL-C by approximately 60% in many studies. Nevertheless, whether combined evolocumab and moderate-intensity statin is as effective in lowering LDL-C and decreasing incidence of MACE in Chinese patients presenting with the acute phase of acute coronary syndrome (ACS) remains unknown. Therefore, the “Evolocumab added to Moderate-Intensity Statin therapy on LDL-C lowering and cardiovascular adverse events in patients with Acute Coronary Syndrome” (EMSIACS) is conducted.Methods: The EMSIACS is a prospective, randomized, open-label, parallel-group, multicenter study involving analyzing the feasibility and efficacy of evolocumab added to moderate-intensity statin therapy on lowering LDL-C levels in adult Chinese patients hospitalized for acute phase ACS. The sample size calculation is based on the primary outcome, and 500 patients will be planned to recruit. Patients are randomized in evolocumab arm (evolocumab 140mg every 2weeks plus rosuvastatin 10mg/day or atorvastatin 20mg/day) and statin-only arm (rosuvastatin 10mg/day or atorvastatin 20mg/day). The primary outcome is the percentage change in LDL-C in weeks 4 and week 12 after treatment. The secondary outcome is the occurrence of MACE after 12weeks and 1year of treatment.Discussion: If the EMSIACS trial endpoints prove statistically significant, the evolocumab added to moderate-intensity statin therapy will have the potential to effectively lower subjects’ LDL-C levels, especially for the Chinese patients with acute phase ACS. However, if the risk of MACE is not significantly different between the two groups, we may extend follow-up time for secondary outcome when the clinical trial is over.Clinical trial registration: The study is registered to ClinicalTrials.gov (NCT04100434), which retrospectively registered on November 24, 2020.

Dietary supplements have improved the prevention of insulin resistance and metabolic diseases, which became a research hotspot in food science and nutrition. Obesity and insulin resistance, caused by a high-fat diet, eventually result in severe metabolic diseases, can be prevented with the dietary supplement D-chiro-inositol (DCI). In this work, we isolated mice primary hepatocytes with palmitic acid stimulation and DCI was applied to compare and contrast its effects of in primary hepatocyte biology. Before and after intervention with DCI, we used RNA-Seq technology to establish a primary hepatocyte transcriptome gene profile. We found that both PA and DCI cause a wide variation in gene expression. Particularly, we found that DCI plays critical role in this model by acting on glycolysis and gluconeogenesis. Overall, we generated extensive transcripts from primary hepatocytes and uncovered new functions and gene targets for DCI.

Different pretreatments can affect the quality of Hypsizygus marmoreus (HM). In this study, the effects of thermal treatment or combined with color protection and hardening on color, texture, microstructure, polyphenol oxidase (PPO) and Peroxidase (POD) C-1: Explain the first time? activities, and the volatile components of HM were investigated. The results showed compared with the control group, both heating group (H group) and color protection, hardening and heating (CHH group) significantly enhanced the color difference, and reduced all texture parameters as well as PPO and POD activities. Additionally, in two treatment groups, the structure of HM became loose, the amounts of alcohols, ketones, and aldehydes were changed significantly. Compared with the H group, the color difference and PPO activities in CHH group were significantly decreased, while all texture parameters were increased significantly, the fibers of HM showed regular arrangement. In conclusion, the combination of CHH performed better effects on hardness, chewiness, microstructure, and enzymes activities related to enzymatic browning.

The Paris Agreement has confirmed that the ultimate climate policy goal is to hold the increase in the global average temperature to well below 2 °C above pre-industrial levels and to pursue efforts to limit the increase to 1.5 °C. Moving the goal from 2 °C to 1.5 °C calls for much more concerted effort, and presents greater challenges and costs. This study uses an Asia-Pacific Integrated Model/Computable General Equilibrium (AIM/CGE) to evaluate the role of socioeconomic factors (e.g. technological cost and energy demand assumptions) in changing mitigation costs and achieving the 1.5 °C and 2 °C goals, and to identify the channels through which socioeconomic factors affect mitigation costs. Four families of socioeconomic factors were examined, namely low-carbon energy-supply technologies, end-use energy-efficiency improvements, lifestyle changes and biomass-technology promotion (technology cost reduction and social acceptance promotion). The results show that technological improvement in low-carbon energy-supply technologies is the most important factor in reducing mitigation costs. Moreover, under the constraints of the 1.5 °C goal, the relative effectiveness of other socioeconomic factors, such as energy efficiency improvement, lifestyle changes and biomass-related technology promotion, becomes more important in decreasing mitigation cost in the 1.5 °C scenarios than in the 2 °C scenarios.

Rheological properties and gel characteristics of Sparassis crispa polysaccharides (SCPs) were investigated under various concentrations, temperature, pH, salt concentrations, and sucrose concentrations. SCP solutions behaved as shear thinning pseudoplastic fluids; apparent viscosity increased with concentrations but decreased with extreme conditions and was highest for 1% SCPs at 80 ℃ under neutral conditions; 5% SCPs solutions formed a hysteresis loop and exhibited thixotropic properties. By oscillatory measurements, SCPs were viscoelastic materials. 0.5% and 1% SCPs solutions exhibited viscous behavior at low frequency and enhanced elastic property with the oscillation frequency increased. With the concentration increased to 3% and 5%, the elastic property was predominant in solutions and exhibited gel-like behavior. SCPs gel textural properties and water holding capacity increased with concentration (to 20%) and decreased with salinity, extreme sucrose, and pH. 10% SCPs gels were optimized at 10% sucrose in neutral conditions. Thus, these results implied SCPs had the potential utilization as a new hydrocolloid source in food industries.

The physicochemical and digestive properties of Pleurotus eryngiiprotein and the effects of heat treatment and ultrasound treatment on the properties were investigated. The physicochemical property results showed that the shear stress and viscosity increased as the protein concentration increased from 3 to 9 g/100 g raw materials and decreased as the temperature increased from 25°C to 45°C. The pH value from 2.0 to 7.0 significantly affected the state of protein because of the change of the disulfide bond and sulfhydryl bond content. The protein might be held closer with higher sulfhydryl bond at pH 7.0 and be less coacervation with higher disulfide bonds at pH 3.5. The addition of calcium from 0.01 to 0.05 mol/L into the protein system could increase the rheology property of the protein. Based on the results of Fourier-transform infrared spectroscopy, the content of α-helix increased after heat treatment and ultrasound treatment, while the content of β-sheet decreased, indicating the change of spatial conformation of protein. The result of differential scanning calorimetry of protein manifested that ultrasound treatment significantly enhanced the protein thermal stability (P

Abstract The nervous and vascular systems, although functionally different, share many common regulators of function maintenance. Long non‐coding RNAs (lncRNAs) are important players in many biological processes and human disorders. We previously identified a role of MALAT1 in microvascular dysfunction. However, its role in neurodegeneration is still unknown. Here, we used the eye as the model to investigate the role of MALAT1 in retinal neurodegeneration. We show that MALAT1 expression is significantly up‐regulated in the retinas, Müller cells, and primary retinal ganglion cells (RGCs) upon stress. MALAT1 knockdown reduces reactive gliosis, Müller cell activation, and RGC survival in vivo and in vitro. MALAT1‐CREB binding maintains CREB phosphorylation by inhibiting PP2A‐mediated dephosphorylation, which leads to continuous CREB signaling activation. Clinical and animal experimentation suggests that MALAT1 dysfunction is implicated in neurodegenerative processes and several human disorders. Collectively, this study reveals that MALAT1 might regulate the development of retinal neurodegeneration through CREB signaling.

Actions tackling with climate change can cause co-benefits and trade-offs with Sustainable Development Goals (SDGs) concerned with air pollution, water scarcity, food security, land use, and sustainable energy. Such interactions can be greatly influenced by socioeconomic conditions. The impacts of socioeconomic conditions on multiple SDGs have not been evaluated separately from climate policies. This paper employs a Representative Concentration Pathways–Shared Socio-economic Pathways (RCP-SSP) framework and the Asia-Pacific Integrated Model/computable general equilibrium (AIM/CGE) integrated assessment model to identify the global multi-sectoral consequences of socioeconomic conditions through 2050 under future SSP scenarios. Results show that changes of socioeconomic conditions consistent with the SSP1 pathway could always improve SDG indicators, with or without climate policies. In many respects, socioeconomic conditions are more important than climate policies in achieving SDGs, particularly SDGs concerned with food security and energy affordability, as well as in simultaneously achieving multiple SDGs. We conclude that the advantages of a joint effort to implement climate policies and promulgate socioeconomic changes should be recognized by policy makers.

Synergies and trade-offs exist between climate mitigation actions and target indicators of the Sustainable Development Goals (SDGs). Some studies have assessed such relationships, but the degree of such interaction remains poorly understood. Here, we show the SDG implications associated with CO _2 emissions reductions. We developed ‘marginal SDG-emissions-reduction values (MSVs)’, which represent the marginal impacts on SDG indicators caused by a unit CO _2 emissions reduction. This metric is applicable to national assessments and was applied to Asia. We found clear relationships between CO _2 emissions reduction rates and many SDG targets. For instance, 1% reduction of CO _2 can avoid 0.57% of air pollution-related premature deaths (SDG3), whereas the mean species richness (SDG15) is decreased by 0.026% with the same reduction (not including climate change impacts). Our findings are useful for assessing the SDG implications associated with CO _2 emissions reduction targets, which will help inform national climate policies.

The Paris Agreement set long-term global climate goals to pursue stabilization of the global mean temperature increase at below 2 °C (the so-called 2 °C goal). Individual countries submitted their own short-term targets, mostly for the year 2030. Meanwhile, the UN’s sustainable development goals (SDGs) were designed to help set multiple societal goals with respect to socioeconomic development, the environment, and other issues. Climate policies can lead to intended or unintended consequences in various sectors, but these types of side effects rarely have been studied in China, where climate policies will play an important role in global greenhouse gas emissions and sustainable development is a major goal. This study identified the extent to which climate policies in line with the 2 °C goal could have multi-sectoral consequences in China. Carbon constraints in China in the 2Deg scenario are set to align with the global 2 °C target based on the emissions per capita convergence principle. Carbon policies for NDC pledges as well as policies in China regarding renewables, air pollution control, and land management were also simulated. The results show that energy security and air quality have co-benefits related to climate policies, whereas food security and land resources experienced negative side effects (trade-offs). Near-term climate actions were shown to help reduce these trade-offs in the mid-term. A policy package that included food and land subsidies also helped achieve climate targets while avoiding the adverse side effects caused by the mitigation policies. The findings should help policymakers in China develop win–win policies that do not negatively affect some sectors, which could potentially enhance their ability to take climate actions to realize the global 2 °C goal within the context of sustainable development.

A series of novel half-titanocene complexes CpTiCl2[S-2-R-6-(PPh2)C6H3] (Cp = C5H5, 2a, R = H; 2b, R = Ph; 2c, R = SiMe3) have been synthesized by treating CpTiCl3 with the sodium of the ligands, 2-R-6-(PPh2)C6H3SNa, which were prepared by the corresponding ligands and NaH. These complexes have been characterized by 1H, 13C and 31P NMR as well as elemental analyses. Structures for 2a–b were further confirmed by X-ray crystallography. Complexes 2a–b adopt five-coordinate, distorted square-pyramid geometry around the titanium center, in which the equatorial positions are occupied by sulfur and phosphorus atoms of the chelating phosphine-thiophenolate and two chlorine atoms, and the cyclopentadienyl ring is coordinated on the axial position. The complexes 2a–c were investigated as the catalysts for ethylene polymerization and copolymerization of ethylene with norbornene in the presence of MMAO or Ph3CB(C6F5)4/iBu3Al as the cocatalyst. All complexes exhibited low to moderate activities towards homopolymerization of ethylene. However, they displayed moderate to high activities towards copolymerization of ethylene with norbornene.

The goal of limiting global temperature rise to “well below” 2 °C has been reaffirmed in the Paris Agreement on climate change at the 21st Conference of the Parties (COP21). Almost all countries submitted their decarbonization targets in their Intended Nationally Determined Contributions (INDC) to the United Nations Framework Convention on Climate Change (UNFCCC) and India did as well. India’s nationally determined contribution (NDC) aims to reduce greenhouse gas (GHG) emissions intensity of national GDP in 2030 by 33–35% compared to 2005. This paper analyzes how India’s NDC commitments compare with emission trajectories consistent with well below 2 °C and 1.5 °C global temperature stabilization goals. A top-down computable general equilibrium model is used for the analysis. Our analysis shows that there are significant emission gaps between NDC and global climate stabilization targets in 2030. The energy system requires significant changes, mostly relying on renewable energy and carbon capture and storage (CCS) technology. The mitigation costs would increase if India delays its abatement efforts and is locked into NDC pathways till 2030. India’s GHG emissions would peak 10 years earlier under 1.5 °C global temperature stabilization compared to the 2 °C goal. The results imply that India would need financial and technological support from developed countries to achieve emissions reductions aligned with the global long-term goal.

Under the Paris Agreement, parties set and implement their own emissions targets as nationally determined contributions (NDCs) to tackle climate change. International carbon emissions trading is expected to reduce global mitigation costs. Here, we show the benefit of emissions trading under both NDCs and a more ambitious reduction scenario consistent with the 2 °C goal. The results show that the global welfare loss, which was measured based on estimated household consumption change in 2030, decreased by 75% (from 0.47% to 0.16%), as a consequence of achieving NDCs through emissions trading. Furthermore, achieving the 2 °C targets without emissions trading led to a global welfare loss of 1.4%–3.4%, depending on the burden-sharing scheme used, whereas emissions trading reduced the loss to around 1.5% (from 1.4% to 1.7%). These results indicate that emissions trading is a valuable option for the international system, enabling NDCs and more ambitious targets to be achieved in a cost-effective manner.

Each country’s Intended Nationally Determined Contribution (INDC) pledges an emission target for 2025 or 2030. Here, we evaluated the INDC inter-generational and inter-regional equity by comparing scenarios with INDC emissions target in 2030 and with an immediate emission reduction associated with a global uniform carbon price using Asian-Pacific Integrated Model/Computable General Equilibrium. Both scenarios eventually achieve 2 °C target. The results showed that, as compared with an immediate emission reduction scenario, the inter-generational equity status is not favorable for INDC scenario and the future generation suffers more from delayed mitigation. Moreover, this conclusion was robust to the wide range of inequality aversion parameter that determines discount rate. On the other hand, the INDC scenario has better inter-regional equity in the early part of the century than does the immediate emission reduction scenario in which we assume a global carbon price during the period up to 2030. However, inter-regional equity worsens later in the century. The additional emissions reduction to the INDC in 2030 would improve both inter- and inter-regional equity as compared to the current INDC. We also suggest that countries should commit to more emissions reductions in the follow-up INDC communications and that continuous consideration for low-income countries is needed for global climate change cooperation after 2030.

Background The locus for familial cortical myoclonic tremor with epilepsy (FCMTE) has long been mapped to 8q24 in linkage studies, but the causative mutations remain unclear. Recently, expansions of intronic TTTCA and TTTTA repeat motifs within SAMD12 were found to be involved in the pathogenesis of FCMTE in Japanese pedigrees. We aim to identify the causative mutations of FCMTE in Chinese pedigrees. Methods We performed genetic linkage analysis by microsatellite markers in a five-generation Chinese pedigree with 55 members. We also used arraycomparative genomic hybridisation (CGH) and nextgeneration sequencing (NGS) technologies (whole-exome sequencing, capture region deep sequencing and wholegenome sequencing) to identify the causative mutations in the disease locus. Recently, we used low-coverage (~10×) long-read genome sequencing (LRS) on the PacBio Sequel and Oxford Nanopore platforms to identify the causative mutations, and used repeat-primed PCR for validation of the repeat expansions. Results Linkage analysis mapped the disease locus to 8q23.3-24.23. Array-CGH and NGS failed to identify causative mutations in this locus. LRS identified the intronic TTTCA and TTTTA repeat expansions in SAMD12 as the causative mutations, thus corroborating the recently published results in Japanese pedigrees. Conclusions We identified the pentanucleotide repeat expansion in SAMD12 as the causative mutation in Chinese FCMTE pedigrees. Our study also suggested that LRS is an effective tool for molecular diagnosis of genetic disorders, especially for neurological diseases that cannot be positively diagnosed by conventional clinical microarray and NGS technologies. [ABSTRACT FROM AUTHOR]

Midazolam is an anesthetic agent commonly used during clinical and surgical procedures, which has been shown to exert ROS-suppressing and apoptosis-modulating pharmacological activities in various cellular systems. However, the effects of midazolam on oxidative stress in neuronal cells require elucidation. The present study investigated the effects of midazolam on buthionine sulfoximine (BSO)- and hydrogen peroxide (H2O2)-induced oxidative stress in primary cortical neuronal cells. In addition, the effects of midazolam on middle cerebral artery occlusion (MCAO) in mice and on ethanol-induced neuroapoptosis in the brains of neonatal mice were determined. Subsequently, cell viability was detected using the MTT assay; intracellular reactive oxygen species (ROS) generation was determined using the 2',7'-dichlorodihydrofluorescein diacetate method with confocal microscopy; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was conducted to detect apoptotic cells; immunohistochemistry was performed to detect activated caspase-3; neuronal deficit and infarct volume analyses were conducted; and quantitative polymerase chain reaction and western blotting were performed to detect the expression levels of genes and proteins associated with apoptosis and cell survival pathways. The results demonstrated that BSO (10 mM) and H2O2 (1 mM) suppressed proliferation of cortical neuronal cells by inducing apoptosis. These effects were suppressed following treatment with midazolam in a dose-dependent manner. In addition, BSO and H2O2 induced ROS generation in neuronal cells; however, this was effectively suppressed by midazolam (100 µM). Beneficial synergistic effects were detected when midazolam was used in combination with the known antioxidant trolox. BSO and H2O2 also suppressed the protein expression levels of c-Jun N-terminal kinases (JNK), phosphorylated (p)JNK, extracellular signal-regulated kinases (ERK)1/2, pERK1/2, AKT and nuclear factor-κB; however, expression was recovered following treatment with midazolam. Midazolam also activated protein kinase C-ε, which was suppressed by BSO, in cortical neuronal cells. In MCAO mice, midazolam post-conditioning significantly suppressed infarct size and reduced the number of TUNEL-positive cells. In addition, the expression levels of caspase-3 and poly (ADP-ribose) polymerase were suppressed in a dose-dependent manner. In neonatal mice, midazolam reduced ethanol-induced activated caspase-3 staining and apoptotic TUNEL staining. The results of the present study demonstrated that midazolam may protect against neuronal degeneration and neuroapoptosis induced by physiological and oxidative stress. [ABSTRACT FROM AUTHOR]

Based on data of 18 cities in Henan over the period 2006-2014, this study examines the relationships between carbon dioxide (CO2) emissions and urban green open spaces (GOP) growth, and uses Moran I to analyse the spatial correlation of multiple indexes. Results show that the total amount of carbon dioxide emissions will not continue to grow as the urban green open spaces. With the development of urbanisation, there is a growing trend of negative correlation between the growth rate of CO2 emissions and the growth rate of urban green open spaces (GOP). In this province, the importance of energy conservation and emission reduction arouses more and more attention to the construction of green open space. The study reveals that the development of economy and urbanisation will affect the CO2 emissions and urban green open spaces growth, and there will be some periodicity in the region. [ABSTRACT FROM AUTHOR]

A series of novel aluminium complexes containing cyclic β-ketiminato ligands of type Me2Al{O- [(ArN=CHC4H4(C6H4))]} (3a, Ar = 2,6-iPr2C6H3; 3b, Ar = C6H5; 3c, Ar = C6F5) have been prepared in high yields. These complexes were identified by 1H, 13C NMR spectroscopy and elemental analysis. X-ray structural analyses for 3a-c revealed that these complexes have a distorted tetrahedral geometry around Al, and both bond distances and bond angles were considerably influenced by the ligand structure. These complexes were tested as catalyst precursors for ring-opening polymerisation of ε-caprolactone (ε-CL) and L-lactide (L-LA) in the presence of 2-propanol as an initiator. Complex 3a could polymerize ε-CL in a controlled manner with high efficiency. Based on the living characteristics, the preparation of well-defined block copolymers PCL-b-PLLA via sequential addition of monomers was performed by 3a. Note that complex 3c exhibited rather high catalytic activity for the ROP of L-LA with narrow molecular weight distribution. The monomer conversion reached completion only in 4 h when the L-LA/Al molar ratio was 100 at 80 °C. PLLA-b-PCL copolymers were thus easily produced by 3c. [ABSTRACT FROM AUTHOR]