Scalable Dual In Situ Synthesis of Polyester Nanocomposites for High-Energy Storage.

Incorporating ultralow loading of nanoparticles into polymers has realized increases in dielectric constant and breakdown strength for excellent energy storage. However, there are still a series of tough issues to be dealt with, such as organic solvent uses, which face enormous challenges in scalable preparation. Here, a new strategy of dual in situ synthesis is proposed, namely polymerization of polyethylene terephthalate (PET) synchronizes with growth of calcium borate nanoparticles, making polyester nanocomposites from monomers directly. Importantly, this route is free of organic solvents and surface modification of nanoparticles, which is readily accessible to scalable synthesis of polyester nanocomposites. Meanwhile, uniform dispersion of as ultralow as 0.1 wt% nanoparticles and intense bonding at interfaces have been observed. Furthermore, the PET-based nanocomposite displays obvious increases in both dielectric constant and breakdown strength as compared to the neat PET. Its maximum discharged energy density reaches 15 J cm-3 at 690 MV m-1 and power density attains 218 MW cm-3 under 150 Ω resistance at 300 MV m-1, which is far superior to the current dielectric polymers that can be produced at large scales. This work presents a scalable, safe, low-cost, and environment-friendly route toward polymer nanocomposites with superior capacitive performance.

The FGG c.952G>A variant causes congenital dysfibrinogenemia characterized by recurrent cerebral infarction: a case report.

Background: Congenital dysfibrinogenemia (CD) is a rare hereditary coagulation disorder resulting from mutations in fibrinogen genes. CD primarily presents with bleeding symptoms, but it can also lead to thrombotic events, including ischemic stroke. Case presentation: This report describes the case of a 52-year-old Chinese man who was admitted to the hospital twice due to recurrent cerebral infarction, characterized by sudden speech impairment and weakness in the right upper extremity. Brain MRI revealed multiple ischemic changes, predominantly in the left frontal and parietal lobes. Coagulation tests demonstrated reduced plasma fibrinogen (Clauss method), prolonged prothrombin time and thrombin time, and an elevated international normalized ratio. However, the ELISA assay indicated elevated levels of fibrinogen γ-chain protein. Despite a 2-month-old treatment regimen with aspirin, clopidogrel, and atorvastatin after the first hospitalization, the patient experienced a second ischemic stroke. Genetic analysis using whole-exome sequencing (WES) and Sanger sequencing identified a rare heterozygous missense variation, FGG c.952G>A (rs267606810), in both the stroke patient and his asymptomatic sister. Both individuals exhibited the same alterations in fibrinogen, characterized by reduced functional levels but increased antigenic protein. Subsequently, the patient was diagnosed with ischemic stroke associated with congenital dysfibrinogenemia. Conclusion: This case report expands the clinical phenotype spectrum associated with FGG c.952G>A (rs267606810) and underscores the significance of considering CD as a potential etiology for unexplained ischemic stroke, particularly in patients with a family history of coagulation disorders.

Aptamer-based kinetically controlled DNA reactions coupled with metal-organic framework nanoprobes for sensitive detection of SARS-CoV-2 spike protein.

Since the outbreak in 2019, COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the deadliest infectious disease worldwide for people of all ages, from children to older adults. As a main structural protein of SARS-CoV-2, spike protein is reported to play a key role in the entry of the virus into host cells and is considered as an effective antigenic marker for COVID-19 diagnosis. Herein, we develop a new aptamer-based fluorescence method for SARS-CoV-2 spike protein detection based on using kinetically controlled DNA reactions and metal-organic framework nanoprobes. Specifically, the binding of SARS-CoV-2 spike protein to its aptamer is designed to precisely control the kinetics of a DNA displacement reaction, leading to the release of free signaling probes. By reasonable integration of magnetic enrichment and exonuclease-fuelled recycling, the released probes efficiently disrupt the interaction within metal-organic framework nanoprobes, thereby generating a remarkable fluorescent response. Experimental results show that the method not only exhibits a wide linear range and a low detection limit of 7.8 fg mL-1 for SARS-CoV-2 spike protein detection but also demonstrates desirable specificity and utility in complex samples. Therefore, the method may provide a valuable tool for the detection of SARS-CoV-2 spike protein, and has bright prospects in the rapid diagnosis of COVID-19, which is of great significance for guiding rational treatment during a pandemic of respiratory infectious diseases and reducing the occurrence of severe disease in children.

Synthesis and performance study of PAM-g-PAA/PHEA and its application in purifying tellurium aerosol.

In this study, grafted polymers (PAM-g-PAA/PHEA) with different grafting rates are prepared by solution method grafting polymer with polyacrylamide as the main chain, acrylic acid (AA) and 2-hydroxyethyl acrylate (HEA) as the modified monomers. Evidence of graft polymerization of AA and HEA on polyacrylamide side chains is obtained by FT-IR and 1HNMR. Scanning electron microscopy and thermogravimetric characterization further confirm the synthesis of grafted polymers. The properties of the grafting polymer are evaluated using grafting rate, viscosity, and surface tension measurements. The performance of polymer aqueous solution as an aerosol fixative for capturing and removing tellurium aerosol as a simulated polonium aerosol is examined. According to the results, grafting two monomers, acrylic acid, and 2-hydroxyethyl acrylate, effectively improve the cross-sectional structure of the polymer, increase the thermal stability of the polymer, and reduced the surface tension of the aqueous polymer solution to 42.47 mN/m. In addition, aerosol settling and fixation experiments showed that PAM-g-PAA/PHEA had a trapping and scavenging effect on tellurium aerosols with an immobilization rate of 94.86%, which revealed the immobilization mechanism of the immobilizer with tellurium aerosols.

[Corrigendum] The tetraspanin CD151­ARSA mutant inhibits angiogenesis via the YRSL sequence.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 4A on p. 839, the 'CD151/24 h' and 'CD151­ARSA/48 h' panels appeared to contain overlapping sections of data, such that they were potentially derived from the same original source, where these panels were intended to show the results from differently performed experiments. The authors have re­examined their original data, and realize that the 'CD151­ARSA/48 h' panel was inadvertently placed incorrectly in the figure. The revised version of Fig. 4, now containing the correct data for the 'CD151­ARSA/48 h' experiment in Fig. 4A, is shown below. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 7: 836­842, 2013; DOI: 10.3892/mmr.2012.1250].

Optimizing the dielectric constant of the shell layer in core-shell structures for enhanced energy density of polymer nanocomposites.

Improved dielectric constant and breakdown strength facilitates excellent energy storage density of polymer dielectrics, which is positive to miniaturize dielectric capacitors in electronic and electrical systems. Although coating polar substances on nanoparticles enhances the dielectric constants of polymer nanocomposites, it usually causes local electric field concentration, leading to poor breakdown strength. Here, fluoropolymers with tailorable fluorine content (PF0, PF30 and PF60) are coated on BaTiO3 (BT) nanoparticles to construct typical core-shell structures that are further blended with poly(vinylidenefluoride-co-hexafluoropropylene) (P(VDF-HFP)) to obtain BT@PF/P(VDF-HFP) nanocomposites. Uniform dispersion of nanoparticles and excellent compatibility of interfaces are observed for the samples. In addition, the dielectric constant gradually increases from 8.03 to 8.26 to 9.12 for the nanocomposites filled with 3 wt% BT@PF0, BT@PF30 and BT@PF60, respectively. However, 3 wt% BT@PF30/P(VDF-HFP) has the highest breakdown strength (455 kV mm-1) among the nanocomposites, which is as good as neat P(VDF-HFP). More importantly, BT@PF30 rather than BT@PF60 possesses the maximum discharged energy density (11.56 J cm-3 at 485 kV mm-1), which is about 1.65 times that of neat P(VDF-HFP). This work proposes a facile experimental route to optimize the dielectric constants of the shell layer to couple the dielectric constants between the nanoparticles, shell layer and polymer matrix, which contributes to alleviating the local electric field concentration for excellent breakdown strength and electrical energy storage of polymer nanocomposites.

Spatio-temporal evolution characteristics of eco-efficiency in the Yellow River Basin of China based on the super-efficient SBM model.

It is of great significance to study the trends and internal differences of eco-efficiency in the Yellow River Basin for ecological protection and high-quality development of the Yellow River Basin. According to the characteristics of the Yellow River Basin in China, the eco-efficiency evaluation system was constructed, and the super-efficiency slack-based measure (SBM) model and the super-efficiency SBM model of undesired output were used to calculate the eco-efficiency levels of provinces in the Yellow River Basin from 2005 to 2020, and the variation trend and internal differences were analyzed. The results show that when only the expected output was considered, the eco-efficiency of the Yellow River Basin as a whole and each province showed a fluctuating upward trend, but there were obvious differences. Qinghai Province, Sichuan Province, and Ningxia Autonomous Region had high eco-efficiency, while Shaanxi Province, Shanxi Province, and Inner Mongolia Autonomous Region had low eco-efficiency. Compared with only considering the expected outputs, eco-efficiency of Qinghai Province had improved significantly when considering non-expected outputs. The eco-efficiency of Shandong Province and Henan Province had improved significantly after 2016, while the eco-efficiency of the two provinces had decreased significantly before 2016. The eco-efficiency of Shaanxi, Shanxi, Inner Mongolia, Ningxia, and Gansu had declined to varying degrees. Finally, the reasons for the differences in eco-efficiency in various provinces in the Yellow River Basin were analyzed, and suggestions for improving the eco-efficiency of the Yellow River Basin were put forward.

Flexible and Mechanically Enhanced Polyurethane Composite for γ-ray Shielding and Thermal Regulation.

Microencapsulation of paraffin with lead tungstate shell (Pn@PWO) shows the drawbacks of low wettability and poor leakage-proof property and thermal reliability, restricting the application of phase change microcapsules. Herein, a novel paraffin@lead tungstate@silicon dioxide double-shelled microcapsule (Pn@PWO@SiO2) has been successfully constructed by the emulsion-templated interfacial polycondensation and applied in the waterborne polyurethane (WPU). The results indicated that a SiO2 layer with controlled thickness was formed on the PbWO4 shell. The Pn@PWO@SiO2 microcapsules have exhibited superior leakage-proof properties and thermal reliability through double-shelled protection, and the leakage rate decreased by at least 54.11% compared to that of Pn@PWO microcapsules. The SiO2 layer with abundant polar groups ameliorated the wettability of microcapsules and the interfacial compatibility between microcapsules and the WPU matrix. The tensile strength of WPU/Pn@PWO@SiO2-2 composites reached 10.98 MPa, which was over 7 times greater than that of WPU/Pn@PWO composites. In addition, WPU/Pn@PWO@SiO2-2 composites with a latent heat capacity of over 41 J/g exhibited efficient phase change stability and γ-ray shielding properties. Also, the mass attenuation coefficients reached 1.38 cm2/g at 105.3 keV and 1.12 cm2/g at 86.5 keV, respectively. These properties will greatly promote the application of WPU/Pn@PWO@SiO2 composites into γ-ray-shielding devices with thermal regulation.

Comprehensive Diagnostic Criteria for MELAS Syndrome; a Case Study Involving an Elderly Patient With MT-TWm.5541C>T Mutation.

INTRODUCTION: The mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a matrilineal hereditary multisystem disease caused by mutations in the mitochondrial DNA. Although the initial diagnostic criteria correlate with a range of clinical phenotypes, including clinical onset after the age of 40, there is still lack of a unified single diagnostic standard for MELAS. CASE REPORT: A 71-year-old female patient with recurrent stroke was reported. Magnetic resonance imaging showed a cerebral gyrus-like diffusion weighted imaging high signal lesion in the parietal-occipital lobe and the area of this lesion expanded with disease progression. The MRS result showed significantly inverted Lac/Lip peaks. The nucleic acid sequencing result displayed a MT-TWm.5541C>T mutation, and a 12.86% mutation rate in the blood sample. The patient had a 6-year history of type 2 diabetes. CONCLUSION: Patients with the MELAS syndrome may present with a variety of clinical manifestations. Our data demonstrated that, for patients with atypical cerebral infarction and suspected MELAS syndrome, gene sequencing and muscle biopsy should be performed in time. This case provides a reference for the diagnostic criteria of MELAS syndrome.

Insect kinin mimics act as potential control agents for aphids: Structural modifications of Trp4.

Insect kinins are endogenous, biologically active peptides with various physiological functions. The use of insect kinins in plant protection is being evaluated by many groups. Some kinins have been chosen as lead compounds for pest control. We previously reported an insect kinin mimic IV-3 that had insecticidal activity. And by introducing a strong electron withdrawing group (-CF3 ) on the benzene ring (Phe2 ), we discovered a compound, L7 , with better activity than lead IV-3. In this work, taking L7 as the lead compound, we designed and synthesized 13 compounds to evaluate the influence of position 4 (Trp4 ) of insect kinin on insecticidal activity, by replacing the H atom on tryptophan with -CH3 and -Cl or substituting the indole ring of tryptophan with the benzene, naphthalene, pyridine, imidazole, cyclohexane, and alkyl carboxamides. The aphid bioassay results showed that the compounds M1 , M3 , and M5 were more active than the positive control, pymetrozine. Especially, replacing the side chain by an indole ring with 4-Cl substitution (M1 , LC50 = 0.0029 mmol/L) increased the aphicidal activity. The structure-activity relationships (SARs) indicated that the side chain benzene ring at this position may be important to the aphicidal activity. In addition, the toxicity prediction by Toxtree, and the toxicity experiments on Apis mellifera suggested that M1 was no toxicity risk on a non-target organism. It could be used as a selective and bee-friendly insecticide to control aphids.

Ataxia with oculomotor apraxia type 2 caused by a novel homozygous mutation in SETX gene, and literature review.

Objectives: Autosomal recessive inherited ataxia with oculomotor apraxia type 2 (AOA2), caused by SETX gene mutations, is characterized by early-onset, progressive cerebellar ataxia, peripheral neuropathy, oculomotor apraxia and elevated serum α-fetoprotein (AFP). This study aimed to expand and summarize the clinical and genetic characteristics of SETX variants related to AOA2. Methods: The biochemical parameters, electromyogram and radiological findings of the patient were evaluated. Whole-exome sequencing (WES) was performed on the patient using next-generation sequencing (NGS), the variants were confirmed by Sanger sequencing and the pathogenicity of the variants was classified according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. We reviewed 57 studies of AOA2 patients with SETX mutations and collected clinical and genetic information. Results: The patient was a 40-year-old Chinese woman who primarily presented with numbness and weakness of the lower limbs in her teenage years. She had elevated AFP, increased serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and decreased anti-Müllerian hormone (AMH) levels. We identified a novel homozygous missense mutation of the SETX gene, c.7118 C>T (p. Thr2373Ile), in the patient via Whole-exome and Sanger sequencing. The variant was located in the DNA/RNA helicase domain and is highly conserved. The protein prediction analysis verified the SETX variant as a damaging alteration and ACMG/AMP guidelines classified it as likely pathogenic. Through a literature review, we identified 229 AOA2 cases with SETX variants, and among the variants, 156 SETX variants were exonic. We found that 107 (46.7%) patients were European, 50 (21.8%) were African and 48 (21.0%) were Asian. Among the Asian patients, five from two families were Mainland Chinese. The main clinical features were cerebellar ataxia (100%), peripheral neuropathy (94.6%), cerebellar atrophy (95.3%) and elevated AFP concentration (92.0%). Most reported SETX mutations in AOA2 patients were missense, frameshift and nonsense mutations. Conclusion: We discovered a novel homozygous variant of the SETX gene as a cause of AOA2 in the current patient and expanded the genotypic spectrum of AOA2. Moreover, the clinical features of AOA2 and genetic findings in SETX were assessed in reported cohorts and are summarized in the present study.

A novel bee-friendly peptidomimetic insecticide: Synthesis, aphicidal activity and 3D-QSAR study of insect kinin analogs at Phe2 modification.

BACKGROUND: As one of the most abundant and destructive pests in agriculture, aphids cause significant damage to crops due to their sap-taking and as virus vectors. Chemical insecticides are the most effective method to control aphids, but they bring insecticide resistance problems and harm nontarget organisms, especially bees, therefore the search for novel eco-friendly aphid control agents with low bee toxicity is urgent. Insect kinins are a class of small neuropeptides that control important functions in insects. In our previous study, we found insect kinin analog IV-3 has good aphicidal activity and the location of the aromatic ring on the side chain of Phe2 is the key to the formation of the ß-turn resulting in the biological activity of insect kinin analogs. However, there are few studies on insect kinin Phe2 substitution and modification, and its structure-activity relationship is still unclear. RESULTS: In this project, 44 insect kinin analogs with the Phe2 modification, replacing it with different natural or unnatural amino acids, were designed and synthesized based on the lead IV-3 to explore the role of the Phe2 residues. Bioassays with soybean aphids of Aphis glycines indicated that nine analogs have better aphicidal activity than the lead IV-3. In particular, compound L25 exhibits excellent aphicidal activity (LC50  = 0.0047 mmol L-1 ) and has low toxicity to bees. Furthermore, a reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) was established to produce a helpful clue that introducing hydrophobic groups away from the backbone chain is beneficial to improve aphicidal activity. CONCLUSION: The residue Phe2 of insect kinin analogs is the key position and has a significant impact on the activity. L25 has a high toxicity for aphids, while a low toxicity to bees, and therefore can be considered as a lead compound to develop new biosafe aphid control agents. Finally, we provide a useful 3D-QSAR model as theoretical guidance for further structural optimization. © 2022 Society of Chemical Industry.

High loading BaTiO3 nanoparticles chemically bonded with fluorinated silicone rubber for largely enhanced dielectric properties of polymer nanocomposites.

Integrating high-loading dielectric nanoparticles into polar polymer matrices potentially can profit the intrinsic polarization of each phase and allow for greatly enhanced dielectric properties in polymer nanocomposites. It is however challenging to achieve desirable highly filled polar polymer composites because of the lack of efficient approaches to disperse nanoparticles and maintain interfacial compatibility. Here, we report a versatile route to fabricate highly filled barium titanate/fluorinated silicone rubber (BT/FSR) nanocomposites by "thiol-ene click" and isostatic pressing techniques. The loaded BT nanoparticles (from 82 wt% to 90 wt%) are chemically bonded with FSR in the nanocomposites. The existence of the polar group (-CH2CF3) of the polymer matrix does not affect the uniform dispersion of the nanoparticles or the good interfacial compatibility. The 90 wt% BT/FSR nanocomposite shows the highest dielectric constant of 57.8 at 103 Hz, while the loss tangent can be kept below 0.03. Besides, BT/FSR nanocomposites display higher breakdown strength than BT/SR nanocomposites. This work offers a facile strategy towards superior dielectric properties of polymer nanocomposites.

Clinical Characteristics and Outcomes among Patients with Covid-19 in Different Regions of the World.

The SARS-CoV-2 outbreak began in China in December 2019 and rapidly spread globally. Up to July 2020, the number of cases of coronavirus disease 2019 (COVID-19) had been increasing in the USA, Italy, England, Spain and numerous other countries. Patients with this disease in different countries present with different clinical manifestations and different prognosis. The present study aimed to analyse the clinical characteristics of patients infected with SARS-CoV-2 in different regions of the world and provide special advices for the different regions to prevent the spread and a second outbreak of COVID-19. Key Words: COVID-19, SARS-CoV-2, Characteristics, Worldwide.

Clinical Characteristics and Outcomes among Patients with Covid-19 in Different Regions of the World.

The SARS-CoV-2 outbreak began in China in December 2019 and rapidly spread globally. Up to July 2020, the number of cases of coronavirus disease 2019 (COVID-19) had been increasing in the USA, Italy, England, Spain and numerous other countries. Patients with this disease in different countries present with different clinical manifestations and different prognosis. The present study aimed to analyse the clinical characteristics of patients infected with SARS-CoV-2 in different regions of the world and provide special advices for the different regions to prevent the spread and a second outbreak of COVID-19. Key Words: COVID-19, SARS-CoV-2, Characteristics, Worldwide.

Synthesis and Preparation of (Acrylic Copolymer) Ternary System Peelable Sealing Decontamination Material.

Traditional methods that are used to deal with radioactive surface contamination, which are time-consuming and expensive. As one effective measure of radioactive material purification, strippable coating, which effectively coats the pollutant, and settles them on the surface of objects. However, there are some shortcomings in terms of film formation and peelability, such as a brittle coating and poor peelability. Therefore, in order to meet the treatment methods for radioactive contaminants needs, the strippable coating must have excellent sealing, corrosion resistance, weather resistance, low environmental pollution, short film formation time, and good mechanical properties; in addition, the spraying process should be simple, with moderate adhesion, and it should be capable of being quickly and completely peeled off. In this paper, a ternary system was prepared by pre-emulsion polymerization with butyl-acrylate, methyl methacrylate, acrylic acid as the reactive monomer, sodium dodecyl sulfate as the active agent, potassium persulfate as the initiator, and water as the dispersion medium. The Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (1H-NMR), ICP emission spectrometer, surface tension tester, and universal testing machine were used to characterize the structure and morphology of the composite materials. The results show that the decontaminant can quickly wet the powder particles and the surface pollutants. The sealing efficiency of Fe and Cu was over 90%. After the decontaminant was cured, it could be continuously formed on the surface of different substrates and be completely peeled off, as well as having excellent film formation and peelability.

Association of Serum Lipoprotein-Associated Phospholipase A2 and A379V Gene Polymorphisms with Carotid Plaques.

Objective: Lipoprotein-associated phospholipase A2 (LP-PLA2) is closely related to the development of atherosclerosis. The A379V gene polymorphism, located in exon 11 of the PLA2G7 gene, can affect LP-PLA2 levels and the inflammatory response. However, the association between the A379V polymorphism and formation of carotid plaques is unclear. Materials and Methods: A total of 516 ischemic stroke patients were classified according to carotid intima-media thickness as measured by ultrasound into the plaque group (n = 375, including 258 and 117 cases having vulnerable and stable plaques, respectively) and the nonplaque group (n = 141). The LP-PLA2 gene A379V polymorphism was determined by DNA sequencing, and Lp-PLA2 serum protein levels were determined simultaneously. Results: The serum Lp-PLA2 levels (p < 0.0005), CT+TT genotype frequency (odds ratio [OR]: 1.730, 95% confidence interval [CI]: 1.114-2.686, p = 0.014), and T allele frequency (OR: 1.592, 95% CI: 1.082-2.342, p = 0.018) in the plaque group were significantly higher than those in the nonplaque group. Lp-PLA2 serum levels in the vulnerable plaque subgroup were significantly higher than those in the stable plaque subgroup (p = 0.003). However, there were no significant differences in the frequency of the A379V polymorphism between the vulnerable and stable plaque subgroups. For all subjects, Lp-PLA2 serum levels for patients having a CC genotype were significantly lower than those for patients having a CT (p = 0.003), TT (p = 0.014), or CC+TT genotype (p = 0.001). Logistic regression showed that the Lp-PLA2 level was a risk factor for carotid plaque formation (OR: 1.024, 95% CI: 1.011-1.030, p = 0.001), but the A379V gene polymorphism was not (OR: 1.037, 95% CI: 0.357-3.012, p = 0.947). Conclusion: The A379V gene polymorphism might be associated with serum Lp-PLA2 levels and carotid plaque formation, but not with plaque vulnerability in a Chinese Han population. Serum Lp-PLA2 level was shown to be a risk factor for carotid plaque formation.

Synthesis, aphicidal activity and conformation of novel insect kinin analogues as potential eco-friendly insecticides.

BACKGROUND: The discovery of ecofriendly insecticides through a new strategy for aphid control is important because of the substantial resistance and unexpected eco-toxicity to honeybees caused by traditional insecticides. The insect kinins, a class of multifunctional insect neuropeptides, are considered for potential application in pest control. In our previous work we developed several series of insect kinin analogues and found a promising lead II-1 with good aphicidal activity. To seek further eco-friendly aphicides, the optimization of II-1 is carried out in this study. RESULTS: Fifteen novel Yaa3 modified analogues based on the lead II-1 were synthesized. The aphicidal tests indicated that IV-3, IV-5 and IV-10 exhibited significant activity against the soybean aphid Aphis glycines with LC50 values of 0.0029, 0.0072 and 0.0086 mmol L-1 , respectively, higher than that of lead II-1 and the commercial Pymetrozine. The molecular modeling results showed that analogues II-1, IV-3, IV-5, IV-7 and IV-10 formed a ß-turn-like conformation, while the conformation of analogues IV-1, IV-2 and IV-9 seemed to be linear. Some structural elements favorable for the activity were proposed based on the conformation-activity relationship of the analogues. CONCLUSION: Insect kinin analogues derived from lead II-1 by modifying the hydrolysis site Yaa3 with natural, sterically hindered α- and ß-amino acids showed great potential as eco-friendly insecticides. Inspiringly, the most active analogue IV-3 can be a candidate for further development. The ß-turn-like conformation and the orientation of the aromatic rings of the side chain of Phe2 and Trp4 may be critical factors beneficial to activity. © 2019 Society of Chemical Industry.

A de novo Mutation in the MTUS1 Gene Decreases the Risk of Non-compaction of Ventricular Myocardium via the Rac1/Cdc42 Pathway.

Background: The MTUS1 gene encodes a microtubule-associated protein involved in multiple processes including cell polarity and microtubule balance during myocardial development. Aims: To investigate the association between a de novo c. 2617A->C mutation in MTUS1 (NM_001001924.2) and non-compaction of ventricular myocardium (NVM) and explore the potential mechanisms. Methods: A de novo mutation in MTUS1 was identified for a familial pedigree with NVM. Lentiviral vectors containing MTUS1 wild type or the mutation MTUS1 were constructed and co-infected into HEK-293 cells. MTUS1, Rac1/Cdc42, α-tubulin, α/ß-tubulin, polarity protein (PAR6), and the morphology of daughter cells were measured by real-time PCR, Western blot, and immunofluorescence assays, respectively. Results: The lentiviral vectors were constructed successfully. Immunofluorescence assays revealed the fluorescence intensity of α-tubulin to be decreased and α/ß-tubulin to be increased in the mutation MTUS1 group. The fluorescence intensity of PAR6 was higher and morphology of the daughter cells in the mutation group was different from the wild type group. The phosphorylation of Rac1/Cdc42 in the mutation group was significantly lower than in the wild type group. Conclusions: A de novo mutation in MTUS1 decreased the stability of microtubules and increased cell polarity via the Rac1/Cdc42 pathway, which may partly elucidate the mechanism underlying cellular protection in NVM.

An EGLN1 mutation may regulate hypoxic response in cyanotic congenital heart disease through the PHD2/HIF-1A pathway.

Cyanotic congenital heart disease (CCHD), a term describing the most severe congenital heart diseases are characterized by the anatomic malformation of a right to left shunt. Although the incidence of CCHD are far less than the that of congenital heart diseases (CHD), patients with CCHD always present severe clinical features such as hypoxia, dyspnea, and heart failure. Chronic hypoxia induces hypoxemia that significantly contributes to poor prognosis in CCHD. Current studies have demonstrated that the prolyl-4-hydroxylase2 (PHD2, encoded by EGLN1)/hypoxia-inducible factor-1A (HIF-1A) pathway is a key regulator of hypoxic response. Thus, we aim to assess the associations of single polymorphisms (SNPs) of the EGLN1 gene and hypoxic response in CCHD. A missense variant of EGLN1 c.380G>C (rs1209790) was found in 46 patients (46/126), with lower hypoxia incidence and higher rate of collateral vessel formation, compared with the wild type (P < 0.05). In vitro experiments, during hypoxia, EGLN1 mutation reduced EGLN1 expression compared with the wild type, with higher HIF-1A, VEGF and EPO expression levels in the mutant. No difference in HK1 expression was observed between the mutant and wild type. CCHD patients with c.380G>C showed improved response to hypoxia compared with the wild-type counterparts. The EGLN1 c.380G>C mutation improves hypoxic response through the PHD2/HIF-1A pathway, which may provide a molecular mechanism for hypoxic response in CCHD. The effects of the EGLN1 c.380G>C mutation on CCHD prognosis deserve further investigation.