The expression of RBPJ and its potential role in rheumatoid arthritis.

BACKGROUND: Recombination signal-binding protein for immunoglobulin kappa J region (RBPJ) is a transcriptional regulator that plays an important role in maintaining immune homeostasis. This study aimed to estimate the expression of RBPJ in rheumatoid arthritis (RA) patients and investigate its relationship with RA. METHODS: A total of 83 newly diagnosed RA patients and 70 healthy controls were included. mRNA was extracted from peripheral blood mononuclear cells (PBMCs), and the expression of RBPJ was detected using quantitative real-time PCR (qRT‒PCR). An RA dataset (GSE89408) was obtained from the Gene Expression Omnibus (GEO) database, and RA synovial tissues were divided into two groups. The differentially expressed genes (DEGs) were selected with the "DESeq2" R package. RESULTS: RBPJ expression was lower in RA patients than in health controls and was negatively correlated with the DAS28 score, C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR). RA synovial tissues from GSE89408 were classified into RBPJ-low (≤ 25%) and RBPJ-high (≥ 75%) groups according to RBPJ expression, and 562 DEGs were identified. Gene Ontology (GO) enrichment analyses revealed that the DEGs significantly affected the regulation of T cell activation and lymphocyte/mononuclear cell differentiation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the most enriched pathways of DEGs were the T cell receptor signaling pathway, Th1/2 and Th17 cell differentiation, the PI3K - Akt signaling pathway and cytokine‒cytokine receptor interaction. CytoHubba Plugin revealed that most of the top 10 genes were involved in osteoclast differentiation, the T cell receptor signaling pathway and cytokine‒cytokine receptor interaction. CONCLUSIONS: RBPJ expression was significantly lower in RA patients and negatively correlated with disease activity. GEO dataset analysis demonstrated that RBPJ may be involved in osteoclast differentiation, T cell activation and differentiation, and the T cell receptor signaling pathway. Our research may contribute to understanding the potential mechanisms by which RBPJ regulates T cell differentiation and cytokine‒cytokine receptor interaction in RA patients.

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.

High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

Enhanced dielectric constant and breakdown strength of sandwiched polymer nanocomposite film for excellent energy storage.

Enhanced dielectric constant and high breakdown strength offers immense promise for excellent energy storage performance, which is of critical significance in modern electronics and power systems. However, polymer nanocomposites with traditional routes have to balance between dielectric constant and breakdown strength, hence hindering substantive increases in energy density. Herein, a sandwiched polymer nanocomposite film has been constructed to take full advantage of the individual component layers. BaTiO3 nanoparticles are coated with a fluoropolymer to form core-shell structures and then introduced into a polymer as the top and the bottom layers of a sandwich film for enhancing polarization. Moreover, boron nitride nanosheets (BNNSs) in the middle layer of the sandwich film exert positive effects on the inhibition of current leakage for high breakdown resistance. The breakdown strength increases from 480 MV m-1 of the neat polymer to 580 MV m-1 of the sandwiched film. Additionally, the film exhibits a higher dielectric constant in comparison with the neat polymer. The sandwiched film displays a superior energy density (15.75 J cm-3), which is about 1.9 times that of the neat polymer. This work proposes a feasible route to achieve excellent energy storage of polymer dielectrics by synergistically introducing insulating fillers and additional dipoles in a sandwiched polymer nanocomposite film.

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.

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.

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.

Height, VKORC1 1173, and CYP2C9 Genotypes Determine Warfarin Dose for Pediatric Patients with Kawasaki Disease in Southwest China.

Long-term oral warfarin is recommended in pediatric Kawasaki disease patients with large coronary artery aneurysms; however, heterogeneity is considerable. This study aimed to determine variables affecting warfarin dosage in Kawasaki disease. The enrolled individuals (194 children) were divided into four groups: (1) Cases with severe coronary artery lesions (CAL) of IV to V degrees or thrombogenesis treated with oral warfarin were assigned to Group A; (2) Group B, CAL of I degrees; (3) Group C, CAL of II and III degrees cases with small or medium-sized CAL not treated with warfarin; (4) Group D, normal children without Kawasaki disease. The relevant genotypes of CYP2C9, VKORC1 (1173, - 1639, and 3730), and CYP4F2 were assessed. There were no statistically significant differences in CYP2C9, VKORC1, and CYP4F2 mutation frequencies among the 4 groups. In the 44 Group A patients, demographic features, clinical characteristics, and genotypes were recorded, and their associations with warfarin dose variability were assessed. Multivariate linear regression analysis revealed that height, VKORC1 1173, and CYP2C9 accounted for 61.2%, 7.9%, and 4.3% of dosing variability, respectively. Conclusions: Patient height is the main factor determining warfarin dosage, while genotype effects on warfarin dosage vary among studies. New formula should be defined using data obtained from children in cases with demonstrated efficacy.

Case Report: Charcot-marie-tooth disease caused by a de novo MORC2 gene mutation - novel insights into pathogenicity and treatment.

Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy involving approximately 80 pathogenic genes. Whole-exome sequencing (WES) and confirmatory Sanger sequencing analysis was applied to identify the disease-causing mutations in a Chinese patient with lower limb weakness. We present an 18-year-old male with a 2.5-year history of progressive lower limb weakness and an unsteady gait. Upon admission, a physical examination revealed hands tremulousness, bilateral calf muscle wasting and weakness, pes cavus, and elevated serum creatine kinase (CK) levels. Electromyography demonstrated axonal neuropathy affecting both upper and lower limbs. A de novo heterozygous missense mutation was identified in the MORC2 gene, NM_001303256.3: c.1199A>G, NP_001290186.1: p.Gln400Arg. Consequently, these clinical and genetic findings suggested a diagnosis of hereditary peripheral neuropathy, CMT type 2Z. Oral mecobalamin and coenzyme Q10 was initiated as subsequent treatment. Our study firstly reports the MORC2 c.1199A>G mutation occurring de novo, highlighting its causal association with CMT2Z, and prompting its reclassification as likely pathogenic. Oral mecobalamin and coenzyme Q10 might be a potential treatment approach for early-stage CMT2Z. We recommend genetic testing for CMT patients to identify the genetic etiology, thereby improving clinical management and facilitating genetic counseling.

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.

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.

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.

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.

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.

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.

[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].

Lack of independent relationship between the MMP-12 gene polymorphism and carotid plaque susceptibility in the Chinese Han population.

The purpose of this study was to investigate whether a polymorphism in the matrix metalloproteinase-12 gene (MMP-12 -82A/G) is correlated with serum protein levels or with the susceptibility for carotid plaques in the Chinese Han population. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed on the -82A/G polymorphism in the MMP-12 gene for 1314 patients with acute cerebral infarctions; 710 of these cases were diagnosed with stable plaques, 340 cases were diagnosed with vulnerable plaques and 264 cases had no plaques. At the same time, serum MMP-12 levels were measured using the enzyme-linked immunosorbent assay (ELISA). Compared to the AA genotype, the frequency of the AG+GG genotypes was not significantly different between the three groups (χ(2) = 1.242, p = 0.537), and the frequency of the G allele of the MMP-12 gene was not different within the three subgroups (χ(2) = 1.218, p = 0.544). There were no significant differences in MMP-12 protein levels among the three groups (F = 0.675, p = 0.510); similarly, there was no difference in MMP-12 protein levels between the stable plaque group and the vulnerable plaque group (p = 0.755). There was also no difference between the vulnerable plaque group and the no plaque group (p = 0.420). The current data suggest that the inter-individual variability in the MMP-12 gene variation may not be a risk factor for vulnerable plaques in the Chinese Han population.

[Association between matrix metalloproteinase-8 -799C/T polymorphism and instability of carotid plaque].

OBJECTIVE: To investigate the association between a -799C/T polymorphism in the promotor region of matrix metalloproteinase-8 (MMP-8) gene and instability of carotid plaque in Chinese Han population. METHODS: A total of 451 acute infarction patients from the Department of Neurology of Taizhou Hospital were divided into carotid vulnerable plaque group and carotid stable plaque group according to the results of carotid B-mode ultrasonography. Serum MMP -8 level was measured by the means of enzyme-linked immunosorbent assay (ELISA). At the same time, the MMP-8 -799C/T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Serum level of MMP-8 in the carotid vulnerable plaque group was higher than that in the carotid stable plaque group (t= 2.894, P= 0.004). The genotype distribution of -799C/T polymorphism between the two groups was significantly different (Chi-square = 13.65, P= 0.000). Serum level of MMP-8 in patients with TT genotype was higher than that in patients with CC genotype (t= 3.141, P= 0.001). CONCLUSION: The present study suggested that serum level of MMP-8 and the -799C/T polymorphism of MMP-8 gene are associated with carotid vulnerable plaque in Chinese Han population, and the T allele may be a predictor for the susceptibility of carotid vulnerable plaque.

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.