Case Report: Recurrent Autoimmune Hypoglycemia Induced by Non-Hypoglycemic Medications

We present a case of recurrent autoimmune hypoglycemia induced by non-hypoglycemic agents. We review reported cases of autoimmune hypoglycemia related to non-hypoglycemic agents, and discuss the effects of different detection methods for insulin autoantibodies on the results obtained. We aim to provide information for clinicians and a warning for medication usage. Considering the increasing number of clopidogrel-induced AIH cases and the hypoglycemia-induced increase in the risk of cardiovascular events, we recommend that cardiovascular disease patients being treated with clopidogrel be informed of this rare side effect and that clinicians be vigilant for the possibility of autoimmune hypoglycemia in this patient population

A Rapid Flp-In System for Expression of Secreted H5N1 Influenza Hemagglutinin Vaccine Immunogen in Mammalian Cells

Continuing transmissions of highly pathogenic H5N1 viruses in poultry and humans underscores the need for a rapid response to potential pandemic in the form of vaccine. Recombinant technologies for production of immunogenic hemagglutinin (HA) could provide an advantage over the traditional inactivated vaccine manufacturing process. Generation of stably transfected mammalian cells secreting properly folded HA proteins is important for scalable controlled manufacturing.We have developed a Flp-In based 293 stable cell lines through targeted site-specific recombination for expression of secreted hemagglutinin (HA) proteins and evaluated their immunogenicity. H5N1 globular domain HA1(1-330) and HA0(1-500) proteins were purified from the supernatants of 293 Flp-In stable cell lines. Both proteins were properly folded as confirmed by binding to H5N1-neutralizing conformation-dependent human monoclonal antibodies. The HA0 (with unmodified cleavage site) was monomeric, while the HA1 contained oligomeric forms. Upon rabbit immunization, both HA proteins elicited neutralizing antibodies against the homologous virus (A/Vietnam/1203/2004, clade 1) as well as cross-neutralizing antibodies against heterologous H5N1 clade 2 strains, including A/Indonesia/5/2005. These results exceeded the human antibody responses against the inactivated sub-virion H5N1 vaccine.Our data suggest that the 293 Flp-In system could serve as a platform for rapid expression of HA immunogens in mammalian cells from emerging influenza strains

Pathway-based assessment of single chemicals and mixtures by a high-throughput transcriptomics approach

The ever-increasing number of chemicals and complex mixtures demands a high-throughput and cost-effective approach for chemical safety assessment. High-throughput transcriptomics (HTT) is promising in investigating genome-scale perturbation of chemical exposure in concentration-dependent manner. However, the application of HTT has been limited due to lack of methodology for single chemicals and mixture assessment. This study aimed to evaluate the ability of a newly-developed human reduced transcriptomics (RHT) approach to assess pathway-based profiles of single chemicals, and to develop a biological pathway-based approach for benchmarking mixture potency using single chemical-based prediction model. First, concentration-dependent RHT were used to qualitatively and quantitatively differentiate pathway-based patterns of different chemicals, using three model toxicants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), triclosan (TCS) and 5-Chloro-6-hydroxy-2,2′,4,4′-tetrabromodiphenyl ether (5-Cl-6-OH-BDE-47). AHR-regulated genes and pathways were most sensitively induced by TCDD, while TCS and 5-Cl-6-OH-BDE-47 were much less potent in AHR-associated activation, which was concordant with known MoA of each single chemical. Second, two artificial mixtures and their components of twelve individual chemicals were performed with concentration-dependent RHT. Concentration addition (CA) and independent action (IA) models were used to predict transcriptional potency of mixtures from transcriptomics of individual chemicals. For overall bioactivity, CA and IA models can both predict potency of observed responses within 95% confidence interval. For specific biological processes, multiple biological processes such as hormone signaling and DNA damage can be predicted using CA models for mixtures. The concentration-dependent RHT can provide a powerful approach for qualitative and quantitative assessment of biological pathway perturbated by environment chemical and mixtures.</p

Treatment with succinate dehydrogenase inhibitor Y12196 protects strawberries from boscalid-resistant Botrytis cinerea with the H272R mutation in SDH B

Abstract Gray mold, caused by Botrytis cinerea, poses a significant threat to the strawberry industry worldwide. B. cinerea is a high-risk pathogen in the sense of fungicide resistance. The sensitivities of B. cinerea isolates collected from Zhejiang Province, China, to the succinate dehydrogenase inhibitors (SDHIs) boscalid and Y12196 were determined based on discriminatory dose or 50% effective concentration (EC50). Of the 42 isolates collected in 2018, 15 were resistant to boscalid (35.7%), and 3 were resistant to Y12196 (7.1%). Among the 84 isolates collected in 2019, the EC50 values for boscalid ranged from 0.097 to 54.162 mg/L, while the EC50 values for Y12196 ranged from 0.284 to 20.147 mg/L. Sequence analysis showed that the B. cinerea isolates carrying P225F (proline → phenylalanine) and N230I (asparagine → isoleucine) mutations in SDH subunit B exhibited cross-resistance between boscalid and Y12196. However, boscalid-resistant isolates with a point mutation at position 272 of SDH B (H272R, histidine → arginine) were more sensitive to Y12196. Consistent with this, Y12196, but not boscalid, could successfully inhibit the growth of B. cinerea carrying the H272R mutation (BcSDHB−H272R) on detached strawberries and leaves. Molecular docking simulations further revealed that the hydrogen bonds and π-π interactions were formed between Y12196 and BcSDHB−H272R, but not between boscalid and BcSDHB−H272R, explaining why the boscalid-resistant B. cinerea H272R mutant isolates were sensitive to Y12196. Together, our results suggested that Y12196 could effectively control boscalid resistance associated with the H272R mutation

Associations of serum and urinary magnesium with the pre-diabetes, diabetes and diabetic complications in the Chinese Northeast population.

The effect of magnesium (Mg) deficiency on the prevalence of diabetes and diabetic complications has received a great attention. The present study investigated the association of Mg level in the serum or urine of the patients, lived in the Northeast areas of China, with either pre-diabetes or diabetes with and without complications. From January 2010 to October 2011, patients with type 1 diabetes (T1D, n = 25), type 2 diabetes (T2D, n = 137), impaired fasting glucose (IFG, n = 12) or impaired glucose tolerance (IGT, n = 15), and age/gender matched control (n = 50) were enrolled in the First Hospital of Jilin University. In T2D group, there were 24, 34, and 50 patients with nephropathy, retinopathy or peripheral neuropathy. Serum Mg levels in the patients with IGT, IFG, T2D, and T1D were significantly lower than that of control. The urinary Mg levels were significantly increased only in T2D and T1D patients compared to control. There was no difference for these two changes among T2D with and without complications; In addition, there was a significantly positive correlation of serum Mg levels with serum Ca levels only in T2D patients, and also a significantly positive correlation of urinary Mg levels with urinary Ca levels in control, IGT patients, and T2D patients. Simvastatin treatment in T2D patients selectively reduced serum Ca levels and urinary Mg levels. These results suggest that the potential impact of Mg deficiency on metabolic syndrome, diabetes and diabetic complications needs to be received special attention

Case analysis of integrated maintenance technology for multi-dimensional rapid detection and trenchless reinforcement

China’s highway construction has moved from “construction-oriented” to the development stage of “equal attention to construction and maintenance”. The infrastructure represented by urban expressways, under heavy and complex traffic loads, is prone to a variety of diseases that take place in the middle and lower layers of pavement such as “frost boils” and “voids”, which cannot be repaired ideally with the help of conventional detection and treatment techniques. In order to solve the above problems, this paper adopts nondestructive testing plans such as ground penetrating radar and falling weight deflectometer to conduct multidimensional rapid detection of the road surface to obtain the image information and mechanical data of the road structure. Based on the improved calculation method, the pavement disease area, depth and type can be effectively judged. Combined with the observation of water level, the polymer grouting reinforcement plan is designed to eliminate the problems in the middle and lower layers of the road surface. It can effectively reduce the incidence of diseases in the upper layer of the sidewalk, and significantly improve the efficiency and service level of the sidewalk

Research on Application Effect of Mixconverter in Cement Concrete Pavement

In order to improve the strength of cement concrete pavement and reduce pavement cracking, the application effect of the hydration reaction enhancer Mixconverter in cement concrete pavement was studied by testing the compressive strength, bending strength, crack resistance and chloride ion permeability of concrete indoors. The test results show that the addition of Mixconverter to concrete can significantly improve the compressive and flexural strength of concrete, effectively prevent the expansion of plastic shrinkage and cracking of concrete, and significantly reduce the chloride ion diffusion coefficient. Finally, the test road pavement further proves the improvement effect of Mixconverter on concrete strength and cracking

Study on the Performance of the Physical Foaming Warm-mix Recycled Asphalt Mixture

In order to evaluate the performance of the physical foaming warm-mix recycled asphalt mixture (WRAM), the hot mix plant recycling technology was adopted to develop AC-20 hot-mix recycled asphalt mixture (HRAM) and the WRAM of different reclaimed asphalt pavement (RAP) contents. The high temperature stability, water stability and low temperature crack resistance performance of the reclaimed asphalt pavement were evaluated. The results indicate that the physical foaming WRAM feature better high temperature stability, water stability and low temperature crack resistance compared to those of HRAM. With the increase in RAP contents, the high temperature stability of the physical foaming WRAM and HRAM rises notably but the water stability and low temperature crack resistance performance continues to drop

Design method of the mix ratio of hot mix plant recycled asphalt mixture containing high mixture content

This paper mainly used the Superpave and the Marshall design methods to design the mix ratio of the hot mix plant recycled asphalt mixture. The road performance of AC-20, SUP-20 with 30% RAP content and AC-20 with 50% RAP content was studied to evaluate the water stability and high temperature stability and low temperature crack resistance of the recycled asphalt mixture. Research shows that the road performance of AC-20 mixed with 50% RAP content meets the technical requirements of the same type of asphalt mixture. It is recommended to use the Marshall design method for hot mix plant recycled asphalt mixture design