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Abstract Background Painful diabetic neuropathy (PDN) is closely linked to inflammation, which has been demonstrated to be associated with pyroptosis. Emerging evidence has implicated TANK-binding kinase 1 (TBK1) in various inflammatory diseases. However, it remains unknown whether activated TBK1 causes hyperalgesia via pyroptosis. Methods PDN mice model of type 1 or type 2 diabetic was induced by C57BL/6J or BKS-DB mice with Lepr gene mutation. For type 2 diabetes PDN model, TBK1-siRNA, Caspase-1 inhibitor Ac-YVAD-cmk or TBK1 inhibitor amlexanox (AMX) were delivered by intrathecal injection or intragastric administration. The pain threshold and plantar skin blood perfusion were evaluated through animal experiments. The assessments of spinal cord, dorsal root ganglion, sciatic nerve, plantar skin and serum included western blotting, immunofluorescence, ELISA, and transmission electron microscopy. Results In the PDN mouse model, we found that TBK1 was significantly activated in the spinal dorsal horn (SDH) and mainly located in microglia, and intrathecal injection of chemically modified TBK1-siRNA could improve hyperalgesia. Herein, we described the mechanism that TBK1 could activate the noncanonical nuclear factor κB (NF-κB) pathway, mediate the activation of NLRP3 inflammasome, trigger microglia pyroptosis, and ultimately induce PDN, which could be reversed following TBK1-siRNA injection. We also found that systemic administration of AMX, a TBK1 inhibitor, could effectively improve peripheral nerve injury. These results revealed the key role of TBK1 in PDN and that TBK1 inhibitor AMX could be a potential strategy for treating PDN. Conclusions Our findings revealed a novel causal role of TBK1 in pathogenesis of PDN, which raises the possibility of applying amlexanox to selectively target TBK1 as a potential therapeutic strategy for PDN.

The functional property is an important factor to measure the quality of fish gelatin, which directly relates to the practical application range and value of fish gelatin. In order to explore the effect of extraction temperature on the functional properties of mullet scale gelatin, this study used a hot water extraction method. Different temperatures (60, 70, 80, 90, 100 ℃) were examined to assess their impact on the surface morphology of fish scales, fish scale gelatin yield, and functional properties (foaming capacity, emulsifying activity, gel strength, gel temperature, and melting temperature). Furthermore, the structural characteristics of fish scale gelatin were investigated using SDS-PAGE, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results showed that as the extraction temperature increased from 60 ℃ to 100 ℃, the damage to the surface of mullet scales became increasingly severe. The fish scale gelatin yield increased from 31.72% to 50.97%, foaming capacity improved from 23.33% to 73.33%, and emulsifying activity increased from 15.13 m2/g to 17.27 m2/g. However, gel strength, gel temperature, and melting temperature decreased from 677.82 g, 20.80 ℃, and 28.70 ℃ to 372.91 g, 15.80 ℃, and 23.90 ℃, respectively. Additionally, with the increase in extraction temperature, the characteristic bands of mullet scale gelatin α1, α2, and β chains on the electrophoresis pattern became increasingly blurred. The infrared spectroscopy results showed that the fish scale gelatin had characteristic absorption peaks (amide A, amide Ⅰ, amide Ⅱ, and amide Ⅲ), with the wavenumber of amide A first increasing and then decreasing. The scanning electron microscopy results showed that the tightness of the porous grid structure of the fish scale gelatin decreased. These findings provide a theoretical basis for the industrialization of mullet scale gelatin.

To study the preservation effect of chitosan coating with different molecular weights on postharvest passion fruit, the "Qinmi No.9" was coated with chitosan of molecular weights of 30, 50, 100, 150 and 200 kDa (1.5%, w/v) to determine the quality of passion fruit during storage. The results showed that chitosan coating with different molecular weights was able to delay the shrinkage and yellowing, reduce the weight loss rate and inhibit the decay of passion fruit. Moreover, chitosan with a larger molecular weight was more conducive to delaying the ripening and senescence of passion fruit, as well as reducing shrinkage, and decay. At the end of storage, the weight loss of fruits coated with 200 kDa chitosan was nearly 10% less than that coated with 30 kDa chitosan, and the fruits coated with 150 and 200 kDa chitosan did not decay. The lower molecular weight (30 and 50 kDa) and higher molecular weight (150 kDa) chitosan were more effective in inhibiting weight loss, total soluble solids and soluble sugar metabolism, and maintaining titratable acid, flavonoid and total phenol contents of fruit during storage. The chitosan with 150 kDa had the best effect in maintaining the vitamin C content, which was 1.12 times higher than the control group at the end of storage. In conclusion, chitosan with different molecular weights was effective to delay senescence, slow down water loss and shrink of passion fruit and maintain the quality, chitosan with 150 kDa was more suitable to maintain the quality of postharvest passion fruit.

Gliomas are highly heterogeneous and aggressive. Malignant cells in gliomas can contact normal neurons through a synapse-like structure (called neuron-to-glioma synapse, NGS) to promote their proliferation, but it is unclear whether NGS gene expression and regulation show species- and tumor-specificity. This question is important in that many anti-cancer drugs are developed upon mouse models. To address this question, we conducted a pan-glioma analysis using nine scRNA-seq datasets from humans and mice. We also experimentally validated the key element of our methods and verified a key result using TCGA datasets of the same glioma types. Our analyses revealed that NGS gene expression and regulation by lncRNAs are highly species- and tumor-specific. Importantly, simian-specific lncRNAs are more involved in NGS gene regulation than lncRNAs conserved in mammals, and transgenic mouse gliomas have little in common with PDX mouse models and human gliomas in terms of NGS gene regulation. The analyses suggest that simian-specific lncRNAs are a new and rich class of potential targets for tumor-specific glioma treatment, and provide pertinent data for further experimentally and clinically exmining the targets.

ObjectivesThis study aims to explore the interaction of different pathogens in Hand, foot and mouth disease (HFMD) by using a mathematical epidemiological model and the reported data in five regions of China.MethodsA cross-regional dataset of reported HFMD cases was built from four provinces (Fujian Province, Jiangsu province, Hunan Province, and Jilin Province) and one municipality (Chongqing Municipality) in China. The subtypes of the pathogens of HFMD, including Coxsackievirus A16 (CV-A16), enteroviruses A71 (EV-A71), and other enteroviruses (Others), were included in the data. A mathematical model was developed to fit the data. The effective reproduction number (Reff) was calculated to quantify the transmissibility of the pathogens.ResultsIn total, 3,336,482 HFMD cases were collected in the five regions. In Fujian Province, the Reff between CV-A16 and EV-A71&CV-A16, and between CV-A16 and CV-A16&Others showed statistically significant differences (P < 0.05). In Jiangsu Province, there was a significant difference in Reff (P < 0.05) between the CV-A16 and Total. In Hunan Province, the Reff between CV-A16 and EV-A71&CV-A16, between CV-A16 and Total were significant (P < 0.05). In Chongqing Municipality, we found significant differences of the Reff (P < 0.05) between CV-A16 and CV-A16&Others, and between Others and CV-A16&Others. In Jilin Province, significant differences of the Reff (P < 0.05) were found between EV-A71 and Total, and between Others and Total.ConclusionThe major pathogens of HFMD have changed annually, and the incidence of HFMD caused by others and CV-A16 has surpassed that of EV-A71 in recent years. Cross-regional differences were observed in the interactions between the pathogens.

In this work, covalent organic frameworks (COF) derived porous carbon was prepared through employing TpPa-1 as self-sacrificed template and used as solid phase microextraction (SPME) fiber coating. Owing to the high specific surface area and uniform pore size distribution, the resulting porous carbon exhibited excellent extraction ability toward PAHs. Coupled with gas-chromatography mass spectrometry (GC–MS), direct immersion SPME based on the resulting porous carbon was applied for analyzing eight polycyclic aromatic hydrocarbons (PAHs). Under the optimal conditions, the developed method exhibited a wide linear range for PAHs (30–30,000 μg kg−1) along with low limits of detection (LODs, 3.12–8.55 μg kg−1) and limits of quantification (LOQs, 10.4–28.5 μg kg−1). Moreover, the proposed method exhibited high reliability in its application on the determination of PAHs in soil samples, highlighting the application potential of COF derived porous carbons in monitoring aromatic pollutants in the environmental samples.

Abstract Gynostemma yixingense, an important medicinal member of the Cucurbitaceae family, is an endemic herbaceous species distributed in East China. It is morphologically similar to the plants in the same genus, which resulted in some confusion in identification and application. Meanwhile, there are still some controversies in taxonomy. Herein, the complete chloroplast genome sequence of G. yixingense was obtained by Illumina paired-end sequencing technology and compared to other chloroplast genome sequences of congeneric species. The complete chloroplast genome of G. yixingense is 157,910 bp in length with 36.94% GC content and contains a large single-copy (LSC) region of 86,791 bp, a small single-copy (SSC) region of 18,635 bp and a pair of inverted repeat (IR) regions of 26,242 bp. The whole genome contains 133 unique genes, including 87 protein-coding genes, 37 tRNA genes, eight rRNA genes and one pseudogene. In addition, 74 simple sequence repeats (SSRs) were identified, most of which were A/T rich. The phylogenetic analysis indicated that G. yixingense had the closest relationship to G. laxiflorum. The result of this study provided an important theoretical basis for chloroplast genome and phylogenetic analysis of G. yixingense.

Introduction Type 2 diabetes mellitus (T2DM) is a substantial health problem worldwide. Pre-diabetic state is associated with increased risk for the development of diabetes. There are various pharmacological therapies with glucose-lowering activity for diabetes prevention. Of those, most are being compared with placebo instead of active agents. The relative effects and safety of different glucose-lowering drugs still remain uncertain. To address this gap, we will conduct a systematic review and network meta-analysis (NMA) to evaluate comparative efficacy and safety of glucose-lowering agents for T2DM prevention in patients with pre-diabetes.Methods and analysis PubMed, the Cochrane library and Embase will be searched from inception to December 2019 for relevant randomised controlled trials (RCTs) that examined anti-diabetic drugs for diabetes prevention in patients with pre-diabetes. Two reviewers working independently will screen titles, abstracts and full papers. Data extraction will also be completed by two independent authors. The primary outcome will be the incidence of T2DM in patients with pre-diabetes at baseline. Secondary outcomes will include the achievement of normoglycaemia, all-cause mortality, cardiovascular mortality and hypoglycaemic event. Pairwise meta-analysis and NMA will be conducted for each outcome using a frequentist random-effects model. Additionally, subgroup analyses will also be performed. The comparison-adjusted funnel plot will be used to assess publication bias. The overall quality of evidence will be rated with the Grading of Recommendations Assessment, Development and Evaluation framework. Data analysis will be conducted using Stata V.14.0.Ethics and dissemination Ethics approval is not required. We plan to submit the results of this study to a peer-review journal.PROSPERO registration number CRD42019119157.