FGF13 enhances the function of TRPV1 by stabilizing microtubules and regulates acute and chronic itch.

Itching is an aversive somatosensation that triggers the desire to scratch. Transient receptor potential (TRP) channel proteins are key players in acute and chronic itch. However, whether the modulatory effect of fibroblast growth factor 13 (FGF13) on acute and chronic itch is associated with TRP channel proteins is unclear. Here, we demonstrated that conditional knockout of Fgf13 in dorsal root ganglion neurons induced significant impairment in scratching behaviors in response to acute histamine-dependent and chronic dry skin itch models. Furthermore, FGF13 selectively regulated the function of the TRPV1, but not the TRPA1 channel on Ca2+ imaging and electrophysiological recordings, as demonstrated by a significant reduction in neuronal excitability and current density induced by TRPV1 channel activation, whereas TRPA1 channel activation had no effect. Changes in channel currents were also verified in HEK cell lines. Subsequently, we observed that selective modulation of TRPV1 by FGF13 required its microtubule-stabilizing effect. Furthermore, in FGF13 knockout mice, only the overexpression of FGF13 with a tubulin-binding domain could rescue TRP channel function and the impaired itch behavior. Our findings reveal a novel mechanism by which FGF13 is involved in TRPV1-dependent itch transduction and provide valuable clues for alleviating pathological itch syndrome.

Review of the Idaeaproximaria complex (Lepidoptera, Geometridae, Sterrhinae) with descriptions of four new species.

The Idaeaproximaria complex is reviewed and four new species are described from China: Idaearectangularis Cheng & Han, sp. nov. from Guangxi and Fujian provinces, Idaearectispina Cheng & Han, sp. nov. from Hunan province, Idaeasetosa Xue & Han, sp. nov. from Hainan province, and Idaealinearis Xue & Han, sp. nov. from Hubei and Shaanxi provinces. Illustrations of adults and genitalia of the new species and known species are presented, and the variations in the form of the aedeagus of Idaeaproximaria are discussed.

Beyond iron-storage pool: functions of plant apoplastic iron during stress.

Iron (Fe) is an essential micronutrient for plants, and its storage in the apoplast represents an important Fe pool. Plants have developed various strategies to reutilize this apoplastic Fe pool to adapt to Fe deficiency. In addition, growing evidence indicates that the dynamic changes in apoplastic Fe are critical for plant adaptation to other stresses, including ammonium stress, phosphate deficiency, and pathogen attack. In this review, we discuss and scrutinize the relevance of apoplastic Fe for plant behavior changes in response to stress cues. We mainly focus on the relevant components that modulate the actions and downstream events of apoplastic Fe in stress signaling networks.

Effect of Aging Treatment on the Precipitation Behavior of a Novel Al-Cu-Zr Cast Alloy.

A novel Al-Cu-Zr alloy is designed in this paper, which provides a method for further improving the strength of Al-Cu alloys. In this paper, the addition of the micro-alloying element Zr in Al-Cu alloy was studied. The effect of aging treatment on the mechanical properties and precipitation behavior of the alloy was studied. With the addition of Zr, Al3Zr phases were formed in the alloy, which acts as obstacles to dislocation motion. In addition, Al3Zr phases can be used as the nucleation site of θ' phases to promote precipitation. All this can improve the strength of Al-Cu alloys. After one-step aging, corresponding to the highest hardness, the largest amount of θ' phases were observed in the alloy matrix. By contrast, after two-step aging, the θ' phases were finer, and a large amount of Guinier-Preston (GP) zones formed during the pre-aging step, which were transformed into denser and finer θ' phases in the secondary aging step. After the same solution treatment (540 °C/12 h), undergoing 120 °C/4 h + 175 °C/10 h two-step aging, the ultimate tensile strength, yield strength, and elongation of the Al-Cu-Zr alloy were 398.7 MPa, 313.3 MPa, and 7.9%, respectively.

Four new species of Ditrigona Moore (Lepidoptera, Drepanidae) in China and an annotated catalogue.

The Chinese species of the genus Ditrigona Moore, 1888 are reviewed and an annotated catalogue is provided. Four new species are described from China: Ditrigonasinespina Jiang & Han, sp. nov., Ditrigonaparva Jiang & Han, sp. nov., Ditrigonaconcava Guo & Han, sp. nov., and Ditrigonafusca Guo & Han, sp. nov. Derocacrystalla Chu & Wang, 1987 and Auzatellapentesticha Chu & Wang, 1987 are newly combined into, respectively, the derocina and quinaria species groups of Ditrigona. Ditrigonadiana Wilkinson is newly recorded in China. This results in 43 species of Ditrigona for the fauna of China. Illustrations of habitus and genitalia of the new species and most known species are presented.

Multifunctional ionic liquid-assisted interfacial engineering towards ZnS nanodots with ultrastable high-rate lithium storage performance.

In this article, a new zinc-containing ionic liquid (IL) [HMMIm]2[ZnCl4] (HMMIm = 1-hexyl-2,3-dimethyl-imidazolium) is designed, which acts as a multifunctional source for the interfacial engineering of ZnS nanodots (NDs). Given the electrostatic interaction driven by the imidazolium cation, the steric effect of the alkyl chain, and the in situ released Zn ion from the IL, [HMMIm]2[ZnCl4] shows great advantages in controlling the formation of ZnS NDs. Based on this strategy, a nanocomposite consisting of homodispersed ZnS NDs anchored on sulfur/nitrogen dual-doped reduced graphene oxide (ZnS-NDs@SNG) is prepared. When evaluated as an anode material for lithium-ion batteries (LIBs), the nanocomposite delivers high reversible specific capacity, excellent high-rate performance, and superior cycling life. In particular, a discharge capacity of 648.1 mA h g-1 can be achieved at a high current density (10.0 A g-1) over 5000 cycles. Benefitting from the multifunctional IL and the simple synthesis protocol, the IL-assisted interfacial engineering strategy will enable a new avenue for the controllable synthesis of metal-sulfide-based anode materials.

Estimating hybridization as a consequence of climatic fluctuations: A case study of two geometridae species.

In some cases, the phylogenetic analysis based on the mitochondrial DNA (mtDNA) and the nuclear DNA (ncDNA) are discordant. There are three major causes of the discordance within insects, including hybridization, incomplete lineage sorting (ILS) and infection by Wolbachia. In this study, we used a combination of multilocus and coalescent analyses to explore these processes occurred during the evolutionary history of Limbatochlamys rosthorni Rothschild, 1894 and Limbatochlamys pararosthorni Han and Xue, 2005. The ncDNA phylogenetic tree supported two reciprocally monophyletic species, whereas the mtDNA results failed to reveal such a structure and revealed an extensive level of admixture between two species. Because of very low Wolbachia infection rates (<20%), we firstly excluded this reason for the discordance. The fixed nucleotide differences and large genetic distances (1.5-2.5%) at the ncDNA genes suggested that the lineage sorting process between these two species is nearly complete and two species have experienced a prolonged period of independent evolution. Thus, we secondly excluded ILS. Sharing haplotypes, mtDNA gene flow occurring and the transitional samples with morphological features supported hybridization. The distribution contraction during glaciations and postglacial distribution expansion might have facilitated hybridization. Taken together, our study indicates that the current genetic structure of L. rosthorni and L. pararosthorni is the results of contraction and fragmentation into separated refugia during glaciations, followed by postglacial expansion and admixture.

Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution.

The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8+ T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8+ T and immune-suppressive TNFRSF4+ Treg cells in tumours might derive from peripheral CX3CR1+CD8+ T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3+ DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3+ DCs, Treg, exhausted CD8+ T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.

Effect of six-stitch pancreaticojejunostomy on pancreatic fistula: A propensity score-matched comparative cohort study.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most common and severe complication after pancreaticoduodenectomy (PD). Despite the development of numerous anastomotic surgical techniques to minimize CR-POPF, more than 30% of patients who undergo PD develop CR-POPF. Herein, we propose a novel pancreaticojejunostomy (PJ) technique and evaluate its efficacy and safety compared to traditional PJ. METHODS: This retrospective study enrolled 164 consecutive patients who underwent PJ after PD between January 2012 and June 2017. Of them, 78 (47.6%) underwent traditional PJ and 86 (52.4%) underwent six-stitch PJ. The primary outcome was CR-POPF at 1-month follow-up defined according to the revised 2016 International Study Group on Pancreatic Fistula definition. To adjust for baseline differences and selection bias, patients were matched by propensity scores, which left 63 patients with traditional PJ and 63 with six-stitch PJ. RESULTS: Compared to patients who underwent traditional PJ (mean age 56.2 ± 9.4 years), patients who underwent six-stitch PJ (mean age 57.4 ± 11.4 years) had a lower CR-POPF rate. The risk of CR-POPF among patients who underwent six-stitch PJ was decreased by 81.7% after adjustment for age, sex, body mass index, and disease severity compared to patients who underwent traditional PJ. Additionally, the surgery time was reduced from 29 min for traditional PJ to 15 min for six-stitch PJ (P <0.001). Adverse effects such as abdominal fluid collection, abdominal bleeding, and wound infection were similar between two groups. CONCLUSION: Six-stitch PJ may be an effective and efficient PJ technique for patients who undergo PD surgery.

An anti-CD103 antibody-drug conjugate prolongs the survival of pancreatic islet allografts in mice.

CD103 mediates T-cell infiltration and organ allograft rejection, and depletion of CD103-expressing cells is a promising therapeutic strategy for allograft intolerance. Recently, we verified that M290-MC-MMAF, an anti-CD103 antibody-drug conjugate, potently eliminates CD103-positive cells in vivo, with high specificity and minimal toxicity. However, the contribution of M290-MC-MMAF to blocking the CD103/E-cadherin pathway involved in transplant rejection remains unclear. Herein, we examined the impact of systemic administration of M290-MC-MMAF on allografts in an islet transplantation model. M290-MC-MMAF treatment maintained the long-term survival of islet allografts (>60 days) compared to mock injection or unconjugated M290 antibody treatment (<18 days). The change was associated with a decrease in CD103+CD8+ effector T cells and an increase in CD4+CD25+ regulatory T cells. CD103+CD8+ effector T-cell transfer or CD4+CD25+ regulatory T-cell depletion resulted in a rapid loss of allografts in long-surviving islet hosts. Moreover, M290-MC-MMAF treatment reduced IL-4, IL-6, and TNF-α expression levels and increased IL-10 expression in the grafts, which presented an immunosuppressive cytokine profile. In conclusion, targeting CD103 with M290-MC-MMAF induced immunosuppression and prolonged the survival of pancreatic islet allografts in mice, indicating the potential clinical value of M290-MC-MMAF in therapeutic interventions for allograft rejection.

Influence of alkalinity on the synthesis of hierarchical LTA zeolite by using bridged polysilsesquioxane.

The mechanism of formation of hierarchical LTA zeolite involved the methoxyl groups of bridged polysilsesquioxane hydrolyzing into hydroxyl groups. The covalent Si-O-Si bond between silicon hydroxyl in the above solution and other silica sources forms by dehydration, avoiding phase separation. The influence of alkalinity on the synthesis of hierarchical LTA zeolites was investigated by using bridged polysilsesquioxane. XRD patterns indicate the synthesis of sodalite at the same molar composition of the hierarchical LTA zeolites without bridged polysilsesquioxane. The characterization results from TG and DTG revealed that bridged polysilsesquioxane was successfully incorporated into the as-synthesized hierarchical LTA zeolite. N2-adsorption/desorption results proved that mesopores and the porosities of the hierarchical LTA zeolites are adjustable by a change of alkalinity. SEM images indicated that the morphologies of the hierarchical LTA zeolites changed with increasing alkalinity. The hierarchical LTA zeolites showed faster initial exchange rates of Na+ to Mg2+ compared with conventional LTA.

Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells.

Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid ß peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.

Four New Diterpene Glucosides from Perovskia atriplicifolia.

Four new diterpene glucosides, namely perovskiaditerpenosides A - D (1 - 4), were isolated from the BuOH extract of Perovskia atriplicifolia. Their structures were well elucidated by chemical methods and comprehensive spectroscopic analyses including MS, IR, and NMR (1D and 2D). The newly isolated compounds were screened for their cytotoxic activity against HepG2, NB4, HeLa, K562, MCF7, PC3, and HL60. The obtained results indicated that the new compounds possessed considerable cytotoxic activity.

VEGFA Expression Is Inhibited by Arsenic Trioxide in HUVECs through the Upregulation of Ets-2 and miRNA-126.

Arsenic trioxide (ATO) has been used to treat patients with acute promyelocytic leukemia. Recently, studies have shown that ATO can induce apoptosis in leukemic cells and blood vessel endothelial cells in a time- and dose-dependent manner through the inhibition of vascular endothelial growth factor A (VEGFA) production. VEGFA is a key factor in angiogenesis initiation. Targeted inhibition of VEGF or VEGFA expression can suppress angiogenesis; however, little is known about the mechanism by which ATO inhibits VEGFA expression. In this study, we investigated the role of miRNA-126 in the mechanism of action of ATO in human umbilical vein endothelial cells (HUVECs). ATO significantly decreased the viability and proliferation of HUVECs and decreased their migration at 48 h. Cell proliferation was inhibited by 50% (IC50) when 5.0 µmol/L ATO was used. ATO treatment induced miR-126 upregulation and HUVEC apoptosis. Transfection with a miR-126 mimic significantly downregulated VEGFA mRNA levels, and transfection with a miR-126 inhibitor significantly upregulated VEGFA mRNA levels. Finally, we showed that ATO treatment upregulated Ets-2 and miR-126 expression in HUVECs. These results demonstrate that ATO inhibits the growth of HUVECs and induces apoptosis by downregulating VEGFA. One mechanism by which this occurs is Ets-2 upregulation, which results in an increase in miR-126 levels and downregulation of VEGFA expression.

Genetic landscape of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.

Effects of Traditional Chinese Medicinal Plants on Anti-insulin Resistance Bioactivity of DXMS-Induced Insulin Resistant HepG2 Cells.

ABSTRACT: Medicinal plants have a long history of use in China to treat diabetic symptoms. Ancient Chinese medical manuscripts and ethnobotanical surveys document plant remedies that continue to be actively used in China for the treatment of diabetic symptoms. Based on a systematic ancient Chinese medical manuscripts review in combination with ethnobotanical survey, 16 medicinal plants for the traditional treatment of diabetic symptoms were identified for the evaluation of anti-insulin resistance bioactivity. The biological activity of 16 medicinal plants was tested on dexamethasone (DXMS)-induced insulin resistant HepG2 cells. The result shows that 11 of the 16 medicinal plants enhanced glucose uptake of DXMS-induced insulin resistant HepG2 cells, thereby demonstrating their ability to increase insulin sensitivity, other five medicinal plants including Astragalus membranaceus were found ineffective. The study shows that ancient Chinese medical manuscripts and ethnobotanical surveys on plants for the prevention and treatment of diabetic symptoms provide a promising knowledge base for drug discovery to mitigate the global diabetes epidemic.

[Essential procedure and key methods for survey of traditional knowledge related to Chinese materia medica resources].

The survey of traditional knowledge related to Chinese materia medica resources is the important component and one of the innovative aspects of the fourth national survey of the Chinese materia medica resources. China has rich traditional knowledge of traditional Chinese medicine (TCM) and the comprehensive investigation of TCM traditional knowledge aims to promote conservation and sustainable use of Chinese materia medica resources. Building upon the field work of pilot investigations, this paper introduces the essential procedures and key methods for conducting the survey of traditional knowledge related to Chinese materia medica resources. The essential procedures are as follows. First is the preparation phrase. It is important to review all relevant literature and provide training to the survey teams so that they have clear understanding of the concept of traditional knowledge and master key survey methods. Second is the field investigation phrase. When conducting field investigations, survey teams should identify the traditional knowledge holders by using the 'snowball method', record the traditional knowledge after obtaining prior informed concerned from the traditional knowledge holders. Researchers should fill out the survey forms provided by the Technical Specification of the Fourth National Survey of Chinese Materia Medica Resources. Researchers should pay particular attention to the scope of traditional knowledge and the method of inheriting the knowledge, which are the key information for traditional knowledge holders and potential users to reach mutual agreed terms to achieve benefit sharing. Third is the data compilation and analysis phrase. Researchers should try to compile and edit the TCM traditional knowledge in accordance with intellectual property rights requirements so that the information collected through the national survey can serve as the basic data for the TCM traditional knowledge database. The key methods of the survey include regional division of Chinese materia medica resources, interview of key information holders and standardization of information.' In particular, using "snowball method" can effectively identify traditional knowledge holder in the targeted regions and ensuring traditional knowledge holders receiving prior informed concerned before sharing the information with researcher to make sure the rights of traditional knowledge holders are protected. Employing right survey methods is not only the key to obtain traditional knowledge related to Chinese materia medica resources, but also the pathway to fulfill the objectives of access and benefit sharing stipulated in Convention on Biological Resources. It will promote the legal protection of TCM traditional knowledge and conservation of TCM intangible, cultural heritage.

[Spectral reflectance characteristics of dominant plant species at different eco-restoring stages in the semi-arid grassland].

The objective of the research is to apply hyperspectral technique into eco-restoring monitoring. Through the ASD Fields HH portable field spectrometer, the hyperspectral data of dominant plant species in vegetation at different eco-restoring stages in semi-arid grassland in Helin County, Inner Mongolia were collected. The original spectrum reflected data were pretreated by wavelet threshold denoising through ViewSpecPro software before analysis. Using the first derivative spectra between 660 and 800 nm, and the methods of detrended canonical correspondence analysis (DCCA) by Canoco 4. 5 software, the canopy hyperspectral datum of 6 dominant plant species was calculated. The results indicated that the dominant plant species at early succession stage were Setaria viridis and Caragana microphylia, at 5 years eco-restoring stage they were Salsola collina and Caragana microphylia and at late succession stage they were Pinus sylvestnis var. mongolica and Salsola collina, same as field survey. The graph of DCCA indicated that the influential bands of dominant species canopy at early eco-succession stage were short bands, with a large variation among species, the influential bands at 5 years eco-restoring stage were near infrared bands between 1 000 and 1 050 nm, and that at late stage were near infrared bands of 1 040-1 075 nm. The DCCA also showed obviously differences in canopy spectrum among 6 dominant species, and obviously differences among 3 eco-restoring stages.

[Ecological characteristics of preferred habitat of reindeer of Daxing'an Mountain forest area Northeast China in summer].

In July and August of 2012 and 2013, habitat selection and use patterns of reindeer were studied using both line and strip-transect surveys. Twenty-three habitat factors were measured and compared in known reindeer range areas in northwestern China. A total of 72 sampling sites were designated as being used by reindeer, and 162 sites were designated as unused control plots. The results indicated that, compared to the non-used habitat plots, reindeer selected summer habitats with higher values in altitude (26.9 ± 0.8 m), arbor canopy (17.9% ± 2.4%), arbor DBH (35.5 ± 2.1 cm), arbor height (8.2 ± 0.5 m), arbor density (6.9 ± 0.5 ind · 400 m(-2)) and stump quan- tity (1.3 ± 0.2 ind · 400 m(-2)), and with a lower shrub height (54.2 ± 2.0 cm). Moreover, reindeer also selected habitats at intermediate positions of intermediate slope gradient, which provided good water accessibility, more distance from human disturbance and herder influence, but bad concealment and lee condition. Results of the principal component analysis showed that the disturbance intensity (i. e. residential dispersion, anthropogenic-disturbance dispersion), arbor characteristics (arbor height and arbor density, arbor DBH and arbor canopy), geography characteristics (i. e. slope position, slope aspect and soil moisture), food abundance (ground-plant cover and shrub cover), openness (concealment and lee condition) and slope gradient were the most important factors influencing the habitat selection of reindeer in summer. In summary, the summer habitat selection of reindeer is a multidimensional process, through which reindeer adapt according to their ecological needs of food resources, safety and anti-predation. Furthermore, the pattern of habitat selection of reindeer showed that reindeer in China has not yet been domesticated, and reindeer populations and their core habitats should be conserved from intensive disturbance.