Prevalence and diversity of small rodent-associated Bartonella species in Shangdang Basin, China.

The aim of this study was to investigate the occurrence and molecular characteristics of Bartonella infections in small rodents in the Shangdang Basin, China. Small rodents were captured using snap traps, and their liver, spleen, and kidney tissues were harvested for Bartonella detection and identification using a combination of real-time PCR of the ssrA gene (296 bp) and conventional PCR and sequencing of the gltA gene (379 bp). Results showed that 55 of 147 small rodents to be positive for Bartonella, with a positivity rate of 37.41%, and 95% confidence interval of 29.50%- 45.33%. While the positivity rate across genders (42.62% in males and 33.72% in females, χ2 = 1.208, P = 0.272) and tissues (28.57% in liver, 33.59% in spleen, and 36.76% in kidney, χ2 = 2.197, P = 0.333) of small rodents was not statistically different, that in different habitats (5.13% in villages, 84.44% in forests, and 54.17% in farmlands, χ2 = 80.105, P<0.001) was statistically different. There were 42 Bartonella sequences identified in six species, including 30 B. grahamii, three B. phoceensis, two B. japonica, two B. queenslandensis, one B. fuyuanensis and four unknown Bartonella species from Niviventer confucianus, Apodemus agrarius and Tscherskia triton. In addition to habitat, Bartonella species infection could be affected by the rodent species as well. Among the Bartonella species detected in this area, B. grahamii was the dominant epidemic species (accounting for 71.43%). B. grahamii exhibited four distinct clusters, and showed a certain host specificity. In addition, 11 haplotypes of B. grahamii were observed using DNASP 6.12.03, among which nine haplotypes were novel. Overall, high occurrence and genetic diversity of Bartonella were observed among small rodents in the Shangdang Basin; this information could potentially help the prevention and control of rodent-Bartonella species in this area.

Molecular detection and genetic characterization of small rodents associated Bartonella species in Zhongtiao Mountain, China.

The prevalence and molecular characteristics of Bartonella infections in small rodents in the Zhongtiao Mountain, China have been explored. In this study, the liver, spleen and kidney tissues of captured rodents were used for Bartonella spp. detection and identification by combination of real-time PCR of transfer-mRNA (ssrA) gene and traditional PCR and sequencing of citrate synthase (gltA) gene. It was shown that 49.52% of the rodents (52/105) were positive for Bartonella spp.. The infection rate in different gender (χ2 = 0.079, P = 0.778) and tissues (χ2 = 0.233, P = 0.890) of small rodents did not have statistical difference, but that in different small rodents (Fisher's exact test, P < 0.001) and habitats (χ2 = 5.483, P = 0.019) had statistical difference. And, the sequencing data suggests that Bartonella sequences (n = 31) were identified into three species, including 14 of B. grahamii, 3 of B. queenslandensis and 14 of unknown Bartonella species. Phylogenetic analysis showed that B. grahamii sequences were clustered with the isolates from South Korea and China, and B. queenslandensis sequences were mainly closely related to the isolates from China and Thailand. The genetic diversity analysis showed that B. grahamii and B. queenslandensis sequences exhibited noticeable intraspecies diversity. Taken together our data demonstrates the high prevalence and genetic diversity of Bartonella infections in small rodents in the Zhongtiao Mountain, especially a potential novel Bartonella specie was detected, which could benefit the prevention and control of rodent-Bartonella species in this area.

Genomic Variation Landscape of the Model Salt Cress Eutrema salsugineum.

Eutrema salsugineum has long been used as the model for examining salt and other abiotic stress in plants. In addition to the forward genetics approaches widely used in the lab, natural variations undoubtedly will provide a rich genetic resource for studying molecular mechanisms underlying the stress tolerance and local adaptation of this species. We used 90 resequencing whole genomes of natural populations of this species across its Asian and North American distributions to detect the selection signals for genes involved in salt and other stresses at the species-range level and local distribution. We detected selection signals for genes involved in salt and other abiotic tolerance at the species level. In addition, several cold-induced and defense genes showed selection signals due to local adaptation in North America-NE Russia or northern China, respectively. These variations and findings provide valuable resources for further deciphering genetic mechanisms underlying the stress tolerance and local adaptations of this model species.

Spatiotemporal clustering and meteorological factors affected scarlet fever incidence in mainland China from 2004 to 2017.

OBJECTIVE: To analyze the spatiotemporal dynamic distribution and detect the related meteorological factors of scarlet fever from an ecological perspective, which could provide scientific information for effective prevention and control of this disease. METHODS: The data on scarlet fever cases in mainland China were downloaded from the Data Center of the China Public Health Science, while monthly meteorological data were extracted from the official website of the National Bureau of Statistics. Global Moran's I, local Getis-Ord Gi⁎ hotspot statistics, and Kulldorff's retrospective space-time scan statistical analysis were used to detect the spatial and spatiotemporal clusters of scarlet fever across all settings. A spatial panel data model was conducted to estimate the impact of meteorological factors on scarlet fever incidence. RESULTS: Scarlet fever in China had obvious spatial, temporal, and spatiotemporal clustering, high-incidence spatial clusters were located mainly in the north and northeast of China. Nine spatiotemporal clusters were identified. A spatial lag fixed effects panel data model was the best fit for regression analysis. After adjusting for spatial individual effects and spatial autocorrelation (ρ = 0.5623), scarlet fever incidence was positively associated with a one-month lag of average temperature, precipitation, and total sunshine hours (all P-values < 0.05). Each 10 °C, 2 cm, and 10 h increase in temperature, precipitation, and sunshine hours, respectively, was associated with a 6.41% increment and 1.04% and 1.41% decrement in scarlet fever incidence, respectively. CONCLUSION: The incidence of scarlet fever in China showed an upward trend in recent years. It had obvious spatiotemporal clustering, with the high-risk areas mainly concentrated in the north and northeast of China. Areas with high temperature and with low precipitation and sunshine hours tended to have a higher scarlet fever incidence, and we should pay more attention to prevention and control in these places.

MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma.

PURPOSE: Moesin-ezrin-radixin-like protein (Merlin) has been identified as a tumor suppressor in several types of cancers. However, the biological function of Merlin in osteosarcoma remains unclear. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we sought to evaluate the regulation of Merlin expression by miR-25-3p and the role of the miR-25-3p/Merlin axis in osteosarcoma progression, with the aim of identifying a potential therapeutic target for osteosarcoma. MATERIALS AND METHODS: TCGA (The Cancer Genome Atlas) database was used to analyze the correlation between Merlin expression and prognosis. RT-qPCR and Western blotting analyses were performed to compare Merlin expression between normal and malignant cells. A dual-luciferase reporter assay was performed to evaluate the direct targeting of Merlin by miR-25-3p. We overexpressed miR-25-3p, or/and Merlin, in U-2 OS and 143B cells, and studied their cellular functions in vitro. MTT and colony formation assays were performed to determine the effects on cell growth. EdU and cell cycle assays were performed to analyze the effects in cell replication. We used annexin V-fluorescein isothiocyanate and propidium iodide to stain apoptotic cells, and analyzed the cells using flow cytometry. The effects on cell metastasis were studied in wound healing and transwell assays. Lastly, the underlying mechanism was determined in RT-qPCR and Western blotting experiments. RESULTS: Low Merlin expression was linked to poor prognosis. miR-25-3p was observed to directly target Merlin and downregulate its expression. miR-25-3p promoted cell growth, migration, and invasion, and inhibited apoptosis induced by cisplatin. Moreover, the overexpression of Merlin reversed the abovementioned effects of miR-25-3p. Further, the miR-25-3p/Merlin axis was observed to play an important role in the Hippo pathway, and regulated the expression of genes such as BIRC5, CTGF, and CYR61. CONCLUSION: miR-25-3p functions as an oncogenic microRNA in osteosarcoma by targeting Merlin, and may serve as a potential therapeutic target for osteosarcoma.

TARBP2 inhibits IRF7 activation by suppressing TRAF6-mediated K63-linked ubiquitination of IRF7.

Interferon regulatory factor 7 (IRF7), a crucial regulator of type I interferons (IFNs), plays a crucial role in resistance to viral infection. The abnormal production of type I IFNs is associated with many types of disease, such as cancer and inflammatory disorders. Thus, understanding the post-translational modifications of IRF7 is essential to promoting an appropriate immune response. We have recently showed that the TAR RNA binding protein 2 (TARBP2) suppresses IFN-ß production and the innate antiviral response by targeting MAVS. Here, we further identified TARBP2 as a novel inhibitor of IRF7, which inhibits IRF7-mediated IFN-ß production triggered by the Sendai virus in 293 T cells. Overexpression of TARBP2 inhibits the phosphorylation as well as the K63-linked ubiquitination of IRF7, whilst TARBP2 also impairs the stability of endogenous TRAF6. Furthermore, TARBP2 participates in the interaction between IRF7 and TRAF6, thereby suppressing TRAF6-mediated K63-linked ubiquitination of IRF7, which is a prerequisite of IRF7 phosphorylation. Our findings further reveal the mechanism by which TARBP2 regulates the antiviral signaling pathways of the innate immune system.

THO Complex Subunit 7 Homolog Negatively Regulates Cellular Antiviral Response against RNA Viruses by Targeting TBK1.

RNA virus invasion induces a cytosolic RIG-I-like receptor (RLR) signaling pathway by promoting assembly of the Mitochondrial antiviral-signaling protein (MAVS) signalosome and triggers the rapid production of type I interferons (IFNs) and proinflammatory cytokines. During this process, the pivotal kinase TANK binding kinase 1 (TBK1) is recruited to the MAVS signalosome to transduce a robust innate antiviral immune response by phosphorylating transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor (NF)-κB and promoting their nuclear translocation. However, the molecular mechanisms underlying the negative regulation of TBK1 are largely unknown. In the present study, we found that THO complex subunit 7 homolog (THOC7) negatively regulated the cellular antiviral response by promoting the proteasomal degradation of TBK1. THOC7 overexpression potently inhibited Sendai virus- or polyI:C-induced IRF3 dimerization and phosphorylation and IFN-ß production. In contrast, THOC7 knockdown had the opposite effects. Moreover, we simulated a node-activated pathway to show that THOC7 regulated the RIG-I-like receptors (RLR)-/MAVS-dependent signaling cascade at the TBK1 level. Furthermore, THOC7 was involved in the MAVS signalosome and promoted TBK1 degradation by increasing its K48 ubiquitin-associated polyubiquitination. Together, these findings suggest that THOC7 negatively regulates type I IFN production by promoting TBK1 proteasomal degradation, thus improving our understanding of innate antiviral immune responses.

RACK1 attenuates RLR antiviral signaling by targeting VISA-TRAF complexes.

Virus-induced signaling adaptor (VISA), which mediates the production of type I interferon, is crucial for the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway. Upon viral infection, RIG-I recognizes double-stranded viral RNA and interacts with VISA to mediate antiviral innate immunity. However, the mechanisms underlying RIG/VISA-mediated antiviral regulation remain unclear. In this study, we confirmed that receptor for activated C kinase 1 (RACK1) interacts with VISA and attenuates the RIG/VISA-mediated antiviral innate immune signaling pathway. Overexpression of RACK1 inhibited the interferon-ß (IFN-ß) promoter; interferon-stimulated response element (ISRE); nuclear factor kappa B (NF-κB) activation; and dimerization of interferon regulatory factor 3 (IRF3) mediated by RIG-I, VISA, and TANK-binding kinase 1 (TBK1). A reduction in RACK1 expression level upon small interfering RNA knockdown increased RIG/VISA-mediated antiviral transduction. Additionally, RACK1 disrupted formation of the VISA-tumor necrosis factor receptor-associated factor 2 (TRAF2), VISA-TRAF3, and VISA-TRAF6 complexes during RIG-I/VISA-mediated signal transduction. Additionally, RACK1 enhanced K48-linked ubiquitination of VISA, attenuated its K63-linked ubiquitination, and decreased VISA-mediated antiviral signal transduction. Together, these results indicate that RACK1 interacts with VISA to repress downstream signaling and downregulates virus-induced IFN-ß production in the RIG-I/VISA signaling pathway.

FKBP8 inhibits virus-induced RLR-VISA signaling.

The mitochondrial antiviral signal protein mitochondrial antiviral signaling protein, also known as virus-induced signaling adaptor (VISA), plays a key role in regulating host innate immune signaling pathways. This study identifies FK506 binding protein 8 (FKBP8) as a candidate interacting protein of VISA through the yeast two-hybrid technique. The interaction of FKBP8 with VISA, retinoic acid inducible protein 1 (RIG-I), and IFN regulatory factor 3 (IRF3) was confirmed during viral infection in mammalian cells by coimmunoprecipitation. Overexpression of FKBP8 using a eukaryotic expression plasmid significantly attenuated Sendai virus-induced activation of the promoter interferons ß (IFN-ß), and transcription factors nuclear factor κ-light chain enhancer of activated B cells (NF-κB) and IFN-stimulated response element (ISRE). Overexpression of FKBP8 also decreased dimer-IRF3 activity, but enhanced virus replication. Conversely, knockdown of FKBP8 expression by RNA interference showed opposite effects. Further studies indicated that FKBP8 acts as a negative interacting partner to regulate RLR-VISA signaling by acting on VISA and TANK binding kinase 1 (TBK1). Additionally, FKBP8 played a negative role on virus-induced signaling by inhibiting the formation of TBK1-IRF3 and VISA-TRAF3 complexes. Notably, FKBP8 also promoted the degradation of TBK1, RIG-I, and TRAF3 resulting from FKBP8 reinforced Sendai virus-induced endogenous polyubiquitination of RIG-I, TBK1, and TNF receptor-associated factor 3 (TRAF3). Therefore, a novel function of FKBP8 in innate immunity antiviral signaling regulation was revealed in this study.

TARBP2 negatively regulates IFN-ß production and innate antiviral response by targeting MAVS.

MAVS as an essential receptor protein for anti-virus innate immunity plays an important role in the production of virus-induced typeⅠ interferon and regulation of interferon regulatory factor 3/7. Understanding the MAVS-mediated antiviral signaling pathway can provide detailed insights. In this study, we identify transactivation response element RNA-binding protein (TARBP2), as an inhibitor of the cellular protein kinase PKR, negatively regulates virus -induced IFN-ß production by targets MAVS. Overexpression of TARBP2 inhibits virus-induced IFN-ß production as well as cellular antiviral response. Then knockdown of TARBP2 inhibited virus-induced IFN-ß signaling. Further studies demonstrated that TARBP2 interacted with MAVS and targeted MAVS to abrogate MAVS-RIG-I and MAVS-TRAF3 association. Our findings suggest that TARBP2 is an important non-redundant virus-mediated negative regulator of typeⅠ interferon.

Characterization of the complete chloroplast genome of Biondia chinensis (Apocynaceae: Asclepiadoideae: Asclepiadeae), a rare and threatened liana endemic to China.

The complete chloroplast genome of Biondia chinensis, a rare liana of the Asclepiadoideae endemic to China, was determined in this study. It is classified as Vulnerable species because of the sharp decline in its population size due to the habitat destruction. The whole chloroplast genome was 160,308 bp long, comprising of a large single copy (LSC) region of 91,335 bp and a small single copy (SSC) region of 19,185 bp, which were separated by a pair of 24,894 bp long inverted repeat (IR) regions. It encoded a total of 131 genes, including 86 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Most of the gene species appeared as a single copy, while 22 gene species appeared in double copies. The overall A + T content was 62.2%, while the corresponding values of the LSC, SSC, and IR regions were 63.9, 68.1, and 56.7%, respectively. Phylogenetic analysis suggested that, among all the species which have been analyzed B. chinensis was relatively close to Vincetoxicum rossisum.

Complete chloroplast genome sequence of Parnassia brevistyla (Celastraceae) and phylogenetic analysis with related species.

The taxonomic status of Parnassia has been widely discussed, which has been placed in more than five families, Parnassiaceae, Droseraceae, Saxifragaceae, and Celastraceae. Due to the lack of reliable genetic data, we sequenced and analyzed P. brevistyla chloroplast genome for future genetic study. The complete chloroplast genomes of Parnassia brevistyla was sequenced with NovaSeq 6000. The full length of P. brevistyla chloroplast genomes is 151,728 bp. A total of 114 unique genes, including 30 tRNA genes, four rRNA genes, and 80 protein-coding genes were found in the chloroplast genome. Using the whole chloroplast genome sequences alignment of 10 species from Celastraceae and Saxifragaceae, the phylogenetic relationship was built. The phylogenetic position of P. brevistyla was closely clustered with Celastraceae. The complete chloroplast genome of P. brevistyla provides utility information for further research of phylogenetic relationship and taxonomic status of Parnassia.

A micron-scale laminar MAPbBr3 single crystal for an efficient and stable perovskite solar cell.

Nowadays, obtaining a thin and large-area perovskite single-crystal (SC) is still challenging. Herein, we report a novel strategy to prepare a laminar MAPbBr3 SC with a controllable thickness of 16 µm and a size of 6 × 8 mm. Additionally, the SC solar cell achieves an intriguing efficiency of 7.11% with an impressive stability, maintaining 93% initial PCE after aging for 1000 h.

In Situ Growth of 120 cm2 CH3 NH3 PbBr3 Perovskite Crystal Film on FTO Glass for Narrowband-Photodetectors.

Organometal trihalide perovskites have been attracting intense attention due to their enthralling optoelectric characteristics. Thus far, most applications focus on polycrystalline perovskite, which however, is overshadowed by single crystal perovskite with superior properties such as low trap density, high mobility, and long carrier diffusion length. In spite of the inherent advantages and significant optoelectronic applications in solar cells and photodetectors, the fabrication of large-area laminar perovskite single crystals is challenging. In this report, an ingenious space-limited inverse temperature crystallization method is first demonstrated to the in situ synthesis of 120 cm2 large-area CH3 NH3 PbBr3 crystal film on fluorine-doped tin oxide (FTO) glass. Such CH3 NH3 PbBr3 perovskite crystal film is successfully applied to narrowband photodetectors, which enables a broad linear response range of 10-4 -102 mW cm-2 , 3 dB cutoff frequency (f 3 dB ) of ≈110 kHz, and high narrow response under low bias -1 V.

[Preparation and in vitro drug release behavior of a novel matrine-loading chitosan/glycerol film].

OBJECTIVE: To prepare a drug-loading film using chitosan and carboxymethyl chitosan as the carrier materials for delivering matrine to oral ulcers. METHODS: Matrine-loading films using chitosan or carboxymethyl chitosan as the carrier materials were prepared by solution casting method and orthogonal experiment at room temperature. The mechanical properties, surface morphology and drug-loading capacity of the drug-loading film were characterized using tensile test, scanning electron microscopy (SEM), swelling test and in vitro drug release test. RESULTS: When the molecular weight of chitosan was 650 000 and the mass ratio of chitosan/glycerol was 1:1.4, the prepared film had the maximum mechanical strength and tensile modulus reaching 0.7875 MPa. SEM observation showed that matrine aggregated at the bottom of the drug-loading film with an asymmetrical distribution. The in vitro drug release test showed that the film had a high drug-loading capacity and a sustained drug release property. The duration of drug release from the drug-loading film was prolonged as the molecular weight of chitosan increased, reaching 23 h when the molecular weight of chitosan was 650 000. The duration of drug release was further increased to 108 h when the bottom of the drug-loading film was coated with a layer of 1% carboxymethyl chitosan. CONCLUSION: The matrix materials of the drug-loading film are natural, green, nontoxic and biodegradable, and the preparation of the film is simple without using large quantities of organic solvents. The novel drug-loading film can obviously prolong the duration of drugs release for better local drug delivery to oral ulcers in a sustained manner.

Spatial transmission and meteorological determinants of tuberculosis incidence in Qinghai Province, China: a spatial clustering panel analysis.

BACKGROUND: Tuberculosis (TB) is the notifiable infectious disease with the second highest incidence in the Qinghai province, a province with poor primary health care infrastructure. Understanding the spatial distribution of TB and related environmental factors is necessary for developing effective strategies to control and further eliminate TB. METHODS: Our TB incidence data and meteorological data were extracted from the China Information System of Disease Control and Prevention and statistical yearbooks, respectively. We calculated the global and local Moran's I by using spatial autocorrelation analysis to detect the spatial clustering of TB incidence each year. A spatial panel data model was applied to examine the associations of meteorological factors with TB incidence after adjustment of spatial individual effects and spatial autocorrelation. RESULTS: The Local Moran's I method detected 11 counties with a significantly high-high spatial clustering (average annual incidence: 294/100 000) and 17 counties with a significantly low-low spatial clustering (average annual incidence: 68/100 000) of TB annual incidence within the examined five-year period; the global Moran's I values ranged from 0.40 to 0.58 (all P-values < 0.05). The TB incidence was positively associated with the temperature, precipitation, and wind speed (all P-values < 0.05), which were confirmed by the spatial panel data model. Each 10 °C, 2 cm, and 1 m/s increase in temperature, precipitation, and wind speed associated with 9 % and 3 % decrements and a 7 % increment in the TB incidence, respectively. CONCLUSIONS: High TB incidence areas were mainly concentrated in south-western Qinghai, while low TB incidence areas clustered in eastern and north-western Qinghai. Areas with low temperature and precipitation and with strong wind speeds tended to have higher TB incidences.

Bartonella Species Detected in the Plateau Pikas (Ochotona curzoiae) from Qinghai Plateau in China.

Bartonella species can infect a variety of mammalian hosts and cause a broad spectrum of diseases in humans, but there have been no reports of Bartonella infection in Ochotonidae. This is the first study to detect Bartonella in plateau pikas in the Qinghai plateau, providing baseline data for the risk assessment of human Bartonella infection in this area. We obtained 15 Bartonella strains from 79 pikas in Binggou and Maixiu areas of Qinghai with a positive rate of 18.99%. Based on the phylogenetic analysis of the Bartonella citrate synthase (gltA) gene sequences, most strains were closely related to B. taylorii (3/15) and B. grahamii (12/15). The latter is a pathogenic strain in humans. Our results suggest that a corresponding prevention and control strategy should be taken into consideration in the Qinghai province.

Three-dimensional TiO2/ZnO hybrid array as a heterostructured anode for efficient quantum-dot-sensitized solar cells.

The development of a novel nanoarray photoanode with a heterostructure on a transparent conducting oxide substrate provides a promising scheme to fabricate efficient energy conversion devices. Herein, we successfully synthesize the vertically aligned hierarchical TiO2 nanowire/ZnO nanorod or TiO2 nanowire/ZnO nanosheet hybrid arrays, which are proven to be excellent anode candidates for superior light utilization. Consequently, the quantum-dot-sensitized solar cells based on such hybrid arrays exhibit an impressive power conversion efficiency (PCE) under AM 1.5G one sun illumination with improved short-circuit current density (JSC) and fill factor compared to pristine TiO2 nanowire arrays. Combined with the chemical-bath-deposited Cu2S counter electrode, the eventual PCE can be further optimized to as high as 4.57% for CdS/CdSe co-sensitized quantum dot solar cells.