Clinical studies show that chronic pain is accompanied by memory deficits and reduction in hippocampal volume. Experimental studies show that spared nerve injury (SNI) of the sciatic nerve induces long-term potentiation (LTP) at C-fiber synapses in spinal dorsal horn, but impairs LTP in the hippocampus. The opposite changes may contribute to neuropathic pain and memory deficits, respectively. However, the cellular and molecular mechanisms underlying the functional synaptic changes are unclear. Here, we show that the dendrite lengths and spine densities are reduced significantly in hippocampal CA1 pyramidal neurons, but increased in spinal neurokinin-1-positive neurons in mice after SNI, indicating that the excitatory synaptic connectivity is reduced in hippocampus but enhanced in spinal dorsal horn in this neuropathic pain model. Mechanistically, tumor necrosis factor-alpha (TNF-␣) is upregulated in bilateral hippocampus and in ipsilateral spinal dorsal horn, whereas brain-derived neurotrophic factor (BDNF) is decreased in the hippocampus but increased in the ipsilateral spinal dorsal horn after SNI. Importantly, the SNI-induced opposite changes in synaptic connectivity and BDNF expression are prevented by genetic deletion of TNF receptor 1 in vivo and are mimicked by TNF-␣ in cultured slices. Furthermore, SNI activated microglia in both spinal dorsal horn and hippocampus; pharmacological inhibition or genetic ablation of microglia prevented the region-dependent synaptic changes, neuropathic pain, and memory deficits induced by SNI. The data suggest that neuropathic pain involves different structural synaptic alterations in spinal and hippocampal neurons that are mediated by overproduction of TNF-␣ and microglial activation and may underlie chronic pain and memory deficits.Key words: memory deficit; microglia; neuropathic pain; SNI; synaptic plasticity; TNF-␣ Significance StatementChronic pain is often accompanied by memory deficits. Previous studies have shown that peripheral nerve injury produces both neuropathic pain and memory deficits and induces long-term potentiation (LTP) at C-fiber synapses in spinal dorsal horn (SDH) but inhibits LTP in hippocampus. The opposite changes in synaptic plasticity may contribute to chronic pain and memory deficits, respectively. However, the structural and molecular bases of these alterations of synaptic plasticity are unclear. Here, we show that the complexity of excitatory synaptic connectivity and brain-derived neurotrophic factor (BDNF) expression are enhanced in SDH but reduced in the hippocampus in neuropathic pain and the opposite changes depend on tumor necrosis factor-alpha/tumor necrosis factor receptor 1 signaling and microglial activation. The regiondependent synaptic alterations may underlie chronic neuropathic pain and memory deficits induced by peripheral nerve injury.

BackgroundAs a type of recently discovered noncoding RNA, circular RNAs (circRNAs) exert pivot biological functions in diverse cancers. However, the role of circRNA_102171 in papillary thyroid cancer (PTC) has not been investigated. Our study was focused on the functional investigation toward circRNA_102171 in PTC progression. And we also aimed to reveal its potential molecular mechanism.MethodsThe expression pattern of circRNA_102171 was determined using quantitative polymerase chain reaction (qPCR) in PTC samples and cell lines. Cell proliferation was examined utilizing CCK8, colony formation and EdU incorporation assays. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. Cell migration and invasion was measured using Transwell assay. Tumor growth in vivo was determined through a xenograft assay. RNA-pulldown, RNA-IP (RIP) and RNA-EMSA were used to analyze the interaction between circRNA_102171 and CTNNBIP1.ResultsCircRNA_102171 expression was upregulated in tumor tissues and cell lines. CircRNA_102171 silencing suppressed PTC cell proliferation, migration and invasion while promoting apoptosis. CircRNA_102171 knockdown inhibited PTC growth in vivo. CircRNA_102171 interacted with CTNNBIP1 to block its interaction with the β-catenin/TCF3/TCF4/LEF1 complex, leading to activation of Wnt/β-catenin pathway.ConclusionsCircRNA_102171 overexpression promotes PTC progression through activating Wnt/β-catenin pathway in a CTNNBIP1-dependent way.

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Bacillus cereus is widely distributed in different food products and can cause a variety of symptoms associated with food poisoning. Since ready-to-eat (RTE) foods are not commonly sterilized by heat treatment before consumption, B. cereus contamination may cause severe food safety problems. In this study, we investigated the prevalence of B. cereus in RTE food samples from different regions of China and evaluated the levels of bacterial contamination, antibiotic resistance, virulence gene distribution, and genetic polymorphisms of these isolates. Of the tested retail RTE foods, 35% were positive for B. cereus, with 39 and 83% of the isolated strains harboring the enterotoxin-encoding hblACD and nheABC gene clusters, respectively. The entFM gene was detected in all B. cereus strains. The cytK gene was present in 68% of isolates, but only 7% harbored the emetic toxin-encoding gene cesB. Antimicrobial susceptibility testing revealed that the majority of the isolates were resistant not only to most β-lactam antibiotics, but also to rifamycin. Multilocus sequence typing (MLST) revealed that the 368 isolates belonged to 192 different sequence types (STs) including 93 new STs, the most prevalent of which was ST26. Collectively, our study indicates the prevalence, bacterial contamination levels, and biological characteristics of B. cereus isolated from RTE foods in China and demonstrates the potential hazards of B. cereus in RTE foods.

ABSTRACT Increasing data indicate that insects serve as major reservoirs and vectors of viruses, which account for the continuously increasing ecological burden and infectious disease outbreaks. Uncovering the hidden diversity of viruses in insects will further the understanding of the ecological and evolutionary perspectives in the emergence of insect-associated virus diseases. In this study, we queried transcriptome sequencing (RNA-Seq) data from more than 600 species across 32 insect orders dwelling in different ecological habitats and recovered more than 1,213 RNA viruses that were recapitulated in 40 families, 2 unclassified genera, and many unspecified viral groups. These novel viruses included the well-known insect-associated viruses within Flaviviridae, Picornavirales, Bunyavirales, Mononegavirales, Nidovirales, Reoviridae, and Negevirus. More appeared to form novel clusters within previously described taxa or could be resolved as paraphyletic, including the first astrovirus identified in insects, in which many were sufficiently divergent to warrant the establishment of new virus genera or families. Additionally, some viruses were closely related to the recognized plant-, fungus-, and vertebrate-specific species, implying the importance of relationships between insect behavior and virus spread. Comparative genome analyses also revealed high genomic variability with respect to the flexible gene pool and genome architecture of these newly described viruses, including the evidence for genome reshuffling first discovered in Dicistroviridae. The data reflecting the genetically and ecologically diverse viral populations in insects greatly expand our understanding of RNA viruses in nature and highlight that the biodiversity of RNA viruses remains largely unexplored. IMPORTANCE Insects comprise the largest proportion of animals on earth and are frequently implicated in the transmission of vector-borne diseases. However, considerable attention has been paid to the phytophagous and hematophagous insects, with results that provide insufficient and biased information about the viruses in insects. Here, we have delivered compelling evidence for the exceptional abundance and genetic diversity of RNA viruses in a wide range of insects. Novel viruses were found to cover major categories of RNA viruses, and many formed novel clusters divergent from the previously described taxa, dramatically broadening the range of known RNA viruses in insects. These newly characterized RNA viruses exhibited high levels of genomic plasticity in genome size, open reading frame (ORF) number, intergenic structure, and gene rearrangement and segmentation. This work provides comprehensive insight into the origin, spread, and evolution of RNA viruses. Of course, a large-scale virome project involving more organisms would provide more-detailed information about the virus infections in insects.

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Bacillus cereus is a food-borne opportunistic pathogen that can induce diarrheal and emetic symptoms. It is widely distributed in different environments and can be found in various foods, including fresh vegetables. As their popularity grows worldwide, the risk of bacterial contamination in fresh vegetables should be fully evaluated, particularly in vegetables that are consumed raw or processed minimally, which are not commonly sterilized by enough heat treatment. Thereby, it is necessary to perform potential risk evaluation of B. cereus in vegetables. In this study, 294 B. cereus strains were isolated from vegetables in different cities in China to analyze incidence, genetic polymorphism, presence of virulence genes, and antimicrobial resistance. B. cereus was detected in 50% of all the samples, and 21/211 (9.95%) of all the samples had contamination levels of more than 1,100 MPN/g. Virulence gene detection revealed that 95 and 82% of the isolates harbored nheABC and hblACD gene clusters, respectively. Additionally, 87% of the isolates harbored cytK gene, and 3% of the isolates possessed cesB . Most strains were resistant to rifampicin and β-lactam antimicrobials but were sensitive to imipenem, gentamicin, ciprofloxacin, kanamycin, telithromycin, ciprofloxacin, and chloramphenicol. In addition, more than 95.6% of the isolates displayed resistance to three kinds of antibiotics. Based on multilocus sequence typing, all strains were classified into 210 different sequence types (STs), of which 145 isolates were assigned to 137 new STs. The most prevalent ST was ST770, but it included only eight isolates. Taken together, our research provides the first reference for the incidence and characteristics of B. cereus in vegetables collected throughout China, indicating a potential hazard of B. cereus when consuming vegetables without proper handling.