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Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-α, IL-1β, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.

Anomalies from the LHCb lepton flavour universality and Fermilab muon anomalous magnetic moment show tantalizing hints of possible new physics from the lepton sectors. Due to its large mass and shorter lifetime than muon, the tau lepton is believed to couple more to possible new physics beyond the Standard Model. Traditionally, tau leptons are probed through their decay products due to tau’s short lifetime. On the other hand, at a high energy scale, a large fraction of tau leptons could be boosted to a much longer lifetime and fly a visible distance from several centimetres up to kilometer length scale yet very informative to new physics beyond the standard model or high energy cosmic rays. In this article, we investigate rare, yet promising, tau-physics phenomena, where long-lived taus are exploited either as a microscope (for the measurement of tau’s anomalous magnetic moment to an unprecedented level of accuracy) or as a macroscope (for the detection of 1 TeV to 1 PeV cosmic neutrinos).

Background. BRAF exon 15 p.V600E (BRAF V600E) mutation has been established as an important molecular marker for papillary thyroid carcinoma diagnosis by ultrasound-guided fine-needle aspiration biopsy (FNAB). Sanger sequencing is the gold standard for detecting BRAF V600E mutations but fails to identify low-frequency mutations. However, droplet digital PCR (ddPCR) is a popular new method for detecting low-frequency mutations. Here, we compare the efficiency of droplet digital PCR (ddPCR) and Sanger sequencing for detection of the BRAF V600E mutation in thyroid fine-needle aspiration (FNA) samples. Methods. Thyroid fine-needle aspiration samples from 278 patients with 310 thyroid nodules were collected. Sanger sequencing and ddPCR were conducted to detect the BRAF V600E mutation. Results. The BRAF V600E mutation was found in 94 nodules (30.32%) by ddPCR and 40 nodules (12.90%) by Sanger sequencing in 310 FNA samples. A total of 119 nodules were confirmed PTC by postsurgical pathology. Among which the BRAF mutation was found in 80 (67.23%) nodules by ddPCR and 31 (26.05%) by Sanger sequencing. All nodules carrying the mutation detected by Sanger sequencing (SS+) were verified by ddPCR (ddPCR+). Also, all nodules with no mutation detected by ddPCR were interpreted as wild-type by Sanger sequencing (SS−). In addition. Almost all SS+/ddPCR + nodules (95.00%; 38/40) and SS−/ddPCR + nodules (100.00%; 54/54) displayed a BRAF mutation rate of >5% and

An electron-muon collider with an asymmetric collision profile targeting multi-ab-1 integrated luminosity is proposed. This novel collider, operating at collision energies of, e.g., 20–200 GeV, 50–1000 GeV, and 100–3000 GeV, would be able to probe charged lepton flavor violation and measure Higgs boson properties precisely. The collision of an electron and muon beam leads to less physics background compared with either an electron-electron or a muon-muon collider, since electron-muon interactions proceed mostly through higher-order vector boson fusion and vector boson scattering processes. The asymmetric collision profile results in collision products that are boosted towards the electron beam side, which can be exploited to reduce beam-induced background from the muon beam to a large extent. With this in mind, one can imagine a lepton collider complex, starting from colliding order 10 GeV electron and muon beams for the first time in history and to probe charged lepton flavor violation, then to be upgraded to a collider with 50-100 GeV electron and 1-3 TeV muon beams to measure Higgs properties and search for new physics and finally to be transformed to a TeV-scale muon-muon collider. The cost should vary from order 100 million to a few billion dollars, corresponding to different stages, which make the funding situation more practical.

Fibroblast-like synoviocytes (FLS) in the synovial tissue of rheumatoid arthritis (RA) exhibit over-proliferative and aggressive phenotypes, which participate in the pathophysiology of RA. In RA, little is known about the nonantioxidant effect of nuclear factor erythroid 2-related factor 2 (nrf2), the master regulator of redox homeostasis. In this study, we aimed to explore the expression and upstream regulatory factors of nrf2 and revealed its functions in modulating the proliferation and invasion in RA-FLS. FLS were isolated from RA and osteoarthritis patients. Expression of nrf2 in the synovial tissues and FLS was analyzed by immunohistochemistry, real-time PCR, Western blotting, and immunofluorescence staining. Cell proliferation was examined by Cell Counting Kit-8. Cell invasion was tested by transwell assay. Phosphorylation of JNK was determined by Western blotting. The results showed that nrf2 expression in the RA synovial tissues was upregulated. TNF-α promoted expression and nuclear translocation of nrf2 in RA-FLS and increased the intracellular reactive oxygen species (ROS) level. Nrf2 nuclear translocation was blocked by ROS inhibitor N-acetylcysteine. Both knockdown of nrf2 by siRNA and inhibition of nrf2 by ML385 significantly promoted the TNF-α-induced proliferation and invasion of RA-FLS. Activation of nrf2 by sulforaphane (SFN) profoundly inhibited the TNF-α-induced proliferation and invasion of RA-FLS. Knockdown of nrf2 also enhanced the TNF-α-induced matrix metalloproteinases (MMPs) expression and phosphorylation of JNK in RA-FLS. Proliferation and invasion of RA-FLS incubated with TNF-α and nrf2 siRNA were inhibited by pretreatment with JNK inhibitor SP600125. In conclusion, nrf2 is overexpressed in synovial tissues of RA patients, which may be promoted by TNF-α and ROS levels. Activation of nrf2 may suppress TNF-α-induced proliferation, invasion, and MMPs expression in RA-FLS by inhibiting JNK activation, indicating that nrf2 plays a protective role in relieving the severity of synovitis in RA. Our results might provide novel insights into the treatment of RA.

Background. The relationship between vitamin D and insulin resistance is still controversial. Many factors could influence this relationship. In addition, this relationship in different genders was still unclear. Methods. A total of 6597 subjects, including 2813 males and 3784 females, were analyzed. The serum levels of 25(OH)D, fasting blood glucose (FBG), fasting insulin, HbA1c, and other metabolic parameters were tested. The waist circumference (WC), weight, and height were also measured. Questionnaires regarding smoking and drinking were collected from these subjects. Results. Serum 25(OH)D was categorized into quartiles. Increasing 25(OH)D levels were associated with reduced trend of homeostasis model assessment of insulin resistance (HOMA-IR) in both males and females. Pearson’s correlation indicated 25(OH)D level was inversely associated with the HOMA-IR for male subjects (r=−0.055, P=0.028) but not for female subjects (r=−0.005, P=0.798). Age, triglyceride (TG), and low-density lipoprotein (LDL) were associated with the vitamin D levels in males and females. In regression analysis, serum 25(OH)D concentration was significantly associated with HOMA-IR only in overweight males. Conclusion. We found an inverse association between 25(OH)D and HOMA-IR in Chinese overweight males. Vitamin D supplementation might be beneficial in this population. However, further clinical trials are needed to confirm this association.

The mechanisms underlying osteoarthritis (OA) have recently been hypothesized to involve a dysfunctional immune system. In this study, we collected synovium, synovial fluid (SF), and peripheral blood from 21 patients. Mononuclear cells were characterized using FCM. H&E staining and mIHC histological assessment of synovium were performed. Cytokine levels in the SF were measured using ELISA. We observed similar frequencies of immune cells in the synovium and SF, which were enriched in DCs. Notably, CD1c+CD163+ DC3s were expanded in the synovium and SF. Furthermore, we found that DC3s were primarily located within the ectopic lymphoid-like structure (ELLS) in close proximity to CD8+ T cells. Finally, the level of TNF-α and IL12p70 in the SF correlated with the severity of OA. These data suggest that OA is an immune system-related disease and that DC3s may play an active role in OA progression by promoting ELLS formation and inflammatory responses. [ABSTRACT FROM AUTHOR]

Although endeavors have been made to identify useful wild rice genes that can be used to improve cultivated rice, the virtual reservoir of genetic variation hidden within the wild relatives of cultivated rice is largely untapped. Here, using next-generation sequencing technology, we investigated the leaf transcriptome of a wild rice O. officinalis with CC genome. Approximately 23 million reads were produced in the species leaf transcriptome analysis and de novo assembly methods constructed 68,132 unigenes. Functional annotations for the unigenes were conducted using sequence similarity comparisons against the following databases: the nonredundant nucleotide database, the nonredundant protein database, the SWISS-PROT database, the Clusters of Orthologous Groups of proteins database, the Kyoto Encyclopedia of Genes and Genomes database, the Gene Ontology Consortium database, and the InterPro domains database. In addition, a total of 476 unigenes related to disease resistance were identified in O. officinalis, and these unigenes can serve as important genetic resources for cultivated rice breeding and quality improvement. The present study broadens our understanding of the genetic background of non-AA genomic wild rice species and it also provides a bridge to extend studies to other Oryza species with CC genomes. [ABSTRACT FROM AUTHOR]