We study the e^{+}e^{-}→γωJ/ψ process using 11.6 fb^{-1} e^{+}e^{-} annihilation data taken at center-of-mass energies from sqrts=4.008 GeV to 4.600 GeV with the BESIII detector at the BEPCII ...storage ring. The X(3872) resonance is observed for the first time in the ωJ/ψ system with a significance of more than 5σ. The relative decay ratio of X(3872)→ωJ/ψ and π^{+}π^{-}J/ψ is measured to be R=1.6_{-0.3}^{+0.4}±0.2, where the first uncertainty is statistical and the second systematic (the same hereafter). The sqrts-dependent cross section of e^{+}e^{-}→γX(3872) is also measured and investigated, and it can be described by a single Breit-Wigner resonance, referred to as the Y(4200), with a mass of 4200.6_{-13.3}^{+7.9}±3.0 MeV/c^{2} and a width of 115_{-26}^{+38}±12 MeV. In addition, to describe the ωJ/ψ mass distribution above 3.9 GeV/c^{2}, we need at least one additional Breit-Wigner resonance, labeled as X(3915), in the fit. The mass and width of the X(3915) are determined. The resonant parameters of the X(3915) agree with those of the Y(3940) in B→KωJ/ψ and of the X(3915) in γγ→ωJ/ψ observed by the Belle and BABAR experiments within errors.
Summary
The contamination of inactivated vaccine with non‐structural proteins (NSPs) leads to a high false‐positive rate, which is a substantial barrier to accurately differentiate foot‐and‐mouth ...disease virus (FMDV)‐infected animals from vaccinated animals. To address this problem, a new chemiluminescence immunoassay (CLIA) method was developed to detect antibodies targeting the two recombinant epitope‐based proteins located in 3A and 3B. The 3Aepitp‐3Bepitp CLIA exhibited a diagnostic sensitivity of 94.0% and a diagnostic specificity of 97.5% for the detection of serum samples (naïve bovines, n = 52, vaccinated bovines, n = 422, infected bovines, n = 116) from animals with known status. The CLIA method also had a concordance rate of 88.1% with the PrioCHECK FMDV NSP ELISA based on the detection of 270 serum samples from the field. Importantly, the 3Aepitp‐3Bepitp CLIA produced no false‐positives when used to detect FMDV in samples from bovines that had been vaccinated up to five times, and it was demonstrated a low false‐positive rate when the bovines had been vaccinated up to ten (2.15%) and fifteen times (5.93%). Therefore, the 3Aepitp‐3Bepitp CLIA detects FMDV in samples from frequently vaccinated bovines with high accuracy and represents an alternative method to differentiate FMDV‐infected and vaccinated bovines.
Summary Objective To determine whether autophagy contributes to the pathogenesis of degenerative disc disease (DDD) or retards the intervertebral disc (IVD) degeneration, and investigate the possible ...relationship between compression-induced autophagy and intracellular reactive oxygen species (ROS) in nucleus pulposus (NP) cells in vitro. Methods The autophagosome and autophagy-related markers were used to explore the role of autophagy in rat NP cells under compressive stress, which were measured directly by electronic microscopy, monodansylcadaverine (MDC) staining, immunofluorescence, western blot, and indirectly by analyzing the impact of pharmacological inhibitors of autophagy such as 3-methyladenine (3-MA) and chloroquine (CQ). And the relationship between autophagy and apoptosis was investigated by Annexin-V/propidium iodide (PI)-fluorescein staining. In addition, ROS were measured to determine whether these factors are responsible for the development of compression-induced autophagy. Results Our results indicated that rat NP cells activated autophagy in response to the same strong apoptotic stimuli that triggered apoptosis by compression. Autophagy and apoptosis were interconnected and coordinated in rat NP cells exposed to compression stimuli. Compression-induced autophagy was closely related to intracellular ROS production. Conclusions Enhanced degradation of damaged components of NP cells by autophagy may be a crucial survival response against mechanical overload, and extensive autophagy may trigger autophagic cell death. Regulating autophagy and reducing the generation of intracellular ROS may retard IVD degeneration.
The cross sections of e^{+}e^{-}→π^{+}π^{-}h_{c} at center-of-mass energies from 3.896 to 4.600 GeV are measured using data samples collected with the BESIII detector operating at the Beijing ...Electron Positron Collider. The cross sections are found to be of the same order of magnitude as those of e^{+}e^{-}→π^{+}π^{-}J/ψ and e^{+}e^{-}→π^{+}π^{-}ψ(2S), but the line shape is inconsistent with the Y states observed in the latter two modes. Two structures are observed in the e^{+}e^{-}→π^{+}π^{-}h_{c} cross sections around 4.22 and 4.39 GeV/c^{2}, which we call Y(4220) and Y(4390), respectively. A fit with a coherent sum of two Breit-Wigner functions results in a mass of (4218.4_{-4.5}^{+5.5}±0.9) MeV/c^{2} and a width of (66.0_{-8.3}^{+12.3}±0.4) MeV for the Y(4220), and a mass of (4391.5_{-6.8}^{+6.3}±1.0) MeV/c^{2} and a width of (139.5_{-20.6}^{+16.2}±0.6) MeV for the Y(4390), where the first uncertainties are statistical and the second ones systematic. The statistical significance of Y(4220) and Y(4390) is 10σ over one structure assumption.
Twenty‐three published proxy temperature series over China spanning the last 2000 years were selected for an uncertainty analysis in five climate regions. Results indicated that, although large ...uncertainties are found for the period prior to the 16th century, high level of consistency were identified in all regions during the recent 500‐years, highlighted by the two cold periods 1620s–1710s and 1800s–1860s, and the warming during the 20th century. The latter started in Tibet, Northwest and Northeast, and migrated to Central East and Southeast. The analysis also indicates that the warming during the 10–14th centuries in some regions might be comparable in magnitude to the warming of the last few decades of the 20th century which was unprecedented within the past 500 years.
MicroRNAs (miRNAs) have been demonstrated to have critical roles in regulating cancer cell proliferation, survival and sensitivity to chemotherapy. The potential application of using miRNAs to ...predict therapeutic response to cancer treatment holds high promise, but miRNAs with predictive value remain to be identified and underlying mechanisms have not been completely understood. Here, we show a strong correlation between miR-621 expression and chemosensitivity to paclitaxel plus carboplatin (PTX/CBP) regimen, an effective neoadjuvant chemotherapy for breast cancer patients. High level of miR-621 predicts better response to PTX/CBP regimen neoadjuvant chemotherapy in breast cancer patients, who also tend to achieve pathological complete response. Ectopic overexpression of miR-621 promoted apoptosis and increased chemosensitivity to PTX and CBP both in cultured breast cancer cells and in xenograft tumor model. We further show that FBXO11 is a direct functional target of miR-621 and miR-621 level is negatively correlated with FBXO11 expression in breast cancer patients. Ectopic expression of FBXO11 attenuated increased apoptosis in breast cancer cells overexpressing miR-621 upon PTX or CBP treatment. Consistently, high FBXO11 expression significantly correlated with poor survival in breast cancer patients. Mechanistically, we found in breast cancer cells FBXO11 interacts with p53 and promotes its neddylation, which suppressed the p53 transactivity. Accordingly, miR-621-dependent FBXO11 suppression enhanced p53 activity and increased apoptosis in breast cancer cells exposed to chemotherapeutics. Taken together, our data suggest that miR-621 enhances chemosensitivity of breast cancer cells to PTX/CBP chemotherapy by suppressing FBXO11-dependent inhibition of p53. miR-621 may serve as a predictive biomarker and a potential therapeutic target in breast cancer treatment.
Background
Lenalidomide has immunomodulatory and anti‐angiogenic effects and showed moderate anti‐tumour efficacy in patients with. advanced hepatocellular carcinoma (HCC)
Aim
To explore potential ...biomarkers of lenalidomide efficacy as second‐line therapy for HCC.
Methods
Eligible patients were diagnosed with advanced HCC, documented progression on sorafenib, and Child‐Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1‐21 every 4 weeks. The primary endpoint was 6 month progression‐free survival rate. Early α‐fetoprotein response was defined as a > 20% decline of α‐fetoprotein levels from baseline within the first 4 weeks of treatment. Vascular response, evaluated using dynamic contrast‐enhanced magnetic resonance imaging, was defined as a > 40% decline in Ktrans after 2 weeks of treatment. The percentage of peripheral blood lymphocyte subsets were also analysed.
Results
Fifty‐five patients were enrolled. The response rate was 13%, and the disease‐control rate was 53%. The 6 month progression‐free survival rate was 9.1%. The median progression‐free and overall survival was 1.8 months and 8.9 months respectively. Early α‐fetoprotein response was significantly associated with higher disease‐control rate (76% vs 22%, P = .001) and longer progression‐free survival (P = .020). Vascular response was not associated with any treatment outcomes. Patients with a high pre‐treatment B cell percentage were more likely to have disease control (70% vs 36%, P = .010) and exhibited longer progression‐free survival (P < .001) and overall survival (P = .042).
Conclusions
Lenalidomide exhibited moderate activity as second‐line therapy for advanced HCC. Its immunomodulatory effects should be further explored (www.clinicaltrials.gov NCT01545804).
The evolutions of MHD instability behaviors and enhancement of both electrostatic and electromagnetic turbulence towards the plasma disruption have been clearly observed in the HL-2A plasmas. Two ...types of plasma disruptive discharges have been investigated for similar equilibrium parameters: one with a distinct stage of a small central temperature collapse (Formula: see text 5-10%) around 1 millisecond before the thermal quench (TQ), while the other without. For both types, the TQ phase is preceded by a rotating 2/1 tearing mode, and it is the development of the cold bubble from the inner region of the 2/1 island O-point along with its inward convection that causes the massive energy loss. In addition, the micro-scale turbulence, including magnetic fluctuations and density fluctuations, increases before the small collapse, and more significantly towards the TQ. Also, temperature fluctuations measured by electron cyclotron emission imaging enhances dramatically at the reconnection site and expand into the island when approaching the small collapse and TQ, and the expansion is more significant close to the TQ. The observed turbulence enhancement near the X-point cannot be fully interpreted by the linear stability analysis by GENE. Evidences suggest that nonlinear effects, such as the reduction of local Formula: see text shear and turbulence spreading, may play an important role in governing turbulence enhancement and expansion. These results imply that the turbulence and its interaction with the island facilitate the stochasticity of the magnetic flux and formation of the cold bubble, and hence, the plasma disruption.
Intervertebral disc (IVD) degeneration is frequently associated with Low back pain (LBP), which can severely reduce the quality of human life and cause enormous economic loss. However, there is a ...lack of long-lasting and effective therapies for IVD degeneration at present. Recently, stem cell based tissue engineering techniques have provided novel and promising treatment for the repair of degenerative IVDs. Numerous studies showed that stem/progenitor cells exist naturally in IVDs and could migrate from their niche to the IVD to maintain the quantity of nucleus pulposus (NP) cells. Unfortunately, these endogenous repair processes cannot prevent IVD degeneration as effectively as expected. Therefore, theoretical basis for regeneration of the NP in situ can be obtained from studying the mechanisms of endogenous repair failure during IVD degeneration. Although there have been few researches to study the mechanism of cell death and migration of stem/progenitor cells in IVD so far, studies demonstrated that the major inducing factors (compression and hypoxia) of IVD degeneration could decrease the number of NP cells by regulating apoptosis, autophagy, and necroptosis, and the particular chemokines and their receptors played a vital role in the migration of mesenchymal stem cells (MSCs). These studies provide a clue for revealing the mechanisms of endogenous repair failure during IVD degeneration. This article reviewed the current research situation and progress of the mechanisms through which IVD stem/progenitor cells failed to repair IVD tissues during IVD degeneration. Such studies provide an innovative research direction for endogenous repair and a new potential treatment strategy for IVD degeneration.
For locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (nCRT), there are no reliable indicators to accurately predict pathological complete response (pCR) before ...surgery. For patients with clinical complete response (cCR), a "Watch and Wait" (W&W) approach can be adopted to improve quality of life. However, W&W approach may increase the recurrence risk in patients who are judged to be cCR but have minimal residual disease (MRD). Magnetic resonance imaging (MRI) is a major tool to evaluate response to nCRT; however, its ability to predict pCR needs to be improved. In this prospective cohort study, we explored the value of circulating tumor DNA (ctDNA) in combination with MRI in the prediction of pCR before surgery and investigated the utility of ctDNA in risk stratification and prognostic prediction for patients undergoing nCRT and total mesorectal excision (TME). We recruited 119 Chinese LARC patients (cT3-4/N0-2/M0; median age of 57; 85 males) who were treated with nCRT plus TME at Fudan University Shanghai Cancer Center (China) from February 7, 2016 to October 31, 2017. Plasma samples at baseline, during nCRT, and after surgery were collected. A total of 531 plasma samples were collected and subjected to deep targeted panel sequencing of 422 cancer-related genes. The association among ctDNA status, treatment response, and prognosis was analyzed. The performance of ctDNA alone, MRI alone, and combining ctDNA with MRI was evaluated for their ability to predict pCR/non-pCR. The model combining ctDNA and MRI improved the predictive performance compared with the models derived from individual information, and combining ctDNA with HR_feature can stratify patients with a high risk of recurrence. Therefore, ctDNA can supplement MRI to better predict nCRT response, and it could potentially help patient selection for nonoperative management and guide the treatment strategy for those with different recurrence risks.
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