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Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel bunyavirus. Since 2007, SFTS disease has been reported in China with high fatality rate up to 30%, which drew high attention from Centre for Disease Control and Prevention and government. SFTSV is endemic in the centra l and eastern China, Korea and Japan. There also have been similar cases reported in Vietnam. The number of SFTSV infection cases has a steady growth in these years. As SFTSV could transmitted from person to person, it will expose the public to infectious risk. In 2018 annual review of the Blueprint list of priority diseases, World Health Organisation has listed SFTSV infection as prioritised diseases for research and development in emergency contexts. However, the pathogenesis of SFTSV remains largely unclear. Currently, there are no specific therapeutics or vaccines to combat infections of SFTSV. This review discusses recent findings of epidemiology, transmission pathway, pathogenesis and treatments of SFTS disease. [ABSTRACT FROM AUTHOR]

Adjuvant hormonal therapy (HT) is important for the management of hormone‐sensitive breast cancer. However, the timeliness for adjuvant HT and the consequences of delayed initiation of treatment have not been analyzed. The purpose of this study was to characterize delays to HT and assess the impact on clinical outcomes. The study cohort consisted of female patients with invasive ductal and/or lobular, hormone receptor‐positive breast cancer diagnosed between 2010 and 2015. Initiation of HT >6 months (180 days) after surgery was defined as delayed. Patients receiving chemotherapy were excluded from the study cohort. Multivariable logistic regression modeling was performed to establish associations between delayed HT and demographic, facility, and clinical factors. Survival analysis was performed using the Kaplan‐Meier estimation and Cox proportional hazards regression to evaluate overall survival. Of 179 590 women assessed in the National Cancer Database, 3.2% had a delay in the initiation of adjuvant HT. Positive demographic‐related risk factors were younger age, ethnic minority groups, and multiple comorbidities. Clinical factors significantly associated with delayed initiation of adjuvant HT were high‐grade tumor, larger tumor size, greater lymph node involvement, having an unplanned readmission within 30 days of surgery, and positive final surgical margins. Adjusted survival analysis showed a survival disadvantage of delayed initiation of HT. Risk factors for delayed initiation of HT specific to demographic and clinical characteristics were identified. Delayed initiation of HT was associated with a survival detriment. [ABSTRACT FROM AUTHOR]

Highlights • Homeologous recombination in a mammalian genome is enabled by nearby homology. • The mechanism of recombination is impacted by proximity to a double-strand break. • Mismatch repair may at times facilitate homeologous recombination in mammals. Abstract We investigated the homology dependency of recombination in thymidine kinase (tk)-deficient mouse fibroblasts. Cells were transfected with DNA constructs harboring a herpes tk gene (the "recipient") rendered non-functional by an oligonucleotide containing the recognition site for endonuclease I-SceI. Constructs also contained a "donor" tk sequence that could restore function to the recipient gene through spontaneous gene conversion or via repair of a double-strand break (DSB) at the I-SceI site. Recombination events were recoverable by selection for tk-positive clones. Three different donors were used containing 16, 25, or 33 mismatches relative to the recipient. The mismatches were clustered, forming an interval of "homeology" relative to the recipient sequences. We show that when homeologous sequences were surrounded by high homology, mismatches were frequently included in gene conversion events. Notably, conversion tracts from spontaneous recombination included either all or none of the mismatches, suggesting that recombination must begin and end in high homology. This requirement was relaxed for events that occurred near an induced DSB, as a significant number of these latter conversion tracts had one end positioned within homeology. Knock-down of mismatch repair showed that incorporation of mismatches into gene conversion tracts can involve repair of mismatched heteroduplex intermediates, indicating that mismatch repair does not necessarily impede homeologous genetic exchange. Our results illustrate (1) genetic exchange between homeologous sequences in a mammalian genome is enabled by nearby homology, (2) proximity to a DSB impacts the homology requirements for where genetic exchange may begin and end, and (3) mismatch correction and previously documented anti-recombination activity are separable functions of the mismatch repair machinery in mammalian cells. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Mecci et al paper. To view this article, visit https://doi.org/10.1111/apt.15296. [ABSTRACT FROM AUTHOR]

Hydrogen is the most abundant chemical element in the universe, and has been used as an inert gas for a long time. More recent studies have shown that molecular hydrogen as a kind of antioxidant, anti-inflammatory, anti-apoptosis, gene expression and signal modulation molecule, can be used for the treatment of many diseases. This review mainly focuses on the research progresses of hydrogen in various medical fields and the possible action mechanisms. [ABSTRACT FROM AUTHOR]

Hypoxia is a risk factor for severe chronic obstructive pulmonary disease, which aggravates the disease and may cause mortality by inducing hypoxic pulmonary hypertension (HPH). Proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) may mediate this effect. Resveratrol is a phenolic compound extracted from a plant and has been reported to alleviate HPH, although the underlying mechanisms remained to be elucidated. In cancer, resveratrol has been reported to abrogate the phosphoinositide 3-kinase/protein kinase B (AKT) signaling pathway, thereby inhibiting tumor development. Therefore, the present study aimed to investigate the role of resveratrol in preventing PASMCs from proliferating and migrating. Resveratrol was demonstrated to be inhibitory in a dose-dependent manner on hypoxia-induced cell proliferation and migration, and protein expression levels of phosphorylated AKT and AKT. Additionally, resveratrol was identified to act synergistically with LY-294002, a phosphorylation inhibitor of AKT, but antagonistically with insulin-like growth factor-1, an agonist of AKT phosphorylation. This suggested that resveratrol may reduce proliferation and migration by diminishing expression and phosphorylation of AKT, thereby preventing development of HPH. [ABSTRACT FROM AUTHOR]

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that has been demonstrated to be clinically useful for the treatment of patients with non-small cell lung cancer (NSCLC). However, ~50% of patients do not respond to EGFR TKI treatment through the emergence of mutations, such as T790M. Therefore, it is important to determine which patients are eligible for treatment with gefitinib. As a preferred dimerization partner for EGFR, the role of EGFR 2 (HER2) in mediating sensitivity to gefitinib is poorly understood. In the present study, full-length human HER2 cDNA was introduced to the NSCLC cell lines H1975 and H1299, which have a low endogenous expression level of HER2. In addition, it was observed in the present study that the H1975 cell line harbored the L858R and T790M mutations in the EGFR kinase domain. Western blot analysis and MTT assay were used to evaluate the TKI sensitivity of HER2 expression status, and the activation of HER3 and HER2 downstream effectors. The results indicated that the sensitivity of H1975 cells to gefitinib was restored by the overexpression of HER2, which stimulated HER2-driven signaling cascades accompanied by the activation of protein kinase B. By contrast, ectopic HER2 overexpression in H1299 cells did not significantly alter the sensitivity to gefitinib treatment. In conclusion, the current study results suggested that the relatively resistance of the H1975 cell line to gefitinib could be reversed by the overexpression of HER2. Therefore, the expression of HER2 could also be considered when evaluate the patients' potential response to gefitinib, particularly in the subgroup of lung cancer patients who harbor an EGFR mutation. [ABSTRACT FROM AUTHOR]

β-Agonists fed to animals for human consumption pose a serious threat to human health. Fast, broad-spectrum detection methods are needed for on-site screening of various types of β-agonists from animal feeds, meats, and animal body fluids. We developed a colorimetric assay that uses gold nanoparticle (AuNP) plasmon absorption to realize quick detection of β-agonists from liquid samples. β-Agonists showed the capability of directly reducing HAuCl4 into atomic gold, which involved oxidation of the amine or phenol group on the benzene ring of the β-agonists. The resulting atomic gold formed AuNPs spontaneously, which had strong plasmon absorption at 528 nm. The linear relationship between the concentrations of β-agonists and the AuNPs plasmon absorbance granted quantitative determination of β-agonists in solution. The AuNPs colorimetric assay showed different sensitivities toward β-agonists with different substituent groups on the aromatic ring. β-Agonists with phenol groups had a lower limit of quantitation (LOQ) than those with amine groups. High-resolution transmission electron microscopy (TEM) images revealed the sizes of the AuNPs were in the range 15-25 nm, while X-ray energy-dispersive spectroscopic data suggested the smaller particles observed in TEM with lower contrast may be salt particles from the buffer solution. The developed colorimetric assay can potentially be used for the detection of β-agonists and their analogues from serum, urine, and other liquid samples in the presence of interference from common antibiotics and glucose. [ABSTRACT FROM AUTHOR]

Background: We studied the efficacy and safety of a second dose of lasmiditan for acute treatment of migraine.Methods: SAMURAI and SPARTAN were double-blind, placebo-controlled Phase 3 studies in which individuals with migraine were randomized to oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo. Study drug was to be taken within 4 h (h) of onset of a migraine attack (moderate or severe pain). A second dose of study drug was provided for rescue (patient not pain-free at 2 h and took a second dose 2-24 h post-first dose) or recurrence (patient pain-free at 2 h, but experienced recurrence of mild, moderate, or severe migraine pain and took a second dose 2-24 h after first dose). Randomization to second dose occurred at baseline; patients originally assigned lasmiditan were randomized to the same lasmiditan dose or placebo (2:1 ratio), and those originally assigned placebo received placebo. Data from SAMURAI and SPARTAN were pooled for efficacy and safety assessment of a second dose of lasmiditan.Results: The proportion of patients taking a second dose was lower with lasmiditan versus placebo, and decreased with increasing lasmiditan dose; the majority who took a second dose did so for rescue. In patients taking lasmiditan as first dose, outcomes (pain free, most bothersome symptom [MBS] free) at 2 h after a second dose for rescue were similar whether the second dose was lasmiditan or placebo (p > 0.05 in all cases). In patients taking lasmiditan for first dose, outcomes at 2 h after a second dose for recurrence were as follows: lasmiditan pooled versus placebo - pain free, 50% vs 32% (p > 0.05); MBS free, 71% vs 41% (p = 0.02); pain relief, 77% vs 52% (p = 0.03). In patients whose first dose was lasmiditan, the incidence of treatment emergent adverse events (TEAEs) reported after the second dose was similar whether second dose was lasmiditan or placebo.Conclusions: A second dose of lasmiditan showed some evidence of efficacy when taken for headache recurrence. There was no clear benefit of a second dose of lasmiditan for rescue treatment. The incidences of TEAEs were similar whether the second dose was lasmiditan or placebo.Trial Registration: SAMURAI ( NCT02439320 ) [April 2015]. SPARTAN ( NCT02605174 ) [May 2016]. [ABSTRACT FROM AUTHOR]

Review: [overview of the asymmetric synthesis of dihydrobenzoxazinone- and dihydroquinazolinone-based anti-HIV agents. [ABSTRACT FROM AUTHOR]

The balance between oxidation and reduction is important for maintaining a healthy biological system. Oxidative stress results from an imbalance between excessive formation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) and limited endogenous defense systems, and this imbalance can adversely alter lipids, proteins and DNA, causing a number of human diseases. Thus, exogenous antioxidants that can neutralize the effect of free radicals are needed to diminish the cumulative effects of oxidative damage over human life span. Current research reveals that phenolic compounds in plants possess high antioxidant activity and free radical scavenging capacity and can prevent the body from oxidative damage over human life span. This review focuses on the present understanding of free radicals and antioxidants and their importance in human health and disease. Information about the chemical features of free radicals as well as their deleterious effects on cell structures is reviewed. The chemical structure and anti-oxidative mechanisms of essential polyphenols and their potential health benefits are presented. In addition, the limitation of natural antioxidants and a perspective on likely future trends in this field are also discussed. [ABSTRACT FROM AUTHOR]

Abstract: Chronic renal ischemia and hypoxia in the tubulointerstitium are involved in the mechanisms of progressive chronic kidney disease. Previous studies showed that the decoction of a combination of two Chinese herbs, Astragalus membranaceus var. mongholicus and Angelica sinensis (A & A) has antifibrotic effects through multiple pathways in different animal models. In this study, remnant kidney model was employed to investigate whether A & A affect the expression of VEGF, the density of the renal microvasculature and thus alleviate the renal injury. Rats were divided randomly into four groups: sham group (N =31), 5/6 Nx group (5/6 nephrectomy, N =43), A & A treated group (A & A group, N =40, A & A 12 g/kg/d po), enalapril treated group (Ena group, N =56, enalapril 4 mg/kg/d po). Rats from each group were sacrificed at the 2th, 4th, 8th and 12th weeks respectively after surgery and treatment. The 24 h urinary protein excretion, serum creatinine (Scr) and urea were measured. The collagen IV (COL-IV), fibronectin (FN), aminopeptidase P (APP) and VEGF were stained using immunohistochemistry. The COL-IV, FN and APP were semi-quantitatively analyzed. Peritubular capillary density in the cortical interstitial area was quantified. The level of VEGF was assayed by ELISA. The results revealed that Scr, urea and urinary protein excretion remained constant at each time point in sham group. Compared to sham group, 5/6 Nx group was shown severe glomerulosclerosis, tubulointerstitial lesions and vascular damage, as well as higher level of Scr from the 2nd week (72.3±5.2 vs. 48.6±2.6 μmol/L, P <0.05) to the 12th week (71.9±8.0 vs. 55.7±4.5 μmol/L, P <0.05). Although there was no significant difference in Scr level after treatment of enalapril or A & A (P >0.05), kidney damage was alleviated at the 8th and the 12th week in the two treatment groups (P <0.05, vs. 5/6 Nx group). The urinary protein excretion of 5/6 Nx group was significantly increased from the 4th week, it was 1.5, 2.4 and 3.8 fold of that of sham group at the 4th, 8th and 12th week, respectively. Compared to 5/6 Nx group, proteinuria was decreased by enalapril to 59%, 33% at 8th and 12th week. After A & A administration, urinary protein excretion decreased to 66%, 56%, 75%, 55% of 5/6 Nx group at the 2nd, 4th, 8th and 12th, respectively (P <0.05). Compared with sham group, there was increased expression of FN and COL-IV in rats with 5/6 Nx. After A & A or enalapril administration, the expression of FN and COL-IV was significantly decreased compared with that in the 5/6 Nx group at 8th and 12th week (P <0.05). On the other hand, the capillary density was decreased at the 8th and 12th week in 5/6 Nx rats (P <0.01). In A & A-treated group, similarly with enalapril group, the amount of APP-positive glomerular capillary increased by 36% (P <0.01), and the peritubular capillary density was increased 94% at 8th week and 52% at 12th week compared with 5/6 Nx group (P <0.05). The renal level of VEGF was decreased in 5/6 Nx rats, but increased at the 8th and 12th week in A & A group (P <0.05, vs. 5/6 Nx group). In conclusion, A & A has renoprotective effects by suppression of extra cellular matrix deposition in 5/6 Nx rat. The renoprotective effects may be associated with reduction of proteinuria, up-regulation of VEGF which may reduce the loss of capillaries and improve microstructure dysfunction. [Copyright &y& Elsevier]

The natural course of radiation encephalopathy following nasopharyngeal carcinoma (NPC) radiotherapy remains poorly understood. The present study aimed to investigate the magnetic resonance imaging (MRI) characteristics and evolution of radiation encephalopathy. A series of 162 follow‑up MRI examinations from 68 NPC patients with radiation encephalopathy in the temporal lobes were analyzed retrospectively. Each component of radiation encephalopathy was defined as follows: i) contrast enhanced lesions were enhanced lesions on contrast enhanced T1‑weighted images (T1WI); ii) white matter lesions were lesions of homogeneous hyperintensity on T2‑weighted images (T2WI) and hypointensity on T1WI; iii) cysts were round or oval well‑defined lesions of hyperintensity on T2WI; iv) hemosiderin deposition were nodular or annular hypointense lesions with lower hypointense than normal white matter on both T1WI and T2WI; v) gray matter lesions were defined as disruption or erosion of hyperintensity in the cortex on T2WI. Contrast enhanced lesions, white matter lesions, gray matter lesions, cysts and hemosiderin deposition were detected in 105 (100.0%), 98 (93.3%), 94 (89.5%), 2 (1.7%) and 2 (1.7%) cases of the 105 initial diagnosed temporal lobe lesions. Contrast enhanced lesions were the most commonly observed, followed by white matter lesions, gray matter lesions, temporal lobe atrophy, cysts and hemosiderin deposition. In addition, 12 new lesions were identified during the follow‑up, 4 of which presented as solid enhanced nodular lesions. Importantly, in 11 of the 117 (9.4%) affected temporal lobes, solid enhanced nodular lesions were observed to be the only initial abnormalities to occur. For those enhanced nodular lesions measuring <0.8 cm, no necrosis could be detected. On the contrary, all the contrast enhanced lesions measuring >2.0 cm exhibited a necrotic core. To the best of our knowledge, the present study revealed for the first time solid enhanced nodular lesions as the earliest MRI abnormalities of radiation encephalopathy following NPC radiotherapy. [ABSTRACT FROM AUTHOR]

Summary Objectives Many studies have suggested the effectiveness of single control measures in the containment and mitigation of pandemic influenza A (H1N1) 2009. The effects of combined interventions by multiple control measures in reducing the impact of an influenza A (H1N1) 2009 outbreak in a closed physical training camp in Beijing, China were evaluated. Methods Oseltamivir was prescribed for the treatment of confirmed cases and possible cases and as prophylaxis for all other participants in this training camp. Public health control measures were applied simultaneously, including the isolation of patients and possible cases, personal protection and hygiene, and social distancing measures. Symptom surveillance of all participants was initiated, and the actual attack rate was calculated. For comparison, the theoretical attack rate for this outbreak was projected using the Newton–Raphson numerical method. Results A total of 3256 persons were present at the physical training camp. During the outbreak, 405 (68.3%) possible cases and 26 (4.4%) confirmed cases were reported before the intervention and completed oseltamivir treatment; 162 (27.3%) possible cases were reported after the intervention and received part treatment and part prophylaxis. The other 2663 participants completed oseltamivir prophylaxis. Of the possible cases, 181 with fever ≥38.5 °C were isolated. The actual attack rate for this outbreak of pandemic influenza A (H1N1) 2009 was 18.2%, which is much lower than the theoretical attack rate of 80% projected. Conclusions Combined interventions of large-scale antiviral ring prophylaxis and treatment and public health control measures could be applied to reduce the magnitude of influenza A (H1N1) 2009 outbreaks in closed settings. [ABSTRACT FROM AUTHOR]

Recent data indicates that DJ-1 plays a role in the cellular response to stress. Here, we aimed to examine the underlying molecular mechanisms mediating the actions of DJ-1 in the heart following myocardial ischemia–reperfusion (I/R) injury. In response to I/R injury, DJ-1 KO mice displayed increased areas of infarction and worsened left ventricular function when compared to WT mice, confirming a protective role for DJ-1 in the heart. In an effort to evaluate the potential mechanism(s) responsible for the increased injury in DJ-1 KO mice, we focused on SUMOylation, a post-translational modification process that regulates various aspects of protein function. DJ-1 KO hearts after I/R injury were found to display enhanced accumulation of SUMO-1 modified proteins and reduced SUMO-2/3 modified proteins. Further analysis, revealed that the protein expression of the de-SUMOylation enzyme SENP1 was reduced, whereas the expression of SENP5 was enhanced in DJ-1 KO hearts after I/R injury. Finally, DJ-1 KO hearts were found to display enhanced SUMO-1 modification of dynamin-related protein 1, excessive mitochondrial fission, and dysfunctional mitochondria. Our data demonstrates that the activation of DJ-1 in response to myocardial I/R injury protects the heart by regulating the SUMOylation status of Drp1 and attenuating excessive mitochondrial fission. [ABSTRACT FROM AUTHOR]

Background: Because the prevalence of connective tissue disease (CTD)-associated interstitial lung disease (ILD; CTD-ILD) in China is unknown, we wanted to analyze the clinical characteristics of this disease in Chinese patients.Methods: The medical records of patients who received a diagnosis of ILD and treated in Shanghai Pulmonary Hospital from January 1999 to January 2013 were reviewed. Based on the records, patients who also received a diagnosis of CTD were identified, and their records of follow-up examinations for a minimum of 12 months until the end of December 2013 were reviewed.Results: Of the 2,678 patients who received a diagnosis of ILD, 1,798 (67%) were identified as having CTD-ILD; 299 (11.2%) had idiopathic pulmonary fibrosis (IPF). Complete clinical data were available for 1,044 patients with CTD-ILD and 178 with IPF. We found that 332 of the 1,044 patients with CTD-ILD (32%) did not receive an accurate diagnosis at the initial hospital admission, 195 (18.7%) of the 1,044 patients showed persistent negative test results for autoantibodies, and 262 (25.1%) of the 1,044 patients had negative autoantibodies at the initial hospital admission and then became positive at follow-up examinations. Of the 288 patients who had confirmed CTD-ILD, 41 (14%) showed pulmonary symptoms as the initial clinical manifestation (PSIM) and 247 (86%) showed extrapulmonary symptoms as the initial clinical manifestation (EPSIM). For the 756 patients who had undifferentiated CTD-ILD, the proportion of PSIM and EPSIM was 44% and 56%, respectively. For patients who presented with PSIM, 23 who had confirmed CTD-ILD (56%) and 216 who had unconfirmed CTD-ILD (65%) did not receive an accurate diagnosis at the initial visit but were ultimately diagnosed at subsequent follow-up examinations.Conclusions: Patients with CTD-ILD do not receive an accurate diagnosis at the initial hospital admission possibly because of negative serologic test results for autoantibodies and the absence of obvious extrapulmonary symptoms. Thus, patients with ILD should be examined for extrapulmonary symptoms and tested for autoantibodies at follow-up examinations. [ABSTRACT FROM AUTHOR]

We have developed an electrostatic interaction based biosensor for thrombin detection using surface-enhanced Raman spectroscopy (SERS). This method utilized the electrostatic interaction between capture (thrombin aptamer) and probe (crystal violet, CV) molecules. The specific interaction between thrombin and aptamer could weaken the electrostatic barrier effect from the negative charged aptamer SAMs to the diffusion process of the positively charged CV from the bulk solution to the Au nanoparticle surface. Therefore, the more the bound thrombin, the more the CV molecules near the Au nanoparticle surface and the stronger the observed Raman signal of CV, provided the Raman detections were set at the same time point for each case. This procedure presented a highly specific selectivity and a linear detection of thrombin in the range from 0.1 nM to 10 nM with a detection limit of about 20 pM and realized the thrombin detection in human blood serum solution directly. The electrostatic interaction based technique provides an easy and fast-responding optical platform for a "signal-on" detection of proteins, which might be applicable for the real lime assay of proteins. [ABSTRACT FROM AUTHOR]