This paper presents a new class of dual-, tri- and quad-band BPF by using proposed open stub-loaded shorted stepped-impedance resonator (OSLSSIR). The OSLSSIR consists of a two-end-shorted ...three-section stepped-impedance resistor (SIR) with two identical open stubs loaded at its impedance junctions. Two 50- Ω tapped lines are directly connected to two shorted sections of the SIR to serve as I/O ports. As the electrical lengths of two identical open stubs increase, many more transmission poles (TPs) and transmission zeros (TZs) can be shifted or excited within the interested frequency range. The TZs introduced by open stubs divide the TPs into multiple groups, which can be applied to design a multiple-band bandpass filter (BPF). In order to increase many more design freedoms for tuning filter performance, a high-impedance open stub and the narrow/broad side coupling are introduced as perturbations in all filters design, which can tune the even- and odd-mode TPs separately. In addition, two branches of I/O coupling and open stub-loaded shorted microstrip line are employed in tri- and quad-band BPF design. As examples, two dual-wideband BPFs, one tri-band BPF, and one quad-band BPF have been successfully developed. The fabricated four BPFs have merits of compact sizes, low insertion losses, and high band-to-band isolations. The measured results are in good agreement with the full-wave simulated results.
Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of heart disease is uncertain. We ...performed a meta-analysis to investigate the link between radiotherapy and long-term cardiovascular morbidity and mortality in patients with breast cancer.
We performed a literature search using MEDLINE (January 1966 to January 2015) and EMBASE (January 1980 to January 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95%CIs for the associations of interest were included. Pooled effect estimates were obtained by using random-effects meta-analysis. Thirty-nine studies involving 1 191 371 participants were identified. Patients who received left-sided radiotherapy, as compared with those receiving right-sided radiotherapy, experienced increased risks of developing coronary heart disease (RR 1.29, 95%CI 1.13-1.48), cardiac death (RR 1.22, 95%CI 1.08-1.37) and death from any cause (RR 1.05, 95%CI 1.01-1.10). In a comparison of patients with radiotherapy and without radiotherapy, the RRs were 1.30 (95%CI 1.13-1.49) for coronary heart disease and 1.38 (95%CI 1.18-1.62) for cardiac mortality. Radiotherapy for breast cancer was associated with an absolute risk increase of 76.4 (95%CI 36.8-130.5) cases of coronary heart disease and 125.5 (95%CI 98.8-157.9) cases of cardiac death per 100 000 person-years. The risk started to increase within the first decade for coronary heart disease and from the second decade for cardiac mortality.
Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent risk of coronary heart disease and cardiac mortality.
Biothiols, such as glutathione (GSH), homocysteine (Hcy) and cysteine (Cys), are important biomarkers and play crucial roles in many physiological processes. Thus, the detection of biothiols is ...highly important for early diagnosis of diseases and evaluation of disease progression. Herein, new types of BODIPY-based fluorescent probes (probe 1, probe 2 and probe 3) capable of cysteine (Cys)/homocysteine (Hcy) sensing with high selectivity over other amino acids were developed. In addition, we further studied the influence of different electronegativity substituents on these probes to sensing Cys/Hcy. Ultimately, we concluded that the electron withdrawing group on probe 1 can accelerate the probe response to Cys/Hcy, and probe 1 was successfully applied for selective imaging Cys/Hcy in living cells.
Display omitted
•A series of novel BODIPY-based fluorescent probes for cysteine and homocysteine were developed.•All three fluorescent probes have advantage of high sensitivity and selectivity.•Probe 1 was capable of detecting Cys/Hcy in living cells.
Maintaining cellular Na+/K+ homeostasis is pivotal for plant survival in saline environments. However, knowledge about the molecular regulatory mechanisms of Na+/K+ homeostasis in plants under salt ...stress is largely lacking. In this report, the Arabidopsis double mutants atrbohD1/F1 and atrbohD2/F2, in which the AtrbohD and AtrbohF genes are disrupted and generation of reactive oxygen species (ROS) is pronouncedly inhibited, were found to be much more sensitive to NaCl treatments than wild-type (WT) and the single null mutant atrbohD1 and atrbohF1 plants. Furthermore, the two double mutant seedlings had significantly higher Na+ contents, lower K+ contents, and resultant greater Na+/K+ ratios than the WT, atrbohD1, and atrbohF1 under salt stress. Exogenous H2O2 can partially reverse the increased effects of NaCl on Na+/K+ ratios in the double mutant plants. Pre-treatments with diphenylene iodonium chloride, a widely used inhibitor of NADPH oxidase, clearly enhanced the Na+/K+ ratios in WT seedlings under salt stress. Moreover, NaCl-inhibited inward K+ currents were arrested, and NaCl-promoted increases in cytosolic Ca2+ and plasma membrane Ca2+ influx currents were markedly attenuated in atrbohD1/F1 plants. No significant differences in the sensitivity to osmotic or oxidative stress among the WT, atrbohD1, atrbohF1, atrbohD1/F1, and atrbohD2/F2 were observed. Taken together, these results strongly suggest that ROS produced by both AtrbohD and AtrbohF function as signal molecules to regulate Na+/K+ homeostasis, thus improving the salt tolerance of Arabidopsis.
Early diagnosis is important for the clinical management of diseases caused by dengue virus (DENV) infections. We investigated the performance of three commercially available DENV nonstructural ...protein 1 (NS1) rapid diagnostic tests (RDTs) using 173 acute-phase sera collected from dengue fever-suspected patients during the 2012-2013 DENV outbreak in Taiwan. The results of the NS1 RDTs were compared with those of qRT-PCR to calculate the sensitivity and specificity of the NS1 RDTs. The anti-DENV IgM and IgG RDT results were included to increase the probability of detecting acute DENV infection. The anti-DENV IgM/IgG RDT results were also compared with those of IgM/IgG captured ELISA. The sera from DENV qRT-PCR-positive patients were subjected to NS1 RDTs, as well as IgM/IgG captured ELISA. These results suggested that there was no significant difference in the sensitivities of the three commercially available DNEV NS1 RDTs; the SD NS1 RDT results showed the highest agreement with the qRT-PCR reference results, followed in order by the Bio-Rad and CTK NS1 RDT results when the specificity was considered. Inclusion of the IgM or IgG RDT results increased the likelihood of diagnosing either a primary or secondary DENV infection. NS1 RDTs were more sensitive for the detection of primary infections than secondary infections, related to DENV viremia levels determined by qRT-PCR. These results suggested that anti-DENV antibodies reduced the sensitivity of NS1 rapid tests. We also analyzed the sensitivity for the detection of different DENV serotypes, and the results suggested that the NS1 RDTs used in this study were valuable for rapid screening of acute DENV infection with DENV-1, DENV-2 and DENV-3. Our results suggest that the NS1 RDT is a good alternative to qRT-PCR analysis for timely dengue disease management and prevention in dengue-endemic regions where medical resources are lacking or during large dengue outbreaks. However, the relatively low sensitivity for DENV-4 might miss the detection of DENV-4-infected cases.
The therapeutic options for thrombocytopenia in non-severe aplastic anaemia (NSAA) are limited. Avatrombopag (AVA) is prescribed for thrombocytopenic diseases but not for NSAA.
Herein, we conducted a ...phase 2, non-randomized, single-arm trial to explore the efficacy and safety of AVA in refractory/relapsed/intolerant NSAA. AVA dose was initiated at 20 mg/d and titrated to a maximum of 60 mg/d. The primary endpoint was the haematological response at 3 months.
Twenty-five patients were analyzed. The overall response rate (ORR) at 3 months was 56% (14/25), with 12% (3/25) achieving a complete response (CR). At a median follow-up of 7 (3-10) months, the OR and CR rates were 52% and 20%, respectively. Responders had a shorter duration of diagnosis of AVA administration than non-responders (10 (6-80) vs 37 (6-480) months, p = 0.027) and belonged to the relapsed/intolerant NSAA type (71% vs 27%, p = 0.047); 44% (8/18) patients previously treated with eltrombopag before enrollment responded at 3 months, with an average prior eltrombopag dose of median 72.5 (50-100) mg/d and an average AVA dose for a response of median 43.5 (20-60) mg/d. 3-month ORR had no significant correlation with eltrombopag exposure (p = 0.09), prior eltrombopag length (R
2
=0.11), or cumulative eltrombopag dose (R
2
=0.30). Only one patient relapsed after stopping AVA for 1 month. No serious AVA-related side effects or clone evolution were detected.
AVA is effective and well-tolerated in NSAA patients who are refractory, relapsed, or intolerant to CsA/tacrolimus ± eltrombopag. Earlier treatment and relapsed/intolerant AA may show a better short-term response rate. More studies are needed to define the optimal dose and the long-term efficacy (NCT04728789).
Nutrient excess, a major driver of obesity, diminishes hypothalamic responses to exogenously administered leptin, a critical hormone of energy balance. Here, we aimed to identify a physiological ...signal that arises from excess caloric intake and negatively controls hypothalamic leptin action. We found that deficiency of the gastric inhibitory polypeptide receptor (Gipr) for the gut-derived incretin hormone GIP protected against diet-induced neural leptin resistance. Furthermore, a centrally administered antibody that neutralizes GIPR had remarkable antiobesity effects in diet-induced obese mice, including reduced body weight and adiposity, and a decreased hypothalamic level of SOCS3, an inhibitor of leptin actions. In contrast, centrally administered GIP diminished hypothalamic sensitivity to leptin and increased hypothalamic levels of Socs3. Finally, we show that GIP increased the active form of the small GTPase Rap1 in the brain and that its activation was required for the central actions of GIP. Altogether, our results identify GIPR/Rap1 signaling in the brain as a molecular pathway linking overnutrition to the control of neural leptin actions.
BackgroundWorkplace violence is a global public health issue and a major occupational hazard cross borders and environments. Nurses are the primary victims of workplace violence due to their ...frontline roles and continuous interactions.ObjectiveThe present study aimed to investigate the status of workplace violence, turnover intention, compassion fatigue, and psychological resilience among Chinese nurses, and explore the mediating role of compassion fatigue and the moderating role of psychological resilience on relationship between workplace violence and turnover intention among Chinese nurses.MethodA cross-sectional study was conducted among a convenience sample of clinical registered nurses from public hospitals in Changsha, Hunan, China. Data was collected through an online questionnaire, which included a demographic information form, the Workplace Violence Scale (WVS), the Turnover Intention Questionnaire (TIQ), the Compassion Fatigue Scale (CF-CN), and the Connor-Davidson Resilience Scale (CD-RISC). Descriptive statistics and correlation analysis were employed to examine the relationships among the main variables. A moderated mediation analysis was further conducted using the PROCESS macro for SPSS (Model 4 and Model 8) to examine the mediating role of compassion fatigue and the moderating role of psychological resilience.ResultThe present survey recruited a convenience sample of 1,141 clinical registered nurses, who reported experiencing multiple types of workplace violence during the past year. Correlation analysis revealed significant positive correlations between workplace violence and turnover intention (r = 0.466, P < 0.01) as well as compassion fatigue (r = 0.452, P < 0.01), while negative correlation between workplace violence and psychological resilience (r=-0.414, P < 0.01). Moderated mediation analysis revealed that compassion fatigue mediated, while psychological resilience moderated, the positive relationship between workplace violence and turnover intention (all P < 0.05).ConclusionThis study underscores the mediating effect of compassion fatigue and the moderating role of psychological resilience in the relationship between workplace violence and turnover intention among Chinese nurses. Future efforts should be undertaken to develop effective preventive measures and intervention strategies at individual, organizational, and national levels to mitigate workplace violence and foster supportive work environment.Clinical trial numberNot applicable.
Systemic lupus erythematosus (SLE) characterized by immune dysfunction is possibly more vulnerable to herpes simplex virus (HSV) infection. The infection has been intensively considered a common ...onset and exacerbation of SLE. This study is aimed at elucidating the causal association between SLE and HSV. A bidirectional two‐sample Mendelian Randomization (TSMR) analysis was systematically conducted to explore the causal effect of SLE and HSV on each other. The causality was estimated by inverse variance weighted (IVW), MR‐Egger and weighted median methods based on the summary‐level genome‐wide association studies (GWAS) data from a publicly available database. Genetically proxied HSV infection exhibited no causal association with SLE in the forward MR analysis using IVW method (odds ratio OR = 0.987; 95% confidence interval CI: 0.891–1.093; p = 0.798), nor did HSV‐1 IgG (OR = 1.241; 95% CI: 0.874–1.762; p = 0.227) and HSV‐2 IgG (OR = 0.934; 95% CI: 0.821–1.062; p = 0.297). Similar null results with HSV infection (OR = 1.021; 95% CI: 0.986–1.057; p = 0.245), HSV‐1 IgG (OR = 1.003; 95% CI: 0.982–1.024; p = 0.788) and HSV‐2 IgG (OR = 1.034; 95% CI: 0.991–1.080; p = 0.121) were observed in the reverse MR where SLE served as the exposure. Our study demonstrated no causal association between the genetically predicted HSV and SLE.
Display omitted
•Astrocytic Kir6.1 deletion aggravates lipopolysaccharide-induced neurodegeneration.•Astrocytic Kir6.1 deletion increases C3 expression in astrocytes via NF-κB.•Astroglial C3/neuronal ...C3aR inhibition rescues Kir6.1 deletion-induced neuron death.
Complement pathway over-activation has been implicated in a variety of neurological diseases. However, the signaling pathways governing astrocytic complement activation in Parkinson’s disease (PD) are poorly understood. Kir6.1, a pore-forming subunit of ATP-sensitive potassium (K-ATP) channel, is prominently expressed in astrocytes and exhibits anti-inflammatory effects. Therefore, we hypothesize that Kir6.1/K-ATP channel may regulate astrocytic complement activation in the pathogenesis of PD. In this study, astrocytic Kir6.1 knockout (KO) mice were used to examine the effect of astrocytic Kir6.1/K-ATP channel on astrocytic complement activation triggered by the lipopolysaccharide (LPS). Here, we found that astrocytic Kir6.1 KO mice showed more dopaminergic neuron loss and more astrocyte reactivity in substantia nigra compacta than controls. We also found that astrocytic Kir6.1 KO increased the expression of complement C3 in astrocytes in LPS-induced mouse model of PD. Mechanistically, astrocytic Kir6.1 KO promoted astroglial NF-κB activation to elicit extracellular release of C3, which in turn interacted with neuronal C3aR to induce neuron death. Blocking complement function by NF-κB inhibitor or C3aR antagonist rescued the aggravated neuron death induced by Kir6.1 KO. Collectively, our findings reveal that astrocytic Kir6.1/K-ATP channel prevents neurodegeneration in PD via astrocyte-neuron cross talk through NF-κB/C3/C3aR signaling and suggest that targeting astroglial Kir6.1/K-ATP channel-NF-κB-C3-neuronal C3aR signaling represents a novel therapeutic strategy for PD.
PDF
