Abstract
Background
Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether ...these findings translate to epidermal growth factor receptor (EGFR)–mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual.
Methods
Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided.
Results
A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial.
Conclusions
As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.
Ambient electrochemical ammonia (NH3) synthesis is one promising alternative to the energy‐intensive Haber–Bosch route. However, the industrial requirement for the electrochemical NH3 production with ...amperes current densities or gram‐level NH3 yield remains a grand challenge. Herein, we report the high‐rate NH3 production via NO2− reduction using the Cu activated Co electrode in a bipolar membrane (BPM) assemble electrolyser, wherein BPM maintains the ion balance and the liquid level of electrolyte. Benefited from the abundant Co sites and optimal structure, the target modified Co foam electrode delivers a current density of 2.64 A cm−2 with the Faradaic efficiency of 96.45 % and the high NH3 yield rate of 279.44 mg h−1 cm−2 in H‐type cell using alkaline electrolyte. Combined with in situ experiments and theoretical calculations, we found that Cu optimizes the adsorption behavior of NO2− and facilitates the hydrogenation steps on Co sites toward a rapid NO2− reduction process. Importantly, this activated Co electrode affords a large NH3 production up to 4.11 g h−1 in a homemade reactor, highlighting its large‐scale practical feasibility.
A high‐efficiency electrochemical ammonia (NH3) synthesis from NOx on a Cu‐activated Co foam electrode was developed as a promising alternative for the Haber–Bosch process. The new synthesis can convert pollutants into elevated value‐added NH3 applicable for agriculture, energy storage, etc., imposing a sustainable nitrogen cycle.
Previous studies have found that herpesviruses are associated with aggressive periodontitis (AgP). However, these findings are controversial. This meta-analysis was aimed at clarifying the ...association between herpesviruses and AgP.
We identified eligible case-control studies evaluating the association between herpesviruses and AgP from PubMed and Embase databases in October 2015. Original data were extracted and quality assessment was done. Overall odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Random-effects model was determined. The stability was evaluated by sensitivity analysis. Finally, Egger's funnel plot was used to investigate the publication bias.
Twelve case-control studies involving 322 patients and 342 controls were included in the present meta-analysis. The included case-control studies were assessed as high quality. The quantitative synthesis results for Epstein-Barr virus (EBV) showed significance (10 studies: p = 0.0008, OR = 6.11, 95% CI = 2.13-17.51); nevertheless, evidence of publication bias for EBV was considerable (EBV: Egger's test, p<0.001). Human cytomegalovirus (HCMV) and Herpes simplex virus type 1 (HSV-1) had significant association with AgP (12 studies for HCMV: p = 0.009, OR = 3.63, 95% CI = 2.15-6.13; 4 studies for HSV-1: p<0.001, OR = 19.19, 95% CI = 4.16-79.06). Sensitivity analyses showed the results yielded consistency, and no significant publication bias was observed for HCMV. The association between Herpes simplex virus type 2 (HSV-2) and AgP was inconclusive (2 studies: p = 0.20, OR = 3.46, 95% CI = 0.51-23.51).
This meta-analysis suggests that HCMV and HSV-1 are significantly associated with AgP. However, due to the heterogeneity among studies these conclusions should be cautiously interpreted. There is insufficient evidence to draw any conclusion between EBV, HSV-2 and AgP based on the currently limited data.
Immune checkpoint blockade has shown significant clinical benefit in multiple cancer indications, but many patients are either refractory or become resistant to the treatment over time. HER2/neu ...oncogene overexpressed in invasive breast cancer patients associates with more aggressive diseases and poor prognosis. Anti-HER2 mAbs, such as trastuzumab, are currently the standard of care for HER2-overexpressing cancers, but the response rates are below 30% and patients generally suffer relapse within a year. In this study we developed a bispecific antibody (BsAb) simultaneously targeting both PD1 and HER2 in an attempt to combine HER2-targeted therapy with immune checkpoint blockade for treating HER2-positive solid tumors. The BsAb was constructed by fusing scFvs (anti-PD1) with the effector-functional Fc of an IgG (trastuzumab) via a flexible peptide linker. We showed that the BsAb bound to human HER2 and PD1 with high affinities (EC
values were 0.2 and 0.14 nM, respectively), and exhibited potent antitumor activities in vitro and in vivo. Furthermore, we demonstrated that the BsAb exhibited both HER2 and PD1 blockade activities and was effective in killing HER2-positive tumor cells via antibody-dependent cellular cytotoxicity. In addition, the BsAb could crosslink HER2-positive tumor cells with T cells to form PD1 immunological synapses that directed tumor cell killing without the need of antigen presentation. Thus, the BsAb is a new promising approach for treating late-stage metastatic HER2-positive cancers.
Tartary buckwheat (Fagopyrum tataricum) is a traditional coarse cereal that exhibits strong plasticity in its adaptation to harsh and complicated environmental stresses. In an attempt to study the ...strong tolerance of tartary buckwheat, the FtMYB9 gene, which encodes an R2R3-MYB transcription factor protein, was functionally investigated. FtMYB9 expression was rapidly and strongly induced by ABA, cold, salt, and drought treatments in the seedling stage. A yeast one-hybrid system assay indicated that FtMYB9 is an activator of transcriptional activity, consistent with its roles as a transcription factor. Its overexpression in plants resulted in increased sensitivity to ABA at the germination and seedling stages compared to wild type. The overexpression of FtMYB9 increased tolerance to drought and salt stresses by the activation of some stress-related genes from both ABA-independent and ABA-dependent pathways in transgenic Arabidopsis. Furthermore, enhanced proline content and the activation of the P5CS1 gene implied that FtMYB9 may be involved in proline synthesis in plants. Collectively, these results suggest that FtMYB9 functions as a novel R2R3-MYB TF which plays positive roles in salt and drought tolerance by regulating different stress-responsive signaling pathways.
By modifying the bonding of graphene (GR) and Fe3O4, a stable structure of GR-Fe3O4, namely magnetic GR, was obtained. Under the induction of a magnetic field, it can be orientated in an epoxy resin ...(EP) matrix, thus preparing EP/GR-Fe3O4 composites. The effects of the content of GR and the degree of orientation on the thermal conductivity of the composites were investigated, and the most suitable Fe3O4 load on GR was obtained. When the mass ratio of GR and Fe3O4 was 2:1, the thermal conductivity could be increased by 54.8% compared with that of pure EP. Meanwhile, EP/GR-Fe3O4 composites had a better thermal stability, dynamic thermomechanical properties, and excellent electrical insulation properties, which can meet the requirements of electronic packaging materials.
The hydroxyapatite nanoparticles (nHAPs) were synthesized rapidly by the self-assembled dual-frequency ultrasonic method. The ultrasonic time and power effect on the morphology and phase composition ...of nHAPs were investigated through field-emission scanning electron microscopy (FE-SEM), X-ray diffraction, energy dispersive spectrometer (EDS) spectrometer, and Fourier transform infrared spectroscopy, which showed that the most uniform nanoparticles were obtained when the ultrasonic time was 30 min and the ultrasonic power was 280 W. Cytotoxicity and hemolysis tests showed that an indistinctive cytotoxic effect was within the concentration of 25–400 μg/mL and the hemolytic ratio was below 2.0% at concentration of 25–200 μg/mL, respectively, revealing a good biocompatibility of nHAPs. By loading tetracycline hydrochloride onto nHAPs spheres, the drug release results showed that the drug loading and encapsulation efficiency were (26.34 ± 2.99)% and (52.68 ± 5.98)%, respectively. The drug-loaded sample shows a slow-release property, indicating that nHAPs may be promising as drug carriers.
•Altered microbiota and microbial metabolites are correlated with Parkinson’s disease.•Roles of short-chain fatty acids are highly ambiguous from current research.•Metabolites of H2 and H2S link ...microbiota to Parkinson’s disease.•Gut microbiota shed new light on early diagnosis and innovative treatments.
Parkinson’s disease (PD) is a complicated neurodegenerative disease attributed to multifactorial changes. However, its pathological mechanism remains undetermined. Accumulating evidence has revealed the emerging functions of gut microbiota and microbial metabolites, which can affect both the enteric nervous system and the central nervous system via the microbiota-gut-brain axis. Accordingly, intestinal dysbiosis might be closely associated with PD. This review explores alterations to gut microbiota, correlations with clinical manifestations of PD, and briefly probes the underlying mechanisms. Next, the highly controversial roles of microbial metabolites including short-chain fatty acids (SCFAs), H2 and H2S are discussed. Finally, the pros and cons of the current treatments for PD, including those targeting microbiota, are assessed. Advancements in research techniques, further studies on levels of specific strains and longitudinal prospective clinical trials are urgently needed for the identification of early diagnostic markers and the development of novel therapeutic approaches for PD.
Stretchable triboelectric nanogenerators (TENGs) attract much attentions in the field of wearable electronics owing to their unique capabilities of ambient energy harvesting, especially from human ...activities, serving as sustainable power source as well as functional sensing device. The essential challenge of super-stretchable triboelectric nanogenerator (SS-TENG) is to overcome the non-stretchable drawback of conventional electrodes and endow them with remarkable extension capability. In this work, we developed a carbon nanotubes (CNT)-silicone rubber liquid composite with outstanding conductivity and fluidity, which provides an essential opportunity to realize a SS-TENG with the remarkable capability of 900% stretchable deformation. This newly developed SS-TENG successfully achieved the integration of bio-mechanical energy harvesting and multi-functional sensing. The electric output performance was comprehensively investigated and a maximum power density of 21.7 W/m2 was obtained, which is large enough to power common low-power-consumption electronic devices. As for passive sensing, the proposed SS-TENG can be utilized as a strain gauge with good sensitivity (gauge factor (GF) of 11.4) and low hysteresis (degree of hysteresis (DH) of 0.71%). Moreover, as for active sensing, the detection of dynamic motions of human body joints was realized due to the correlation between gesture and corresponding electrical signal. Eventually, a self-powered wearable keyboard based on SS-TENG arrays with outstanding conformability on curved surfaces was demonstrated, which reveals a promising potential of the proposed liquid conductive composite and the developed SS-TENG for self-powered wearable electronic applications, especially in the healthcare field.
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•A CNT-SR liquid composite with outstanding conductivity and fluidity is developed.•A 900% super-stretchable triboelectric nanogenerator (SS-TENG) is realized.•The SS-TENG achieves the integration of bio-mechanical energy harvesting and multi-functional sensing.•The proposed multi-functional sensing is the combination of passive-strain sensing and active-motion detecting.•A self-powered wearable keyboard with outstanding conformability on curved surfaces is demonstrated.
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