Developing highly efficient and economical bifunctional catalysts for overall water splitting is challenging but a great concern for the renewable energy conversion and applied catalysis towards a ...sustainable development. Herein, by employing first principles calculations, the catalytic performance of various transition metal (TM) atoms supported on single-layer ternary Ga2FeS4 for water splitting has been systematically investigated. Strikingly, it was evidenced that the sandwich Ga2FeS4 can form a tunable interfacial polarization field under external strain, which can effectively regulate its catalytic performance. Specifically, Au-Ga2FeS4 under a 0.5% tensile strain presents good bifunctional catalytic performance, with the low overpotentials of 0.03 and 0.48 eV, respectively, for the HER and OER, outperforming the experimentally identified Pt and IrO2. Considering the massive possibilities of these ternary substrates and the easily accessible characteristic of external strain, the findings highlighted here can provide a useful theoretical guideline for designing efficient bifunctional SACs in overall water splitting.
Purpose. A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor-tyrosine kinase inhibitors ...(EGFR-TKIs) with antiangiogenic inhibitors (A+T) and EGFR-TKI monotherapy in patients with treatment-naïve advanced EGFR-mutant non-small-cell lung cancer (NSCLC). Methods. PubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression-free survival (PFS), overall survival (OS), 1- and 2-year OS rates, objective response rate (ORR), and grade≥3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs). Results. Data were collected from six eligible RCTs, which included 1,244 participants (619 in the A+T group and 625 in the TKI alone group). PFS was significantly improved with A+T compared to TKI alone (HR=0.60; P<0.01) regardless of EGFR mutation types (exon 19 deletion or L858R) and brain metastasis status (with or without brain metastases). There was no significant difference in median OS between the A+T and TKI alone groups (HR=0.933; P=0.551) regardless of EGFR mutation type. The ORR for A+T combination therapy was significantly increased compared to TKI monotherapy in exon 19 deletion subgroups (RR=0.774; P=0.008). There was no difference in the positive rates of acquired T790M mutation between the two groups (RR=0.967; P=0.846). More patients in the TKI alone group received a variety of subsequent systemic treatments than those in the A+T group (RR=0.881; P=0.002). Conclusion. Addition of antiangiogenic inhibitors to first-line EGFR-TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR-mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Regulatory B cells (Breg) are considered as immunosuppressive cells. Different subsets of Breg cells have been identified both in human beings and in mice. However, there is a lack of unique markers ...to identify Breg cells, and the heterogeneity of Breg cells in different organs needs to be further illuminated. In this study, we performed high-throughput single-cell RNA sequencing (scRNA-seq) and single-cell B-cell receptor sequencing (scBCR-seq) of B cells from the murine spleen, liver, mesenteric lymph nodes, bone marrow, and peritoneal cavity to better define the phenotype of these cells. Breg cells were identified based on the expression of immunosuppressive genes and IL-10-producing B (B10) cell-related genes, to define B10 and non-B10 subsets in Breg cells based on the score of the B10 gene signatures. Moreover, we characterized 19 common genes significantly expressed in Breg cells, including
,
,
,
, and
, and further analyzed the transcription factor activity in defined Breg cells. Last, a BCR analysis was used to determine the clonally expanded clusters and the relationship of Breg cells across different organs. We demonstrated that
may potentially modulate the function of Breg cells as a transcription factor and that seven organ-specific subsets of Breg cells are found. Depending on gene expression and functional modules, non-B10 Breg cells exhibited activated the TGF-β pathway, thus suggesting that non-B10 Breg cells have specific immunosuppressive properties different from conventional B10 cells. In conclusion, our work provides new insights into Breg cells and illustrates their transcriptional profiles and BCR repertoire in different organs under physiological conditions.
The dependence of the structure of (TiZrHf)N coatings deposited by reactive magnetron sputtering on different working pressures and their mechanical and electro-optical properties were investigated. ...The increased working pressure contributed to the decreased oxygen contamination. With increased working pressure, the compressive stress was transitioned to tensile one. Compressively stressed coatings consisted of tightly packed columns with a smooth surface. The tensile stressed coatings presented void network structure surrounding the columnar grains with a rough surface. Moreover, the grain size initially increased and subsequently decreased. Accordingly, the (TiZrHf)N coatings deposited at high working pressure were characterized with poor hardness, low electrical conductivity, and low light reflectivity due to the porous structure and high oxygen contamination. In addition, the coating color changed from bright gold to dark gray. In this study, the working pressure was proven a sensitive deposition parameter in controlling the microstructure, mechanical, and electro-optical properties of the coating. The wide structural variation in the (TiZrHf)N coatings allowed a diverse physical performance suitable for a broad range of applications.
•The (TiZrHf)N coatings with various working pressure was synthetized.•The stress evolution and growth mechanism with working pressure was defined.•Their mechanical and electro-optical properties was conceptualized and quantified.•The (TiZrHf)N coatings developed a wide variation of structure and physical properties.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In this study, a series of 2,2′ and 3,3′ substituted thienoisoindigo (TII)-based small molecules (H3–H7) were synthesized by using 1,3-di(9H-carbazol-9-yl) benzene, N-phenylcarbazole, ...triphenylamine, and benzene as electron donor (D) at the periphery, while TII as electron acceptor (A) at the core. The highest occupied molecular orbital energy levels of H3–H7 range from −5.31 to −5.43 eV, while their lowest unoccupied molecular orbital energy levels range from −3.43 to −3.59 eV. Under AM 1.5 condition, the perovskite solar cell (PSC) with inverted p–i–n device structure using H7 as the dopant-free hole transporting material achieved a power conversion efficiency (PCE) of 12.1%, which is comparable to that using PEDOT:PSS as the hole transporting material (12.0%). Under an argon atmosphere, the PCE of H7-based PSC did not decay within 168 h, and it can retain 86.3% of its original PCE after 1000 h. The morphology study revealed that the film of H3–H7 was smooth and hydrophobic, while the perovskite film spin-coated on H3–H7 film was uniform with the grain size in micrometer scale. Although the time-resolved photoluminescence spectra of the perovskite films suggested that the hole extraction capability of H7 is weaker than that of PEDOT:PSS, the improved film morphology of the film in H7-based PSC accounts for its comparable PCE to PEDOT:PSS-based PSC.
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IJS, KILJ, NUK, PNG, UL, UM
Background
PEGylated nanoparticles (PEG-NPs) are not effective for hematologic malignancies as they lack the enhanced permeability and retention effect (EPR effect). Tumor-targeted PEG-NPs can ...systemically track lymphoma and actively internalize into cancer cells to enhance therapeutic efficacy. We generated an anti-PEG bispecific antibody (BsAb; mPEG × CD20) which was able to simultaneously bind to methoxy PEG on liposomes and CD20 to form multivalent αCD20-armed liposomes. This αCD20-armed liposome was able to crosslink CD20 on lymphoma cells to enhance cellular internalization and the anti-cancer efficacy of the liposomes to lymphoma. We generated mPEG × CD20 and used this bispecific antibody to modify PEGylated liposomal doxorubicin (PLD) through a one-step formulation.
Results
αCD20-armed PLD (αCD20/PLD) specifically targeted CD20
+
Raji cells and enhanced PLD internalization 56-fold after 24 h. αCD20/PLD also increased cytotoxicity to Raji cells by 15.2-fold in comparison with PLD and control mPEG × DNS-modified PLD (αDNS/PLD). mPEG × CD20 significantly enhanced the tumor accumulation 2.8-fold in comparison with mPEG × DNS-conjugated PEGylated liposomal DiD in Raji tumors. Moreover, αCD20/PLD had significantly greater therapeutic efficacy as compared to αDNS/PLD (
P
< 0.0001) and PLD(
P
< 0.0001), and αCD20/PLD-treated mice had a 90% survival rate at 100-day post-treatment.
Conclusions
Modification of mPEG × CD20 can confer PLD with CD20 specificity to enhance the internalization and the anti-cancer efficacy of PEG-NPs. This therapeutic strategy can conveniently be used to modify various PEG-NPs with anti-PEG BsAb to overcome the lack of EPR effect of hematologic malignancies and improve therapeutic efficacy.
The edge-based computing paradigm (ECP) becomes one of the most innovative modes of processing distributed Interneit of Things (IoT) sensor data. However, the edge nodes in ECP are usually ...resource-constrained. When more services are executed on an edge node, the resources required by these services may exceed the edge node's, so as to fail to maintain the normal running of the edge node. In order to solve this problem, this paper proposes a resource-constrained smart service migration framework for edge computing environment in IoT (IoT-RECSM) and a dynamic edge service migration algorithm. Based on this algorithm, the framework can dynamically migrate services of resource-critical edge nodes to resource-rich nodes. In the framework, four abstract models are presented to quantificationally evaluate the resource usage of edge nodes and the resource consumption of edge service in real-time. Finally, an edge smart services migration prototype system is implemented to simulate the edge service migration in IoT environment. Based on the system, an IoT case including 10 edge nodes is simulated to evaluate the proposed approach. According to the experiment results, service migration among edge nodes not only maintains the stability of service execution on edge nodes, but also reduces the sensor data traffic between edge nodes and cloud center.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background:
Patients with different molecular subtypes of breast cancers have different recurrence risks and prognoses. Clinical support and evidence to guide management are absent for patients with ...breast cancer coexisting with HER-2 amplification and EGFR mutations.
Case presentation:
We report a case of breast cancer coexisting with HER-2 amplification and EGFR exon 19 deletion (E19 del). The patient presented with solitary pulmonary nodule and enlargement of hilar and mediastinal lymph nodes 2 years after radical mastectomy. Biopsy of the subcarinal lymph node showed suspected adenocarcinoma. The specimen was too small for further immunohistochemistry, but an EGFR E19 del was discovered. Due to the primary diagnosis of EGFR-mutant lung adenocarcinoma, EGFR-TKI gefitinib was administered and resulted in 1 year of stable disease until the patient developed progression in the right pulmonary nodule with new metastatic cervical lymph nodes. According to histopathological findings of re-biopsy of the pulmonary nodule and left cervical and subcarinal lymph nodes, the patient was diagnosed with breast cancer with lung metastasis and multiple lymph node metastases. The patient received multiple anti-HER-2-targeted therapies (trastuzumab for 9.7 months, lapatinib for 9 months, and pyrotinib for 4+ months) and survived for more than 36 months after lung metastasis.
Conclusions:
This case suggested that breast cancer coexisting with HER-2 amplification and EGFR E19 del may be driven by both HER-2 and EGFR signaling pathways, and patients can benefit from EGFR-TKI and anti-HER-2 therapy.
Minimal hepatic encephalopathy (MHE) is an early and reversible form of hepatic encephalopathy. The documentations on the treatment with probiotics are inconsistent. The present meta-analysis was to ...verify the role of probiotics in the treatment of cirrhotic patients with MHE.
Seven electronic databases were searched for relevant randomized controlled trials (RCTs) published until July 2015. The effects of probiotics on serum ammonia, endotoxin, and MHE were evaluated.
A total of 14 RCTs (combined n = 1132) were included in the meta-analysis. When probiotics were compared to placebo or no treatment, probiotics were more likely to reduce values in the number connection test (NCT; week 4: MD = −30.25, 95% CI: −49.85 to −10.66), improve MHE (week 4: OR = 0.18, 95% CI: 0.07 to 0.47; week 12: OR = 0.15, 95% CI: 0.07 to 0.32), and prevent overt HE progression (week 4: OR = 0.22, 95% CI: 0.07 to 0.67) in patients with liver cirrhosis. When probiotics was compared to lactulose, probiotics tended to reduce serum ammonia levels (week 4: MD = −0.33 µmol/L, 95% CI: −5.39 to 4.74; week 8: MD = 6.22 µmol/L, 95% CI: −24.04 to 36.48), decrease NCT (week 8: MD = 3.93, 95% CI: −0.72 to 8.58), improve MHE (week 4: OR = 0.93, 95% CI: 0.45 to 1.91; week 12: OR = 0.73, 95% CI: 0.35 to 1.51) and prevent the development of overt HE (week 4: OR = 0.96, 95% CI: 0.17 to 5.44; week 12: OR = 2.7, 95% CI: 0.50 to 14.64) in patients with liver cirrhosis. However, lactulose appears to be more effective in reducing NCT values as compared to probiotics (week 4: MD = 6.7, 95% CI: 0.58 to 12.82).
Probiotics can decrease serum ammonia and endotoxin levels, improve MHE, and prevent overt HE development in patients with liver cirrhosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Attention is important for effectively comparing incoming perceptual information with the contents of visual short-term memory (VSTM), such that any differences can be detected. However, how ...attentional mechanisms operate upon these comparison processes remains largely unknown. Here we investigate the underlying neural mechanisms by which attention modulates the comparisons between VSTM and perceptual representations using functional magnetic resonance imaging (fMRI). Participants performed a cued change detection task. Spatial cues were presented to orient their attention either to the location of an item in VSTM prior to its comparison (retro-cues), or simultaneously (simultaneous-cues) with the probe array. A no-cue condition was also included. When attention cannot be effectively deployed in advance (i.e. following the simultaneous-cues), we observed a distributed and extensive activation pattern in the prefrontal and parietal cortices in support of successful change detection. This was not the case when participants can deploy their attention in advance (i.e. following the retro-cues). The region-of-interest analyses confirmed that neural responses for successful change detection versus correct rejection in the visual and parietal regions were significantly different for simultaneous-cues compared to retro-cues. Importantly, we found enhanced functional connectivity between prefrontal and parietal cortices when detecting changes on the simultaneous-cue trials. Moreover, we demonstrated a close relationship between this functional connectivity and d' scores. Together, our findings elucidate the attentional and neural mechanisms by which items held in VSTM are compared with incoming perceptual information.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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