Combining non-invasive liquid biopsy and a methylation analysis to assess surgical risk for early esophageal cancer.

Background: While the widespread use of endoscopic submucosal dissection (ESD) has significantly reduced the incidence of early esophageal cancer (ESCA), the limited ability of ESD to strip deep infiltrating esophageal lesions results in a considerable risk of intraoperative perforation. Circulating-free DNA (cfDNA) is widely used in modern tumor screening due to its non-invasive detection capabilities. A methylation analysis offers vital insights into the condition and advancement of malignancies due to its unique positioning, such as a marker of cancer. This study investigated the potential of combining a non-invasive liquid biopsy technique, along with a methylation analysis, to assess the surgical perforation risk of ESCA patients. Methods: In this study, we conducted an analysis of gene expression differences between stage I esophageal squamous carcinoma samples and healthy tissue samples using data from The Cancer Genome Atlas (TCGA) database. We also identified the genes associated with progression-free survival (PFS) in esophageal squamous carcinoma. Integrating the framework of the methylation analysis, we explored the methylated sites of these distinct genes. To refine this process, we used the Shiny Methylation Analysis Resource Tool (SMART) to conduct a comprehensive analysis of these sites. We then confirmed the stability of the methylation sites in different lesion conditions using methylation-specific quantitative polymerase chain reaction (MS-qPCR) with paraffin tissue samples collected after ESD. Results: We analyzed RNA-sequencing data from 42 early stage ESCA patients and 17 controls, identifying 1,263 up-regulated and 460 down-regulated genes. Functional analyses revealed involvement in key pathways such as cell cycle regulation and immune responses. Furthermore, we identified 38 differentially expressed genes associated with PFS. Using SMART analysis, we found 217 hyper-methylated regions in 38 genes, suggesting potential early markers for ESCA. Validation experiments confirmed the reliability of 29 hyper-methylated regions in FFPE tissue samples and 6 regions in cfDNA. A LunaCAM model showed high accuracy [area under the curve (AUC) =0.89] in discriminating early ESCA. Integrated assessment of six highly methylated regions significantly improved predictive performance, with 90.56% sensitivity, highlighting the importance of combinatorial biomarker evaluation for early cancer detection. Conclusions: This study established a novel approach that integrates non-invasive testing with a methylation analysis to assess the surgical risk of early ESCA patients. The significance of changes in methylation sites in relation to lesion status should not be underestimated, as they have the potential to offer vital insights for proactive risk assessments before surgery.

Association between quadriceps fat pad edema and patellofemoral osteoarthritis: a quantitative Q-Dixon-based magnetic resonance imaging (MRI) analysis.

Background: Anterior knee pain (AKP) is a common symptom of patellofemoral osteoarthritis (PFOA). There is limited prospective evidence supporting the relationships between patellofemoral maltracking parameters, AKP, and PFOA. Thus, this prospective cross-sectional study aimed to determine the association between quadriceps fat pad (QFP) edema and patellofemoral maltracking in patients with chronic AKP and to evaluate the feasibility and diagnostic performance of a PFOA assessment using fat fraction (FF) and T2* based on Q-Dixon. Methods: This was a cross-sectional study with prospective data collection. Patients with chronic AKP were recruited from an orthopedic outpatient magnetic resonance imaging (MRI) waiting room at Shanghai Tongren Hospital between November 1, 2022, and April, 30, 2023. Exclusion criteria included age of <18 years, knee trauma, major internal derangement, prior surgery/arthroscopy, pre-existing joint diseases, and contraindications to MRI. MRI was performed using a 3.0-T instrument, and patellofemoral maltracking parameters were measured. Patellofemoral feature-relevant items, including patellar cartilage defects, patellar bone marrow lesions (BMLs), patellar osteophytes, anterior femoral osteophytes, Hoffa synovitis, and synovitis-effusion, from the semi-quantitative MRI Osteoarthritis Knee Score (MOAKS) were measured. The Anterior Knee Pain Scale (AKPS) was used to assess pain and function. FF/T2* measurement differences between groups and their associations with maltracking metrics, osteoarthritis grading based on the Iwano grading system, MOAKS, and AKPS, were investigated. Based on Iwano grading, the participants were categorized as having no-PFOA (n=40), mild PFOA (n=40), and advanced PFOA (n=40). Chi-squared and one-way analysis of variance were used to assess potential differences between the groups. Spearman's correlation test was used to analyze the correlation between the morphological parameters, AKPS, Iwano grade, MOAKS, and MRI quantitative values. Receiver operating characteristic (ROC) curves assessed the area under the curve (AUC), sensitivity, and specificity of quantitative values for distinguishing PFOA from no-PFOA. Results: Among the 120 included patients, those in the mild (86.2±8.5) and advanced (83.9±9.5) PFOA groups had significantly lower AKPS scores than those in the no-PFOA group (88.8±7.3) (P=0.03). The mean FF and T2* values of the QFP were significantly higher in the no-PFOA group than those in the mild and advanced PFOA groups (P<0.001 for FF and P=0.02 for T2*). Quantitative data on the QFP and patellofemoral maltracking parameters showed no association. FF (r=-0.686, P<0.001) and T2* (r=-0.314, P=0.008) showed a negative correlation with the Iwano grade. The AUCs for PFOA diagnosis were 0.906 [95% confidence interval (CI), 0.853-0.960] (FF) and 0.744 (95% CI, 0.657-0.831) (T2*). Conclusions: QFP FF and T2* were not associated with patellofemoral maltracking parameters but with increased PFOA in patients with AKP, suggesting that QFP abnormalities play a role in PFOA. Therefore, a quantitative QFP assessment (FF and T2*) based on Q-Dixon technology could be a convenient and reliable new imaging biomarker for PFOA severity during clinical diagnosis, treatment, and follow-up.

Creating High-entropy Single Atoms on Transition Disulfides through Substrate-induced Redox Dynamics for Efficient Electrocatalytic Hydrogen Evolution.

The controllable anchoring of multiple metal single-atoms (SAs) into a single support exhibits scientific and technological opportunities, while marrying the concentration-complex multimetallic SAs and high-entropy SAs (HESAs) into one SAC system remains a substantial challenge. Here, we present a substrate-mediated SAs formation strategy to successfully fabricate a library of multimetallic SAs and HESAs on MoS2 and MoSe2 supports, which can precisely control the doping location of SAs. Specially, the contents of SAs can continuously increase until the accessible Mo atoms on TMDs carriers are completely replaced by SAs, thus allowing the of much higher metal contents. In-depth mechanistic study shows that the well-controlled synthesis of multimetallic SAs and HESAs is realized by controlling the reversible redox reaction occurred on the TMDs/TM ion interface. As a proof-of-concept application, a variety of SAs-TMDs were applied to hydrogen evolution reaction. The optimized HESAs-TMDs (Pt,Ru,Rh,Pd,Re-MoSe2) delivers a much higher activity and durability than state of-the-art Pt. Thus, our work will broaden the family of single-atom catalysts and provide a new guideline for the rational design of high-performance single-atom catalysts.

Establishment of in-hospital nutrition support program for middle-aged and elderly patients with acute decompendated heart failure.

OBJECTIVE: To construct a nutrition support program for middle-aged and elderly patients with acute decompensated heart failure (ADHF) during hospitalization. METHODS: Based on the JBI Evidence-Based Health Care Model as the theoretical framework, the best evidence was extracted through literature analysis and a preliminary nutrition support plan for middle-aged and elderly ADHF patients during hospitalization was formed. Two rounds of expert opinion consultation were conducted using the Delphi method. The indicators were modified, supplemented and reduced according to the expert's scoring and feedback, and the expert scoring was calculated. RESULTS: The response rates of the experts in the two rounds of consultation were 86.7% and 100%, respectively, and the coefficient of variation (CV) for each round was between 0.00% and 29.67% (all < 0.25). In the first round of expert consultation, 4 items were modified, 3 items were deleted, and 3 items were added. In the second round of the expert consultation, one item was deleted and one item was modified. Through two rounds of expert consultation, expert consensus was reached and a nutrition support plan for ADHF patients was finally formed, including 4 first-level indicators, 7 s-level indicators, and 24 third-level indicators. CONCLUSION: The nutrition support program constructed in this study for middle-aged and elderly ADHF patients during hospitalization is authoritative, scientific and practical, and provides a theoretical basis for clinical development of nutrition support program for middle-aged and elderly ADHF patients during hospitalization.

Bioinformatic Identification and Expression Analyses of the MAPK-MAP4K Gene Family Reveal a Putative Functional MAP4K10-MAP3K7/8-MAP2K1/11-MAPK3/6 Cascade in Wheat (Triticum aestivum L.).

The mitogen-activated protein kinase (MAPK) cascades act as crucial signaling modules that regulate plant growth and development, response to biotic/abiotic stresses, and plant immunity. MAP3Ks can be activated through MAP4K phosphorylation in non-plant systems, but this has not been reported in plants to date. Here, we identified a total of 234 putative TaMAPK family members in wheat (Triticum aestivum L.). They included 48 MAPKs, 17 MAP2Ks, 144 MAP3Ks, and 25 MAP4Ks. We conducted systematic analyses of the evolution, domain conservation, interaction networks, and expression profiles of these TaMAPK-TaMAP4K (representing TaMAPK, TaMAP2K, TaMAP3K, and TaMAP4K) kinase family members. The 234 TaMAPK-TaMAP4Ks are distributed on 21 chromosomes and one unknown linkage group (Un). Notably, 25 of these TaMAP4K family members possessed the conserved motifs of MAP4K genes, including glycine-rich motif, invariant lysine (K) motif, HRD motif, DFG motif, and signature motif. TaMAPK3 and 6, and TaMAP4K10/24 were shown to be strongly expressed not only throughout the growth and development stages but also in response to drought or heat stress. The bioinformatics analyses and qRT-PCR results suggested that wheat may activate the MAP4K10-MEKK7-MAP2K11-MAPK6 pathway to increase drought resistance in wheat, and the MAP4K10-MAP3K8-MAP2K1/11-MAPK3 pathway may be involved in plant growth. In general, our work identified members of the MAPK-MAP4K cascade in wheat and profiled their potential roles during their response to abiotic stresses and plant growth based on their expression pattern. The characterized cascades might be good candidates for future crop improvement and molecular breeding.

Well-dispersed Pt/Nb2O5on zeolitic imidazolate framework derived nitrogen-doped carbon for efficient oxygen reduction reaction.

In this work, an advanced hybrid material was constructed by incorporating niobium pentoxide (Nb2O5) nanocrystals with nitrogen-doped carbon (NC) derived from ZIF-8 dodecahedrons, serving as a support, referred to as Nb2O5/NC. Pt nanocrystals were dispersed onto Nb2O5/NC using a simple impregnation reduction method. The obtained Pt/Nb2O5/NC electrocatalyst showed high oxygen reduction reaction (ORR) activity due to three-phase mutual contacting structure with well-dispersed Pt and Nb2O5NPs. In addition, the conductive NC benefits electron transfer, while the induced Nb2O5can regulate the electronic structure of Pt element and anchor Pt nanocrystals, thereby enhancing the ORR activity and stability. The half-wave potential (E1/2) for Pt/Nb2O5/NC is 0.886 V, which is higher than that of Pt/NC (E1/2= 0.826 V). The stability examinations demonstrated that Pt/Nb2O5/NC exhibited higher electrocatalytic durability than Pt/NC. Our work provides a new direction for synthesis and structural design of precious metal/oxides hybrid electrocatalysts.

[Design and application of distal radial artery hemostat].

Transradial approach is the classical access for coronary angiography and percutaneous coronary intervention (PCI). With the increase in the number of interventional procedures, some disadvantages of the transradial approach have also been found, it is easy to lead to various complications, such as radial artery occlusion, radial nerve injury, and puncture difficulties after radial artery spasm. Therefore, some experts put forward the approach of distal radial artery approach for interventional therapy, which has the advantages of convenient positioning, easy postoperative hemostasis, less damage to the proximal radial artery and improving patients' comfort. However, there is no special distal radial artery hemostat in clinic, which limits the development of this approach to a certain extent. Therefore, based on the principles of anatomy and physics, cardiovascular physician at Jiading District District Central Hospital in Shanghai designed and invented a distal radial artery hemostatic device, which is convenient for clinical hemostasis of distal radial artery puncture, and obtained the National Utility Model Patent (patent number: ZL 2021 2 2097829.6). The hemostatic device consists of a glove body with a silicone gasket protruding towards the skin on the inner surface and a binding component. The patient's hand is inserted into the glove body, and after being fixed by the restraint component, the silicone gasket can effectively compress the location of the radial artery puncture point, and play a good hemostatic effect with less pressure, avoid the common complications of proximal radial artery hemostatic, and reduce the discomfort of the patient. Has good application value.

Analgesic efficacy of an opioid-free postoperative pain management strategy versus a conventional opioid-based strategy following laparoscopic radical gastrectomy: an open-label, randomized, controlled, non-inferiority trial.

OBJECTIVE: In patients undergoing laparoscopic radical gastrectomy, the use of subcostal transversus abdominis plane block (STAPB) for completely opioid-free postoperative pain management lacks convincing clinical evidence. METHODS: This study included 112 patients who underwent laparoscopic radical gastrectomy at the 900TH Hospital of the Joint Logistics Support Force from October 2020 to March 2022. Patients were randomly divided into (1:1) continuous opioid-free STAPB (C-STAPB) group and conventional group. In the C-STAPB group, 0.2% ropivacaine (bilateral, 20 ml per side) was injected intermittently every 12 h through a catheter placed on the transverse abdominis plane for postoperative pain management. The conventional group was treated with a conventional intravenous opioid pump (2.5 µg/kg sufentanil and 10 mg tropisetron, diluted to 100 ml with 0.9% NS). The primary outcomes were the accumulative area under the curve of the numeric rating scale (NRS) score at 24 and 48 h postoperatively at rest and during movement. The secondary outcomes were postoperative recovery outcomes, postoperative daily food intake, and postoperative complications. RESULTS: After exclusion (n = 16), a total of 96 patients (C-STAPB group, n = 46; conventional group, n = 49) were included. We found there were no significant differences in the cumulative AUC of NRS score PACU-24 h and PACU-48 h between the C-STAPB group and conventional group at rest [(mean difference, 1.38; 95% CI, - 2.21 to 4.98, P = 0.447), (mean difference, 1.22; 95% CI, - 6.20 to 8.65, P = 0.744)] and at movement [(mean difference, 2.90; 95% CI, - 3.65 to 9.46; P = 0.382), (mean difference, 4.32; 95% CI, - 4.46 to 13.1; P = 0.331)]. The 95% CI upper bound of the difference between rest and movement in the C-STAPB group was less than the inferior margin value (9.5 and 14 points), indicating the non-inferiority of the analgesic effect of C-STPAB. The C-STAPB group had faster postoperative recovery profiles including earlier bowel movement, defecation, more volume of food intake postoperative, and lower postoperative nausea and vomiting compared to conventional groups (P < 0.001). CONCLUSIONS: After laparoscopic radical gastrectomy, the analgesic effect of C-STAPBP is not inferior to the traditional opioid-based pain management model. TRIAL REGISTRATION: ChiCTR2100051784.

ZnSe/SnSe Heterostructure Incorporated with Selenium/Nitrogen Co-Doped Carbon Nanofiber Skeleton for Sodium-Ion Batteries.

Effective strategies toward building exquisite nanostructures with enhanced structural integrity and improved reaction kinetics will carry forward the practical application of alloy-based materials as anodes in batteries. Herein, a free-standing 3D carbon nanofiber (CNF) skeleton incorporated with heterostructured binary metal selenides (ZnSe/SnSe) nanoboxes is developed for Na-ion storage anodes, which can facilitate Na+ ion migration, improve structure integrity, and enhance the electrochemical reaction kinetics. During the carbonization and selenization process, selenium/nitrogen (Se/N) is co-doped into the 3D CNF skeleton, which can improve the conductivity and wettability of the CNF matrices. More importantly, the ZnSe/SnSe heterostructures and the Se/N co-doping CNFs can have a synergistic interfacial coupling effect and built-in electric field in the heterogeneous interfaces of ZnSe/SnSe hetero-boundaries as well as the interfaces between the CNF matrix and the selenide heterostructures, which can enable fast ion/electron transport and accelerate surface/internal reaction kinetics for Na-ion storage. The ZnSe/SnSe@Se,N-CNFs exhibit superior Na-ion storage performance than the comparative ZnSe/SnSe, ZnSe and SnSe powders, which deliver an excellent rate performance (882.0, 773.6, 695.7, 634.2, and 559.0 mAh g-1 at current rates of 0.1, 0.2, 0.5, 1, and 2 A g-1) and long-life cycling stability of 587.5 mAh g-1 for 3500 cycles at 2 A g-1.

RNA barcode segments for SARS-CoV-2 identification from HCoVs and SARSr-CoV-2 lineages.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for coronavirus disease 2019 (COVID-19), continues to evolve, giving rise to more variants and global reinfections. Previous research has demonstrated that barcode segments can effectively and cost-efficiently identify specific species within closely related populations. In this study, we designed and tested RNA barcode segments based on genetic evolutionary relationships to facilitate the efficient and accurate identification of SARS-CoV-2 from extensive virus samples, including human coronaviruses (HCoVs) and SARSr-CoV-2 lineages. Nucleotide sequences sourced from NCBI and GISAID were meticulously selected and curated to construct training sets, encompassing 1733 complete genome sequences of HCoVs and SARSr-CoV-2 lineages. Through genetic-level species testing, we validated the accuracy and reliability of the barcode segments for identifying SARS-CoV-2. Subsequently, 75 main and subordinate species-specific barcode segments for SARS-CoV-2, located in ORF1ab, S, E, ORF7a, and N coding sequences, were intercepted and screened based on single-nucleotide polymorphism sites and weighted scores. Post-testing, these segments exhibited high recall rates (nearly 100%), specificity (almost 30% at the nucleotide level), and precision (100%) performance on identification. They were eventually visualized using one and two-dimensional combined barcodes and deposited in an online database (http://virusbarcodedatabase.top/). The successful integration of barcoding technology in SARS-CoV-2 identification provides valuable insights for future studies involving complete genome sequence polymorphism analysis. Moreover, this cost-effective and efficient identification approach also provides valuable reference for future research endeavors related to virus surveillance.

Challenges and approaches of single-crystal Ni-rich layered cathodes in lithium batteries.

High energy density and high safety are incompatible with each other in a lithium battery, which challenges today's energy storage and power applications. Ni-rich layered transition metal oxides (NMCs) have been identified as the primary cathode candidate for powering next-generation electric vehicles and have been extensively studied in the last two decades, leading to the fast growth of their market share, including both polycrystalline and single-crystal NMC cathodes. Single-crystal NMCs appear to be superior to polycrystalline NMCs, especially at low Ni content (≤60%). However, Ni-rich single-crystal NMC cathodes experience even faster capacity decay than polycrystalline NMC cathodes, rendering them unsuitable for practical application. Accordingly, this work will systematically review the attenuation mechanism of single-crystal NMCs and generate fresh insights into valuable research pathways. This perspective will provide a direction for the development of Ni-rich single-crystal NMC cathodes.

GDU-952, a novel AhR agonist ameliorates skin barrier abnormalities and immune dysfunction in DNFB-induced atopic dermatitis in mice.

The aryl hydrocarbon receptor (AhR) is widely expressed in the skin. It controls immune-mediated skin responses to various external environmental signals, promote terminal differentiation of epidermal keratinocytes and participates the maintenance of the skin barrier function. As a therapeutic target, AhR activation modulates many diseases progression driven by immune/inflammatory processes such as atopic dermatitis (AD) and psoriasis. In this study, we revealed that GDU-952 is a novel AhR agonist, which is able to decreases IgE serum levels, to inhibit pro-inflammatory cytokines such as IL-6 and TNF-α and to induce immunoregulatory effects through restoring Th1/Th2 immune balance and promoting CD4+FOXP3+regulatory T (Treg) populations in AD skin lesions. Furthermore, GDU-952 can strengthen the skin barrier function through upregulating epidermal differentiation-related and tight junction proteins. This may alleviate AD symptoms, such as dermatitis scores, epidermal hyperplasia and mast cell infiltration. These results offer a rationale for further preclinical/clinical studies to evaluate the possible use of GDU-952 in the management of AD.

Enhancing the SCC Resistance of the Anchor Steel with Microalloying in a Simulated Mine Environment.

This work explored a new idea for enhancing the resistance to stress corrosion cracking (SCC) of mining anchor steel through microalloying. Microalloyed anchor steels with Nb, Cu, Ni, Sb, and C were prepared through vacuum smelting and hot rolling. Electrochemical measurements, slow strain rate tensile (SSRT) tests, and fracture morphology observations were used to study the electrochemical and SCC behavior in the simulated mine environment. The results proved that the microstructure of microalloyed steels varies slightly. Adding Ni, Cu, and Sb can improve the mechanical properties of the anchor steel, while reducing C content decreases tensile strength as a result of loss of the solution-strengthening effect. The addition of Sb, Cu, Ni, and reducing the content of C enhances the resistance to corrosion and SCC by mitigating anodic dissolution (AD), while adding Nb improves SCC resistance by inhibiting hydrogen embrittlement (HE). The combined addition of 1% Ni, 0.5% Cu, 0.05% Nb, 0.1% Sb, and 0.5% C presented the highest SCC resistance, which is a promising prospect for the development of high-performance, low-alloy anchor steels. The combined addition of 1% Ni, 0.5% Cu, 0.05% Nb, and 0.1% Sb resulted in the inhibition of electrochemical reactions and corrosion. As a result of the synergistic effect of the microalloy, both AD and HE mechanisms were simultaneously inhibited, which greatly enhanced SCC resistance.

A tightly controlled gene induction system that contributes to the study of lethal gene function in Streptococcus mutans.

Effective control of gene expression is crucial for understanding gene function in both eukaryotic and prokaryotic cells. While several inducible gene expression systems have been reported in Streptococcus mutans, a conditional pathogen that causes dental caries, the significant non-inducible basal expression in these systems seriously limits their utility, especially when studying lethal gene functions and molecular mechanisms. We introduce a tightly controlled xylose-inducible gene expression system, TC-Xyl, for Streptococcus mutans. Western blot results and fluorescence microscopy analysis indicate that TC-Xyl exhibits an extremely low non-inducible basal expression level and a sufficiently high expression level post-induction. Further, by constructing a mutation in which the only source FtsZ is under the control of TC-Xyl, we preliminarily explored the function of the ftsz gene. We found that FtsZ depletion is lethal to Streptococcus mutans, resulting in abnormal round cell shape and mini cell formation, suggesting FtsZ's role in maintaining cell shape stability.

Association among peripatellar fat pad edema and related patellofemoral maltracking parameters: a case-control magnetic resonance imaging study.

BACKGROUND: The peripatellar fat pads are critical for protective cushioning during movement, and their endocrine function has been shown to affect osteoarthritis. Magnetic resonance imaging (MRI) is frequently used to visualize edema of the peripatellar fat pads due to injury. In this study, we aimed to assess the relationship between peripatellar fat pad edema and patellofemoral maltracking MRI parameters and investigate the association among cases of peripatellar fat pad edema. METHODS: Age- and sex-matched peripatellar fat pad edema cases were identified and divided into superolateral Hoffa, quadriceps, and prefemoral groups. Images were assessed according to tibial tuberosity lateralization, trochlear dysplasia, patellar alta, patellar tilt, and bisect offset. McNemar's test or paired t-tests and Spearman's correlation were used for statistical analysis. Interobserver agreement was assessed with the intraclass correlation coefficient. RESULTS: Of 1210 MRI scans, 50, 68, and 42 cases were in the superolateral Hoffa, quadriceps, and prefemoral groups, respectively. Subjects with superolateral Hoffa fat pad edema had a lower lateral trochlear inclination (p = 0.028), higher Insall-Salvati (p < 0.001) and modified Insall-Salvati (p = 0.021) ratios, and lower patellotrochlear index (p < 0.001) than controls. The prefemoral group had a lower lateral trochlear inclination (p = 0.014) and higher Insall-Salvati (p < 0.001) and modified Insall-Salvati (p = 0.004) ratios compared with the control group. In contrast, the patellotrochlear index (p = 0.001) was lower. Mean patellar tilt angle (p = 0.019) and mean bisect offset (p = 0.005) were significantly different between cases and controls. The quadriceps group showed no association. Superolateral Hoffa was positively correlated with prefemoral (p < 0.001, r = 0.408) and negatively correlated with quadriceps (p < 0.001, r = -0.500) fat pad edema. CONCLUSIONS: Superolateral Hoffa and prefemoral fat pad edemas were associated with patellar maltracking parameters. Quadriceps fat pad edema and maltracking parameters were not associated. Superolateral Hoffa fat pad edema was positively correlated with prefemoral and negatively correlated with quadriceps fat pad edema.

Design, synthesis and evaluation of novel pyrimidinylaminothiophene derivatives as FGFR1 inhibitors against human glioblastoma multiforme.

Vascular endothelial growth factor receptors (VEGFRs) have emerged as the most promising anti-angiogenic therapeutic targets for the treatment of recurrent glioblastomas (GBM). However, anti-VEGF treatments led to the high proportion of non-responder patients or non lasting clinical response and the tumor progression to the greater malignant stage. To overcome these problems, there is an utmost need to develop innovative anti-angiogenic therapies. In this study, we report the development of a series of new FGFR1 inhibitors. Among them, compound 4i was able to potently inhibit FGFR1 kinase activities both in vitro and in vivo. This compound displayed strong anti-angiogenic activity in HUVECs and anti-tumor growth and anti-invasion effects in U-87MG cell line. These results emphasize the importance of FGFR1-mediated signaling pathways in GBM and reveal that pharmacological inhibition of FGFR1 can enhance the anti-tumoral, anti-angiogenic and anti-metastatic efficiency against GBM. These data support targeting of FGFR1 as a novel anti-angiogenic strategy and highlight the potential of compound 4i as a promising anti-angiogenic and anti-metastatic candidate for GBM therapy.

Revealing the role of hydrogen bond coupling structure for enhanced performance of the solid-state electrolyte.

Achieving practical applications of PEO-based composite solid electrolyte (CPE) batteries requires the precise design of filler structures at the molecular level to form stable composite interfacial phases, which in turn improve the conductivity of Li+ and inhibit the nucleation growth of lithium dendrites. Some functional fillers suffer from severe agglomeration due to poor compatibility with the polymer base or grain boundary migration, resulting in limited improvement in cell performance. In this paper, ILs@KAP1 is reported as a filler to enhance the performance of PEO-based batteries. Thereinto, the hypercrosslinked phosphorus ligand polymer-containing KAP1, designed at the molecular level, has an abundant porous structure, hydrogen bonding network, and a rigid skeleton structure of benzene rings. These can be used both to improve the flammability with PEO-based and to reduce the crystallinity of the polymer electrolyte. Ionic liquids (ILs) are encapsulated in the nanochannels of KAP1, and thus a 3D Li+ conducting framework could be formed. In this case, it could not only facilitate the wettability of the contact interface with the electrode, significantly promoting its compatibility and providing a fast Li+ transport path, but also facilitate the formation of LiF, Li3N and Li2O rich SEI components, further fostering the uniform deposition/exfoliation of lithium. The LFP||CPE||Li battery assembled with ILs@KAP1-PEO-CPE has a high initial discharge specific capacity about 156 mAh/g at 1C and a remaining capacity about 121.8 mAh/g after 300 cycles (capacity retention of 78.07%).

Intercalation of salicylaldoxime into layered double hydroxide: Ultrafast and highly selective uptake of uranium from different water systems via versatile binding modes.

We report the first example of MgAl layered double hydroxide intercalated with salicylaldoxime (SA-LDH) which exhibits excellent uranium (U(VI)) capture performance. In U(VI) aqueous solutions, the SA-LDH shows a tremendous maximum U(VI) sorption capacity (qmU) of 502 mg·g-1, surpassing most known sorbents. For the aqueous solution with an initial U(VI) concentration (C0U) of âˆ¼ 10 ppm, ≥99.99 % uptake is achieved in a wide pH range of 3-10. At C0U âˆ¼ 20 ppm, >99 % uptake is reached within only 5 min, and pseudo-second-order kinetics rate constant (k2) of 44.9 g·mg-1·min-1 reaches the record value, placing the SA-LDH amongst the fastest U adsorbing materials reported to date. In contaminated seawater with 35 ppm of U while highly concentrated metal ions of Na+, Mg2+, Ca2+, and K+, the SA-LDH still displays exceptionally high selectivity and ultrafast extraction for UO22+, giving >95 % uptake of U(VI) within 5 min, and the k2 value of 0.308 g·mg-1·min-1 for seawater surpasses most reported values for aqueous solutions. Versatile binding modes toward U by SA-LDH, including complexation (UO22+ with SA- and/or CO32-), ion exchange and precipitation, contribute to the preferable uptake of U at different concentrations. X-ray absorption fine structure (XAFS) analyses demonstrate that one uranyl ion (UO22+) binds to two SA- anions and two H2O molecules forming 8-coordinated configuration. The U coordinates with O atom of the phenolic hydroxyl group and N atom of the -CN-O- group of SA-, forming a stable six-membered ring motif, which endows the fast and robust capture of U. The wonderful uranium trapping ability makes the SA-LDH among the best adsorbent used for uranium extraction from various solution systems including seawater.

Enhanced electrocatalytic performance for oxygen evolution reaction via active interfaces of Co3O4arrays@FeOx/Carbon cloth heterostructure by plasma-enhanced atomic layer deposition.

Oxygen evolution reaction (OER) is a necessary procedure in various devices including water splitting and rechargeable metal-air batteries but required a higher potential to improve oxygen evolution efficiency due to its slow reaction kinetics. In order to solve this problem, a heterostructured electrocatalyst (Co3O4@FeOx/CC) is synthesized by deposition of iron oxides (FeOx) on carbon cloth (CC) via plasma-enhanced atomic layer deposition, then growth of the cobalt oxide (Co3O4) nanosheet arrays. The deposition cycle of FeOxon the CC strongly influences thein situgrowth and distribution of Co3O4nanosheets and electronic conductivity of the electrocatalyst. Owing to the high accessible and electroactive areas and improved electrical conductivity, the free-standing electrode of Co3O4@FeOx/CC with 100 deposition cycles of FeOxexhibits excellent electrocatalytic performance for OER with a low overpotential of 314.0 mV at 10 mA cm-2and a small Tafel slope of 29.2 mV dec-1in alkaline solution, which is much better than that of Co3O4/CC (448 mV), and even commercial RuO2(380 mV). This design and optimization strategy shows a promising way to synthesize ideally designed catalytic architectures for application in energy storage and conversion.