Inducing Directional Charge Delocalization in 3D-Printable Micro-Supercapacitors Based on Strongly Coupled Black Phosphorus and ReS2 Nanocomposites.

The growing interest in so-called interface coupling strategies arises from their potential to enhance the performance of active electrode materials. Nevertheless, designing a robust coupled interface in nanocomposites for stable electrochemical processes remains a challenge. In this study, an epitaxial growth strategy is proposed by synthesizing sulfide rhenium (ReS2 ) on exfoliated black phosphorus (E-BP) nanosheets, creating an abundance of robust interfacial linkages. Through spectroscopic analysis using X-ray photoelectron spectroscopy and X-ray absorption spectroscopy, the authors investigate the interfacial environment. The well-developed coupled interface and structural stability contribute to the impressive performance of the 3D-printed E-BP@ReS2 -based micro-supercapacitor, achieving a specific capacitance of 47.3 mF cm-2 at 0.1 mA cm-2 and demonstrating excellent long-term cyclability (89.2% over 2000 cycles). Furthermore, density functional theory calculations unveil the positive impact of the strongly coupled interface in the E-BP@ReS2 nanocomposite on the adsorption of H+ ions, showcasing a significantly reduced adsorption energy of -2.17 eV. The strong coupling effect facilitates directional charge delocalization at the interface, enhancing the electrochemical performance of electrodes and resulting in the successful construction of advanced micro-supercapacitors.

Improving the performance of silicon monoxide anodes via tuning a multiple pre-doping system: a first-principles study.

Silicon monoxide is a potentially viable anode material for high-performance lithium-ion batteries (LIBs). However, a low initial coulombic efficiency and large volume expansion limit its commercial application. Pre-lithiation is an efficient solution, but is expensive because of limited "pre-lithiation" sources. In this work, we theoretically investigated a novel multiple pre-doping SiO system (Li-NaMg-SiO). By comparing its lithiation behavior to that of the traditional Li-doping system (Li-SiO), we revealed the different doping effects during lithiation. Similar to the traditional Li-doping system, the insertion of Na and Mg disintegrates the Si-O host matrix to form Na-O and Mg-O bonds and active Si clusters. At the end of lithiation, the O-Li coordination number (CN) tends to saturate at CNO-Li ≈ 5 in Li-Na-SiO, Li-Mg-SiO, and Li-NaMg-SiO systems, while the value of CNO-Li in the Li-SiO system is more than 6, which suggests that there are reorganizations between Li, Na, and Mg in the silicate matrix. Doping sources of both Na and Mg can prevent the active Li ions from being trapped by O-Li bonds and increase the initial coulombic efficiency. From the density of states (DOS), we notice that all the different pre-doping systems have similar electronic structures, and they can be expected to undergo the same lithiation process. Furthermore, the higher ion-conductivity and smaller volume expansion during the lithiation process characterized by root mean square deviation (RMSD) and volume analysis prove the advantages of the binary doping system (Li-NaMg-SiO) for the improvement of cycle stability for Si-based materials. These advantages benefit from the loose and amorphous structures of doping systems during lithiation. Our work highlights the doping effects of multiple sources and the promotion of "inert compounds" on the entire lithiation process, which provide valuable insight for high-performance anode design.

First in class dual MDM2/MDMX inhibitor ALRN-6924 enhances antitumor efficacy of chemotherapy in TP53 wild-type hormone receptor-positive breast cancer models.

BACKGROUND: MDM2/MDMX proteins are frequently elevated in hormone receptor-positive (ER+) breast cancer. We sought to determine the antitumor efficacy of the combination of ALRN-6924, a dual inhibitor of MDM2/MDMX, with chemotherapy in ER+ breast cancer models. METHODS: Three hundred two cell lines representing multiple tumor types were screened to confirm the role of TP53 status in ALRN-6924 efficacy. ER+ breast cancer cell lines (MCF-7 and ZR-75-1) were used to investigate the antitumor efficacy of ALRN-6924 combination. In vitro cell proliferation, cell cycle, and apoptosis assays were performed. Xenograft tumor volumes were measured, and reverse-phase protein array (RPPA), immunohistochemistry (IHC), and TUNEL assay of tumor tissues were performed to evaluate the in vivo pharmacodynamic effects of ALRN-6924 with paclitaxel. RESULTS: ALRN-6924 was active in wild-type TP53 (WT-TP53) cancer cell lines, but not mutant TP53. On ER+ breast cancer cell lines, it was synergistic in vitro and had enhanced in vivo antitumor activity with both paclitaxel and eribulin. Flow cytometry revealed signs of mitotic crisis in all treatment groups; however, S phase was only decreased in MCF-7 single agent and combinatorial ALRN-6924 arms. RPPA and IHC demonstrated an increase in p21 expression in both combinatorial and single agent ALRN-6924 in vivo treatment groups. Apoptotic assays revealed a significantly enhanced in vivo apoptotic rate in ALRN-6924 combined with paclitaxel treatment arm compared to either single agent. CONCLUSION: The significant synergy observed with ALRN-6924 in combination with chemotherapeutic agents supports further evaluation in patients with hormone receptor-positive breast cancer.

Vertical Graphene Growth on SiO Microparticles for Stable Lithium Ion Battery Anodes.

Silicon-based materials are considered as strong candidates to next-generation lithium ion battery anodes because of their ultrahigh specific capacities. However, the pulverization and delamination of electrochemical active materials originated from the huge volume expansion (>300%) of silicon during the lithiation process results in rapid capacity fade, especially in high mass loading electrodes. Here we demonstrate that direct chemical vapor deposition (CVD) growth of vertical graphene nanosheets on commercial SiO microparticles can provide a stable conducting network via interconnected vertical graphene encapsulation during lithiation, thus remarkably improving the cycling stability in high mass loading SiO anodes. The vertical graphene encapsulated SiO (d-SiO@vG) anode exhibits a high capacity of 1600 mA h/g and a retention up to 93% after 100 cycles at a high areal mass loading of 1.5 mg/cm2. Furthermore, 5 wt % d-SiO@vG as additives increased the energy density of traditional graphite/NCA 18650 cell by ∼15%. We believe that the results strongly imply the important role of CVD-grown vertical graphene encapsulation in promoting the commercial application of silicon-based anodes.

Design, synthesis and pharmacological evaluation of 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents.

Two series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 2,4-imidazolinedione/pyrazolone scaffold were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against HT-29, H460, A549, MKN-45, and U87MG cancer cell lines in vitro. The pharmacological data indicated that most of the tested compounds showed moderate to significant cytotoxicity and high selectivity against HT-29, H460 and A549 cancer cell lines as compared with foretinib. The SAR analyses indicated that compounds with halogen groups, especially trifluoromethyl groups at 2-position on the phenyl ring (moiety B) were more effective. In this study, a promising compound 17 (c-Met IC50=2.20nM, a multi-target tyrosine kinase inhibitor) showed the most potent antitumor activities with IC50 values of 0.14µM, 0.18µM, 0.09µM, 0.03µM, and 1.06µM against HT-29, H460, A549, MKN-45, and U87MG cell lines, respectively.

Synthesis and biological evaluation of novel 4-(2-fluorophenoxy)-2-(1H-tetrazol-1-yl)pyridines bearing semicarbazone moieties as potent antitumor agents.

A series of 4-(2-fluorophenoxy)-2-(1H-tetrazol-1-yl)pyridines bearing semicarbazone moieties were synthesized and evaluated for their in vitro antitumor potency. Some of the compounds (10b, 10c, 10e-10h, 10m-10p, 10r, and 11b) exhibited moderate to excellent antitumor activity as compared to sorafenib and PAC-1, as well as low levels of toxicity toward the human fetal lung fibroblast cell line WI-38. The most promising compound 10p (IC50 = 0.08, 0.36, 0.97 µM) was 45.1-, 6.1-, and 2.4-fold more active than sorafenib (IC50 = 3.61, 2.19, 2.32 µM), and 17, 3.2, and 2.9 times better than PAC-1 (IC50 = 1.36, 1.17, 2.83 µM) against three cancer cell lines (HT-29, H460, and MKN-45), respectively. In addition, further studies examining enzymatic activity suggested that the marked pharmacological activity observed might be ascribed to an inhibitory action against CRAf kinase.

Element quality indicator: A quality assessment and defect detection method for software requirement specification.

A software requirements specification (SRS) provides a detailed description of the requirements of a software system that is to be developed. The Element Quality Indicator (EQI) is a novel method to detect defects and assess the quality of an SRS. It does not hinge on review guidelines and is based on the SRS element questions extraction method (EQEM). In this study, we optimized the EQI and carried out a systematic and comprehensive experiment to validate and evaluate its effectiveness. The controlled experiment, which included 60 software engineering students, found that 100% of the subjects identified defects in the SRS using EQI. Moreover, the results indicated that the average number of defects detected with EQI was greater than that of the classical review technique - perspective-based reading. Furthermore, the controlled experiment demonstrated that EQI provides a comparatively objective and accurate evaluation of the quality of the SRS and markedly diminishes the bias in understanding software requirements due to the ambiguity of natural language.

Discovery of Sulanemadlin (ALRN-6924), the First Cell-Permeating, Stabilized α-Helical Peptide in Clinical Development.

We report the discovery of sulanemadlin (ALRN-6924), the first cell-permeating, stabilized α-helical peptide to enter clinical trials. ALRN-6924 is a "stapled peptide" that mimics the N-terminal domain of the p53 tumor suppressor protein. It binds with high affinity to both MDM2 and MDMX (also known as MDM4), the endogenous inhibitors of p53, to activate p53 signaling in cells having a non-mutant, or wild-type TP53 genotype (TP53-WT). Iterative structure-activity optimization endowed ALRN-6924 with favorable cell permeability, solubility, and pharmacokinetic and safety profiles. Intracellular proteolysis of ALRN-6924 forms a long-acting active metabolite with potent MDM2 and MDMX binding affinity and slow dissociation kinetics. At high doses, ALRN-6924 exhibits on-mechanism anticancer activity in TP53-WT tumor models. At lower doses, ALRN-6924 transiently arrests the cell cycle in healthy tissues to protect them from chemotherapy without protecting the TP53-mutant cancer cells. These results support the continued clinical evaluation of ALRN-6924 as an anticancer and chemoprotection agent.

Scalable Synthesis of Pore-Rich Si/C@C Core-Shell-Structured Microspheres for Practical Long-Life Lithium-Ion Battery Anodes.

Silicon/carbon (Si/C) composites have rightfully earned the attention as anode candidates for high-energy-density lithium-ion batteries (LIBs) owing to their advantageous capacity and superior cycling stability, yet their practical application remains a significant challenge. In this study, we report the large-scale synthesis of an intriguing micro/nanostructured pore-rich Si/C microsphere consisting of Si nanoparticles tightly immobilized onto a micron-sized cross-linked C matrix that is coated by a thin C layer (denoted P-Si/C@C) using a low-cost spray-drying approach and a chemical vapor deposition process with inorganic salts as pore-forming agents. The as-obtained P-Si/C@C composite has high porosity that provides sufficient inner voids to alleviate the huge volume expansion of Si. The outer smooth and robust C shells strengthen the stability of the entire structure and the solid-electrolyte interphase. Si nanoparticles embedded in a microsized cross-linked C matrix show excellent electrical conductivity and superior structural stability. By virtue of structural advantages, the as-fabricated P-Si/C@C anode displays a high initial Coulombic efficiency of 89.8%, a high reversible capacity of 1269.6 mAh g-1 at 100 mA g-1, and excellent cycle performance with a capacity of 708.6 mAh g-1 and 87.1% capacity retention after 820 cycles at 1000 mA g-1, outperforming the reported results of Si/C composite anodes. Furthermore, a low electrode swelling of 18.1% at a high areal capacity of 3.8 mAh cm-2 can be obtained. When assembled into a practical 3.2 Ah cylindrical cell, extraordinary long cycling life with a capacity retention of 81.4% even after 1200 cycles at 1C (3.2 A) and excellent rate performance are achieved, indicating significant advantages for long-life power batteries in electric vehicles.

2-[2-(2-Carb-oxy-phen-yl)hydrazinyl-idene]-3-oxo-N-phenyl-butyramide.

In the title compound, C(17)H(15)N(3)O(4), the mol-ecule is in the keto-hydrazone form. Intra-molecular N-H⋯O hydrogen bonds ensure that the mol-ecule is nearly planar (r.m.s. deviation of non-H atoms is 0.098 Å), with the two benzene rings forming a dihedral angle of 10.04 (2)°. In the crystal, inversion dimers are formed via pairs of O-H⋯O hydrogen bonds involving the -CO(2)H groups.

Positive RT-PCR in urine from an asymptomatic patient with novel coronavirus 2019 infection: a case report.

Introduction: With the emergence of novel coronavirus disease 2019 (COVID-19) in many countries, medical resources currently focus on the treatment of confirmed patients and screening of suspected cases. Asymptomatic patients may be contagious, which makes epidemic control difficult. We describe an asymptomatic patient with a positive real-time polymerase chain reaction (RT-PCR) test in urine.Case report: An asymptomatic girl was identified during the epidemiological investigation of a confirmed COVID-19 patient. When admitted to the hospital on 24 February 2020, she had no clinical manifestations. A throat swab was negative for RT-PCR, but urine was positive. She was given antiviral and symptomatic supportive treatment. On 26 February, a throat swab RT-PCR was positive. RT-PCR in throat swabs and urine were negative on 3 and 5 March, and on 9 and 12 March, throat swabs were still negative. At follow-up on 26 March, she felt well, throat swab RT-PCR was negative, and isolation was lifted.Conclusion: The urine of asymptomatic patients may be contagious. RT-PCR in urine might be a useful supplement in screening when the RT-PCR is negative in throat swabs.

Structure and conductivity enhanced treble-shelled porous silicon as an anode for high-performance lithium-ion batteries.

Silicon is regarded as the next generation anode material for lithium-ion batteries because of its high specific capacity, low intercalation potential and abundant reserves. However, huge volume changes during the lithiation and delithiation processes and low electrical conductivity obstruct the practical applications of silicon anodes. In this study, a treble-shelled porous silicon (TS-P-Si) structure was synthesized via a three-step approach. The TS-P-Si anode delivered a capacity of 858.94 mA h g-1 and a capacity retention of 87.8% (753.99 mA h g-1) after being subjected to 400 cycles at a current density of 400 mA g-1. The good cycling performance was due to the unique structure of the inner silicon oxide layer, middle silver nano-particle layer and outer carbon layer, leading to a good conductivity and a decreased volume change of this silicon-based anode.

Enhancing the Cell Permeability of Stapled Peptides with a Cyclic Cell-Penetrating Peptide.

Stapled peptides recapitulate the binding affinity and specificity of α-helices in proteins, resist proteolytic degradation, and may provide a novel modality against challenging drug targets such as protein-protein interactions. However, most of the stapled peptides have limited cell permeability or are impermeable to the cell membrane. We show herein that stapled peptides can be rendered highly cell-permeable by conjugating a cyclic cell-penetrating peptide to their N-terminus, C-terminus, or stapling unit. Application of this strategy to two previously reported membrane-impermeable peptidyl inhibitors against the MDM2/p53 and ß-catenin/TCF interactions resulted in the generation of potent proof-of-concept antiproliferative agents against key therapeutic targets.

Walnut-structure Si-G/C materials with high coulombic efficiency for long-life lithium ion batteries.

Nano-sized silicon is a potential high energy density anode material for lithium ion batteries. However, the practical use of a nano-Si anode is still challenging due to its low coulombic efficiency, poor scalability and cycling stability. Herein, a Si/graphite/carbon (Si-G/C) composite with a core-shell structure was fabricated by a facile two-step chemical process, stirring-evaporating followed by heat treatment. The composite structure consists of a graphite core, coated first by silicon and then amorphous carbon, which was decomposed by pitch. The as-prepared Si-G/C composite anode demonstrates a first cycle capacity of about 650 mA h g-1, over 90% coulombic efficiency, and high capacity retention of 96.7% after 50 cycles. When paired with a commercial NCA cathode, superior cycling stability with more than 81% capacity retention was achieved for 1200 cycles. These results demonstrate that such a core-shell Si-G/C composite is a promising anode material for high energy Li-ion batteries.

Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models.

T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). We show that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type TCLs. ALRN-6924, a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX has potent in vitro activity and superior in vivo activity across 8 different PDX models compared to the standard-of-care agent romidepsin. ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from subtype-specific preclinical models.

Citrate Suppresses Tumor Growth in Multiple Models through Inhibition of Glycolysis, the Tricarboxylic Acid Cycle and the IGF-1R Pathway.

In this study we have tested the efficacy of citrate therapy in various cancer models. We found that citrate administration inhibited A549 lung cancer growth and additional benefit accrued in combination with cisplatin. Interestingly, citrate regressed Ras-driven lung tumors. Further studies indicated that citrate induced tumor cell differentiation. Additionally, citrate treated tumor samples showed significantly higher infiltrating T-cells and increased blood levels of numerous cytokines. Moreover, we found that citrate inhibited IGF-1R phosphorylation. In vitro studies suggested that citrate treatment inhibited AKT phosphorylation, activated PTEN and increased expression of p-eIF2a. We also found that p-eIF2a was decreased when PTEN was depleted. These data suggest that citrate acts on the IGF-1R-AKT-PTEN-eIF2a pathway. Additionally, metabolic profiling suggested that both glycolysis and the tricarboxylic acid cycle were suppressed in a similar manner in vitro in tumor cells and in vivo but only in tumor tissue. We reproduced many of these observations in an inducible Her2/Neu-driven breast cancer model and in syngeneic pancreatic tumor (Pan02) xenografts. Our data suggests that citrate can inhibit tumor growth in diverse tumor types and via multiple mechanisms. Dietary supplementation with citrate may be beneficial as a cancer therapy.

[Study on a bacterial strain Bt8 for biocontrol against citrus bacterial canker].

Citrus bacterial canker is an important disease of Citrus species in China. The disease severely occurs especially in the coastal area. Integrated control system has been used for the control of the disease, in which chemotherapy plays an important role at present. The chemotherapy-dominant control system brought many problems to the environment, such as chemical residua in the products and induction of resistance to fungicide(s) by the pathogen. To solve these problems, an intensive study on biocontrol of citrus bacterial canker is needed. Isolations and characterizations of biocontrol agents are the basis for biocontrol of the disease. A bacterial strain Bt8 with strong inhibiting ability against Xanthomonas axonopodis pv. citri (Hasse) Vauterin, was isolated from citrus orchard soil in Nanning, China. The isolated bacterial strain was identified and characterized as Acinetobacter baumannii Bouvet et Grimont on the base of its morphology and 16S rDNA sequence analysis as well as physiological and biochemical characters. The inhibiting activity of the bacterium suspension against the pathogen was significantly influenced by environmental factors, such as temperatures, pHs and media. At temperatures of 18 degrees C to 33 degrees C, both the inhibiting activity of the bacterium suspension and the biomass of the bacterium increased with the increases of temperatures, suggesting that the influence of temperature on inhibiting activity of the bacterium suspension was in dependence on the bacterial biomass. In NA liquid medium of pH 10, the bacterium suspension showed the highest inhibiting activity against Xanthomonas axonopodis pv. citri, which was not in dependence on biomass of the bacterium. The bacterium suspension provided 55.2% inhibition against bacterial canker under greenhouse conditions. The results showed that Acinetobacter baumannii has potential as biocontrol agent against bacterial canker disease. Acinetobacter baumannii was reported as the pathogens infecting human and animals. The present study enriched the understanding on biological diversity in Acinetobacter baumannii to sciences. This is the first report on the isolation of Acinetobacter baumannii with strong inhibiting ability against plant pathogen.

Propagation Effect of a Virus Outbreak on a Network with Limited Anti-Virus Ability.

This paper describes a new computer virus spreading model which takes into account the possibility of a virus outbreak on a network with limited anti-virus ability. Then, the model is investigated for the existence of equilibria and their stabilities are proved and illustrated. Moreover, it is found that these two factors are not only relative to the threshold value determining whether the virus becomes extinct or not, but that they are also relative to the virus epidemic levels. Theoretical and experimental results indicate that, in some ways, it would be practically possible to eradicate the virus or suppress its prevalence below a suitable level. Consequently, some suggestions are proposed that may help eradicate or suppress virus propagation over a real computer network.

How PEDF prevents angiogenesis: a hypothesized pathway.

Pigment epithelium-derived factor (PEDF) is a multiple functional protein, coded by the serine proteinase inhibitor, clade F, member 1 (SERPINF1) gene, which has both anti-angiogenic activity and neurotrophic activity at the same time. Its antiangiogenic activity in the mammalian eye is the most potent known at this time. However, the mechanism(s) by which PEDF works in vivo is still uncertain. Some observations suggest that PEDF can simultaneously inhibit the migration and proliferation induced by vascular endothelial growth factor (VEGF), and then further inhibits angiogenesis by interacting with specific cell surface receptors, but no such receptor has been reported to date. Here we propose a hypothesis that PEDF exerts its function by binding with intergrins. Intergrin can therefore serve as the receptor of PEDF.

Type I collagen inhibits hydroxyl radical-induced apoptosis.

The extracellular matrix (ECM) plays an important role in cell differentiation and apoptosis. Collagen is the major component of ECM. Here, an ESR signal of the hydroxyl radicals (.OH) generated via Fe2+ -mediated Fenton reaction was found to be significantly inhibited by type I collagen. Further study showed that type I collagen also inhibited cell apoptosis induced by.OH, as evidenced by morphological criteria (DAPI and annexin V staining) and quantitive assays for apoptotic cells (MTT and flow-cytometric assay for subG1 cells). By addition of type I collagen in HeLa cells, the lipid peroxidation caused by.OH was inhibited and the cellular GSH was protected. In comparison with type I collagen, BSA and the denatured collagen, gelatin, lacked such antioxidative and antiapoptotic effects. Together, the results suggest that type I collagen can uniquely prevent.OH-mediated apoptosis by scavenging free radicals.