Armoring lithium metal anode with soft–rigid gradient interphase toward high-capacity and long-life all-solid-state battery

Solid polymer electrolytes(SPEs)are highly promising for realizing high-capacity,low-cost,and safe Li metal batteries.However,the Li dendritic growth and side reactions between Li and SPEs also plague these systems.Herein,a fluorinated lithium salt coating(FC)with organic-inorganic gradient and soft–rigid feature is introduced on Li surface as an artificial protective layer by the in-situ reaction between Li metal and fluorinated carboxylic acid.The FC layer can improve the interface stability and wettability between Li and SPEs,assist the transport of Li ions,and guide Li nucleation,contributing to a dendrite-free Li deposition and long-lifespan Li metal batteries.The symmetric cell with FC-Li anodes exhibits a high areal capacity of 1 mAh cm^(-2)at 0.5 mA cm^(-2),and an ultra-long lifespan of 2000 h at a current density of 0.1 mA cm^(-2).Moreover,the full cell paired with the LiFePO4 cathode exhibits improved cycling stability,remaining 83.7%capacity after 500 cycles at 1 C.When matching with the S cathode,the FC layer can prevent the shuttle effect,contributing to stable and high-capacity Li–S battery.This work provided a promising way for the construction of stable all-solid-state lithium metal batteries with prolonged lifespan.

Systematical Study on Photodissociation Dynamics of BrCN from 225 nm to 260 nm

The photodissociation dynamics of Br-C bond cleavage for BrCN in the wavelength region from 225 nm to 260 nm has been studied by our homebuilt time-slice velocity-map imaging setup.The images for both of the ground state Br(^(2)P_(3/2))and spin-orbit excited Br^(*)(^(2)P_(1/2))channels are obtained at several photodissociation wavelengths.From the analysis of the translational energy release spectra,the detailed vibrational and rotational distributions of CN products have been measured for both of the Br and Br^(*) channels.It is found that the internal excitation of the CN products for the Br^(*) channel is colder than that for the Br channel.The most populated vibrational levels of the CN products are v=0 and 1 for the Br and Br^(*) channels,respectively.For the Br channel,the photodissociation dynamics at longer wavelengths are found to be different from those at shorter wavelengths,as revealed by their dramatically different vibrational and rotational excitations of the CN products.

MiR-3653 blocks autophagy to inhibit epithelial-mesenchymal transition in breast cancer cells by targeting the autophagy-regulatory genes ATG12 and AMBRA1

Background:Metastasis is the main cause of tumor-associated death and mainly responsible for treatment failure of breast cancer.Autophagy accelerates tumor metastasis.In our work,we aimed to investigate the possibility of microRNAs(miRNAs)which participate in the regulation of autophagy to inhibit tumor metastasis.Methods:MiRNA array and comprehensive analysis were performed to identify miRNAs which participated in the regulation of autophagy to inhibit tumor metastasis.The expression levels of miR-3653 in breast cancer tissues and cells were detected by quantitative real-time polymerase chain reaction.In vivo and in vitro assays were conducted to determine the function of miR-3653.The target genes of miR-3653 were detected by a dual luciferase reporter activity assay and Western blot.The relationship between miR-3653 and epithelial-mesenchymal transition(EMT)was assessed by Western blot.Student’s t-test was used to analyze the difference between any two groups,and the difference among multiple groups was analyzed with one-way analysis of variance and a Bonferroni post hoc test.Results:miR-3653 was downregulated in breast cancer cells with high metastatic ability,and high expression of miR-3653 blocked autophagic flux in breast cancer cells.Clinically,low expression of miR-3653 in breast cancer tissues(0.054±0.013 vs.0.131±0.028,t=2.475,P=0.014)was positively correlated with lymph node metastasis(0.015±0.004 vs.0.078±0.020,t=2.319,P=0.023)and poor prognosis(P<0.001).miR-3653 ameliorated the malignant phenotypes of breast cancer cells,including proliferation,migration(MDA-MB-231:0.353±0.013 vs.1.000±0.038,t=16.290,P<0.001;MDA-MB-468:0.200±0.014 vs.1.000±0.043,t=17.530,P<0.001),invasion(MDA-MB-231:0.723±0.056 vs.1.000±0.035,t=4.223,P=0.013;MDA-MB-468:0.222±0.016 vs.1.000±0.019,t=31.050,P<0.001),and colony formation(MDA-MB-231:0.472±0.022 vs.1.000±0.022,t=16.620,P<0.001;MDA-MB-468:0.650±0.040 vs.1.000±0.098,t=3.297,P=0.030).The autophagy-associated genes autophagy-related gene 12(ATG12)and activating molecule in beclin 1-regulated autophagy protein 1(AMBRA1)are target genes of miR-3653.Further studies showed that miR-3653 inhibited EMT by targeting ATG12 and AMBRA1.Conclusions:Our findings suggested that miR-3653 inhibits the autophagy process by targeting ATG12 and AMBRA1,thereby inhibiting EMT,and provided a new idea and target for the metastasis of breast cancer.

A novel thermomechanically stable LaF_3–CsH_5(PO_4)_2 composite electrolyte with high proton conductivity at elevated temperatures over 150 °C

A facile strategy is introduced to upgrade thermomechanical stability of the cesium pentahydrogen diphosphate(CPD), which is the most efficient inorganic electrolyte among all solid proton conductors,by constructing P–OH···F hydrogen bonds with lanthanum fluoride(LaF_3). The optimal combination of the LaF_3–CPD composite electrolyte is found to be 1:2 in a molar ratio(LaF_3–CPD-2). LaF_3–CPD-2 composite maintains robust solid state, even at a temperature up to 200 °C, which is 50 °C higher than the melting temperature of CPD. Meanwhile, the considerable proton conductivity of CPD is achieved in the LaF_3–CPD-2 composite electrolyte due to the synergistic effect of the P–OH···F hydrogen bonds and the intrinsic proton conductive property of CPD. Last but not least, the LaF_3–CPD-2 composite manifests excellent conductivity durability at 150 °C and low humidity condition with sizeable proton conductivity of0.0262 S cm^(-1) after 60 h operation, implying that the LaF_3–CPD composite could be a promising candidate for intermediate temperature proton conductors.

Lithiophilic seeds and rigid arrays synergistic induced dendrite-free and stable Li anode towards long-life lithium-oxygen batteries

High energy density lithium-oxygen battery(LOB) is currently regraded as a promising candidate for next-generation power system.However,the dendrite and instability issues of Li metal anode lead to its poor cyclic stability and low energy density.In this work,lithiophilic Al_(2) O_(3) seeds induced rigid carbon nanotube arrays(CNTA)/three-dimensional graphene(3 DG) is developed as a host material for Li anode,namely Al_(2) O_(3)-CNTA/3 DG.It is demonstrated that the lithiophilic feature of Al_(2) O_(3) seeds and the enhanced rigidity of arrays can synergistically induce the uniform Li flux,inhibit the collapse of arrays,and stabilize electrolyte/electrode interfaces.As a result,the Al_(2) O_(3)-CNTA/3 DG-Li anode delivers a high Coulombic efficiency above 97% after 140 cycles(8 mAh cm^(-2) at 4 mA cm^(-2)).With this anode and the breathable CNTA/3 DG cathode,the full LOB exhibits a significantly increased life-span up to 160 cycles(500 mAh g^(-1) at 100 mA g^(-1)),which is almost 3 times longer than that with pure Li foil as the anodes.This work demonstrates a new approach to highly reversibly long-cycling performance of LOBs towards practical application.

Tumor-derived miR-20b-5p promotes lymphatic metastasis of esophageal squamous cell carcinoma by remodeling the tumor microenvironment

DEAREDITOR,Esophageal squamous cell carcinoma(ESCC)is one of the most common fatal malignancies worldwide and is especially common in East Asian regions,including China.Screening lymph node metastasis(LNM)-related biomarkers and elucidating the mechanism could provide promising therapeutic targets and help ESCC patients to select reasonable individual therapies.

Cu nanoparticle-decorated two-dimensional carbon nanosheets with superior photothermal conversion efficiency of 65 % for highly efficient disinfection under near-infrared light

Low photothermal conversion efficiency restricts the antibacterial application of photothermal materials.In this work,two-dimensional carbon nanosheets(2D C)were prepared and decorated with Cu nanoparticles(2D C/Cu)by using a simple soluble salt template method combined with ultrasonic exfoliation.The photothermal conversion efficiency of 2 D C/Cu system can be optimized by changing the content of Cu nanoparticles,where the 2D C/Cu2 showed the best photothermal conversion efficiency(á)of 65.05%under 808 nm near-infrared light irradiation.In addition,the photothermal performance can affect the release behavior of Cu ions.This superior photothermal property combined with released Cu ions can endow this 2D hybrid material with highly efficient antibacterial efficacy of 99.97%±0.01%,99.96%±0.01%,99.97%±0.01%against Escherichia coli,Staphylococcus aureus,and methicillin-resistant Staphylococcus aureus,respectively,because of the synergetic effect of photothermy and ion release.In addition,this 2D hybrid system exhibited good cytocompatibility.Hence,this study provides a novel strategy to enhance the photothermal performance of 2D materials and thus will be beneficial for development of antibiotics-free antibacterial materials with safe and highly efficient bactericidal activity.

Discovery of thiosemicarbazone derivatives as effective New Delhi metallo-β-lactamase-1(NDM-1) inhibitors against NDM-1 producing clinical isolates

New Delhi metallo-b-lactamase-1(NDM-1)is capable of hydrolyzing nearly allβ-lactam antibiotics,posing an emerging threat to public health.There are currently less effective treatment options for treating NDM-1 positive"superbug",and no promising NDM-1 inhibitors were used in clinical practice.In this study,structure eactivity relationship based on thiosemicarbazone derivatives wassystematically characterized and their potential activities combined with meropenem(MEM)were evaluated.Compounds 19 bg and 19 bh exhibited excellent activity against 10 NDM-positive isolate clinical isolates in reversing MEM resistance.Further studies demonstrated compounds 19 bg and 19 bh were uncompetitive NDM-1 inhibitors with Ki Z 0.63 and 0.44 mmol/L,respectively.Molecular docking speculated that compounds 19 bg and 19 bh were most likely to bind in the allosteric pocket which would affect the catalytic effect of NDM-1 on the substrate meropenem.Toxicity evaluation experiment showed that no hemolysis activities even at concentrations of 1000 mg/m L against red blood cells.In vivo experimental results showed combination of MEM and compound 19 bh was markedly effective in treating infections caused by NDM-1 positive strain and prolonging the survival time of sepsis mice.Our finding showed that compound 19 bh might be a promising lead in developing new inhibitor to treat NDM-1 producing superbug.

Premature Stop Codon at Residue 101 within HIV-1 Rev Does Not Influence Viral Replication of Clade BC but Severely Reduces Viral Fitness of Clade B

HIV-1 Rev is an accessory protein that plays a key role in nuclear exportation,stabilization,and translation of the viral mRNAs.Rev of HIV-1 clade BC often shows a truncation of 16 AAs due to a premature stop codon at residue 101.This stop codon presents the highest frequency in clade BC and the lowest frequency in clade B.In order to discover the potential biological effect of this truncation on Rev activity and virus replication of clade BC,we constructed Rev expression vectors of clade BC with or without 16 AAs within C-terminal separately,and replaced the stop codon by Q in a CRF07_BC infectious clone.We found that 16 AAs truncation had no effect on expression and activity of Rev in clade BC.Also,the mutation from the stop codon to Q had no effect on virus replication of clade BC.Next,to investigate the effect of this truncation on Rev activity and replication capacity of clade B,Rev expression vectors of clade B carrying or lacking 16 AAs in C-terminal were constructed respectively,and residue Q at position 101 within Rev was substituted by the stop codon in a clade B infectious clone.It was found that 16 AAs truncation significantly down-regulated Rev expression and impaired clade B Rev activity.Furthermore,a Q-to-stop codon substitution within Rev significantly reduced viral replication fitness of clade B.These results indicate that the premature stop codon at residue 101 within Rev exerts diverse impact on viral replication among different HIV-1 clades.

Characterization of human IgM and IgG repertoires in individuals with chronic HIV-1 infection

Advancements in high-throughput sequencing(HTS)of antibody repertoires(Ig-Seq)have unprecedentedly improved our ability to characterize the antibody repertoires on a large scale.However,currently,only a few studies explored the influence of chronic HIV-1 infection on human antibody repertoires and many of them reached contradictory conclusions,possibly limited by inadequate sequencing depth and throughput.To better understand how HIV-1 infection would impact humoral immune system,in this study,we systematically analyzed the differences between the IgM(HIV-IgM)and IgG(HIV-IgG)heavy chain repertoires of HIV-1 infected patients,as well as between antibody repertoires of HIV-1 patients and healthy donors(HH).Notably,the public unique clones accounted for only a negligible proportion between the HIV-IgM and HIV-IgG repertoires libraries,and the diversity of unique clones in HIV-IgG remarkably reduced.In aspect of somatic mutation rates of CDR1 and CDR2,the HIV-IgG repertoire was higher than HIV-IgM.Besides,the average length of CDR3 region in HIV-IgM was significant longer than that in the HH repertoire,presumably caused by the great number of novel VDJ rearrangement patterns,especially a massive use of IGHJ6.Moreover,some of the B cell clonotypes had numerous clones,and somatic variants were detected within the clonotype lineage in HIV-IgG,indicating HIV-1 neutralizing activities.The in-depth characterization of HIV-IgG and HIV-IgM repertoires enriches our knowledge in the profound effect of HIV-1 infection on human antibody repertoires and may have practical value for the discovery of therapeutic antibodies.

Development of the triazole-fused pyrimidine derivatives as highly potent and reversible inhibitors of histone lysine specific demethylase1(LSD1/KDM1A)

Histone lysine specific demethylase 1(LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound 8 a(IC50=3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound 15 u(IC50=49 nmol/L, and Ki= 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3 K4 me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency ofcompound 15 u. Compound 15 u also showed strong antiproliferative activity against four leukemia cell lines(OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC50 values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, 15 u significantly inhibited colony formation and caused remarkable morphological changes. Compound 15 u induced expression of CD86 and CD11 b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation.The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazolefused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1 A inhibitors.

Discovery of novel 4-phenylquinazoline-based BRD4 inhibitors for cardiac fibrosis

Bromodomain containing protein 4(BRD4), as an epigenetic reader, can specifically bind to the acetyl lysine residues of histones and has emerged as an attractive therapeutic target for various diseases,including cancer, cardiac remodeling and heart failure. Herein, we described the discovery of hit 5 bearing4-phenylquinazoline skeleton through a high-throughput virtual screen using 2,003,400 compound library(enamine). Then, structure-activity relationship(SAR) study was performed and 47 new 4-phenylquinazoline derivatives toward BRD4 were further designed, synthesized and evaluated, using HTRF assay set up in our lab. Eventually, we identified compound C-34, which possessed better pharmacokinetic and physicochemical properties as well as lower cytotoxicity against NRCF and NRCM cells, compared to the positive control JQ1. Using computer-based molecular docking and cellular thermal shift assay, we further verified that C-34 could target BRD4 at molecular and cellular levels. Furthermore, treatment with C-34 effectively alleviated fibroblast activation in vitro and cardiac fibrosis in vivo, which was correlated with the decreased expression of BRD4 downstream target c-MYC as well as the depressed TGF-β1/Smad2/3 signaling pathway.Taken together, our findings indicate that novel BRD4 inhibitor C-34 tethering a 4-phenylquinazoline scaffold can serve as a lead compound for further development to treat fibrotic cardiovascular disease.

Nip promotes autophagy through facilitating the interaction of Rab7 and FYCO1

Autophagy is the main degradation pathway to eliminate long-lived and aggregated proteins,aged or malfunctioning organelles,which is essential for the intracellular homeostasis and prevention of malignant transformation.Although the processes of autophagosome biogenesis have been well illuminated,the mechanism of autophagosome transport remains largely unclear.In this study,we demonstrated that the ninein-like protein(Nip),a well-characterized centrosomal associated protein,was able to modulate autophagosome transport and facilitate autophagy.During autophagy,Nip colocalized with autophagosomes and physically interacted with autophagosome marker LC3,autophagosome sorting protein Rab7 and its downstream effector FYCOl.Interestingly,Nip enhanced the interaction between Rab7 and FYC01,thus accelerated autophagic flux and the formation of autophagolysosomes.Furthermore,compared to the wild-type mice,NLP deficient mice treated with chemical agent DMBA were prone to increased incidence of hepatomegaly and liver cancer,which were tight associated with the hepatic autophagic defect.Taken together,our findings provide a new insight for the first time that the well-known centrosomal protein Nip is also a new regulator of autophagy,which promotes the interaction of Rab7 and FYC01 and facilitates the formation of autophagolysosome.

Application of high-throughput sequencing technology in HIV drug resistance detection

Drug resistance via drug-resistant mutations in the human immunodeficiency virus(HIV)genome is the primary cause of antiviral therapy failure.Consequently,HIV drug resistance genotyping has become a critical approach in HIV prevention and control.Compared to the Sanger sequencing technology,high-throughput sequencing(HTS)technology has superior sensitivity and timeliness,with strong detection capabilities for low-frequency mutations.With the continued advancement of HTS technologies,their prominence in HIV drug resistance detection techniques has increased accordingly.This article will review the latest developments in HTS technology and its applications in HIV drug resistance testing.

Synthesis and Antitumor Activity Evaluation of Pyrimidine Analogues Bearing Urea Moiety

A series of 4-anilino-6-phenylpyrimidines containing urea moiety were synthesized and the structures of all products were confirmed by^(1)H NMR,^(13)C NMR and HRMS.The antiproliferative activities of these compounds were evaluated against three human tumor cell lines(MGC-803,MCF-7 and EC-109)by applying the MTT assay method.compounds 4a,4b and 6a showed the most effective activity,among which,6a was more cytotoxic than 5-fluorouracil against all tested human cancer cell lines with IC_(50) values ranging from 1.80 to 2.72μmol·L^(-1).