Secondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway

Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8^(+)GZMB^(+)T cells and the decrease of CD8^(+)PD-1^(+)T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.

Efficient PbS quantum dots tandem solar cells through compatible interconnection layer

Lead sulfide quantum dots(PbS QDs) hold unique characteristics, including bandgap tunability, solutionprocessability etc., which make them highly applicable in tandem solar cells(TSCs). In all QD TSCs, its efficiency lags much behind to their single junction counterparts due to the deficient interconnection layer(ICL) and defective subcells. To improve TSCs performance, we developed three kinds of ICL structures based on 1.34 and 0.96 e V PbS QDs subcells. The control, 1,2-ethanedithiol capped PbS QDs(PbS-EDT)/Au/tin dioxide(SnO_(2))/zinc oxide(Zn O), utilized SnO_(2) layer to obtain high surface compactness.However, its energy level mismatch causes incomplete recombination. Bypassing it, the second ICL(PbS-EDT/Au/Zn O) removed SnO_(2) and boosted the power conversion efficiency(PCE) from 5.75% to 8.69%. In the third ICL(PbS-EDT/poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine](PTAA)/Au/Zn O), a thin layer of PTAA can effectively fill fissures on the surface of PbS-EDT and also protect the front cells from solvent penetration. This TSC obtained a PCE of 9.49% with an open circuit voltage of 0.91 V, a short circuit current density of 15.47 m A/cm~2, and a fill factor of 67.7%. To the best of our knowledge, this was the highest PCE achieved by all PbS QD TSCs reported to date. These TSCs maintained stable performance for a long working time under ambient conditions.

Microstructure,mechanical and corrosion properties of Mg-2Dy-xZn(x=0,0.1,0.5 and 1 at.%)alloys

Microstructure,mechanical and corrosion properties of as-cast Mg-2Dy-xZn(x=0,0.1,0.5,and 1)(at.%)alloys were investigated.The microstructures of the as-cast Mg-2Dy and Mg-2Dy-0.1Zn alloys mainly consisted ofα-Mg phase and Mg_(24)Dy_(5)eutectic phase.With 0.5 at.%Zn addition,Mg_(12)ZnDy phase with 18R-type long period stacking ordered(LPSO)structure and Mg_(2)Dy phase precipitated at the grain boundaries.When the content of Zn is 1 at.%,only the Mg_(3)Zn_(3)Dy_(2)phase formed in theα-Mg matrix.The electrochemical measurements and immersion testing results indicated that the Mg-2Dy-0.1Zn alloy exhibited the best corrosion resistance.It revealed that the morphology,scale,amount and distribution of the second phase have a great effect on the corrosion resistance of alloy.Additionally,the tensile testing results showed that the Mg-2Dy-0.5Zn alloy exhibited the higher tensile strength and good elongation,especially at 200℃.The improvement of mechanical properties was mainly due to the strengthening of LPSO phase and grain refinement of α-Mg.

Propagation properties of chirped Airy vortex beams with x-polarization through uniaxial crystals

The propagation dynamics of a chirped Airy vortex（CAiV） beam with x-polarization in uniaxial crystals orthogonal to the optical axis is studied analytically and numerically. The effect of the ratio of extraordinary and ordinary refractive indices, the chirp parameter, as well as the propagation distance is analyzed, which shows that the focused position of the CAi V beams can be controlled through changing the ratio of the extraordinary and ordinary refractive indices. In addition,with the propagation distance increasing, the asymmetry of the intensity and the angular momentum of the CAi V beam during propagation becomes much more visible. The variation of the chirp parameters can change the attenuation velocity of the vortex as well.

Excess properties and spectroscopic studies for binary system polyethylene glycol 600 + dimethyl sulfoxide at T =(298.15, 303.15,308.15, 313.15, and 318.15) K

The work presents density(ρ) and viscosity(η) data of binary system polyethylene glycol 600(PEG) + dimethyl sulfoxide(DMSO) over the entire concentration range at T =(298.15, 303.15, 308.15, 313.15 and 318.15) K and atmospheric pressure. On the basis of density and viscosity values, the excess properties of PEG(1) + DMSO(2) mixtures, including excess molar volume(V_m^E), viscosity deviation(Δη), excess free energies of activation(ΔG^(*E)), and isobaric thermal expansion coefficient(αp), were calculated. At the same time, in order to conjecture the density viscosity under different conditions, the density and viscosity data were fitted with the corresponding formula. The calculated results of V_m^E, Δη, and ΔG^(*E) were fitted with the Redlich–Kister equation to derive coefficients and estimate the standard deviations(σ) between the experimental and calculated values. Moreover, the intermolecular interaction of PEG with DMSO was discussed on the basis of FTIR and UV–Vis spectral results of PEG(1) + DMSO(2) mixtures. The results indicated that there were the hydrogen bonding and interactions of hydroxyl hydrogen atoms in PEG with oxygen atoms in DMSO.

Facile and controllable synthesis of BaCO_3 crystals superstructures using a CO_2-storage material

We here report a new CO_2 capture and storage method that converts CO_2 into a novel alkyl carbonate salt, denoted as CO_2 SM, by a system consisting of equimolar 1,4-butanediol(BDO) and 1,2-ethylenediamine(EDA). This novel CO_2 SM was then used to prepare BaCO_3 crystals through a simple and fast hydrothermal synthesis under mild conditions. The CO_2 SM was both the source of CO_2 and the modifier to regulate the nucleation and growth of BaCO_3 crystals. The morphology of the BaCO_3 crystals could be tuned from rod to shuttle by adjusting the key influencing factors, including CO_2 SM concentration, mineralization temperature, and mineralization time. A possible mechanism for the synthesis of BaCO_3 crystals from the CO_2 SM was also presented. After the BaCO_3 crystals were isolated, the filtrate of the hydrothermal reaction could be recycled to again absorb CO_2 and prepare BaCO_3 crystals of the same polymorph. This novel approach appears promising for preparing well-formed metal carbonates.

Optical microfiber or nanofiber:a miniature fiber-optic platform for nanophotonics

An optical micro/nanofiber(MNF)is a quasi-one-dimensional free-standing optical waveguide with a diameter close to or less than the vacuum wavelength of light.Combining the tiny geometry with highrefractive-index contrast between the core and the surrounding,the MNF exhibits favorable optical properties such as tight optical confinement,strong evanescent field,and large-diameter-dependent waveguide dispersion.Meanwhile,as a quasi-one-dimensional structure with extraordinarily high geometric and structural uniformity,the MNF also has low optical loss and high mechanical strength,making it favorable for manipulating light on the micro/nanoscale with high flexibility.Over the past two decades,optical MNFs,typically being operated in single mode,have been emerging as a miniaturized fiber-optic platform for both scientific research and technological applications.In this paper,we aim to provide a comprehensive overview of the representative advances in optical MNFs in recent years.Starting from the basic structures and fabrication techniques of the optical MNFs,we highlight linear and nonlinear optical and mechanical properties of the MNFs.Then,we introduce typical applications of optical MNFs from nearfield optics,passive optical components,optical sensors,and optomechanics to fiber lasers and atom optics.Finally,we give a brief summary of the current status of MNF optics and technology,and provide an outlook into future challenges and opportunities.

Parallel fabrication of silica optical microfibers and nanofibers

Optical micro/nanofibers(MNFs)taper-drawn from silica fibers possess intriguing optical and mechanical properties.Recently,MNF array or MNFs with identical geometries have been attracting more and more attention,however,current fabrication technique can draw only one MNF at a time,with a low drawing speed(typically 0.1 mm/s)and a complicated process for high-precision control,making it inefficient in fabricating multiple MNFs.Here,we propose a parallel-fabrication approach to simultaneously drawing multiple(up to 20)MNFs with almost identical geometries.For fiber diameter larger than 500 nm,measured optical transmittances of all as-drawn MNFs exceed 96.7%at 1550-nm wavelength,with a diameter deviation within 5%.Our results pave a way towards high-yield fabrication of MNFs that may find applications from MNF-based optical sensors,optical manipulation to fiber-to-chip interconnection.

High-power continuous-wave optical waveguiding in a silica micro/nanofibre

As miniature fibre-optic platforms,micro/nanofibres(MNFs)taper-drawn from silica fibres have been widely studied for applications from optical sensing,nonlinear optics to optomechanics and atom optics.While continuous-wave(CW)optical waveguiding is frequently adopted,so far almost all MNFs are operated in low-power region(e.g.,<0.1 W).Here,we demonstrate high-power low-loss CW optical waveguiding in MNFs around 1550-nm wavelength.We show that a pristine MNF,even with a diameter down to 410 nm,can waveguide an optical power higher than 10 W,which is about 30 times higher than demonstrated previously.Also,we predict an optical damage threshold of 70 W.In highpower CW waveguiding MNFs,we demonstrate high-speed optomechanical driving of microparticles in air,and second harmonic generation efficiency higher than those pumped by short pulses.Our results may pave a way towards high-power MNF optics,for both scientific research and technological applications.

Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylationmediated mitophagy

Parkin,an E3 ubiquitin ligase,plays a role in maintaining mitochondrial homeostasis through targeting damaged mitochondria for mitophagy.Accumulating evidence suggests that the acetylation modification of the key mitophagy machinery influences mitophagy level,but the underlying mechanism is poorly understood.Here,our study demonstrated that inhibition of histone deacetylase(HDAC)by treatment of HDACis activates mitophagy through mediating Parkin acetylation,leading to inhibition of cervical cancer cell proliferation.Bioinformatics analysis shows that Parkin expression is inversely correlated with HDAC2 expression in human cervical cancer,indicating the low acetylation level of Parkin.Using mass spectrometry,Parkin is identified to interact with two upstream molecules,acetylase acetyl-Co A acetyltransferase 1(ACAT1)and deacetylase HDAC2.Under treatment of suberoylanilide hydroxamic acid(SAHA),Parkin is acetylated at lysine residues 129,220 and 349,located in different domains of Parkin protein.In in vitro experiments,combined mutation of Parkin largely attenuate the interaction of Parkin with PTEN induced putative kinase 1(PINK1)and the function of Parkin in mitophagy induction and tumor suppression.In tumor xenografts,the expression of mutant Parkin impairs the tumor suppressive effect of Parkin and decreases the anticancer activity of SAHA.Our results reveal an acetylation-dependent regulatory mechanism governing Parkin in mitophagy and cervical carcinogenesis,which offers a new mitophagy modulation strategy for cancer therapy.

A novel Cu-doped high entropy alloy with excellent comprehensive performances for marine application

High entropy alloy(HEA)has attracted great interests as one of the promising multifunctional materials in marine applications.However,Cu as an effective biocide tends to form segregation in HEA,which could deteriorate corrosion and induce brittle fracture.Herein,we report a strategy to tailor the existing form of Cu in HEA from undesired large-scale segregation to uniform distribution with dispersed nanoscale precipitation,while retaining the unique structure characteristics of HEA.Eliminating Cu segregation improves toughness and avoids serious corrosion in the grain boundary.Uniform distribution with dispersed nanoscale precipitation of Cu further enhances the antifouling and lubricating abilities of Cu-doped HEA.Tailored AlCoCrFeNiCu_(0.5)HEA in this work has excellent comprehensive properties combining good mechanical properties,outstanding antifouling abilities,superior resistance to corrosion and wear.Furthermore,the corresponded mechanisms are discussed in terms of Cu-segregation-eliminated,nanoscale-Cu-precipitate-forming and comprehensive properties.

Chelerythrine chloride from Macleaya cordata induces growth inhibition and apoptosis in human gastric cancer BGC-823 cells

This study aimed to investigate the ability of chelerythrine chloride(CHE),the main active ingredient of Macleaya cordata,to induce apoptosis in human gastric cancer BGC-823 cells.The results demonstrate that CHE inhibits cell proliferation in a time-and dose-dependent manner with accompanying S phase arrest.It also induces apoptosis by a mechanism involving a reduction in the mitochondrial mem brane potential,the release of cytochrome c,activation of caspase 3 and cleavage of poly-ADP-ribose polymerase.In addition,CHE-induced apoptosis is accompanied by down-regulation of Bcl-x1 and Bcl-2 proteins with no change in the levels of Bax proteins.Taken together,the results support the development of CHE as a potentially useful anticancer drug for the treatment of gastric cancer.

In situ monitoring of the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET

Microemulsions are promising drug delivery systems for the oral administration of poorly watersoluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized,especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering(SAXS) and fluorescence resonance energy transfer(FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET spectra indicated micelles with smaller particle sizes were generated during lipolysis, which could be affected by CaCl_2, bile salts and lecithin. Then, the effect of mucus on the structural change of lipolysed microemulsions was studied. The results of SAXS and FRET indicated that the liquid crystalline phases disappeared, and more micelles were generated. In summary, we studied the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET, and successfully monitored the appearance and disappearance of the liquid crystalline phases and micelles.

Genome-wide identification and expression analysis of the β-amylase genes strongly associated with fruit development,ripening, and abiotic stress response in two banana cultivars

β-amylase(BAM) is an important enzyme involved in conversion of starch to maltose in multiple biological processes in plants. However, there is currently insufficient information on the BAM gene family in the important fruit crop banana. This study identified 16 BAM genes in the banana genome. Phylogenetic analysis showed that Ma BAMs were classified into four subfamilies. Most Ma BAMs in each subfamily shared similar gene structures. Conserved motif analysis showed that all identified Ma BAM proteins had the typical glyco hydro14 domains. Comprehensive transcriptomic analysis of two banana genotypes revealed the expression patterns of Ma BAMs in different tissues, at various stages of fruit development and ripening, and in responses to abiotic stresses. Most Ma BAMs showed strong transcript accumulation changes during fruit development and late-stage ripening. Some Ma BAMs showed significant changes under cold, salt, and osmotic stresses. This finding indicated that Ma BAMs might be involved in regulating fruit development, ripening, and responses to abiotic stress. Analysis of five hormone-related and seven stressrelevant elements in the promoters of Ma BAMs further revealed that BAMs participated in various biological processes. This systemic analysis provides new insights into the transcriptional characteristics of the BAM genes in banana and may serve as a basis for further functional studies of such genes.

Stable and Efficient Red Perovskite Light-Emitting Diodes Based on Ca^(2+)-Doped CsPbI_(3) Nanocrystals

α-CsPbI3 nanocrystals(NCs)with poor stability prevent their wide applications in optoelectronic fields.Ca^(2+)(1.00Å)as a new B-site doping ion can successfully boost CsPbI3 NC performance with both improved phase stability and optoelectronic properties.With a Ca^(2+)/Pb^(2+)ratio of 0.40%,both phase and photoluminescence(PL)stability could be greatly enhanced.Facilitated by increased tolerance factor,the cubic phase of its solid film could be maintained after 58 days in ambient condition or 4 h accelerated aging process at 120℃.The PL stability of its solution could be preserved to 83%after 147 days in ambient condition.Even using UV light to accelerate aging,the T_(50) of PL could boost 1.8-folds as compared to CsPbI_(3) NCs.Because Ca^(2+) doping can dramatically decrease defect densities of films and reduce hole injection barriers,the red light-emitting diodes(LEDs)exhibited about triple enhancement for maximum the external quantum efficiency(EQE)up to 7.8%and 2.2 times enhancement for half-lifetime of LED up to 85 min.We believe it is promising to further explore high-quality CsPbI_(3) NC LEDs via a Ca^(2+)-doping strategy.

Cold stress responsive microRNAs and their targets in Musa balbisiana

Cold stress is an environmental factor affecting plant development and production. Recently,micro RNAs(mi RNAs) have been found to be involved in several plant processes such as growth regulation and stress responses. Although mi RNAs and their targets have been identified in several banana species, their participation during cold accumulation in banana remains unknown. In this study, two small RNA libraries were generated from micropropagated plantlets of Musa balbisiana grown at normal and low temperature(5°C).A total of 69 known mi RNAs and 32 putative novel mi RNAs were detected in the libraries by Solexa sequencing. Sixty-four cold-inducible mi RNAs were identified through differentially expressed mi RNAs analysis. Among 43 mi RNAs belonging to 26 conserved mi RNA families with altered expression, 18 were upregulated and 25 downregulated under cold stress. Of21 putative novel mi RNAs with altered expression, four were downregulated and 17 upregulated. Furthermore,eight mi RNAs were validated by stem-loop q RT-PCR and their dynamic differential expression was analyzed. In addition, 393 target genes of 58 identified cold-responsive mi RNAs were predicted and categorized by function.These results provide important information for further characterization and functional analysis of cold-responsive mi RNAs in banana.

Stable and Efficient Red Perovskite Light-Emitting Diodes Based on Ca^(2+)-Doped CsPbI_(3)Nanocrystals

α-CsPbI_(3)nanocrystals(NCs)with poor stability prevent their wide applications in optoelectronic fields.Ca^(2+)(1.00Å)as a new B-site doping ion can successfully boost CsPbI_(3)NC performance with both improved phase stability and optoelectronic properties.With a Ca^(2+)/Pb^(2+)ratio of 0.40%,both phase and photoluminescence(PL)stability could be greatly enhanced.Facilitated by increased tolerance factor,the cubic phase of its solid film could be maintained after 58 days in ambient condition or 4 h accelerated aging process at 120℃.The PL stability of its solution could be preserved to 83%after 147 days in ambient condition.Even using UV light to accelerate aging,the T50 of PL could boost 1.8-folds as compared to CsPbI_(3)NCs.Because Ca^(2+)doping can dramatically decrease defect densities of films and reduce hole injection barriers,the red light-emitting diodes(LEDs)exhibited about triple enhancement for maximum the external quantum efficiency(EQE)up to 7.8%and 2.2 times enhancement for half-lifetime of LED up to 85 min.We believe it is promising to further explore high-quality CsPbI_(3)NC LEDs via a Ca^(2+)-doping strategy.

Efficient regeneration system applicable to five Musa cultivars

Banana(Musa spp.) is an important staple food, economic crop, and nutritional fruit worldwide.Hybridization is seriously hampered by the long generation time, polyploidy, and sterility of most cultivars.Establishment of an efficient regeneration and transformation system for banana is critical for their genetic improvement. An efficient and reproducible transformation system for banana using direct organogenesis was developed. Media containing benzylaminopurine(BA)combined with one of four other growth regulators was evaluated for the regeneration efficiency of five Musa cultivars and the ability to induce/support development of new banana shoots. The result indicated that the greatest number of shoots per explant for all five Musa cultivars was obtained using MS medium supplemented with8.9 mmol$L–1BA and 9.1 mmol$L–1thidiazuron(TDZ).In 240–270 d, one immature male flower could regenerate between 380 and 456, 310–372, 200–240, 130–156, and100–130 well-developed shoots for Gongjiao, Red banana, Rose banana, Baxi, and Xinglongnaijiao, respectively. Such a system will facilitate molecular breeding and functional genomics of banana.