Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer

BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.

A distinctive HPHT platform with different types of large-volume press subsystems at SECUF

Large-volume presses(LVPs)providing large volumes,liquid media,deformation capability,jump compression,and in situ measurements are in great demand for high-pressure research,particularly in the fields of geoscience,condensed matter physics,material science,chemistry,and biology.A high-pressure and high-temperature(HPHT)platform with different LVP subsystems,both solid-state and liquid environments,and nonequilibrium subsystems,has been constructed at the Synergetic Extreme Condition User Facility,Jilin University.This article describes the construction of the different subsystems and provides an overview of the capabilities and characteristics of the different HPHT subsystems.A large sample volume(1000 mm^(3))at 20 GPa is achieved through the use of a belt-type apparatus in the solid-state subsystem.HPHT conditions(1.8 GPa and 1000 K)are realized in the liquid subsystem through the use of a piston-cylinder-type LVP with optical diamond windows for in situ spectroscopic measurements.A maximum pressure jump to 10.2 GPa can be reached within 20 ms in the nonequilibrium subsystem with the use of an improved bladder-pressurization jump press.Some typical results obtained with different LVPs are briefly reviewed to illustrate the applications and advantages of these presses.In summary,the platform described here has the potential to contribute greatly to high-pressure research and to innovations in high-pressure technology.

Synthesis and superconductivity in yttrium superhydrides under high pressure

Flourishing rare earth superhydrides are a class of recently discovered materials that exhibit near-room-temperature superconductivity at high pressures,ushering in a new era of superconductivity research at high pressures.Yttrium superhydrides drew the most attention among these superhydrides due to their abundance of stoichiometries and excellent superconductivities.Here,we carried out a comprehensive study of yttrium superhydrides in a wide pressure range of 140 GPa-300 GPa.We successfully synthesized a series of superhydrides with the compositions of YH_(4),YH_(6),YH_(7),and YH_(9),and reported superconducting transition temperatures of 82 K at 167 GPa,218 K at 165 GPa,29 K at 162 GPa,and230 K at 300 GPa,respectively,as evidenced by sharp drops in resistance.The structure and superconductivity of YH_(4) were taken as a representative example and were also examined using x-ray diffraction measurements and the superconductivity suppression under external magnetic fields,respectively.Clathrate YH_(10),a candidate for room-temperature superconductor,was not synthesized within the study pressure and temperature ranges of up to 300 GPa and 2000 K.The current study established a detailed foundation for future research into room-temperature superconductors in polynary yttrium-based superhydrides.

Stability and band gap engineering of silica-confined lead halide perovskite nanocrystals under high pressure

SiO_(2)is the major mineral substance in the upper mantle of the earth.Therefore,studies of the silica-coated materials under high-pressure are essential to explore the physical and chemical properties of the upper mantle.The silica-confined CsPbBr_(3)nanocrystals(NCs)have recently attracted much attention because of the improved photoluminescence(PL)quantum yield,owing to the protection of silica shell.However,it remains considerable interest to further explore the relationship between optical properties and the structure of CsPbBr_(3)@SiO_(2)NCs.We systemically studied the structural and optical properties of the CsPbBr_(3)@SiO_(2)NCs under high pressure by using diamond anvil cell(DAC).The discontinuous changes of PL and absorption spectra occurred at~1.40 GPa.Synchrotron X-ray diffraction(XRD)studies of CsPbBr_(3)@SiO_(2)NCs under high pressure indicated an isostructural phase transformation at about 1.36 GPa,owing to the pressure-induced tilting of the Pb-Br octahedra.The isothermal bulk moduli for two phases are estimated about 60.0 GPa and 19.2 GPa by fitting the equation of state.Besides,the transition pressure point of CsPbBr_(3)@SiO_(2)NCs is slightly higher than that of pristine CsPbBr_(3)NCs,which attributed to the buffer effect of coating silica shell.The results indicate that silica shell is able to enhance the stabilization without changing the relationship between optical properties and structure of CsPbBr_(3)NCs.Our results were fascinated to model the rock metasomatism in the upper mantle and provided a new‘lithoprobe’for detecting the upper mantle.

Two different emission enhancement of trans-stilbene crystal under high pressure: Different evolution of structure

Mechanoresponsive luminescent(MRL)materials have drawn extensive concern due to their potential applications in mechanical sensors,memory chips,and security inks;especially these possessing high emission efficiency.In this work,we found trans-stilbene crystal exhibited two different pressure-induced emission enhancement(PIEE)behaviors at different pressure areas.The structural characterizations combined with density functional theory calculation indicate that the first emission enhancement was due to the decrease of nonradiation transition by the weaken of energy exchange process between atoms and lattice.And the second emission enhancement was attributed to the strengthen of C-H...C interactions from the non-planarization comformation.The results regarding the mechanoresponsive behavior of trans-stilbene offered a deep insight into PIEE from the structural point of view,which will facilitate the design of and search for high-performance MRL materials.

High pressure geochemistry:Preface

The origin and history of the Earth are manifested as the evolutionary processes of chemistry and physics of its interiors,which can be recognized by deciphering the geochemical signals recorded in minerals and rocks.Deep interiors of the Earth and other rocky planets are under both extreme pressure and temperature,i.e.,approximately 360 gigapascals(GPa)and as high as 7000 K at the center of the Earth.

Evaluation of intermittent-distributed-generation hosting capability of a distribution system with integrated energy-storage systems

The penetration rate of distributed generation is gradually increasing in the distribution system concerned.This is creating new problems and challenges in the planning and operation of the system.The intermittency and variability of power outputs from numerous distributed renewable generators could significantly jeopardize the secure operation of the distribution system.Therefore,it is necessary to assess the hosting capability for intermittent distributed generation by a distribution system considering operational constraints.This is the subject of this study.An assessment model considering the uncertainty of generation outputs from distributed generators is presented for this purpose.It involves different types of regulation or control functions using on-load tap-changers(OLTCs),reactive power compensation devices,energy storage systems,and the reactive power support of the distributed generators employed.A robust optimization model is then attained It is solved by Bertsimas robust counterpart through GUROBI solver.Finally,the feasibility and efficiency of the proposed method are demonstrated by a modified IEEE 33-bus distribution system.In addition,the effects of the aforementioned regulation or control functions on the enhancement of the hosting capability for intermittent distributed generation are examined.

Push-Sum Based Algorithm for Constrained Convex Optimization Problem and Its Potential Application in Smart Grid

Dear Editor,This letter aims to investigate the optimization problem where the decision variable is contained in a closed convex set.By combing the gradient decent-like method with the push-sum algorithm framework,we design the distributed iterative formulas under the condition that the considered graphs sequence is time-varying and unbalanced.

Synthesis of Cyclic Carbonates from Alkenyl and Alkynyl Substrates

As an extensively used chemical product,cyclic carbonate was generally synthesized by transesterification,or the cycloaddition of epoxides,diols with CO2.To reduce the production costs and expand the raw materials,alkenyl and alkynyl substrates have caused much attention in the synthesis of cyclic carbonates,such as olefins,allyl alcohols and propargylic alcohols.Based on the alkenyl substrate,the synthetic process involves a continuous reaction of oxidative carboxylation,with epoxide or halohydrin as an intermediate usually.Therefore,peroxides and nucleophiles （halogens or organic bases） are often necessary in the conversion.Using propargylic alcohols to produce a-alkylidene cyclic carbonates,noble metal catalysts play crucial roles in alkynyl activation,and organic bases are considered to assist the intramolecular and intermolecular proton transfer and combine CO2 molecular.As the carboxyl sources in products,inorganic carbonates and organic carboxylic acids also have some applications instead of CO2.In this review,we summarized the synthetic routes of cyclic carbonates from alkenyl and alkynyl substrates in the aspect of catalyst,mechanism and the development tendency.

High pressure, a protocol to identify the weak dihydrogen bonds:experimental evidence of C–H···H–B interaction

Pressure, as a thermodynamic parameter, provides an appropriate method to detect weak intermolecular interactions. The C–H···H–B dihydrogen bond is so weak that the experimental evidence of this interaction is still limited. A combination of in situ high pressure Raman spectra and angle-dispersive X-ray diffraction(ADXRD) experiments was utilized to explore the dihydrogen bonds in dimethylamine borane(DMAB). Both Raman and ADXRD measurements suggested that the crystal structure of DMAB is stable in the pressure region from 1 atm(1 atm=1.01325×10~5 Pa) to 0.54 GPa. The red shift of CH stretching and CH_3 distortion modes gave strong evidence for the existence of C–H···H–B dihydrogen bonds. Further analysis of Raman spectra and Hirshfeld surface confirmed our proposal. This work provided a deeper understanding of dihydrogen bonds.And we wish that high pressure could be applied to identify other unconfirmed hydrogen or dihydrogen bond.

Disulfide Crosslinking-Induced Aggregation:Towards Solid-State Fluorescent Carbon Dots with Vastly Different Emission Colors

Solid-state fluorescent multi-color carbon dots(SFM-CDs),prepared using the same precursor(s)without the need for dispersion in a solid matrix,are highly demanded for a wide range of applications.Herein,we report a microwave-assisted strategy for the prepara-tion of SFM-CDs with blue,yellow and red emissions within 5 min from the same precursors.The as-prepared B-CDs,Y-CDs,and R-CDs possessed bright fluorescence at 425 nm,550 nm,and 640 nm,and photoluminescence quantum yields(PLQYs)of 54.68%,17.93%,and 2.88%,respectively.The structure of SFM-CDs consisted of 5-oxo-3,5-dihydro-2H-thiazolo[3,2-a]pyridine-7-carboxylic acid(TPCA)immobilized on the surface of a carbon core,with the size of the carbon core and degree of disulfide crosslinking between CDs both increasing on going from the B-CDs to the R-CDs,as verified by mechanochromic experiments.The excellent solid-state fluorescence performance of the SFM-CDs allowed their utilization as the fluorescent converter layer in multi-color LEDs and white LEDs with a high color rendering index.

Pressure-induced emission(PIE)in halide perovskites toward promising applications in scintillators and solid-state lighting

High-pressure chemistry has provided a huge boost to the development of scientific community.Pressure-induced emission(PIE)in halide perovskites is gradually showing its unique charm in both pressure sensing and optoelectronic device applications.Moreover,the PIE retention of halide perovskites under ambient conditions is of great commercial value.Herein,we mainly focus on the potential applications of PIE and PIE retention in metal halide perovskites for scintillators and solid-state lighting.Based on the performance requirements of scintillator and single-component white light-emitting diodes(WLEDs),the significance of PIE and PIE retention is critically clarified,aiming to design and synthesize materials used for high-performance optoelectronic devices.This perspective not only demonstrates promising applications of PIE in the fields of scintillators and WLEDs,but also provides potential applications in display imaging and anti-counterfeiting of PIE materials.Furthermore,solving the scientific disputes that exist under ambient conditions is also simply discussed as an outlook by introducing high-pressure dimension to produce PIE.

糖尿病患者视网膜血管直径的影响因素

目的:了解2型糖尿病患者视网膜血管直径及其影响因素。方法:横断面研究。将2012年7月至2013年5月辽宁省抚顺市将军街道15个社区所有已确诊为2型糖尿病的居民1913例纳入研究。采用计算机辅助软件定量测量视网膜中央动脉直径(CRAE)、视网膜中央静脉直径(CRVE),并计算视网膜动静脉比值(AVR)。不同特征的组间CRAE、CRVE和AVR差异比较采用Student-t检验或者方差分析。采用广义线性回归分别探讨CRAE、CRVE和AVR的影响因素。采用LOWESS下的广义估计方程探讨糖尿病视网膜病变(DR)严重程度与CRAE、CRVE和AVR之间可能存在的非线性关系。结果:身体质量指数(BMI)较大、高血压、高密度脂蛋白较低、糖化血红蛋白较低患者的CRAE较低,差异有统计学意义(均P<0.05);年龄较大、女性、糖尿病病程较长、不吸烟、糖化血红蛋白<7%患者的CRVE较低,差异有统计学意义(均P<0.05);年龄较大、女性、不吸烟、BMI较小、无高血压、高密度脂蛋白较高、甘油三酯较低、糖化血红蛋白<7%患者的AVR较高,差异有统计学意义(均P<0.05)。多因素回归显示男性、高血压、高糖化血红蛋白、较低的高密度脂蛋白和高BMI是较小的CRAE的影响因素(均P<0.05);年龄较大、吸烟、糖尿病病程增加、较高的高密度脂蛋白是较大的CRVE的影响因素(均P<0.05);年龄较小、吸烟、高血压是较小的AVR的影响因素(均P<0.05)。随着DR严重程度增加,CRAE、CRVE、AVR的改变并不呈线性关系,CRAE和CRVE存在先逐渐增加再逐渐减小的趋势;AVR存在先减小再增加的趋势。结论:DR患者的CRAE、CRVE显著降低,AVR显著升高,这种关系在中度非增生型DR和增生性DR患者中更明显。

Pressure effects on metal/covalent-organic frameworks:structural and optical properties

Metal-organic frameworks(MOFs)and covalent organic frameworks(COFs)with highly ordered porous structure,tunable bandgap,large specific surface area and structural diversity,provide an appealing platform for the development of stimulus response,sensing,imaging and optoelectronics.Among various tuning methods,pressure engineering using the diamond anvil cell is a highly powerful in-situ technique,which can efficiently modulate the structural and optical properties of MOFs/COFs.This is beyond the realization of traditional chemical methods.This review outlines the research progress in the experimentoriented discovery of new phases or unique properties under high pressure,including phase transition,abnormal compression,photoluminescence(PL)discoloration and enhancement.Notably,the improvement of PL quantum yield in MOFs could be achieved by pressure-treated engineering and hydrogen-bonding cooperativity effect.We also propose and establish the relationship between structure and optical properties under high pressure.Finally,the challenge and outlook of the current fields are summarized.We hope that this review will supply guidance for comprehending the development of high-pressure MOF/COF-related research fields,and offer novel strategies for designing more high-performance MOF/COF materials to ultimately expand their applications.

Biomarkers for predicting efficacy of chimeric antigen receptor T cell therapy and their detection methods

Cancer immunotherapy has emerged as the fourth most prevalent approach to tumor treatment,alongside surgery,radiotherapy,and chemotherapy.After several decades of development,chimeric antigen receptor T(CAR-T)cell therapy,a promising branch of adoptive T-cell therapy,has demonstrated superior efficacy and safety in comparison to other cell therapies in the treatment of cancer.At present,CAR-T cells are predominantly used to treat hematological malignancies,although their application in solid tumors is being readily investigated.Although numerous studies have examined the biomarkers associated with the safety of CAR-T cell therapy,few have evaluated predictors of CAR-T cell therapeutic efficacy.Thus,the primary objective of this review article was to provide a comprehensive overview of the factors predicting the efficacy of CAR-T cell therapy,with a particular focus on biomarkers and their detection methods.

Chemical Constituents from Pericarpium Citri Reticulatae

Objective To study the chemical constituents from Pericarpium Citri Reticulatae （Citrus reticulata）. Methods The chemical constituents were isolated and purified by silica gel column, Sephadex LH-20, and ODS column chromatography. The structures were identified by spectral data. Results Nineteen compounds were isolated and identified as 4＇,5,6,7-tetramethoxyflavone （1）, 3,3＇,4＇,5,6,7,8-heptmethoxyflavone （2）, sinensetin （3）, 5-O-demethylnobiletin （4）, tangeretin （5）, nobiletin （6）, apigenin （7）, 5-O- desmethyltangeretin （8）, 5,7-dihydroxy-3,3＇,4＇,6-tetramethoxyflavone （9）, pachypodol （10）, 4＇,5,6,7-tetramethoxyflavanone （11）, 3＇,4＇,5,7,8-pentamethoxyflavanone （12）, agestricin C （13）, scoparone （14）, isoscopoletin （15）, hesperidin （16）, didymin （17）, methylhesperidine （18）, and naringin （19）. Conclusion Compounds 9-15 are obtained from this plant for the first time.

The observed difference of macrophage phenotype on different surface roughness of mineralized collagen

Biomaterials regulate macrophages and promote regeneration function,which is a new hot pot in tissue engineering and regenerative medicine.The research based on macrophage materials biology has appeared happy future,but related research on regulating macrophages and promoting tissue regeneration is still in its infancy.The surface roughness of biomaterials is one of the important factors affecting macrophage behavior.Previous study also found that the surface roughness of many biomaterials regulating macrophage polarization,but not including mineralized collagen(MC).In this study,we designed and fabricated MC with different roughness and investigated the influence of MC with different roughness on macrophages.In the study,we found that on the rough surface of MC,macrophages exhibited M1 phenotype-amoeboid morphology and high-level secretory of inflammatory factor(tumor necrosis factor-a and interleukin-6),while smoother surface exhibited M2 phenotype.These data will be beneficial to understand the mechanism deeply and enrich biomaterials tissue regeneration theory,provide a new train of thought biomaterials inducing tissue regeneration and repair and guide the optimum design of new biomaterials,development and reasonable applications.

Phenolic compounds participating in mulberry juice sediment formation during storage

The stability of clarified juice is of great importance in the beverage industry and to consumers.Phenolic compounds are considered to be one of the main factors responsible for sediment formation.The aim of this study is to investigate the changes in the phenolic content in clarified mulberry juice during storage.Hence, separation, identification, quantification, and analysis of the changes in the contents of phenolic compounds, both free and bound forms, in the supernatant and sediments of mulberry juice, were carried out using high performance liquid chromatographic system, equipped with a photo-diode array detector（HPLC-PDA） and HPLC coupled with quadrupole-time of flight mass spectrometric（HPLC-QTOF-MS/MS） techniques.There was an increase in the amount of sediment formed over the period of study.Total phenolic content of supernatant, as well as free phenolic content in the extracts of the precipitate decreased, whereas the bound phenolic content in the sediment increased.Quantitative estimation of individual phenolic compounds indicated high degradation of free anthocyanins in the supernatant and sediment from 938.60 to 2.30 mg/L and 235.60 to 1.74 mg/g, respectively.A decrease in flavonoids in the supernatant was also observed, whereas the contents of bound forms of gallic acid, protocatechuic acid, caffeic acid, and rutin in the sediment increased.Anthocyanins were the most abundant form of phenolics in the sediment, and accounted for 67.2% of total phenolics after 8 weeks of storage.These results revealed that phenolic compounds, particularly anthocyanins, were involved in the formation of sediments in mulberry juice during storage.

Recent advances in organic pressure-responsive luminescent materials

Organic luminescent materials are very sensitive to external stimuli,such as pressure,temperature,and electric field.The luminescent properties of some organic luminescent materials significantly change under high pressure.Some materials may show luminescence discoloration,whereas some may exhibit luminescence enhancement.These properties have many potential applications in anticounterfeiting,force sensor,data recording and storage,and luminescent devices,thereby greatly attracting the attention of scientists.In this review,the progress of research on these materials at high pressure in recent years is summarized.

Whether or Not Emission of Cs4PbBr6 Nanocrystals:High-Pressure Experimental Evidence

The origin of green emission in the zero-dimensional(0D)perovskite Cs4PbBr6 nanocrystals(NCs)remains a considerable debate.Herein,an approach involving a combination of high-pressure experiments and theoretical simulation was employed to elucidate the controversial origin of photoluminescence from emissive Cs4PbBr6 NCs(E416).Results obtained from first-principles density functional theory(DFT)calculations,as implemented in the Vienna ab initio simulation package codes,implied that the photoluminescence energies from bromine vacancy decreased persistently with pressure.Experimentally,the photoluminescence energies tended to decrease in the low-pressure region,followed by an increase beyond∼1.4 GPa.While the emergent disagreement between the first-principles calculation and highpressure experiment excludes the possibility of vacancy-tuning,the consistent change observed in the pressure-dependent emission between E416 and CsPbBr_(3) NCs offered a reliable interpretation for the occurrence of green emission from a CsPbBr_(3) impurity embedded in the Cs4PbBr6 matrix.Further comprehensive analysis demonstrated that the strong green emission of E416 NCs originated from the impurity CsPbBr_(3) NCs embedded in Cs4PbBr6 matrix.Our study represents a significant step forward to a deeper understanding of the emissive origins of Cs4PbBr6 NCs and promotes the application of this novel strategy in light-emitting devices.