Evaluation of the intracellular lipid-lowering effect of polyphenols extract from highland barley in HepG2 cells

Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinations is more significant than a specific food component.This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid(OA).Five indexes,triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein-cholesterol(LDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were used to evaluate the lipidlowering effect of highland barley extract.We also preliminary studied the lipid-lowering mechanism by Realtime fluorescent quantitative polymerase chain reaction(q PCR).The results indicated that highland barley extract contains many components with lipid-lowering effects,such as hyperoside and scoparone.In vitro,the lipase assay showed an 18.4%lipase inhibition rate when the additive contents of highland barley extract were 100μg/m L.The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mmol/L OA-induced HepG2 cells.The results showed that intracellular TG,LDL-C,and T-CHO content decreased by 34.4%,51.2%,and 18.4%,respectively.ALT and AST decreased by 51.6%and 20.7%compared with the untreated hyperlipidemic HepG2 cells.q PCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγand Fabp4.

GhWRKY33 negatively regulates jasmonate-mediated plant defense to Verticillium dahliae

Verticillium wilt,caused by Verticillium dahliae,seriously restricts the yield and quality improvement of cotton.Previous studies have revealed the involvement of WRKY members in plant defense against V.dahliae,but the underlying mechanisms involved need to be further elucidated.Here,we demonstrated that Gossypium hirsutum WRKY DNA-binding protein 33(GhWRKY33) functions as a negative regulator in plant defense against V.dahliae.GhWRKY33 expression is induced rapidly by V.dahliae and methyl jasmonate,and overexpression of GhWRKY33 reduces plant tolerance to V.dahliae in Arabidopsis.Quantitative RT-PCR analysis revealed that expression of several JA-associated genes was significantly repressed in GhWRKY33 overexpressing transgenic plants.Yeast one-hybrid analysis revealed that GhWRKY33 may repress the transcription of both AtERF1 and GhERF2 through its binding to their promoters.Protein-protein interaction analysis suggested that GhWRKY33 interacts with G.hirsutum JASMONATE ZIM-domain protein 3(GhJAZ3).Similarly,overexpression of GhJAZ3 also decreases plant tolerance to V.dahliae.Furthermore,GhJAZ3 acts synergistically with GhWRKY33 to suppress both AtERF1 and GhERF2 expression.Our results imply that GhWRKY33 may negatively regulate plant tolerance to V.dahliae via the JA-mediated signaling pathway.

Real-time co-registered photoacoustic and ultrasonic imaging for early endometrial cancer detection driven by cylindrical diffuser

In illuminating tissues,a cylindrical diffuser(CD)has an advantage over regular laser sources due to its ability to illuminate a larger volume of the target tissue.This paper presents a co-registered large volume photoacoustic(PA)and ultrasonic(US)imaging for early endometrial cancer(EEC)detection using CD.It has the advantage that the US imaging system is outside the body and only the PA excitation device is inside the body,which makes the system more efficient and less invasive for EEC detection.The paper reports on two sets of experiments.Thefirst set produced real-time PA images of blood vessel phantom.The second set demonstrated the imaging of pig uterus ex vivo.The results show that the system has the potential for imaging and characterizing of EEC.

Visible-Light-Induced Domino Cyclization to Access Pyrido[2,3-d]pyrimidine-2,4-diones via a Radical-Polar Crossover Reaction

Comprehensive Summary Catalytic and green strategies for the synthesis of privileged scaffolds are synthetically appealing.We now report a radical-polar crossover(RPC)-enabled three-component cyclization of bromodifluoroalkyls with enaminones and 6-aminouraciles via a visible-light-induced domino cyclization.The reaction exhibited a broad substrate scope(>40 examples)including complex molecules,which highlighted the utility of this strategy for the construction of a library of bioactive analogs.

Switchable Multicomponent Cyclization Reactions to Access Fluoroalkylated Dihydropyrimidines and Pyrimidines under Solvent-Free Conditions

Comprehensive Summary The development of switchable solvent-free multicomponent reactions to build high-value-added products is an important demand for organic synthesis.Herein,we detailed the successful implementation of a switchable strategy for the construction of diverse 4-fluoroalkyl-1,4-dihydropyrimidines and 4-fluoroalkyl-pyrimidines via a solvent/additive-free[3+2+1]annulation,starting from readily available enamines,trifluoroacetaldehyde hydrate or 1-ethoxy-2,2-difluoroethanol and amidines hydrochloride.This reaction conforms to the concept of green synthesis,and provides a new avenue to access valuable fluorinated heterocycles.

A measurement of epidermal thickness of fingertip skin from OCT images using convolutional neural network

In this study,we proposed a method to measure the epidermal thickness(ET)of skin based on deep convolutional neural network,which was used to determine the boundaries of skin surface and the ridge portion in dermal-epidermis junction(DE J)in cross-section optical coherence tomography(OCT)images of fingertip skin.The ET was calculated based on the row difference between the surface and the ridge top,which is determined by search the local maxima of boundary of the ridge portion.The results demonstrated that the region of ridge portion in DEJ was well determined and the ET measurement in this work can reduce the effect of the papillae valley in DEJ by 9.85%.It can be used for quantitative characterization of skin to differentiate the skin diseases.

Gastroscopy-conjugated photoacoustic and ultrasonic dual-mode imaging for detection of submucosal gastric cancer:in vitro study

This paper presents photoacoustic and ultrasonic dual-mode imaging for real-time detection of submucosal gastric cancer with a combination of gastroscopy.The diagnostic capacity was directly addressed via several phantoms and ex vivo experiments.Results demonstrated that superficial and submucosal gastric cancer can be diagnosed with a perceptible depth of 6.33 mm,a lateral accuracy of 2.23 mm,and a longitudinal accuracy of 0.17 mm though capturing the morphology of angiogenesis,which is a main character of the therioma-related change.The capability of gastroscopy-conjugated photoacoustic and ultrasonic dual-mode imaging system will own great potential in improving the clinical diagnostic rate of submucosal gastric cancer.

Interstitial photoacoustic technique and computational simulation for temperature distribution and tissue optical properties in interstitial laser photothermal interaction

Interstitial laser immunotherapy(ILIT)is designed to use photothermal and immunological inter-actions for treatment of metastatic cancers.The photothermal ffect is crucial in inducing anti-tumorimmune responses in the host.Tissue temperature and tssue optical properties are important factorsin this process.In this study,a device combining interstitial photoacoustic(PA)technique andinterstitial laser photothermal interaction is proposed.Together with computational simulation,thisdevice was designed to determine temperature distributions and tissue optical properties during lasertreatment.Experiments were performed usinger-ivoFporcine liver tissue.Our results demonstratedthat interstitial PA signal amplitude was linearly dependent on tisue temperature in the tempera-ture ranges of 20-60℃,as wll as 65-80℃,with a dfferent slope,due to the change of tissue opticalproperties.Using the directly measured temperature in the tissue around the interstitial optical fiberdiffusion tip for calibration,the theoretical temperature distribution predicted by the bioheatequation was used to extract optical properties of tssue.Finally,the three-dimensional temperature distribution was simulated to guide tumor destruction and immunological stimulation,Thus,thisnovel device and method could be used for monitoring and controlling ILIT for cancer treatment.

不同核酸提取方案对EB病毒核酸质量及扩增影响分析

目的通过比较不同核酸提取方法对EB病毒(EBV)-DNA检测的影响,探讨EBV-DNA检测的优化方案。方法收集16例全血EBV-DNA阳性标本(EBV-DNA浓度>1000 copies/ml),分别用手工提取法、A品牌核酸提取仪(A机)和B品牌核酸提取仪(B机)提取全血核酸,检测各样本核酸浓度及A260/A280比值,分析不同提取法所得核酸质量,再采用荧光定量PCR检测EBV-DNA浓度,比较3种核酸提取法检测EBV-DNA的差异。为探究全血与血浆检测EBV-DNA的差异,对19例手工提取后检测结果为阳性的全血标本,用试剂盒配套的血浆提取方法手工提取其血浆核酸,采用荧光定量PCR检测EBV-DNA浓度。结果16例全血EBV-DNA阳性样本经3种不同方法提取核酸后,手工提取核酸浓度均数为624 ng/μl,A机提取核酸浓度均数为141 ng/μl,B机提取核酸浓度均数为273 ng/μl。2种仪器提取法结果与手工提取法比较,均差异有统计学意义(A机P<0.05,B机P<0.01)。荧光定量PCR检测EBV-DNA浓度显示,手工提取全部为阳性,A机有4例未检测出阳性,B机有5例未检测出阳性。结果提示,低浓度EBV标本如采用该研究中的仪器提取核酸可能发生漏检。在同时检测全血与血浆的19例EBV-DNA阳性标本中,只有1例血浆阳性,全血样本EBV-DNA阳性率高于血浆样本,差异具有统计学意义(P<0.01)。经过以上验证,该单位EBV-DNA均使用全血标本通过手工提取法提取核酸进行检测。2021年1月至2022年12月共检测7945例EBV-DNA样本,阳性1160例,阳性率14.60%,与文献报告的阳性率基本符合。结论不同核酸提取方法及标本类型对EBV-DNA检测结果存在明显影响。因此,在项目应用于临床之前应做好方法学比对,与临床协商选择合适的标本类型进行检测。项目进行过程中应对检测结果进行定期评价,为临床提供准确、有效的检测结果。

Joining actions: crosstalk between intermediate filaments and actin orchestrates cellular physical dynamics and signaling

Many key cellular functions are regulated by the interplay of three distinct cytoskeletal networks, made of actin filaments,microtubules, and intermediate filaments(IFs), which is a hitherto poorly investigated area of research. However, there are growing evidence in the last few years showing that the IFs cooperate with actin filaments to exhibit strongly coupled functions.This review recapitulates our current knowledge on how the crosstalk between IFs and actin filaments modulates the migration properties, mechano-responsiveness and signaling transduction of cells, from both biophysical and biochemical point of view.

Clemastine rescues behavioral changes and enhances remyelination in the cuprizone mouse model of demyelination

Increasing evidence suggests that white matter disorders based on myelin sheath impairment may underlie the neuropathological changes in schizophrenia.But it is unknown whether enhancing remyelination is a beneficial approach to schizophrenia.To investigate this hypothesis,we used clemastine,an FDA-approved drug with high potency in promoting oligodendroglial differentiation and myelination,on a cuprizone-induced mouse model of demyelination.The mice exposed to cuprizone（0.2%in chow） for 6 weeks displayed schizophrenia-like behavioral changes,including decreased exploration of the center in the open field test and increased entries into the arms of the Y-maze,as well as evident demyelination in the cortex and corpus callosum.Clemastine treatment was initiated upon cuprizone withdrawal at 10 mg/kg per day for3 weeks.As expected,myelin repair was greatly enhanced in the demyelinated regions with increased mature oligodendrocytes（APC-positive） and myelin basic protein.More importantly,the clemastine treatment rescued the schizophrenia-like behavioral changes in the open field test and the Y-maze compared to vehicle,suggesting a beneficial effect via promoting myelin repair.Our findings indicate that enhancing remyelination may be a potential therapy for schizophrenia.

First Total Synthesis of （±）-Latifolin and Its Antioxidant Mechanism

The first total synthesis of （±）-latifolin has been accomplished in six steps and 47.8% overall yield. To understand the relative importance of phenolic O-H and benzhydryl C-H hydrogen on the antioxidant activity of latifolin, 2,2-diphenyl-1-picrylhydrazyl （DPPH） radical scavenging assay and density functional theory （DFT） studies were carried out. On scavenging DPPH radical in ethanol, the activity of latifolin （1） bearing phenolic hydrogen is remarkably higher than analogue 10 bearing no phenolic hydrogen. Therefore, Phenolic hydrogen is responsible for latifolin＇s antioxidant activity rather than benzhydryl C-H hydrogen. Furthermore, the 5-OH BDE is lower than 2＇-OH and 7-CH BDEs by a DFT calculation, respectively. Based on theoretical results it is definitely concluded that the phenolic 5-OH plays a major role in the antioxidant activity of latifolin.

One-pot synthesis of CNT-SAPO-34 composite supported copper and cerium catalysts with excellent surface resistance to SO_(2) and H_(2)O in NH_(3)-SCR

CuCe/CNT_(x)-SAPO-34(x=0,0.5,1,2) with various CNT doping quantities were synthesized through the one-pot hydrothermal synthesis method using CNT and SAPO-34 as composite supporters.The selected CuCe/CNT_1-SAPO-34 catalyst exhibits remarkable SCR activity and high H_(2)O/SO_(2) resistance in a wide temperature range of 200-450℃.X-ray diffraction(XRD),N_(2) adsorption-desorption,scanning electron microscopy(SEM),X-ray photoelectro n spectroscopy(XPS),H_(2)-temperature programmed reduction(H2-TPR),and NH3-temperature programmed desorption(NH_(3)-TPD) were used to characterize the physiochemical structure,surface state of active sites reducibility,and surface acidity of the catalysts.The characterization results reveal that CuCe/CNT_1-SAPO-34 possesses a hierarchical structure,small particle size,high levels of surface Cu^(2+),Ce^(3+) and chemisorbed oxygen,enhanced reducibility,and suitable surface acidity.For comparison,CuCe/CNT_1-SAPO-34(P) mixed mechanically with CuCe/CNT_0-SAPO-34and CNT was investigated through the NH3-SCR with and without H_(2)O/SO_(2),it also displays lower resistance of H_(2)O and SO_(2) than CuCe/CNT_1-SAPO-34.The catalytic performance made CuCe/CNT_1-SAPO-34 a promising catalyst for the NO_(x) emission control from diesel vehicles.

Fabrication of wide temperature lanthanum and cerium doped Cu/TNU-9 catalyst with excellent NH_(3)-SCR performance and outstanding SO_(2)+H_(2)O tolerance

The effects of La on the catalytic performance,SO_(2)and H2O resistance of Cu-Ce/TNU-9 catalyst were studied in the selective catalytic reduction of NO_(x)via ammonia(NH_(3)-SCR).The results show that the La doped Ce-Cu/TNU-9(CCL/T9)catalyst exhibits better SCR performance than Ce-Cu/TNU-9(CC/T9)and Cu/TNU-9(C/T9)in the wide temperature window(200-450℃)due to La benefiting from enhancing Cu^(+)+Ce^(4+)?Cu^(2+)-+Ce^(3+)to facilitate the electron transfer,which further accelerates the oxidation of NO into NO_(2)that leads to the"Fast SCR".The La can also enhance the surface acidic,redox property and is beneficial to the formation of oxygen vacancy.Meanwhile,the larger co ntent of Ce^(3+) can produce oxygen vacancy,resulting in rising SCR activity.The CCL/T9 has outstanding water and SO_(2) resistance,which may be due to the adso rbed S on the surface of these catalysts mainly existing in the form of a small amount of sulfate and sulfite,the decomposition of ammonium bisulphite under high temperature and the hydrophobicity of TNU-9 zeolite.

Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor

Approximately 140 million people worldwide are homozygous carriers of APOE4(ε4),a strong genetic risk factor for late onset familial and sporadic Alzheimer’s disease(AD),91%of whom will develop AD at earlier age than heterozygous carriers and noncarriers.Susceptibility to AD could be reduced by targeted editing of APOE4,but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies.Here,we first screened eight cytosine base editor variants at four injection stages(from 1-to 8-cell stage),and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate(up to 100%)with the lowest bystander effects.In particular,80%of AD-susceptibleε4 allele copies were converted to the AD-neutralε3 allele in humanε4-carrying embryos.Stringent control measures combined with targeted deep sequencing,whole genome sequencing,and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells.Furthermore,base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage.Finally,we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia.Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos,a potential approach for reducing human susceptibility to AD or other genetic diseases.

One-pot synthesis of Cu-Ce co-doped SAPO-5/34 hybrid crystal structure catalysts for NH_(3)-SCR reaction with SO_(2) resistance

SAPO-34,SAPO-5/34 based catalysts doped with Cu,Ce as active components were synthesized via a one-pot hydrothermal method by using different amounts of additive(a-cellulose),and their catalytic activities were measured for selective catalytic reduction(SCR) of NO with NH3.The synthesized Cu-Ce co-doped products switch from cubic SAPO-34,to flower-like aggregated SAPO-5/34,hybrid crystal SAPO-5/34,and finally to spherical aggregated SAPO-34 with the increase of α-cellulose amount.The Cu-Ce co-doped SAPO-5/34 hybrid crystal structure catalysts with 0.75 mol ratios of C/P(Cu-Ce/SP-0.75)exhibit excellent NH_(3)-SCR activity with higher than 90% NOx conversion in the temperature range of 180-450℃,at WHSV of 20000 mL/(g·h).Furthermore,the catalyst displays outstanding sulfur resistance and NOX conversion maintains above 90% at 200-450℃ after adding 100 ppm of SO_(2).The characteristic results suggest that the high deNOX performance of Cu-Ce/SP-0.75 is due to the enhanced accessibility,abundant activity species,excellent redox property and high adsorptive and activated capacity for NH_(3).

Siloles and Acetenyl Aromatics Copolymers: Synthesis, Characterization and Photophysical Properties

Two copolymers,poly(1,1-dimethyl-3,4-diphenylsilole-alt-N-hexyl-3,6-diethynylcarbazole)(PS-DyCz)and poly-(1,1-dimethyl-3,4-diphenylsilole-alt-2,7-diethynyl-9,9'-dihexylfluorene)(PS-DyF),were synthesized by Sonogashira coupling reaction of 2,5-dibromo-1,1-dimethyl-3,4-diphenylsilole and N-hexyl-3,6-diethynylcarbazole or 2,7-diethynyl-9,9'-dihexylfluorene,respectively.The chemical structures of the copolymers were characterized by NMR,FT-IR techniques.Their thermal and photophysical properties were evaluated by TGA,DSC,UV-Vis and fluorescence spectroscopy,respectively.The weight-averaged molecular weights(Mw)of PS-DyCz and PS-DyF are 1.20×10^(4) and 3.83×10^(4) Da,respectively.The degree of polymerization is 8 and 22 units.Theseπ-conjugated polymers exhibited lower band-gap of 2.25 and 2.70 eV due to the presence of silole rings and C≡C triple bonds in their backbone,the results were consistent with the density functional(DFT)calculations at the B3LYP/6-31G^(*)level.

Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling

The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments supports various cellular functions,including cell morphology,elasticity,migration,organelle localization,and resistance against mechanical or pathological stress.Currently available chemicals targeting vimentin predominantly induce network reorganization and shrinkage around the nucleus.Effective tools for long-term manipulation of vimentin network dispersion in living cells are still lacking,limiting in-depth studies on vimentin function and potential therapeutic applications.Here,we verified that a commercially available small molecule,trametinib,is capable of inducing spatial spreading of the cellular vimentin network without affecting its transcriptional or Translational regulation.Further evidence confirmed its low cytotoxicity and similar effects on different cell types.Importantly,Trametinib has no impact on the other two cytoskeletal systems,actin filaments and the microtubule network.Moreover,Trametinib regulates vimentin network dispersion rapidly and efficiently,with effects persisting for up to 48 h after drug withdrawal.We also ruled out the possibility that Trametinib directly affects the phosphorylation level of vimentin.In summary,we identified an unprecedented regulator Trametinib,which is capable of spreading the vimentin network toward the cell periphery,and thus complemented the existing repertoire of vimentin remodeling drugs in the field of cytoskeletal research.