Reversal of tamoxifen resistance by artemisinin in ER+breast cancer:bioinformatics analysis and experimental validation

Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.

A Review of Cloud-Resolving Model Studies of Convective Processes

Convective processes affect large-scale environments through cloud-radiation interaction, cloud micro- physical processes, and surface rainfall processes. Over the last three decades, cloud-resolving models （CRMs） have demonstrated to be capable of simulating convective-radiative responses to an imposed large-scale forcing. The CRM-produced cloud and radiative properties have been utilized to study the convective- related processes and their ensemble effects on large-scale circulations. This review the recent progress on the understanding of convective processes with the use of CRM simulations, including precipitation processes; cloud microphysical and radiative processes; dynamical processes; precipitation efficiency; diurnal variations of tropical oceanic convection; local-scale atmosphere-ocean coupling processes; and tropical convective-radiative equilibrium states. Two different ongoing applications of CRMs to general circulation models （GCMs） are discussed： replacing convection and cloud schemes for studying the interaction between cloud systems and large-scale circulation, and improving the schemes for climate simulations.

A multi-location joint field observation of the stratosphere and troposphere over the Tibetan Plateau

The unique geographical location and high altitude of the Tibetan Plateau can greatly influence regional weather and climate.In particular, the Asian summer monsoon(ASM) anticyclone circulation system over the Tibetan Plateau is recognized to be a significant transport pathway for water vapor and pollutants to enter the stratosphere. To improve understanding of these physical processes, a multi-location joint atmospheric experiment was performed over the Tibetan Plateau from late July to August in 2018, funded by the fiveyear(2018–2022) STEAM(stratosphere and troposphere exchange experiment during ASM) project, during which multiple platforms/instruments—including long-duration stratospheric balloons, dropsondes, unmanned aerial vehicles, special sounding systems, and ground-based and satellite-borne instruments—will be deployed. These complementary methods of data acquisition are expected to provide comprehensive atmospheric parameters(aerosol, ozone, water vapor, CO_2, CH_4, CO, temperature, pressure,turbulence, radiation, lightning and wind); the richness of this approach is expected to advance our comprehension of key mechanisms associated with thermal, dynamical, radiative, and chemical transports over the Tibetan Plateau during ASM activity.

Flexibility improvement evaluation of hydrogen storage based on electricity-hydrogen coupled energy model

To achieve carbon neutrality by 2060,decarbonization in the energy sector is crucial.Hydrogen is expected to be vital for achieving the aim of carbon neutrality for two reasons:use of power-to-hydrogen(P2H)can avoid carbon emissions from hydrogen production,which is traditionally performed using fossil fuels;Hydrogen from P2H can be stored for long durations in large scales and then delivered as industrial raw material or fed back to the power system depending on the demand.In this study,we focus on the analysis and evaluation of hydrogen value in terms of improvement in the flexibility of the energy system,particularly that derived from hydrogen storage.An electricity-hydrogen coupled energy model is proposed to realize the hourly-level operation simulation and capacity planning optimization aiming at the lowest cost of energy.Based on this model and considering Northwest China as the region of study,the potential of improvement in the flexibility of hydrogen storage is determined through optimization calculations in a series of study cases with various hydrogen demand levels.The results of the quantitative calculations prove that effective hydrogen storage can improve the system flexibility by promoting the energy demand balance over a long term,contributing toward reducing the investment cost of both generators and battery storage and thus the total energy cost.This advantage can be further improved when the hydrogen demand rises.However,a cost reduction by 20%is required for hydrogen-related technologies to initiate hydrogen storage as long-term energy storage for power systems.This study provides a suggestion and reference for the advancement and planning of hydrogen storage development in regions with rich sources of renewable energy.

压疮信息化管理平台应用效果评价

目的建设及应用压疮信息化管理平台,构建院内压疮管理的标准化综合管理体系,提高压疮护理质量及管理效能。方法运用具有压疮风险评估、原因分析、标准化防治、后期情况追踪、动态质量监管等多功能的压疮信息化管理平台对我院压疮及高危人群实施动态防治与质量监控。结果压疮信息化管理平台应用后,护士对压疮管理的认可度、对压疮防治的认知及处理能力较应用前提高,P<0.05。压疮主动上报率由84.48%提高至97.62%,院内压疮发生率由0.1%下降至0.03%,压疮治愈率由23.88%提高至45.28%,P<0.05。结论压疮信息化管理平台的应用,构建了压疮护理标准化体系,是实现压疮防治与监管的有效手段,值得应用推广。

Seasonal and Diurnal Variations of Cloud Systems over the Eastern Tibetan Plateau and East China:A Cloud-resolving Model Study

The seasonal and diurnal variations of cloud systems are profoundly affected by the large-scale and local environments.In this study,a one-year-long simulation was conducted using a two-dimensional cloud-resolving model over the Eastern Tibetan Plateau(ETP)and two subregions of Eastern China:Southern East China and Central East China.Deep convective clouds(DCCs)rarely occur in the cold season over ETP,whereas DCCs appear in Eastern China throughout the year,and the ETP DCCs are approximately 20%−30%shallower than those over Eastern China.Most strong rainfall events(precipitation intensity,PI>2.5 mm h−1)in Eastern China are related to warm-season DCCs with ice cloud processes.Because of the high elevation of the ETP,the warm-season freezing level is lower than in Eastern China,providing favorable conditions for ice cloud processes.DCCs are responsible for the diurnal variations of warm-season rainfall in all three regions.Warm-season DCCs over the ETP have the greatest total cloud water content and frequency in the afternoon,resulting in an afternoon rainfall peak.In addition,rainfall events in the ETP also exhibit a nocturnal peak in spring,summer,and autumn due to DCCs.Strong surface heat fluxes around noon can trigger or promote DCCs in spring,summer,and autumn over the ETP but produce only cumulus clouds in winter due to the cold and dry environment.

Mechanism of Macrophage Action in Osteoarthritis

Osteoarthritis(OA)is the most common chronic joint disease and the main cause of pain and disability in adults(typical clinical OA characteristics),and women are more predisposed to this disease than men.About 400 million people worldwide and more than 100 million in China suffer from arthritis.OA was named the 11th largest contributor of mortality in the world,with a disability rate of as high as 53%,and is among the three major killers threatening the health of the elderly.Colloquially,OA is called the"number one disabling disease of the 21st century."It is the main reason for the malfunctioned mobility of the elderly.Generally,women and men start to have OA at 40 and 50,respectively.Incidence rates increased dramatically between the ages of 55 and 60.The prevalence rate among older persons over 70 years of age is almost 80-90%.In addition,the disease is a chronic progressive disease,which can not only lead to the decline of life function and the reduction or even loss of quality of life,but also has an important and huge impact on health care and social costs.This disease may also demand higher economic requirements of the affected families.Until now,since the pain mechanism of the disease is not clear,there are no effective treatment methods,and surgical joint replacement is the only choice to treat the end-stage disease.This paper focuses on the role of macrophages in OA development,with particular attention to the occurrence of pain and possible mediators involved.

Physiochemical and biological characteristics of fouling on landfill leachate treatment systems surface

Fouling of landfill leachate,a biofilm formation process on the surface of the collection system,migration pipeline and treatment system causes low efficiency of leachate transportation and treatment and increases cost for maintenance of those facilities.In addition,landfill leachate fouling might accumulate pathogens and antibiotic resistance genes(ARGs),posing threats to the environment.Characterization of the landfill leachate fouling and its associated environmental behavior is essential for the management of fouling.In this study,physicochemical and biological properties of landfill leachate fouling and the possible accumulation capacity of pathogens and ARGs were investigated in nitrification(aerobic condition)and denitrification(anaerobic condition)process during landfill leachate biological treatment,respectively.Results show that microbial(bacterial,archaeal,eukaryotic,and viral)community structure and function(carbon fixation,methanogenesis,nitrification and denitrification)differed in fouling under aerobic and anaerobic conditions,driven by the supplemental leachate water quality.Aerobic fouling had a higher abundance of nitrification and denitrification functional genes,while anaerobic fouling harbored a higher abundance of carbon fixation and methanogenesis genes.Both forms of leachate fouling had a higher abundance of pathogens and ARGs than the associated leachate,suggesting the accumulation capacity of fouling on biotic pollutants.Specifically,aerobic fouling harbored three orders of magnitude higher multidrug resistance genes mex D than its associated leachate.This finding provides fundamental knowledge on the biological properties of leachate fouling and suggests that leachate fouling might harbor significant pathogens and ARGs.

Multi-dimension apportionment of clean air “parade blue”phenomenon in Beijing

The mass concentration and major chemical components of fine particulate matter were measured before,during and after Beijing＇s massive parade commemorating 70th anniversary of the Chinese Victory in World War II on September 3,2015.Regional emission inventory,positive matrix factorization（PMF）,observations from space and backward air mass trajectories were jointly applied to identify the major pollution sources and their temporal and spatial variations.The contributions of emissions variations and the meteorological conditions related to the＂parade blue＂phenomenon in Beijing and its surrounding areas were investigated in detail.The main cause of the decreased PM（2.5）mass concentration was attributed to the absolute reduction in emissions of primary air pollutants.The chemical composition of PM（2.5）varied significantly before,during and after the parade.Fugitive dust particles were well controlled,the secondary formation of PM（2.5）was reduced along with the controlled gaseous precursors＇emissions from vehicles and industrial sources during the temporary intensified control period.During the parade period,the SO2and NO2column concentrations in Beijing and the surrounding areas decreased sharply,indicating that the coordinated reduction in primary emissions from the surrounding areas of Beijing played an important role in lowering the ambient concentration of SO2and NO2and accordingly lowered PM（2.5）and improved the regional air quality.A comparison of the temperature,humidity,and wind speed and direction during the same periods in 2014 and 2015 showed that the meteorological conditions positively influenced the achievement of＂parade blue＂.

Exploring the N-terminus region： Synthesis, bioactivity and 3D-QSAR of allatostatin analogs as novel insect growth regulators

Allatostatins （ASTs）, a family of insect neuropeptide, can inhibit juvenile hormone （JH） biosynthesis by the corpora allata （CA） in Diploptera punctata, and therefore be regarded as potential leads for the discovery of new insect growth regulators （1GRs）. But several shortcomings, such as their sensitivity to peptidases and high cost, impeded their practical application in pest management. In order to discover new IGRs, one AST analog B1 possessing non-peptide group was discovered with high ability to inhibit JH biosynthesis in vitro （IC50： 0.09 μmol/L） in our previous studies. In the present work, two series of B1 analogs with different substituents on the N-terminus region were designed and synthesized. The result suggested that benzene showed better activity than other heterocycles, and the para-substitution on the benzene was beneficial for activity. Moreover, analogs with logP value over 2.0 exhibited good activity, which indicated the hydrophobicity is important to the bioactivity. Three dimension quantitative structure-activity relationship （3D-QSAR） studies were performed to highlight the structural require- ments of ASTanalogs, which demonstrated introduction of bulkier substituents on the N-terminus would increase the activity. Analog Ⅱ12 （IC50： 0.08 μmol/L） exhibited similar inhibitory activity to the lead B1, but its synthetic route was simpler than B1. Therefore, Ⅱ12 could be used as a new lead compound for the discovery eco-friendly IGRs.

Comparison of surface water extraction performances of different classic water indices using OLI and TM imageries in different situations

Recently,water extraction based on the indices method has been documented in many studies using various remote sensing data sources.Among them,Landsat satellites data have certain advantages in spatial resolution and cost.After the successful launch of Landsat 8,the Operational Land Imager(OLI)data from the satellite are getting more and more attention because of its new improvements.In this study,we used the OLI imagery data source to study the water extraction performance based on the Normalized Difference Vegetation Index,Normalized Difference Water Index,Modified Normalized Water Index(MNDWI),and Automated Water Extraction Index(AWEI)and compared the results with the Thematic Mapper(TM)imagery data.Two test sites in Tianjin City of north China were selected as the study area to verify the applicability of OLI data and demonstrate its advantages over TM data.We found that the results of surface water extraction based on OLI data are slightly better than that based on TM in the two test sites,especially in the city site.The AWEI and MNDWI indices performs better than the other two indices,and the thresholds of water indices show more stability when using the OLI data.So,it is suitable to combine OLI imagery with other Landsat sensor data to study water changes for long periods of time.

Exosomes in Parkinson's Disease

Exosomes, nano-sized extracellular vesicles secreted by most cell types, are found in all kinds of biological fluids and tissues, including the central nervous system（CNS）. The proposed functions of these vesicles include roles in cell–cell signaling, removal of cellular debris, and transfer of pathogens between cells. Many studies have revealed that exosomes derived from the CNS occur in the cerebrospinal fluid and peripheral body fluids,and their contents are altered during disease, making them an appealing target for biomarker development in Parkinson＇s disease（PD）. Exosomes have been shown to spread toxic a-synuclein（asyn） between cells and induce apoptosis, which suggests a key mechanism underlying the spread of asyn aggregates in the brain and the acceleration of pathology in PD. However, potential neuroprotective roles of exosomes in PD have also been reported. On the treatment side, as drug delivery vehicles, exosomes have been used to deliver small interfering RNAs and catalase to the brain, and have shown clear therapeutic effects in a mouse model of PD. These features of exosomes in PD make them extremely interesting from the point of view of developing novel diagnostic and therapeutic approaches.

Exploring the heavy air pollution in Beijing in the fourth quarter of 2015： assessment of environmental benefits for red alerts

In recent years, Beijing has experienced severeair pollution which has caused widespread public concern.Compared to the same period in 2014, the first threequarters of 2015 exhibited significantly improved airquality. However, the air quality sharply declined in thefourth quarter of 2015, especially in November andDecember. During that time, Beijing issued the first redalert for severe air pollution in history. In total, 2 red alerts,3 orange alerts, 3 yellow alerts, and 3 blue alerts wereissued based on the adoption of relatively temporaryemergency control measures to mitigate air pollution. Thisstudy explored the reasons for these variations in airquality and assessed the effectiveness of emergency alertsin addressing severe air pollution. A synthetic analysis ofemission variations and meteorological conditions wasperformed to better understand these extreme air pollutionepisodes in the fourth quarter of 2015. The results showedthat compared to those in the same period in 2014, thedaily average emissions of air pollutants decreased in thefourth quarter of 2015. However, the emission levels ofprimary pollutants were still relatively high, which was themain intrinsic cause of haze episodes, and unfavorablemeteorological conditions represented important externalfactors. Emergency control measures for heavy airpollution were implemented during this red alert period,decreasing the emissions of primary air pollutants byapproximately 36% and the PMa.5 concentration by 11%-21%.

Comparison of the accuracy of powder and single-crystal X-ray diffraction techniques in determining organic crystal structure

This study demonstrates the accuracy of powder X-ray diffraction(PXRD)in determining the crystal structures of four organic molecules by comparing the structural information obtained from both single-crystal X-ray diffraction(SXRD)and PXRD techniques.Results showed that the PXRD technique had approximately the same precision as the SXRD technique.The majority of the relative deviations from PXRD-derived lattice parameters were within±0.2%of the correct values(average of the SXRD data),whereas the relative deviations in bond lengths and angles are within±1.0%.All of the relative deviations were subjected to normal statistical distributions(l=0)and coincided with the SXRD data.As an auxiliary implement of SXRD,PXRD is clearly an effective and powerful technique in establishing an accurate characterization of organic molecules.

Assembly of plant communities in coastal wetlands--the role of saltcedar Tamarix chinensis during early succession

Aims The mechanisms of plant community assembly are hypothesized to vary at different stages of succession.Here,we explore the local assemblage structure of a herbaceous plant community at its early stage of succession in a supratidal wetland.specifically,we assess the role of Chinese saltcedar(Tamarix chinensis),the lone dominant shrub species,in shaping the spatial structure and species composi-tion in the local plant community,after landscape alteration.Methods We used the multivariate trend-surface analysis for analyzing the spatial structure of the community composition.a null model was also used to detect potential biotic interactions between species.statistical significance was derived from a permutation test by randomizing the presence-absence matrix and functional traits independently.sensitivity analysis by randomly selecting 50 subplots and repeating the null model tests was also done.Finally,rank correlation analysis was used to study the relationship between effect sizes and distance to nearest T.chinensis individuals.Important Findings The herbaceous plant community was highly structured and shaped by the presence of T.chinensis.at local scale,two functional traits,plant height and leaf area,were found to be significantly convergent.Dispersal,environmental stress and interspecific competition played a trivial effect on the local community assembly.The facilitating effect of T.chinensis on the pioneering herbaceous plants,through acting as a wind shelter,was put forward as the dominant community assembly process.

Characteristics of the vertical structure of the atmospheric turbulence in the Tibetan Plateau

The Tibetan Plateau(TP)has unique atmospheric dynamics and thermal structures that originate from its giant terrain and complex climate.High vertical-resolution thermal radiosondes were launched near the central(Lhasa,91°06′E,29°36′N,3670 m above sea level(ASL))and marginal(Da Qaidam,95°21′E,37°51′N,3180 m ASL)areas of the TP during the summers of 2018 and 2020,respectively.Atmospheric turbulence parameters were calculated,and the characteristics of the atmospheric turbulent vertical structure at sunset in these two areas were analyzed and compared.Affected by TP thermal forcing and stably controlled by the summer monsoon anticyclone,the atmospheric refractive index structure constant(C_(n)^(2))tended to increase and then decrease with increasing height,reaching a maximum at the tropopause(~18 km ASL)at the Lhasa site.Although C_(n)^(2) at the Da Qaidam site also tended to increase at the tropopause,the position of the strong turbulent band(STB)(5–7 km ASL)was below the tropopause height corresponding to the potential temperature lapse rate minimum.The vertical distribution of C_(n)^(2) at the two sites,particularly regarding the position of the STB,was highly correlated with the atmospheric stability(Ri)and the thermal mixing scale(L_(T)).The significant correlations among the three parameters(STB,Ri,and L_(T))indicated that the strong fluctuations in temperature caused by thermal mixing were the dominant factor causing the Ri to be less than its critical value of 0.25.Moreover,the suppression strength involving the upward transport of the heat sources was the main reason for the different turbulent vertical structures and STB positions at the two sites.The zonal mean thermodynamic and dynamical fields derived from the reanalysis data also showed a height difference in the heat sources transported to the troposphere at the two sites.In the marginal TP,the material and energy in the lower troposphere were transported by the turbulent atmosphere upward along the slope of the mountain and converged at the central TP(28°N–35°N)with strong thermal forcing up to the tropopause.In the STB of the Lhasa site,the turbulent dissipation rate and eddy diffusion coefficient increased sharply,indicating that the turbulent atmosphere in this central site was highly diffused,and the small-scale turbulence transported the material and energy upward.

Enhanced ferroelectric properties of highly(100)oriented Pb(Zr_(0.52)Ti_(0.48))O_(3) thick films prepared by chemical solution deposition

Ferroelectric Pb(Zr_(0.52)Ti_(0.48))O_(3)(PZT)thick films with highly(100)preferential orientation have been prepared by chemical solution deposition process on Pt/Ti/SiO_(2)/(100)Si substrates and pyrolyzed at 350℃-450℃,then annealed at 650℃.The typical thickness of the films is 3.9
m.Effects of the pyrolysis temperature and excess PbO on the orientation,dielectric and ferroelectric properties of PZT thick films have been discussed.Domain switching and depoling process were studied by piezoelectric force microscopy.(100)oriented PZT films exhibit enhanced electrical properties.The dielectric constant and loss tangent of the films are 1444 and 0.022 at 1 kHz,respectively.The remnant polarization increases from 27.6 to 34.6μC/cm^(2),and the coercive field decreases from 61.4 to 43.5 kV/cm,when the orientation of the films changes from the random orientation to the preferential(100)orientation.The leakage current density is 10^(-8)A/cm^(2) at dc field of 0.25 kV/cm,and then increases to 10^(-6) A/cm^(2) at 40 kV/cm.The piezoelectric response of the oriented films is investigated by Piezoelecric Force Microscopy(PFM).

THICKNESS-DEPENDENCE OF RESIDUAL STRESS IN LEAD-FREE FERROELECTRIC K_(0.5)Na_(0.5)NbO_(3) FILMS

Lead-free ferroelectric K_(0.5)Na_(0.5)NbO_(3)(KNN)films with different thicknesses were prepared by polyvinlypyrrolidone(PVP)-modified chemical solution deposition(CSD)method.Their residual stresses were studied with two methods of X-ray diffraction(XRD)and nanoindentation fracture.It was found that the tensile stress occurs in KNN films with small thickness of 1.3μm after all kinds of stresses were neutralized,which is mainly originated from the interaction across grain boundaries.With increasing the thickness to 2.5μm and above it,the residual stress changed from tensile stresses to compressive stresses,and the compressive stress decreased with the thickness increased.These results could explain why a thicker KNN film can show improved electrical properties and the larger the thickness,the better the ferroelectric and piezoelectric properties.

Structural and dielectric properties of SrFe_(x)Ti_(1-x)O_(3)(x=0.001,0.005 and 0.01)ceramics

Three different SrFe_(x)Ti_(1-x)O_(3)(x=0.001,x=0.005,x=0.01)ceramics were prepared by the conventional solid-state reaction.The crystalline structure,surface morphology and dielectric properties were studied by X-ray diffraction(XRD),scanning electron microscope(SEM)and Agilent 4294A impedance analyzer,respectively.It is shown that both the sintering temperature and doping concentration influence the lttice constant,grain size,dielectric constant and the dielectric loss.When the sintering temperature is higher than 1390℃,the lttice constant,grain size and dieletric constant all decrease with the increase of the doping concentration,except the dielectric loss tangent which shows the opposite trend.Leakage curent tests show that the leakage curent density falls down with the increase of Fe doping concentration in the given region.

Bioinspired Scalable Total Synthesis of Opioids

As one of the largest and most representative families of natural medicines harvested from plants,the mass production of opioids legitimately occupies large,worldwide farmland cultivation of opium poppies,causing severe regulation limitations and supply uncertainty.Due to their complex structures,the chemical synthesis of opioids has been criticized as infeasible for large-scale production in view of lengthy synthetic steps and overall low efficiency.