Apatinib and gamabufotalin co-loaded lipid/Prussian blue nanoparticles for synergistic therapy to gastric cancer with metastasis

Due to the non-targeted release and low solubility of anti-gastric cancer agent,apatinib(Apa),a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects.In order to avoid these drawbacks,lipid-film-coated Prussian blue nanoparticles(PB NPs)with hyaluronan(HA)modification was used for Apa loading to improve its solubility and targeting ability.Furthermore,anti-tumor compound of gamabufotalin(CS-6)was selected as a partner of Apawith reducing dosage for combinational gastric therapy.Thus,HA-Apa-Lip@PB-CS-6 NPs were constructed to synchronously transport the two drugs into tumor tissue.In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor(VEGFR)and matrix metalloproteinase-9(MMP-9).In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs administration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects.In summary,we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer(GC)therapy.

Facilitated Prediction of Micropollutant Degradation via UV-AOPs in Various Waters by Combining Model Simulation and Portable Measurement

The degradation of micropollutants in water via ultraviolet(UV)-based advanced oxidation processes(AOPs)is strongly dependent on the water matrix.Various reactive radicals(RRs)formed in UV-AOPs have different reaction selectivities toward water matrices and degradation efficiencies for target micropollutants.Hence,process selection and optimization are crucial.This study developed a facilitated prediction method for the photon fluence-based rate constant for micropollutant degradation(K′_(p,MP))in various UV-AOPs by combining model simulation with portable measurement.Portable methods for measuring the scavenging capacities of the principal RRs(RRSCs)involved in UV-AOPs(i.e.,HO^(·),SO_(4)^(·-),and Cl^(·))using a mini-fluidic photoreaction system were proposed.The simulation models consisted of photochemical,quantitative structure–activity relationship,and radical concentration steady-state approximation models.The RRSCs were determined in eight test waters,and a higher RRSC was found to be associated with a more complex water matrix.Then,by taking sulfamethazine,caffeine,and carbamazepine as model micropollutants,the k′_(p,MP) values in various UV-AOPs were predicted and further verified experimentally.A lower k′_(p,MP) was found to be associated with a higher RRSC for a stronger RR competition;for example,k′_(p,MP) values of 130.9 and 332.5 m^(2) einstein^(–1),respectively,were obtained for carbamazepine degradation by UV/H_(2)O_(2) in the raw water(RRSC=9.47×10^(4) s^(-1))and sand-filtered effluent(RRSC=2.87×10^(4) s^(-1))of a drinking water treatment plant.The developed method facilitates process selection and optimization for UV-AOPs,which is essential for increasing the efficiency and cost-effectiveness of water treatment.

Decadal prediction skill for Eurasian surface air temperature in CMIP6 models

评估CMIP6年代际预测试验对季节平均SAT的预测技巧的结果表明:模式不能有效预测冬季和秋季SAT的年代际变率.IPSL-CM6A-LR和多模式集合平均对于春季SAT展现了预测技巧,其中对于变率的预测技巧好于振幅的结果.基于蒙古和我国华北地区的显著预测技巧,模式对于夏季SAT表现出最佳的预测水平.与外部强迫相比,模式对于SAT的预测技巧可能来自初始化.模式中的一个明显系统性误差值得注意,即模式中冬季SAT的变率可以持续到其他季节,而在观测中其他季节的SAT变化与冬季SAT相对独立.

Hybrid Seasonal Prediction of Meridional Temperature Gradient Associated with“Warm Arctic-Cold Eurasia”

The meridional gradient of surface air temperature associated with“Warm Arctic–Cold Eurasia”(GradTAE)is closely related to climate anomalies and weather extremes in the mid-low latitudes.However,the Climate Forecast System Version 2(CFSv2)shows poor capability for GradTAE prediction.Based on the year-to-year increment approach,analysis using a hybrid seasonal prediction model for GradTAE in winter(HMAE)is conducted with observed September sea ice over the Barents–Kara Sea,October sea surface temperature over the North Atlantic,September soil moisture in southern North America,and CFSv2 forecasted winter sea ice over the Baffin Bay,Davis Strait,and Labrador Sea.HMAE demonstrates good capability for predicting GradTAE with a significant correlation coefficient of 0.84,and the percentage of the same sign is 88%in cross-validation during 1983−2015.HMAE also maintains high accuracy and robustness during independent predictions of 2016−20.Meanwhile,HMAE can predict the GradTAE in 2021 well as an experiment of routine operation.Moreover,well-predicted GradTAE is useful in the prediction of the large-scale pattern of“Warm Arctic–Cold Eurasia”and has potential to enhance the skill of surface air temperature occurrences in the east of China.

Possible contribution of the PDO to the eastward retreat of the western pacific subtropical high

Previous studies have demonstrated that the western Pacific subtropical high(WPSH)has experienced an eastward retreat since the late 1970s.In this study,the authors propose that this eastward retreat of the WPSH can be partly attributed to atmospheric responses to the positive phase of the Pacific decadal oscillation(PDO),based on idealized SST forcing experiments using the Community Atmosphere Model,version 4.Associated with the positive phase of the PDO,convective heating from the Indian Peninsula to the western Pacific and over the eastern tropical Pacific has increased,which has subsequently forced a Gill-type response to modulate the WPSH.The resulting cyclonic gyre over the Asian continent and the western Pacific in the lower troposphere is favorable for the eastward retreat of the WPSH.Additionally,the resulting anticyclonic gyre in the upper troposphere is favorable for the strengthening and southward expansion of the East Asian westerly jet,which can modulate the jet-related secondary meridional-vertical circulation over the western Pacific and promote the eastward retreat of the WPSH.

Clinical Study of Acupuncture Combined with Emotional Intervention in Patients with Post-Stroke Depression

Objective:To investigate the clinical efficacy of acupuncture combined with emotional intervention in patients with post-stroke depression(PSD).Methods:A total of 100 patients with PSD who met the inclusion criteria were randomly divided into an experimental group(50 cases)and a control group(50 cases)using the random number table method,and the enrollment was in order of admission time.The control group used conventional treatment of oral antidepressant Deanxit tablets(0.5 mg flupenthixol+10 mg melitracen)with the dose appropriately adjusted according to the patient’s medication effect,and modern rehabilitation treatment given selectively according to the patient’s condition.The experimental group had similar treatment as the control group with the addition of traditional Chinese medicine(TCM)acupuncture combined with emotional intervention.The application effects of both groups before and after treatment were verified using the Hamilton Depression Rating Scale(Ham-D),National Institutes of Health Stroke Scale(NIHSS),and Activities of Daily Living(ADL),serotonin levels were measured,and statistical analyses were carried out.Results:The total effective rate of patients in the experimental group was significantly higher than that in the control group,and the Ham-D score,NIHSS score,ADL score,and serotonin level after treatment were significantly higher than those in the control group,and the difference between the two groups was statistically significant(P<0.05).Conclusion:For patients with PSD,adding TCM acupuncture with emotional intervention on top of conventional treatment significantly improve the clinical efficacy and better improve the daily life ability of patients.

The China Alzheimer Report 2022

China’s population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated,especially Alzheimer’s disease(AD)and related dementias(ADRD).AD’s incidence rate,morbidity,and mortality have steadily increased to make it presently the fifth leading cause of death among urban and rural residents in China and magnify the resulting financial burdens on individuals,families and society.The‘Healthy China Action’plan of 2019-2030 promotes the transition from disease treatment to health maintenance for this expanding population with ADRD.This report describes related epidemiological trends,evaluates the economic burden of the disease,outlines current clinical diagnosis and treatment status and delineates existing available public health resources.More specifically,it examines the public health impact of ADRD,including prevalence,mortality,costs,usage of care,and the overall effect on caregivers and society.In addition,this special report presents technical guidance and supports for the prevention and treatment of AD,provides expertise to guide relevant governmental healthcare policy development and suggests an information platform for international exchange and cooperation.

Verification and Improvement of the Ability of CFSv2 to Predict the Antarctic Oscillation in Boreal Spring

The boreal spring Antarctic Oscillation(AAO)has a significant impact on the spring and summer climate in China.This study evaluates the capability of the NCEP's Climate Forecast System,version 2(CFSv2),in predicting the boreal spring AAO for the period 1983-2015.The results indicate that CFSv2 has poor skill in predicting the spring AAO,failing to predict the zonally symmetric spatial pattern of the AAO,with an insignificant correlation of 0.02 between the predicted and observed AAO Index(AAOI).Considering the interannual increment approach can amplify the prediction signals,we firstly establish a dynamical-statistical model to improve the interannual increment of the AAOI(DY AAOI),with two predictors of CFSv2-forecasted concurrent spring sea surface temperatures and observed preceding autumn sea ice.This dynamical-statistical model demonstrates good capability in predicting DY AAOI,with a significant correlation coeffcient of 0.58 between the observation and prediction during 1983-2015 in the two-year-out cross-validation.Then,we obtain an improved AAOI by adding the improved DY AAOI to the preceding observed AAOI.The improved AAOI shows a significant correlation coeffcient of 0.45 with the observed AAOI during 1983-2015.Moreover,the unrealistic atmospheric response to March-April-May sea ice in CFSv2 may be the possible cause for the failure of CFSv2 to predict the AAO.This study gives new clues regarding AAO prediction and short-term climate prediction.

Midterm results of periprosthetic coiling embolization in high-risk patients

Background:With increasing interest in the prevention of typeⅡendoleaks(EⅡ),the aim of this study was to report midterm results on the intraoperative coiling embolization of the periprosthetic aneurysmal sac in patients at high-risk of EⅡ.Methods:A retrospective review study was conducted with 124 patients with infrarenal abdominal aortic aneurysm who accorded with the inclusion criteria,including 66 patients who underwent standard endovascular aortic aneurysm repair(Group A)and 58 patients who underwent aneurysmal sac coiling embolization(Group B).Baseline data and follow-up results were analyzed.Results:A mean of 2.84±1.45 coils(range 1-9)were used in Group B.The general incidence of an EⅡwas 15.32%(19/124)at a mean follow-up time of 46.60±15.14 months,with 22.7%(15/66)in Group A and 6.9%(4/58)in Group B(χ~2=5.62;P=0.018).Logistic multivariate analysis revealed that the independent risk factors of an EII were no sac embolization and a sac volume≥128 cm^3.The Kaplan-Meier subgroup analysis showed no difference in regard to the rate of freedom from EⅡbetween the two groups either with a larger or smaller sac.Conclusions:These results suggest that periprosthetic coiling embolization in patients at high-risk of EⅡis safe and effective in the prevention of EⅡ.The preventive effect seemed to be weakened when the sac volumes were taken into consideration at midterm follow-up.

Predicting climate anomalies:A real challenge

In recent decades,the damage and economic losses caused by climate change and extreme climate events have been increasing rapidly.Although scientists all over the world have made great efforts to understand and predict climatic variations,there are still several major problems for improving climate prediction.In 2020,the Center for Climate System Prediction Research(CCSP) was established with support from the National Natural Science Foundation of China.CCSP aims to tackle three scientific problems related to climate prediction—namely,El Ni?o-Southern Oscillation(ENSO) prediction,extended-range weather forecasting,and interannual-to-decadal climate prediction—and hence provide a solid scientific basis for more reliable climate predictions and disaster prevention.In this paper,the major objectives and scientific challenges of CCSP are reported,along with related achievements of its research groups in monsoon dynamics,land-atmosphere interaction and model development,ENSO variability,intraseasonal oscillation,and climate prediction.CCSP will endeavor to tackle key scientific problems in these areas.

A skillful method for precipitation prediction over eastern China

Precipitation prediction is essential for disaster prevention,yet it still remains a challenging issue in weather and climate studies.This paper proposes an effective prediction method for summer precipitation over eastern China(PEC) by combining empirical orthogonal function(EOF) analysis with the interannual increment approach.Three statistical prediction models are individually developed for respective predictions of the three principal components(PCs) corresponding to the three leading EOF modes for the interannual increment of PEC(hereafter DY;EC).Each model is run for the month of March with two previous predictors derived from sea-ice concentration/soil moisture/sea surface temperature/snow depth/sea level pressure over specific regions.The predicted PCs are projected to the EOF modes derived from observations of DY;EC to produce a new DY;EC.This new DY;EC is then added to the observed PEC of the previous year to obtain the final predicted PEC.The spatial features of the predicted PEC are highly consistent with observations,with the anomaly correlation coefficient skill ranging from 0.32 to 0.64 during 2012-2020.The method is applied for real-time prediction of PEC in 2021.And the results indicate two rain belts located over northeastern China and the Yangtze-Huaihe River valley,respectively,although the chance for the occurrence of a "super" mei-yu with a similar intensity to that in 2020 would be rare in 2021.

The rice miR171b–SCL6-IIs module controls blast resistance,grain yield,and flowering

Micro RNAs(mi RNAs)act as regulators of plant development and multiple stress responses.Here we demonstrate that the rice mi R171 b-SCL6-IIs module regulates the balance between blast resistance,grain yield,and flowering.mi R171 b-overexpressing rice plants(OX171 b)displayed increased rice blast resistance accompanied with enhanced defense responses and late heading,whereas blocking mi R171 b expression in rice(MIM171)led to greater susceptibility to blast disease,associated with compromised defense responses and early heading.Either overexpressing or silencing of mi R171 b significantly affected plant height and number of filled seeds per panicle(seed-setting rate),resulting in decreased grain yield.mi R171 b targets SCL6-IIa,SCL6-IIb,and SCL6-IIc,whose expression was suppressed in OX171 b but increased in MIM171.Mutants of SCL6-IIa,SCL6-IIb,and SCL6-IIc all displayed phenotypes like that of OX171 b,including markedly increased blast disease resistance,slightly decreased grain yield,and delayed flowering.Amounts of mi R171 b increased gradually in leaves during the vegetative stage but decreased gradually in panicles during the reproductive stage,whereas SCL6-IIs displayed the reverse expression pattern.Together,these results suggest that the expression of mi R171 b was time-and space-dependent during the rice growth period and regulated the balance between rice blast disease resistance,grain yield,and flowering via SCL6-IIs,and that appropriate accumulation of mi R171 b is essential for rice development.

Short-term effects of organic amendments on soil fertility and root growth of rubber trees on Hainan Island, China

Rubber[Hevea brasiliensis(Willd.ex A.Juss.)Müll.Arg.]plantations are the largest cultivated forest type in tropical China.Returning organic materials to the soil will help to maintain the quality and growth of rubber trees.Although many studies have demonstrated that organic waste materials can be used to improve soil fertility and structure to promote root growth,few studies have studied the eff ects of organic amendments on soil fertility and root growth in rubber tree plantations.Here,bagasse,coconut husk or biochar were applied with a chemical fertilizer to test their eff ects on soil properties after 6 months and compared with the eff ects of only the chemical fertilizer.Results showed that the soil organic matter content,total nitrogen,available phosphorus and available potassium after the chemical fertilizer(F)treatment were all signifi cantly lower than after the chemical fertilizer+bagasse(Fba),chemical fertilizer+coconut husk(Fco)or chemical fertilizer+biochar(Fbi)(p<0.05).Soil pH in all organic amendments was higher than in the F treatment,but was only signifi cantly higher in the Fbi treatment.In contrast,soil bulk density in the F treatment was signifi cantly higher than in treatments with the organic amendments(p<0.05).When compared with the F treatment,soil root dry mass increased signifi-cantly by 190%,176%and 33%in Fba,Fco and Fbi treatments,respectively(p<0.05).Similar results were found for root activity,number of root tips,root length,root surface area and root volume.Conclusively,the application of bagasse,coconut husk and biochar increased soil fertility and promoted root growth of rubber trees in the short term.However,bagasse and coconut husk were more eff ective than biochar in improving root growth of rubber trees.

Development of Mg-Al LDH and LDO as novel protective materials for deacidification of paper-based relics

Acidification of paper-based relics is a common problem,leading to their degradation and eventual loss.Paper deacidification is highly dependent on a limited variety of alkaline materials,and the development of new materials that are safe,efficient and easy-to-prepare is highly demanded to ensure a high level of safety and effective protection of paper-based relic.This study proposes the introduction of layered double hydroxide(LDH)and its calcined product,mixed metal oxide(layered double oxide(LDO)),as innovative protective materials for the deacidification of paper with varying levels of acidity.The results demonstrate that treatment with Mg-Al LDH/LDO can effectively modify the p H of acidic paper(e.g.,pH~4.0–6.4)to a neutral or weakly basic state,maintaining this desirable p H range even under long-term accelerated aging condition.Remarkably,LDH proves to be well-suited for the protection of slightly acidified paper(e.g.,pH>5.5),while LDO serves as an especially option for the deacidification of severely acidified paper(e.g.,pH≤5.5).During aqueous deacidification,due to the memory effect of the LDH-based materials,LDO is converted to rehydrated LDH,which creates a mild and appropriate alkaline retention in the paper,avoiding damage caused by strong alkalinity such as cellulose degradation and pigment fading during subsequent long-term natural preservation of the paper.Furthermore,Mg-Al LDH/LDO materials also exhibit flame-retardant and bacteriostatic properties.This opens up opportunities for the safe,efficient and multifunctional protection of acidified paper-based relics.

Copper-based nanomaterials as peroxidase candidates for intelligent colorimetric detection and antibacterial applications

With natural polyphenol compound tannic acid(TA)as the ingredient,copper tannate(CuTA)nanolayer material was formed by self-assembly under the conditions of heating and copper ion.Copper ion and tannic acid could coordinate to form Cu-O-C structure which was similar to the Fe-N-C structure of natural heme enzymes.In addition,the obtained CuTA nanomaterial possessed excellent peroxidase-like catalytic activity and stability.Based on this excellent enzymatic activity,CuTA nanomaterials could be used for colorimetric detection of hydrogen peroxide with a smartphone and decomposition of organic dyes.Based on the structural characteristics and catalytic activity,the copper tannate nanozymes could also serve as potential antibacterial reagents to effectively inhibit the growth of gram-negative and positive bacteria in a low hydrogen peroxide level.This work may promote the exploration of novel peroxidase mimetics and broaden the applications of nanozymes.

高产光学纯(R,R)-2,3-丁二醇工程菌株构建与发酵优化

[目的]构建能够专一性合成光学纯(R,R)-2,3-丁二醇的大肠杆菌工程菌,并进行发酵条件优化。[方法]将来源于多粘芽孢杆菌的(R,R)-2,3-丁二醇脱氢酶基因bdh,来源于阴沟肠杆菌的α-乙酰乳酸合成酶基因bud B和α-乙酰乳酸脱羧酶基因bud A与表达载体p Tr C99A连接,导入大肠杆菌中构建人工合成途径。筛选最适的培养基和发酵条件,提高(R,R)-2,3-丁二醇的产量、产率和得率。[结果]获得高效合成(R,R)-2,3-丁二醇的工程菌株GXASB,筛选到最适碳源及其浓度为120 g/L木薯淀粉,最适pH为6.5,最适接种量为10%,在发酵罐中进行同步糖化法发酵,(R,R)-2,3-丁二醇产量达到105.28 g/L,光学纯为99.1%,得率为0.47 g/g,生产强度为1.95 g/(L·h)。[结论]在大肠杆菌中表达基因簇bud B-bud A-bdh能够专一性合成光学纯(R,R)-2,3-丁二醇,经优化发酵条件后,能够显著提高(R,R)-2,3-丁二醇的合成效率。同时工程菌能够利用非粮原料木薯淀粉高效生产(R,R)-2,3-丁二醇,补料发酵产量达到105.28 g/L,为使用廉价原料工业化生产(R,R)-2,3-丁二醇提供参考。

Comparative evaluation of the impact of GRAPES and MM5 meteorology on CMAQ prediction over Pearl River Delta, China

The community multiscale air quality (CMAQ) model was used to forecast air quality over the Pearl River Delta region from December 2013 to January 2014.The pollution forecasting performance of CMAQ coupled with two different meteorological models,i.e.,the global/regional assimilation and prediction system (GRAPES) and the fifth-generation mesoscale model (MM5),was assessed by comparison with observational data.The effects of meteorological factors and physicochemical processes on the forecast results were discussed through process analysis.The results showed that both models exhibited good performance but that of GRAPES-CMAQ was better.GRAPES was superior in predicting the overall variation tendencies of meteorological fields,but it showed large deviations in atmospheric pressure and wind speed.This contributed to the higher correlation coefficients of the pollutants with GRAPES-CMAQ but with greater deviations.The underestimations of nitrate and ammonium salt contributed to the underestimations of both particulate matter and extinction coefficients.Source emissions made the only positive contributions to surface layer SO2,CO,and NO.It was found that O3 originated primarily from horizontal and vertical transport and that its consumption was predominantly via chemical processes.Conversely,NO2 was found derived primarily from chemical production.

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements （TEs） have no longer been totally considered as ＂junk DNA＂ for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Tech- nologies based on 3C （chromosome conformation capture） have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions （hESC： r= 0.9, P〈 2.2 × 10^16; IMRg0 fibroblasts： r= 0.94, P 〈 2.2 ×10^16） and also have asignificant positive correlation with some remote functional DNA elements like enhancers and promoters （Enhancer： hESC： r= 0.997, P= 2.3× 10^-4; IMR90： r- 0.934, P= 2 × 10^-2; Promoter： hESC： r= 0.995, P= 3.8 × 10^-4; IMR90： r= 0.996, P = 3.2 × 10^-4）. Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes.

A Possible Approach for Decadal Prediction of the PDO

The Pacific Decadal Oscillation(PDO)is a leading mode of decadal sea surface temperature variability in the North Pacific.Skillful PDO prediction can be beneficial in many aspects because of its global and regional impacts.However,current climate models cannot provide satisfied decadal prediction of the PDO and related decadal variability of sea surface temperature.In this study,we propose a new approach,i.e.,the increment method,to predicting the PDO.A series of validations demonstrate that the increment method is effective in improving decadal prediction of PDO and it can well capture the phase change of PDO with high accuracy.The prediction processes include three steps.First,a five-year smoothing is performed;second,effective preceding predictors for PDO are selected,with all predictors and predictands in the form of a three-year decadal increment(DI);third,the prediction model is set up for PDO three-year decadal increment(DI_PDO),and PDO prediction can be obtained by adding the predicted DI_PDO to the observed PDO three years ago.This new method can also be applied for decadal climate prediction of other modes(e.g.,Atlantic multidecadal oscillation)and predictands(e.g.,sea surface temperature).