粒细胞样髓源性抑制细胞在非小细胞肺癌中的研究进展

粒细胞样髓源性抑制细胞(granulocytic myeloid-derived suppressor cells,G-MDSCs)是MDSCs的主要亚群之一,在多数癌症中广泛富集,通过表达精氨酸酶1(arginase-1,Arg-1)及活性氧(reactive oxygen species,ROS)等机制抑制淋巴T细胞杀伤功能,重塑肿瘤免疫微环境,促进肿瘤的发生发展。近年来,越来越多的研究发现G-MDSCs与非小细胞肺癌患者的预后和免疫治疗疗效具有显著相关性,使用特异性靶向G-MDSCs的募集、分化和功能的药物能够有效抑制肿瘤的进展。本文主要就G-MDSCs在非小细胞肺癌中的免疫抑制作用及其相关通路靶向药物的研究进展进行综述。

EGFR-TKIs与二甲双胍联合治疗在非小细胞肺癌EGFR-TKIs获得性耐药中的研究进展

靶向表皮生长因子受体(epidermal growth factor receptor, EGFR)的EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors, EGFR-TKIs)对EGFR突变阳性的非小细胞肺癌(non-small cell lung cancer, NSCLC)患者具有较好的疗效,但是会不可避免地出现耐药问题。随着个体化和联合治疗的应用和拓展,越来越多的研究显示二甲双胍联合给药在临床治疗中有效解决了EGFR-TKIs获得性耐药的难题,并延长了NSCLC患者的生存期。EGFR-TKIs联合二甲双胍有望成为NSCLC患者出现EGFR-TKIs耐药后可选择的治疗方法,本文拟对EGFR-TKIs与二甲双胍联合治疗NSCLC EGFR-TKIs获得性耐药中的研究进展进行总结,以期为出现EGFR-TKIs获得性耐药的NSCLC患者的治疗提供新的思路。

NMR diffusion analysis of catalytic conversion mixtures from lignocellulose biomass using PSYCHE-iDOSY

The component analysis and structure characterization of complex mixtures of biomass conversion remain a challenging work.Hence,developing effective and easy to use techniques is necessary.Diffusion-ordered NMR spectroscopy(DOSY)is a non-selective and non-invasive method capable of achieving pseudo-separation and structure assignments of individual compounds from biomass mixtures by providing diffusion coefficients(D)of the components.However,the conventional 1H DOSY NMR is limited by crowded resonances when analyzing complex mixtures containing similar chemical structure resulting in similar coefficient.Herein we describe the application of an advanced diffusion NMR method,Pure Shift Yielded by CHirp Excitation DOSY(PSYCHE-iDOSY),which can record high-resolution signal diffusion spectra efficiently separating compounds in model and genuine mixture samples from cellulose,hemicellulose and lignin.Complicated sets of isomers(D-glucose/D-fructose/D-mannose and 1,2-/1,5-pentadiol),homologous compounds(ethylene glycol and 1,2-propylene glycol),model compounds of lignin,and a genuine reaction system(furfuryl alcohol hydrogenolysis with ring opening)were successfully separated in the diffusion dimension.The results show that the ultrahigh-resolution DOSY technique is capable of detecting and pseudo-separating the mixture components of C_(5)/C_(6) sugar conversion products and its derivative hydrogenation/hydrogenolysis from lignocellulose biomass.

Insights into electrochemical CO_2 reduction on tin oxides from first-principles calculations

Density functional theory calculations were used to unravel the mechanism of CO_2 electroreduction on SnO_x surfaces. Under highly reducing conditions(<-0.6 V vs. RHE), the SnO(101) surface with oxygen vacancies is likely the active phase for CO_2 reduction. We showed that the proton-electron transfer to adsorbed *CO_2 forming *OCHO, a key intermediate for producing HCOOH, is energetically more favorable than the formation of *COOH, justifying the selectivity trends observed on Sn-based electrocatalysts. With linear scaling relations, we propose the free formation energy of *CO_2 at the oxygen vacancy as the reactivity descriptor. By engineering the strain of the SnO(101) surface, the selectivity towards HCOOH can be further optimized at reduced overpotentials.

Cesium-rubidium mineralization in Himalayan leucogranites

This paper presents a study of a newly discovered pollucite-lepidolite-albite granite(PLAG)in the Himalayan leucogranite belt,which marks the first occurrence of pollucite,a major cesium silicate mineral,in the Himalayan orogenic belt(China).The rock appears at the northern part of the Gyirong pluton,coexisting with the tourmaline-bearing two-mica granite(TMG).Primary rare-metal minerals include lepidolite(Li),spodumene(Li),pollucite(Cs),cassiterite(Sn),and microlite(Ta).Micas,mainly lithian muscovite to lepidolite,contain 4.07 wt.%Li_2O and 0.76 wt.%Rb_2O on average.The average Li_2O content of the spodumene is 7.95 wt.%.Pollucite not only has an average Cs_2O content of 34 wt.%,but also has an elevated Rb_2O content of about 0.16 wt.%.Notably,this granite attains industrial grades for rare metals,specifically with Li_2O,Rb_2O,and Cs_2O contents of 0.49–1.19 wt.%,0.12–0.24 wt.%,and 0.69–2.33 wt.%,respectively.Dating results of magmatic accessory cassiterite and monazite indicated that the PLAG was formed at 19–18 Ma,slightly later than the TMG(22–20 Ma)of the Gyirong pluton.Thus,these two types of granites may form within the same magmatic system considering their pulsating intrusive contact,formation ages,and whole-rock and mineral chemical compositions.Furthermore,the abundant presence of pollucite suggests that the PLAG experienced high degrees of magmatic fractionation.In comparison to the Pusila spodumene pegmatite in the Himalaya and the Yashan topaz-lepidolite granite in Jiangxi,South China,the Gyirong PLAG exhibits different whole-rock and mineral compositions,resulting from differences in source materials and fractionation processes.Notably,the difference in fluorine(F)content may determine the degree of rare-metal element enrichment.The discovery of Gyirong PLAG highlights multiple stages and types of rare-metal mineralization in the Himalayan leucogranite belt,which is controlled by the South Tibetan Detachment System.The Cs-bearing geyserite deposit exposed along the Yarlung-Zangbo River,together with Himalayan leucogranites,constitutes two systems of rare-metal elements migration and enrichment.These two systems reflect the interaction among Earth systems across time and space,emphasizing how the Himalayan orogeny controls mineralization.As a result,the Himalayan leucogranite belt has considerable prospecting potential for cesium and rubidium resources and may be a crucial area for future exploration and resource utilization.

Dynamic modeling of tectonic carbon processes:State of the art and conceptual workflow

Plate tectonics plays a critical role in modulating atmospheric CO_(2)concentration on the geological timescale(≥106year).A growing consensus on tectonic and Earth’s CO_(2)history in the Cenozoic and deeper time provides solid restrictions and standards for testing tectonic carbon processes against global measurements.Despite this,modeling the causal relationship between tectonic events and atmospheric CO_(2)levels remains a challenge.We examine the current state of the global tectonic CO_(2)research and suggest a conceptual workflow for numerical experiments that integrates plate tectonics and deep carbon dynamics.Future tectonic carbon cycle modeling should include at least four modules:(1)simulation of carbon-carrying processes,such as carbon ingassing and outgassing at the scale of minerals;(2)calculation of CO_(2)fluxes in tectonic settings like subduction,mantle plume,and plate rifting;(3)reconstruction of carbon cycling within the plates-scale tectonic scenario,particularly involving the processes of supercontinent convergence and dispersion;and(4)comparison with atmospheric CO_(2)history data and iterations,aiming to find the coincidental link between different tectonic carbon fluxes and climate changes.According to our analysis,the recent advancements in each of the four modules have paved the path for a more general assembly.We envision that the large variety of carbon transportation parameters across more than ten orders of magnitude in both time and space is the primary technical hurdle in simulating tectonic carbon dynamics.We propose a boundary-condition-connected approach for simulating the global carbon cycle to realize carbon exchange between the solid earth and surface spheres.

Three Gorges Dam:the changing trend of snail density in the Yangtze River basin between 1990 and 2019

Background The area of Oncomelania hupensis snail remains around 3.6 billion m^(2),with newly emerging and reemergent habitats continuing to appear in recent years.This study aimed to explore the long-term dynamics of snail density before and after the operation of Three Gorges Dam(TGD).Methods Data of snail survey between 1990 and 2019 were collected from electronic databases and national schistosomiasis surveillance.Meta-analysis was conducted to estimate the snail density.Joinpoint model was used to identify the changing trend and inflection point.Inverse distance weighted interpolation(IDW)was used to determine the spatial distribution of recent snail density.Results A total of 3777 snail survey sites with a precise location of village or beach were identified.For the downstream area,snail density peaked in 1998(1.635/0.11 m^(2),95%CI:1.220,2.189)and fluctuated at a relatively high level before 2003,then declined steadily from 2003 to 2012.Snail density maintained lower than 0.150/0.11 m^(2) between 2012 and 2019.Joinpoint model identified the inflection of 2003,and a significant decreasing trend from 2003 to 2012 with an annual percentage change(APC)being−20.56%(95%CI:−24.15,−16.80).For the upstream area,snail density peaked in 2005(0.760/0.11 m^(2),95%CI:0.479,1.207)and was generally greater than 0.300/0.11 m2 before 2005.Snail density was generally lower than 0.150/0.11 m^(2) after 2011.Snail density showed a significant decreasing trend from 1990 to 2019 with an APC being−6.05%(95%CI:−7.97,−7.09),and no inflection was identified.IDW showed the areas with a high snail density existed in Poyang Lake,Dongting Lake,Jianghan Plain,and the Anhui branch of the Yangtze River between 2015 and 2019.Conclusions Snail density exhibited a fluctuating downward trend in the Yangtze River basin.In the downstream area,the operation of TGD accelerated the decline of snail density during the first decade period,then snail density fluctuated at a relatively low level.There still exists local areas with a high snail density.Long-term control and monitoring of snails need to be insisted on and strengthened.

Rapid denudation of the Himalayan orogen in the Nyalam area,southern Tibet, since the Pliocene and implications for tectonics–climate coupling

The Himalayan orogen characterized by very high variability in tectonic and climatic processes,and is thus regarded as a natural laboratory for investigating the coupling of tectonics and climate,as well as the influence of this coupling on geomorphological processes.This study uses apatite fission track(AFT)dating of samples from a45-km-long section crossing the Great Himalaya Crystalline Complex(GHC)in the Nyalam area,southern Tibet,to constrain the timing and rate of late Cenozoic denudation.The AFT ages can be divided into two groups:(1)15–6 Ma,to the north of Nyalam town,for which the bestfit line of elevation-age has a gentle slope of 0.05,and for which a denudation rate of 0.27 mm/a is calculated;and(2)3–1 Ma,south of Nyalam town,for which the best-fit line has a steep slope of 0.64,and for which a denudation rate of 1.32 mm/a is calculated.The whole AFT ages has a positive correlation with sample elevation(i.e.,older ages are found at higher elevations),and the geographical location of the point of inflexion of the two fitted lines corresponds closely to the junction of Poqu River near Nyalam town.By integrating the AFT data with thermotectonic modeling,it can be inferred that the GHC has experienced two different periods of denudation:(1)slow denudation during middle to late Miocene(15–6 Ma)is recorded in the northern part of the GHC;and(2)rapid denudation from the Pliocene to the Pleistocene(3–1 Ma)is recorded in the southern part of the GHC.An abrupt change in denudation rate occurred between the two periods,with the Pliocene–Pleistocene denudation rate being five times higher than that during the Miocene.This abrupt change in denudation rate during Pliocene pervaded the Himalayan orogen,and was roughly synchronous with a marked change in global climate at 4–3 Ma,and intensification of the Asian monsoon.Importantly,the later period of rapid denudation in the study region closely coupled to the mean annual precipitation,while there is no clear evidence for large-scale faulting activity and associated uplift during this period.Therefore,climate(precipitation)is inferred to be the main cause of the rapid denudation of the Himalayan orogen since the Pliocene.

Chemistry,Biosynthesis,and Biological Activity of Halogenated Compounds Produced by Marine Microorganisms

Natural products derived from marine microorganisms have been received great attention as a potential source of new compound entities for drug discovery.The unique marine environment brings us a large group of halogen-containing natural products with abundant biological functionality and good drugability.Meanwhile,biosynthetically halogenated reactions are known as a significant strategy used to increase the pharmacological activities and pharmacokinetic properties of compounds.Given that a tremendous increase in the number of new halogenated compounds from marine microorganisms in the last five years,it is necessary to summarize these compounds with their diverse structures and promising bioactivities.In this review,we have summarized the chemistry,biosynthesis(related halogenases),and biological activity of a total of 316 naturally halogenated compounds from marine microorganisms covering the period of 2015 to May 2021.Those reviewed chlorinated and brominated compounds with the ratio of 9:1 were predominantly originated from 36 genera of fungi(62%)and 9 bacterial strains(38%)with cytotoxic,antibacterial,and enzyme inhibitory activities,structural types of which are polyketides(38%),alkaloids(27%),phenols(11%),and others.This review would provide a plenty variety of promising lead halogenated compounds for drug discovery and inspire the development of new pharmaceutical agents.

Endogenous peroxynitrite activated fluorescent probe for revealing anti-tuberculosis drug induced hepatotoxicity

Py^(+)razinamide (PZA), isoniazid (INH) and rifampicin (RFP) are all commonly used anti-tuberculosis drugs in clinical practice, and long-term medication may cause severe liver damage and toxicity. The level of peroxynitrite (ONOO^(-)) generated in liver has long been regarded as a biomarker for the prediction and measurement of drug-induced liver injury (DILI). In this article, we constructed a BODIPY-based fluorescent probe (BDP-Py^(+)) that enabled quickly and sensitively detect and image ONOO^(-) in vivo. Utilizing this probe, we demonstrated the change of ONOO^(-) content in cells and mice model of DILI induced by acetaminophen (APAP), and for the first time revealed the mechanism of liver injury induced by antituberculosis drug PZA. Moreover, BDP-Py^(+) could be applied to screen out and evaluate the hepatotoxicity of different anti-tuberculosis drugs. Comparing with the existing serum enzymes detection and H&E staining, the probe could achieve early diagnosis of DILI before solid lesions in liver via monitoring the up-regulation of ONOO^(-) levels. Collectively, this work will promote the understanding of the pathogenesis of anti-tuberculosis drug induced liver injury (ATB-DILI), and provide a powerful tool for the early diagnosis and treatment of DILI.

Sulfate Binding with a Tripodal Tris（4-pyridylurea） Receptor

The tris（2-aminoethyl）amine （tren）-based tris（4-pyridylurea） receptor L has been synthesized and its anion binding properties were studied. The ligand forms a 2 ： 1 （host/guest） complex with MgSO4, [SO4^2 L2], in which a sulfate ion is encapsulated by six urea groups from the two ligands through multiple hydrogen bonds. The metal ions do not coordinate to the pyridyl groups but exist as the hydrate [Mg（H2O）6]2＋ and interact with the [SO4 L2] capsules in the outer coordination sphere to form a three dimensional extended structure. The anion binding behav- ior of ligand L in solution was studied.

Elastic organic crystals with ultralong phosphorescence for flexible anti-counterfeiting

Ultralong organic phosphorescence(UOP)crystals have attracted increased attention due to the distinct photophysical property of a long-lived lifetime.However,organic crystals are generally brittle,leading to a serious problem for their application in flexible technology.Herein,we report three types of elastic organic crystals(EOCs)with ultralong phosphorescence via introducing halogen atoms(Cl,Br,I)intoπ-conjugated phosphorescent molecules.Especially,the crystal containing iodine atoms displayed both excellent elasticity(ε=3.01%)and high phosphorescent efficiency(Φ_(Ph)=19.1%)owing to the strong halogen bonds.Taking advantage of its highly efficient UOP and excellent elasticity,we successfully used a DCz4I crystal for anti-counterfeiting application.These findings may provide guidance for the development of elastic crystals with afterglow and expand the scope of potential applications on flexible materials.

Characteristics of Lung Function and Prevalence of Airflow Obstruction Among Individuals Aged 18–74 Years-Beijing,China,2017–2018

What is already known about this topic?Airflow obstruction is the hallmark of many chronic respiratory diseases and may indicate the potential for the development of other progressive diseases.There are currently no representative studies of lung function in Beijing.An up-to-date estimation of the characteristics of lung function and airflow obstruction is thus needed.What is added by this report?The estimated prevalence of airflow obstruction was 14.68%in Beijing,2017–2018.The values of vital capacity,forced vital capacity,and forced expiratory volume in the first second were 3.09 L,2.66 L,2.22 L,respectively.What are the implications for public health practice?Effective public health strategy for lung in Beijing should target older people,current or former smokers,and individuals who live in urban environments,have a low education level,exhibit a high smoking index,and/or have an abnormal body mass index.