Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

GA Associated Dwarf 5 encodes an ent-kaurenoic acid oxidase required for maize gibberellin biosynthesis and morphogenesis

Gibberellin(GA)functions in plant growth and development.However,genes involved in the biosynthesis and regulation of GA in crop plants are poorly understood.We isolated the mutant gad5-1(GAAssociated Dwarf 5),characterized by dwarfing,short internodes,and dark green and short leaves.Map-based gene cloning and allelic verification confirmed that ZmGAD5 encodes ent-kaurenoic acid oxidase(KAO),which catalyzes KA(ent-kaurenoic acid)to GA12 conversion during GA biosynthesis in maize.ZmGAD5 is localized to the endoplasmic reticulum and is present in multiple maize organs.In gad5-1,the expression of ZmGAD5 is severely reduced,and the levels of the direct substrate of KAO,KA,is increased,leading to a reduction in GA content.The abnormal phenotype of gad5-1 was restored by exogenous application of GA3.The biomass,plant height,and levels of GA12 and GA3 in transgenic Arabidopsis overexpressing ZmGAD5 were increased in comparison with the corresponding controls Col-0.These findings deepen our understanding of genes involved in GA biosynthesis,and could lead to the development of maize lines with improved architecture and higher planting-density tolerance.

Ultrasound assisted crystallization of cephalexin monohydrate:Nucleation mechanism and crystal habit control

With the high-quality requirements for cephalexin monohydrate,developing a robust and practical crystallization process to produce cephalexin monohydrate with good crystal habit,appropriate aspect ratio and high bulk density as well as suitable flowability is urgently needed.This research has explored the influence of ultrasound on crystallization of cephalexin monohydrate in terms of nucleation mechanism and crystal habit control.The results of metastable zone width and induction time measurement showed the presence of ultrasound irradiation can narrow the metastable zone and shorten induction time.Cavitation phenomena generated by ultrasound were used to qualitatively explain the mechanism of ultrasound promoting nucleation of cephalexin monohydrate.Furthermore,on the basis of classical nucleation theory and induction time data,a series of nucleation-related parameters(such as crystalliquid interfacial tension,radius of the critical nucleus and etc.)were calculated and showed a decreasing trend under ultrasound irradiation.The diffusion coefficient of the studied system was also determined to increase by 72.73%under ultrasound.The changes in these parameters have quantitatively confirmed the mechanism of ultrasound influence on the nucleation process.In further,the calculated surface entropy factor has confirmed that the growth of cephalexin monohydrate follows continuous growth mechanism under the research conditions of this work.Through the exploration of crystallization conditions,it is found that suitable ultrasonic treatment,seeding,supersaturation control and removal of fine crystals are conducive to improving the quality of cephalexin monohydrate product.Optimizing the crystallization process coupled continuous ultrasound irradiation with fine-crystal dissolution policy has achieved the controllable production of monodisperse cephalexin monohydrate crystal with good performance.

Recent progress of the ECRH system and initial experimental results on the J-TEXT tokamak

In order to broaden the range of the plasma parameters and provide experimental conditions for physical research into high-performance plasma,the development of the electron cyclotron resonance heating(ECRH) system for the J-TEXT tokamak was initiated in 2017.For the first stage,the ECRH system operated successfully with one 105 GHz/500 kW/1 s gyrotron in 2019.More than 400 kW electron cyclotron(EC) wave power has been injected into the plasma successfully,raising the core electron temperature to 1.5 keV.In 2022,another 105 GHz/500 kW/1 s gyrotron completed commissioning tests which signifies that the ECRH system could generate an EC wave power of 1 MW in total.Under the support of the ECRH system,various physical experiments have been carried out on J-TEXT.The electron thermal transport in ECRH plasmas has been investigated.When ECRH is turned on,the electron thermal diffusivity significantly increases.The runaway current is elevated when a disruption occurs during ECRH heating.When the injected EC wave power is 400 kW,the conversion efficiency of runaway current increases from 35% to 75%.Fast electron behavior is observed in electron cyclotron current drive(ECCD) plasma by the fast electron bremsstrahlung diagnostic(FEB).The increase in the FEB intensity implies that ECCD could generate fast electrons.A successful startup with a 200 kW ECW is achieved.With the upgrade of the ECRH system,the J-TEXT operational range could be expanded and further relevant research could be conducted.

Study of the fast electron behavior in electron cyclotron current driven plasma on J-TEXT

In J-TEXT tokamak,fast electron bremsstrahlung diagnostic with 9 chords equipped with multichannel analyzer enables detailed studies of the generation and transport of fast electrons.The spatial profiles and energy spectrum of the fast electrons have been measured in two ECCD cases with either on-axis or off-axis injection,and the profiles processed by Abel-inversion are consistent with the calculated power deposition locations.Moreover,it is observed that the energy of fast electrons increases rapidly after turning off the ECCD,which may be attributed to the acceleration by the recovered loop voltage at low electron density.

Investigation of electron cyclotron current drive efficiency on the J-TEXT tokamak

Electron cyclotron current drive(ECCD) efficiency research is of great importance for the neoclassical tearing mode(NTM) stabilization.Improving ECCD efficiency is beneficial for the NTM stabilization and the ECCD power threshold reduction.ECCD efficiency has been investigated on the J-TEXT tokamak.The electron cyclotron wave(ECW) power scan was performed to obtain the current drive efficiency.The current drive efficiency is derived to be approximately η_(0)=(0.06-0.16)×10^(19)A m^(-2)W^(-1)on the J-TEXT tokamak.The effect of the residual toroidal electric field has been included in the determination of the current drive efficiency,which will enhance the ECCD efficiency.At the plasma current of I_(p)=100 kA and electron density of n_(e)=1.5×10^(19)m^(-3),the ratio of Spitzer conductivity between omhic(OH)and ECCD phases is considered and the experimental data have been corrected.The correction results show that the current drive efficiency η_(1)caused by the fast electron hot conductivity decreases by approximately 79%.It can be estimated that the driven current is approximately 24 kA at 300 kW ECW power.

Countermeasures and Recommendations for High Quality Development of Tan Sheep Industry in Ningxia

Tan sheep industry is a characteristic and superior agricultural industry in Ningxia,and it is also an enriching industry that helps in poverty alleviation and increases farmers’income.The local government has been committing to building the"Yanchi Tan Sheep"brand and has made remarkable achievements.In order to explore the resource efficiency and quality of Tan sheep industry,the current situations and advantages of brand development,this paper made an empirical research through field investigations.The research was mainly concentrated on breeding scale,industrial integration,brand building,breeding benefits,and policy support.After a comprehensive evaluation,it came up with the recommendation that the Tan sheep industry should take the high-quality,high-end and green development road.

Changes of calcitonin gene-related peptide and other serological indicators in vestibular migraine patients

Objective:It aims to evaluate the diagnostic ability of CGRP and other blood indicators in vestibular migraine(VM)patients,and to explain the potential pathological effects of these biomarkers.The hypothesis of VM being a variant of migraine was examined.Methods:A total of 32 VM patients,35 migraine patients,and 30 healthy control subjects(HC)were selected for this cross-sectional study.Detailed statistics on demographic data,clinical manifestations,calcitonin gene-related peptide(CGRP)and common clinical laboratory indicators were measured within 24 hours from the onset of the conditions.Receptor operating characteristic(ROC)curve and area under the curve(AUC)were analyzed for biomarkers.The risk factors of VM and migraine were determined through univariate and multivariate analyses.Results:Compared with HC,serum CGRP levels(p(VM)=0.012,p(Migraine)=0.028)increased and Mg^(2+)levels(p(VM)<0.001,p(Migraine)<0.001)deceased in VM patients and migraine patients.In multiple logistic regression,VM was correlated with CGRP[odds ratio(OR)=1.07;95%confidence interval(CI),1.02-1.12;P=0.01]and Mg^(2+)[odds ratio(OR)=0.03;95%CI,0.07-0.15;P<0.001].Migraine was correlated with CGRP[odds ratio(OR)=1.07;95%CI,1.02-1.12;P=0.01]and Mg^(2+)[odd ratio(OR=0.01;95%CI,0-0.02;P<0.001)].Mg^(2+)discriminated good differentiation between VM and migraine groups,with AUC of 0.649(95%CI,0.518 to 0.780).The optimal threshold for Mg^(2+)to diagnose VM was 0.805.Conclusions:This study demonstrated that CGRP and Mg^(2+)may be promising laboratory indicators to discriminate HC from VM/migraine,while Mg^(2+)may be uded as a discriminator between VM and migraine.

Phosphorylation of KAT-2B by WKS1/Yr36 redirects the lipid flux to jasmonates to enhance resistance against wheat stripe rust

Wheat(Triticum aestivum)is one of the most essential human energy and protein sources.However,wheat production is threatened by devastating fungal diseases such as stripe rust,caused by Puccinia striiformis Westend.f.sp.tritici(Pst).Here,we reveal that the alternations in chloroplast lipid profiles and the accumulation of jasmonate(JA)in the necrosis region activate JA signaling and trigger the host defense.The collapse of chloroplasts in the necrosis region results in accumulations of polyunsaturated membrane lipids and the lipid-derived phytohormone JA in transgenic lines of Yr36 that encodes Wheat Kinase START 1(WKS1),a high-temperature-dependent adult plant resistance protein.WKS1.1,a protein encoded by a full-length splicing variant of WKS1,phosphorylates and enhances the activity of keto-acyl thiolase(KAT-2B),a critical enzyme catalyzing theβ-oxidation reaction in JA biosynthesis.The premature stop mutant,kat-2b,accumulates less JA and shows defects in the host defense against Pst.Conversely,overexpression of KAT-2B results in a higher level of JA and limits the growth of Pst.Moreover,JA inhibits the growth and reduces pustule densities of Pst.This study illustrates the WKS1.1-KAT-2B-JA pathway for enhancing wheat defense against fungal pathogens to attenuate yield loss.

VAMP726 from maize and Arabidopsis confers pollen resistance to heat and UV radiation by influencing lignin content of sporopollenin

Sporopollenin in the pollen cell wall protects male gametophytes from stresses.Phenylpropanoid derivatives,including guaiacyl(G)lignin units,are known to be structural components of sporopollenin,but the exact composition of sporopollenin remains to be fully resolved.We analyzed the phenylpropanoid derivatives in sporopollenin from maize and Arabidopsis by thioacidolysis coupled with nuclear magnetic resonance(NMR)and gas chromatography–mass spectrometry(GC–MS).The NMR and GC–MS results confirmed the presence of p-hydroxyphenyl(H),G,and syringyl(S)lignin units in sporopollenin from maize and Arabidopsis.Strikingly,H units account for the majority of lignin monomers in sporopollenin from these species.We next performed a genome-wide association study to explore the genetic basis of maize sporopollenin composition and identified a vesicle-associated membrane protein(ZmVAMP726)that is strongly associated with lignin monomer composition of maize sporopollenin.Genetic manipulation of VAMP726 affected not only lignin monomer composition in sporopollenin but also pollen resistance to heat and UV radiation in maize and Arabidopsis,indicating that VAMP726 is functionally conserved in monocot and dicot plants.Our work provides new insight into the lignin monomers that serve as structural components of sporopollenin and characterizes VAMP726,which affects sporopollenin composition and stress resistance in pollen.

Suppression of ZEAXANTHIN EPOXIDASE 1 restricts stripe rust growth in wheat

Reducing losses caused by pathogens is an effective strategy for stabilizing crop yields.Daunting challenges remain in cloning and characterizing genes that inhibit stripe rust,a devastating disease of wheat(Triticum aestivum)caused by Puccinia striiformis f.sp.tritici(Pst).We found that suppression of wheat zeaxanthin epoxidase 1(ZEP1)increased wheat defense against Pst.We isolated the yellow rust slower 1(yrs1)mutant of tetraploid wheat in which a premature stop mutation in ZEP1-B underpins the phenotype.Genetic analyses revealed increased H_(2)O_(2) accumulation in zep1 mutants and demonstrated a correlation between ZEP1 dysfunction and slower Pst growth in wheat.Moreover,wheat kinase START 1.1(WKS1.1,Yr36)bound,phosphorylated,and suppressed the biochemical activity of ZEP1.A rare natural allele in the hexaploid wheat ZEP1-B promoter reduced its transcription and Pst growth.Our study thus identified a novel suppressor of Pst,characterized its mechanism of action,and revealed beneficial variants for wheat disease control.This work opens the door to stacking wheat ZEP1 variants with other known Pst resistance genes in future breeding programs to enhance wheat tolerance to pathogens.

芥菜HDA9突变体构建及其与开花整合子SOC1、AGL24启动子互作

芥菜HDA9是去乙酰化酶家族成员,能通过开花信号整合子(SOC1、AGL24)调控开花时间,但其深入的分子调控机制仍不清楚。利用重叠延伸PCR将芥菜HDA9的3个关键活性位点(Asp172、His174和Asp261)分别突变为Ala,构建氨基酸位点突变体HDA9D172A、HDA9H174A和HDA9D261A。进一步将突变体融合到pGADT7载体,酵母单杂交表明,HDA9突变后仍能与开花整合子SOC1、AGL24的启动子结合。双荧光素酶系统深入检测发现,尽管HDA9D172A、HDA9H174A和HDA9D261A与SOC1、AGL24启动子的结合仍存在,但作用强度均显著减弱。由此暗示,芥菜HDA9的第172、174和261这3个关键活性位点可在一定程度上调节它与开花整合子的相互作用。这为HDA9开花分子调控及功能解析等深入研究奠定了基础。

Development of an activity-directed selection system enabled significant improvement of the carboxylation efficiency of Rubisco

Photosynthetic CO2 fixation is the ultimate source of organic carbon on earth and thus is essential for crop production and carbon sequestration, Ribulose-1,5-bis- phosphate carboxylase/oxygenase （Rubisco） catalyzes the first step of photosynthetic CO2 fixation. However, the extreme low carboxylation efficiency of Rubisco makes it the most attractive target for improving pho- tosynthetic efficiency. Extensive studies have focused on re-engineering a more efficient enzyme, but the effort has been impeded by the limited understanding of its structure-function relationships and the lack of an effi- cient selection system towards its activity. To address the unsuccessful molecular engineering of Rubisco, we developed an Escherichia coil-based activity-directed selection system which links the growth of host cell solely to the Rubisco activity therein. A Synechococcus sp. PCC7002 Rubisco mutant with E49V and D82G sub- stitutions in the small subunit was selected from a total of 15,000 mutants by one round of evolution. This mutant showed an 85% increase in specific carboxyla- tion activity and a 45% improvement in catalytic efficiency towards CO2. The small-subunit E49V mutation was speculated to influence holoenzyme catalysis through interaction with the large-subunit Q225. This interaction is conserved among various Rubisco from higher plants and Chlamydomonas reinhardtii. Knowledge of these might provide clues for engineering Rubisco from higher plants, with the potential of increasing the crop yield.

Main Mechanism for Generating Overpressure in the Paleogene Source Rock Series of the Chezhen Depression,Bohai Bay Basin, China

The Chezhen depression,located in the south of Bohai Bay Basin,is an oil-producing basin in China. The third and fourth members of the Shahejie Formation(E(s3) and E(s4)) are the main source rock series in the Chezhen depression. Widespread overpressures occurred in the E(s3) and E(s4) from the depths of approximately 2 000 to 4 600 m,with the maximum pressure coefficient of 1.98 from drillstem tests(DST). Among the sonic,resistivity and density logs,sonic-log is the only reliable pressure indicator and can be used to predict the pore pressure with Eaton's method. All the overpressured mudstones in the source rock series have higher acoustic traveltimes compared with normally pressured mudstones at a given depth. The overpressured mudstones in the E(s3) and E(s4) units are characterized by a normal geothermal gradient,high average density values up to 2.5 g/cm^3,strong present-day hydrocarbon generation capability,abundant mature organic matter and high contents of residual hydrocarbons estimated by the Rock-Eval S1 values and chloroform-soluble bitumen "A" values. All suggest that the dominant mechanism for overpressure in the mudstones of source rock series in the Chezhen depression is hydrocarbon generation. A comparison between the matrix porosity of the normally pressured sandstones and overpressured sandstones,the quantitative evaluation of porosity loss caused by compaction and the conventional thin section inspection demonstrate that the sandstones in the Chezhen depression were normally compacted. The high contents of hydrocarbons in the overpressured reservoirs prove that the overpressure in the sandstones of the source rock series was caused by pressure transmission from the source rocks.

Research advances on antioxidation,neuroprotection,and molecular mechanisms of Lycium barbarum polysaccharides

Lycium barbarum polysaccharides(LBPs)are the major polysaccharides extracted from L.barbarum,which is used in traditional Chinese medicine(TCM)for treating diseases.Studies have shown that LBPs have important biological activities,such as antioxidation,anti-aging,neuroprotection,immune regulation.LBPs inhibit oxidative stress,improve neurodegeneration and stroke-induced neural injury,increase proliferation and differentiation of neural stem cell,and promote neural regeneration.Here we have reviewed latest advances in the biomedical activities of LBPs and improved methods for the isolation,extraction,and purification of LBPs.Then,new discoveries to decrease oxidative stress and cellular apoptosis,inhibit aging progress,and improve neural repair in neurodegeneration and ischemic brain injury have been discussed in detail through in vitro cell culture and in vivo animal studies.Importantly,the molecular mechanisms of LBPs in playing neuroprotective roles are further explored.Lastly,we discuss the perspective of LBPs as biomedical compounds in TCM and modern medicine and provide the experimental and theoretical evidence to use LBPs for the treatment of aging-related neurological diseases and stroke-induced neural injuries.

纳米碳标记对肥胖胃癌患者根治术淋巴结获取数目的影响

目的探讨纳米碳标记对肥胖胃癌患者根治术后淋巴结获取数目的影响。方法回顾性分析2015年1月至2019年12月期间在郑州大学附属肿瘤医院接受胃癌D2根治术127例肥胖患者的临床资料,依据患者术中是否注射纳米碳分为2组:64例患者术中未注射纳米碳者设为对照组,63例患者术中注射纳米碳者设为研究组,分析两组的术中情况及术后淋巴结获取情况。结果对照组手术时间(160±31)min,研究组手术时间(168±28)min,差异无统计学意义(t=-1.521 P=0.445);对照组术中出血量为(234±82)ml,研究组术中出血量(238±84)ml,差异无统计学意义(t=-0.295,P=0.846)。淋巴结检出情况:对照组在第一站淋巴结检出数目、第二站淋巴结检出数目、总淋巴结检出数目、直径<5 mm淋巴结数目方面均少于研究组[(10.4±3.8)枚比(24.5±10.6)枚,t=-10.054;(6.6±2.8)枚比(16.8±7.3)枚,t=-10.381;(17.1±6.4)枚比(41.2±17.6)枚,t=-10.293;(3.9±2.5)枚比(21.2±9.1)枚,t=-14.662],差异均有统计学意义(均P<0.05)。研究组在阳性淋巴结检出数目方面多于对照组[(5.9±6.2)枚比(4.2±3.4)枚,t=-1.963],但两组差异无统计学意义(P>0.05)。研究组共检出黑染淋巴结1542枚,淋巴结黑染率59.44%(1542/2594)。结论术中纳米碳的应用可显著提高肥胖(BMI≥25 kg/m^(2))胃癌患者根治术后淋巴结的获取数目,其临床意义有待进一步明确。

Effectiveness of aerobic pretreatment of municipal solid waste for accelerating biogas generation during simulated landfilling

This study evaluates the effectiveness of aerobic pretreatment of municipal solid waste （MSW） on reducing lag phase and accelerating biogas generation. Aerobic pretreatment degree （APD） was determined on the basis of reduction in volatile solids （VS） on a wet weight basis. In this study, intermittent aeration （IA） was applied to three reactors as a main aeration mode; since a single reactor was operated under continuous aeration mode. However, the purpose of the experiment was to reduce VS content of waste, irrespective of the comparison between aeration modes. Fresh MSW was first pretreated aerobically with different aeration rates （10, 40, 60 and 85 L/min/m3） for the period of 30- 50 days, resulting in VS-loss equivalent to 20%, 27%, 38% and 53q4 on w/w basis for the wastes AI, A2, A3 and A4, respectively. The cumulative biogas production, calculated based on the modified Gompertz model were 384, 195, 353,215, and 114 L/kg VS for the wastes A0, A1, A2, A3 and A4, respectively. Untreated waste （A0） showed a long lag phase; whereas the lag phases of pretreated MSW were reduced by more than 90e/L Aerobically pretreated wastes reached stable methanogenic phase within 41 days compared to 418 days for untreated waste. The waste mass decreased by about 8% to 27% compared to untreated MSW, indicative that even more MSW could be placed in the same landfill. The study confirmed the effectiveness of aerobic pretreatment of MSW prior to landfilling on reducing lag phase and accelerating biogas generation.