Crohn’s disease as the intestinal manifestation of pan-lymphatic dysfunction:An exploratory proposal based on basic and clinical data

Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

Investigation of Ga_(2)O_(3)/diamond heterostructure solar-blind avalanche photodiode via TCAD simulation

A Ga_(2)O_(3)/diamond separate absorption and multiplication avalanche photodiode(SAM-APD)with mesa structure has been proposed and simulated.The simulation is based on an optimized Ga_(2)O_(3)/diamond heterostructure TCAD physical model,which is revised by repeated comparison with the experimental data from the literature.Since both Ga_(2)O_(3)and diamond are ultra-wide bandgap semiconductor materials,the Ga_(2)O_(3)/diamond SAM-APD shows good solar-blind detection ability,and the corresponding cutoff wavelength is about 263 nm.The doping distribution and the electric field distribution of the SAM-APD are discussed,and the simulation results show that the gain of the designed device can reach 5×10^(4)and the peak responsivity can reach a value as high as 78 A/W.

Prognostic role of the ABO blood types in Chinese patients with curatively resected non-small cell lung cancer:a retrospective analysis of 1601 cases at a single cancer center

Background:A positive association between the ABO blood types and survival has been suggested in several malignancies.The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of Chinese patients with curatively resected non-small cell lung cancer(NSCLC).Methods:We retrospectively analyzed 1601 consecutive Chinese patients who underwent curative surgery for NSCLC between January 1,2005 and December 31,2009.The relationship between the ABO blood types and survival was investigated.In addition,univariate and multivariate analyses were performed.Results:Group 1(patients with the blood type O or B) had significantly prolonged overall survival(OS) compared with group 2(patients with the blood type A or AB),with a median OS of 74.9 months versus 61.5 months[hazard ratio(HR) 0.83;95%confidence interval(CI) 0.72-0.96;P = 0.015].Additionally,group 1 had significantly longer disease-free survival(DFS;HR 0.86;95%CI 0.76-0.98;P = 0.022) and locoregional relapse-free survival(LRFS;HR 0.79;95%CI 0.64-0.98;P = 0.024) than group 2.The association was not significantly modified by other risk factors for NSCLC,including smoking status,pathologic tumor-node-metastasis stage,pT category,pN category,and chemotherapy.Conclusions:There is an association between the ABO blood types and the survival of Chinese patients with resected NSCLC.Patients with the blood type O or B had significantly prolonged OS,DFS,and LRFS compared with those with the blood type A or AB.

Diabetes and gut microbiota

The prevalence of diabetes has increased rapidly throughout the world in recent years.Currently,approximately 463 million people are living with diabetes,and the number has tripled over the last two decades.Here,we describe the global epidemiology of diabetes in 2019 and forecast the trends to 2030 and 2045 in China,India,USA,and the globally.The gut microbiota plays a major role in metabolic diseases,especially diabetes.In this review,we describe the interaction between diabetes and gut microbiota in three aspects:probiotics,antidiabetic medication,and diet.Recent findings indicate that probiotics,antidiabetic medications,or dietary interventions treat diabetes by shifting the gut microbiome,particularly by raising beneficial bacteria and reducing harmful bacteria.We conclude that targeting the gut microbiota is becoming a novel therapeutic strategy for diabetes.

Therapeutic potentials of fasudil in liver fibrosis

Fasudil has the potential to prevent liver fibrosis by activating natural killer cells and inhibiting the proliferation of hepatic stellate cells.Fasudil may be a promising clinical therapeutic drug for the prevention and treatment of liver fibrosis.

Nano-friction phenomenon of Frenkel-Kontorova model under Gaussian colored noise

The nano-friction phenomenon in a one-dimensional Frenkel-Kontorova(FK)model under Gaussian colored noise is investigated by using the molecular dynamic simulation method.The role of colored noise is analyzed through the inclusion of a stochastic force via a Langevin molecular dynamics method.Via the stochastic Runge-Kutta algorithm,the relationship between different parameter values of the Gaussian colored noise(the noise intensity and the correlation time)and the nano-friction phenomena such as hysteresis,the maximum static friction force is separately studied here.Similar results are obtained from the two geometrically opposed ideal cases:incommensurate and commensurate interfaces.It was found that the noise strongly influences the hysteresis and maximum static friction force and with an appropriate external driving force,the introduction of noise can accelerate the motion of the system,making the atoms escape from the substrate potential well more easily.Interestingly,suitable correlation time and noise intensity give rise to super-lubricity.It is noteworthy that the difference between the two circumstances lies in the fact that the effect of the noise is much stronger on triggering the motion of the FK model for the commensurate interface than that for the incommensurate interface.

H101对胃癌细胞增殖、迁移、凋亡的调控作用及其相关机制研究

背景溶瘤病毒作为治疗癌症的新手段,具有疗效快,靶向性强,无细胞毒性等特点,H101作为商品化上市的溶瘤病毒表现出了稳定的抗癌特效,为中晚期胃癌患者的腹膜转移治疗提供了可能.目的探讨H101对胃癌细胞增殖、迁移、凋亡的调控作用及其相关机制研究.方法将BGC-823和SGC-7901两种胃癌细胞系培养在6孔板中,分别加入感染复数(multiplicity of infection,MOI)值为1、5、10、15的H101,作用48 h后,用MTS法检测细胞的存活率,免疫印迹法(western blot,WB)检测腺病毒早期区1(adenovirus early region 1,E1A)的表达.选取SGC-7901细胞,用划痕法检测各组细胞48 h的迁移率,Hoechst33342染液,观察H101作用48 h后凋亡小体的形成情况.Western blot检测细胞凋亡相关蛋白的表达.结果WB结果显示,H101中的EIA表达量比对照组更高,差异具有统计学意义(P<0.05).MTS结果显示与MOI值为1时相比,MOI值为15的时候,H101在体外可以明显杀伤BGC-823和SGC-79012种胃癌肿瘤细胞(P<0.05).在增殖实验中发现相对于BGC-823细胞,SGC-7901细胞对H101的敏感性更差,因此选取敏感性相对较差的SGC-7901细胞作为研究重点.48 h后,与对照组和MOI=1组的迁移距离相比,MOI=5组,MOI=10组和MOI=15组的迁移距离明显更低,(P均<0.05).与MOI=1组相比,MOI=5、MOI=10和MOI=15组的凋亡小体数量更多(P均<0.05),与对照组和MOI=1组相比,MOI=5、MOI=5和MOI=10组的B淋巴细胞瘤-2蛋白(B-cell lymphoma-2,Bcl-2)表达量较低(P均<0.05),而凋亡蛋白(BCL2-associated X,Bax)、半胱氨酸蛋白酶-3(cysteinyl aspartate specific proteinase-3,Caspase-3)表达量均更高(P均<0.05).结论H101能够抑制胃癌细胞的增殖、迁移,提高细胞凋亡相关蛋白的表达量,加速细胞的凋亡.

New strategies for asymmetric photocatalysis: asymmetric organocatalytic/photoredox relay catalysis for efficient synthesis of polycyclic compounds containing vicinal amino alcohols

An asymmetric catalytic strategy in photocatalysis utilizing a chirality-induced approach through an organocatalytic/photoredox relay catalysis strategy is successfully achieved for the rapid construction of polycyclic compounds containing vicinal amino alcohols in a one-pot protocol. This methodology facilitates the efficient synthesis of diverse substituted polycyclic tetrahydroquinoline and benzofuran-derived vicinal amino alcohols, each containing five consecutive chiral centers, with high yields,excellent diastereoselectivities and enantioselectivities(up to 95% yield, >20:1 dr and 98% ee), under mild reaction conditions driven by sequential bifunctional squaramide organocatalyst-catalyzed [4+2] annulation and photocatalyst-catalyzed ketyl radical addition cyclization reaction process. Furthermore, investigations into the stereoselectivity mechanism and high-resolution mass spectrometry(HRMS) experiments on free radical trapping have provided evidence for elucidating the detailed mechanism of chirality-induced processes and chiral intermediate conversions in this procedure.

Catalytically generated noncovalent ammonium dienolate:a versatile platform for the development of organocatalytic asymmetric cascade reactions

Organocatalytic cascade reactions represent a powerful strategy for the rapid construction of complex chiral molecules with multiple stereocenters from simple substrates under mild conditions. The intriguing structural feature and diverse reactivity of catalytically generated dienolate species render them competent and versatile intermediates for the development of practical and valuable cascade reactions. Over the past years, a plethora of innovative and pioneering noncovalent ammonium dienolatemediated cascade reactions have been designed and implemented under the catalysis of chiral organocatalysts, making dienolate activation a general, robust, and complementary method for the functionalization of unsaturated carbonyl compounds and related substances. This review illustrates the recent advances in organocatalytic noncovalent ammonium dienolate-mediated cascade reactions(mainly from 2010 to 2023), including the cascade transformations of ammonium dienolates directly generated from unsaturated ketone/aldehyde, ester/lactone/azlactone, amide/lactam/pyrazolone/oxindole, and alkylidene nitrile compounds. The contents are arranged based on the reaction types of the ammonium dienolates, with an emphasis on cascade 2,5-, 3,5-, and 4,5-difunctionalizations of these intermediates. Furthermore, other cascade reactions involving the 1,3-, 2,3-, and even more complex 3,4,5-reactivities of ammonium dienolates were also discussed. The reaction pathway, reaction stereoinduction, and synthetic applications of the ammonium dienolate-mediated cascade reactions were highlighted throughout the article. As a stimulating and ever-growing research area, the organocatalytic noncovalent ammonium dienolate-mediated cascade reactions are expected to continue demonstrating their magic power for constructing chiral targets in the future and further expanding the boundaries of asymmetric catalysis.

Comparison of corrosion mechanisms of 510L low alloy steel treated by ACS and EPS techniques under various service environments

The corrosion mechanism of 510L low alloy steel treated by acid-cleaned surface(ACS)and eco-pickled surface(EPS)techniques in three simulated solutions(S0:atmospheric environment;S1:soil environment;S2:industrial environment)and the influence of interaction between different corrosive anions on corrosion were investigated.The results show that the total corrosion rates of samples in three simulated solutions were in order of S2>S0>S1,which is simultaneously correlated with initial corrosion dissolution processes as well as after the formation of corrosion products.HCO3−will inhibit the initial corrosion owing to the formation of films,whereas HSO3−will accelerate the dissolutions of the matrix based on the synergistic action of HSO3−and Cl−.On the other hand,there is no significant difference in corrosion rates between the samples treated by ACS and EPS techniques.The EPS technique that is safe,reusable and environmentally friendly can be further widely used in future work.

Progress in corrosion-resistant coatings on surface of low alloy steel

Low alloy steels are widely used in bridges,construction,chemical and various equipment and metal components due to their low cost and excellent mechanical strength.Information in the literature related to the preparation,advantages and disadvantages,and applications along with research progress of various types of protective coatings suitable for low-alloy steel surfaces is reviewed,while a conclusive and comparative analysis is also afforded to the numerous factors influencing the protective ability of coatings.The characteristics of coatings drawn from the latest published literature are discussed and suggest that the modification of traditional metal coatings and the development of new organic coatings under the consideration of environmental protection,low cost,simplicity and large-scale industrial application are simultaneously proceeding,which holds promise for improving the understanding of corrosion protection in related fields and helps to address some of the limitations identified with more conventional coating techniques.

Current susceptibilities of brown planthopper Nilaparvata lugens to triflumezopyrim and other frequently used insecticides in China

The brown planthopper is a notorious rice pest in many areas of Asia.The evolution of insecticide resistance in Nilaparvata lugens has become a serious problem in the effective control of this pest in the paddy field.In this article,the current susceptibility of N.lugens field populations to novel mesoionic insecticide triflumezopyrim and major classes of chemical insecticides was determined and compared.The monitoring results indicated that field populations of N.lugens had developed low resistance to triflumezopyrim(resistance ratio,RR:1.3-7.3-fold)during 2015-2018 in China,and the median lethal concentration values varied from 0.05 to 0.29 mg/L.Additionally,during 2017 to 2018,field populations of N.lugens showed high resistance levels to thiamethoxam(RR:456.1-1025.6-fold),imidacloprid(RR:2195.3-6899.0-fold)and buprofezin(RR:1241.57521.7-fold),moderate to high resistance levels to dinotefuran(RR:97.6-320.1-fold),clothianidin(RR:69.4-230.1-fold)and isoprocarb(RR:44.1-108.0-fold),and low to moderate levels of resistance to chlorpyrifos(RR:12.0-29.7-fold)and nitenpyram(RR:6.9-24.1-fold).In contrast,N.lugens just showed low resistance to sulfoxaflor(RR:3.3-8.5-fold)and etofenprox(RR:5.0-9.1-fold)in the field.Additionally,the P450 gene CYP6ER1 was found to be significantly overexpressed in all five field populations of N.lugens collected in 2018 when compared with a laboratory susceptible strain.Our findings will provide useful information to delay the evolution of insecticide resistance in N.lugens.

Visible-light induced generation of bifunctional nitrogen-centered radicals:a concise synthetic strategy to construct bicyclo[3.2.1]octane and azepane cores

A photocatalytic tandem cyclization of o-alkenylbenzaldehydes using pyridinium salts as the amination reagent is described.A variety of valuable seven-membered nitrogenous heterocyclic skeletons are prepared in modest to excellent yields in concise one-step.This transformation features mild reaction conditions and exceptional functional group tolerance.In addition,combining control experiments and density functional theory(DFT)calculations on the mechanism can explain the reaction selectivity.

Deciphering and reconstitution of positional information in the human brain development

Organoid has become a novel in vitro model to research human development and relevant disorders in recent years.With many improvements on the culture protocols, current brain organoids could self-organize into a complicatedthree-dimensional organization that mimics most of the features of the real human brain at the molecular, cellular,and further physiological level. However, lacking positional information, an important characteristic conveyedby gradients of signaling molecules called morphogens, leads to the deficiency of spatiotemporally regulated cellarrangements and cell–cell interactions in the brain organoid development. In this review, we will overview the roleof morphogen both in the vertebrate neural development in vivo as well as the brain organoid culture in vitro, thestrategies to apply morphogen concentration gradients in the organoid system and future perspectives of the brainorganoid technology.

Photoredox-Catalyzed Hydrocarboxymethylation of Alkenes

Direct introduction of a carboxyl group into molecules is one of the most useful methods for the preparation of carboxylic acids,which avoids the conversion of various preexisting functional groups and features good step-and atom-economy.However,the methods for the direct synthesis of two-carbon added carboxylic acids from the precursors remain rare.Herein,we first report a general and mild method for the direct synthesis of a range of aliphatic acids by photoredox-catalyzed hydrocarboxymethylation of alkenes with good toleration of various functional groups in which bromoacetic acid is utilized as an ideal two-carbon synthon.

Regiodivergent Access to 2- or 3-Substituted Indanones: Catalyst-Controlled Carboacylation via C–C Bond Activation

Indanones are ubiquitous in biologically active compounds.Intramolecular hydroacylation of aldehydes and alkenes is an efficient and atomeconomic route to indane rings.However,these reactions are limited to the transfer of a hydride to the alkene.The transfer of aryl groups enabling the formation of C–C bonds during the cyclization would be a new method for the synthesis of substituted indanones.This report describes the regiodivergent carboacylation of alkenes with ketones to furnish both 2-and 3-substituted indanones in a regiocontrolled manner.