融入探究和思政特色的新胶体电泳实验

本案例以解决传统Fe(OH)_(3)胶体电泳实验中存在的胶体废液浪费、缺乏探究性以及思政育人难融入等局限为出发点,通过发展胶溶法、引入表面带不同电荷AgI胶体制备及其带电性质自主判断环节,守正创新,赋予该实验项目以资源节约、绿色环保、富有探究性等特色。尤其重要的是,本案例通过综合采用任务驱动自主学习、翻转课堂、研讨启发等多种教学模式,将经典基础物理化学实验与提高我国数量巨大但来之不易的钢铁资源的循环利用率和改变学生对胶体带电性质的固有认识有机结合起来,在潜移默化中弘扬/培育了学生“绿色”化学理念、可持续发展责任担当、科学辩证思维素养以及创新精神等。本案例已初步推广应用于本校的胶体电泳实验教学中,教学反响热烈,达到了专业知识、技能传授与课程思政育人相济相长的教学效果;为提升传统实验的专业育人和思政育人效果提供有益借鉴。

具有资源循环利用和开放探究特色的新型胶体电泳实验

鉴于传统Fe(OH)_(3)胶体电泳实验存在胶体浪费、渗析耗时、缺乏探究性等局限,故做如下改进:1)以Fe(OH)_(3)废液为原料,利用胶溶法将其再生,实现循环利用;2)改进渗析工艺,提高胶体纯化效率;3)引入AgI胶体探究环节,增强创新性与趣味性;4)引入纸片电泳,科教融合,培养学以致用的意识。经反复验证,上述方案行之有效,并已在本校推广,教学反响热烈。

Optimal Decoupling Control Method and Its Application to a Ball Mill Coal-pulverizing System

The conventional optimal tracking control method cannot realize decoupling control of linear systems with a strong coupling property. To solve this problem, in this paper, an optimal decoupling control method is proposed, which can simultaneously provide optimal performance. The optimal decoupling controller is composed of an inner-loop decoupling controller and an outer-loop optimal tracking controller. First, by introducing one virtual control variable, the original differential equation on state is converted to a generalized system on output. Then, by introducing the other virtual control variable, and viewing the coupling terms as the measurable disturbances, the generalized system is open-loop decoupled. Finally, for the decoupled system,the optimal tracking control method is used. It is proved that the decoupling control is optimal for a certain performance index.Simulations on a ball mill coal-pulverizing system are conducted.The results show the effectiveness and superiority of the proposed method as compared with the conventional optimal quadratic tracking(LQT) control method.

Climate Warming Mitigation from Nationally Determined Contributions

Individual countries are requested to submit nationally determined contributions(NDCs)to alleviate global warming in the Paris Agreement.However,the global climate effects and regional contributions are not explicitly considered in the countries’decision-making process.In this study,we evaluate the global temperature slowdown of the NDC scenario(ΔT=0.6°C)and attribute the global temperature slowdown to certain regions of the world with a compact earth system model.Considering reductions in CO_(2),CH_(4),N_(2)O,BC,and SO_(2),the R5OECD(the Organization for Economic Co-operation and Development in 1990)and R5ASIA(Asian countries)are the top two contributors to global warming mitigation,accounting for 39.3%and 36.8%,respectively.R5LAM(Latin America and the Caribbean)and R5MAF(the Middle East and Africa)followed behind,with contributions of 11.5%and 8.9%,respectively.The remaining 3.5%is attributed to R5REF(the Reforming Economies).Carbon Dioxide emission reduction is the decisive factor of regional contributions,but not the only one.Other greenhouse gases are also important,especially for R5MAF.The contribution of short-lived aerosols is small but significant,notably SO_(2)reduction in R5ASIA.We argue that additional species beyond CO_(2)need to be considered,including short-lived pollutants,when planning a route to mitigate climate change.It needs to be emphasized that there is still a gap to achieve the Paris Agreement 2-degree target with current NDC efforts,let alone the ambitious 1.5-degree target.All countries need to pursue stricter reduction policies for a more sustainable world.

RIOX1-demethylated cGAS regulates ionizing radiation-elicited DNA repair

Exposure to radiation causes DNA damage;hence, continuous surveillance and timely DNA repair are important for genome stability. Epigenetic modifications alter the chromatin architecture, thereby affecting the efficiency of DNA repair. However, how epigenetic modifiers coordinate with the DNA repair machinery to modulate cellular radiosensitivity is relatively unknown. Here, we report that loss of the demethylase ribosomal oxygenase 1(RIOX1) restores cell proliferation and reduces cell death after exposure to ionizing radiation. Furthermore, RIOX1 depletion enhances homologous recombination(HR) repair but not nonhomologous endjoining(NHEJ) repair in irradiated bone marrow cells and oral mucosal epithelial cells. Mechanistic study demonstrates that RIOX1 removes monomethylation at K491 of cyclic GMP-AMP synthase(c GAS) to release c GAS from its interaction with the methyl-lysine reader protein SAGA complex-associated factor 29(SGF29), which subsequently enables c GAS to interact with poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase 1(PARP1) at DNA break sites, thereby blocking PARP1-mediated recruitment of Timeless. High expression of RIOX1 maintains c GAS K491 me at a low level, which impedes HR repair and reduces cellular tolerance to ionizing radiation. This study highlights a novel RIOX1-dependent mechanism involved in the non-immune function of c GAS that is essential for the regulation of ionizing radiation-elicited HR repair.

The acceleration mechanism of shock wave induced by millisecond-nanosecond combined-pulse laser on silicon

The velocity variation law of shock wave induced by millisecond-nanosecond combined-pulse laser has been investigated experimentally. The pulse delay and laser energy are important experimental variables. The method of laser shadowgraphy is used in the experiment.Experimental results show that when the pulse delay is 2.4 ms, the ms and ns laser energy density is 301 J cm^(-2) and 12 J cm^(-2), respectively, the velocity of shock wave is 1.09 times faster than that induced by single ns pulse laser. It is inferred that the shock wave propagates in the plasma is faster than that in air. When the ms and ns laser energy density is 414.58 and 24 J cm^(-2), the velocity of shock wave shows rising trend with pulse delay in a range of 1.4 ms>Δt> 0.8 ms. It is indicated that with the increase of ns laser energy, the laser energy absorbed by laser-supported absorption wave increases. The mechanism of inverse bremsstrahlung absorption acts with target surface absorption simultaneously during the ns laser irradiation. Thus, the phenomenon of the double shock wave is induced. The numerical results of the phenomenon were accordance with experiment. The results of this research can provide a reference for the field of laser propulsion.

Determination of Melamine in Fresh Milk by Electrochemistry with Solid Phase Microextraction at Bismuthyl Chloride Modified Graphite Epoxy Composite Electrode

Melamine as an important chemical raw material and a harmful additive in foods has attracted many people’s attention. In the present paper, The graphite-epoxy composited solid phase electrode was modified with bismuth layer by cyclic voltammetric deposition of bismuth from Bi(NO3)3 aqueous solution including 0.10 M HNO3, and hydrolyzed into micro bismuthyl chloride on-sites. Melamine in fresh milk was extracted with solid phase micro-extraction on the bismuthyl chloride modified graphite-epoxy composited solid electrode. The adsorption of melamine on bismuthyl chloride particle surfaces follows a Freundlich adsorption model, and results in the decrease of the reduction peak current of bismuth in bismuthyl chloride, and determined by differential pulse voltammetry from fresh milk in a larger concentration range of 10–4 ? 10–12 M with detection limit of 2.5 ? 10–12 M and relative standard deviation of 2.7%. The method is sensitive, convenient and was applied in the detection of melamine in fresh milk with relative deviation of 4.2% in content of 0.45 mg/kg melamine in the fresh milk.

Analysis of the adverse reactions of atezolizumab: A real-world study based on FAERS database

Objective In this study,we aimed to determine the incidence of adverse drug reactions(ADRs)of atezolizumab,identify ADR signals that are significantly related to atezolizumab,and provide a reference for the rational use of atezolizumab in the clinic through the statistical analysis of its adverse drug events(ADEs)reported in the American Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database.Methods In total,4796 cases of atezolizumab ADEs reported in the American FAERS database from 2017 to 2019 were retrospectively analyzed.Results The top three ADEs were febrile neutropenia(3.7%),anemia(2.9%),and acute renal failure(2.3%).In addition,the incidence rates of some ADEs were significantly different according to sex and age.The systematic organ classification of atezolizumab ADEs involved 32 systems,among which the top three were blood and lymphatic system disorders(585 cases,12.2%),gastrointestinal disorders(433 cases,9.0%),and infections and infestations(401 cases,8.4%).The reporting odds ratio(ROR)method was used to detect the ADR signals of atezolizumab.The ROR(95%confidence interval)of the top ADE,febrile neutropenia,was 39.236(33.757–45.604).In addition,we found 121 cases of complications associated with immune-related ADEs.Conclusion The ADRs of atezolizumab reported in the FAERS database were consistent with those mentioned in the instructions for atezolizumab use,suggesting that atezolizumab has an acceptable and controllable drug effect.

Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis:A multicenter,randomized,double-blind,placebo-controlled phase 2b trial

Background:Atopic dermatitis(AD)affects approximately 10%of adults worldwide.CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling.This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods:This multicenter,randomized,double-blind,placebo-controlled,phase 2b trial was conducted in 21 medical institutions in China from February to November 2021.Totally 120 eligible patients were enrolled and randomized(1:1:1)to receive subcutaneous injections of 300 mg CM310,150 mg CM310,or placebo every 2 weeks for 16 weeks,followed by an 8-week follow-up period.The primary endpoint was the proportion of patients achieving≥75%improvement in the Eczema Area and Severity Index(EASI-75)score from baseline at week 16.Safety and pharmacodynamics were also studied.Results:At week 16,the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups(70%[28/40]for high-dose and 65%[26/40]for low-dose)than that in the placebo group(20%[8/40]).The differences in EASI-75 response rate were 50%(high vs.placebo,95%CI 31%-69%)and 45%(low vs.placebo,95%CI 26%-64%),with both P values<0.0001.CM310 at both doses also significantly improved the EASI score,Investigator’s Global Assessment score,daily peak pruritus Numerical Rating Scale,AD-affected body surface area,and Dermatology Life Quality Index compared with placebo.CM310 treatment reduced levels of thymus and activation-regulated chemokine,total immunoglobulin E,lactate dehydrogenase,and blood eosinophils.The incidence of treatment-emergent adverse events(TEAEs)was similar among all three groups,with the most common TEAEs reported being upper respiratory tract infection,atopic dermatitis,hyperlipidemia,and hyperuricemia.No severe adverse events were deemed to be attributed to CM310.Conclusion:CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration:ClinicalTrials.gov,NCT04805411.

Single-nucleus profiling unveils a geroprotective role of the Foxo3 in primate skeletal muscle aging

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia,and increases the risk of many aging-related metabolic diseases.Here,we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging.A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types,indicating a higher susceptibility of skeletal muscle fiber to aging.We found a downregulation of Foxo3 in aged primate skeletal muscle,and identi-fied FOxo3 as a hub transcription factor maintaining skeletal muscle homeostasis.Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model,we revealed that silence of Foxo3 accelerates human myotube senescence,whereas genetic activation of endogenous FOxO3 alleviates human myotube aging.Altogether,based on a combination of monkey skeletal muscle and human myotube aging research models,we unraveled the pivotal role of the FOxO3 in safeguarding primate skeletal muscle from aging,providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-relateddisorders.

扬刺百会穴结合舒缓音乐疗法治疗轻度认知功能障碍合并失眠的临床疗效

目的:探讨扬刺百会穴结合舒缓音乐疗法治疗轻度认知功能障碍合并失眠的临床疗效。方法:选取轻度认知功能障碍合并失眠患者70例,随机分为对照组和治疗组(每组35例)。对照组给予阿普唑仑片口服,治疗组采用扬刺百会穴结合舒缓音乐治疗,观察治疗前后的疗效。结果:治疗后,对照组与治疗组的MMSE评分、PSQI评分均明显优于治疗前,差异有统计学意义(P<0.05);治疗组的MoCA评分、MMSE评分和PSQI评分显著优于对照组,差异有统计学意义(P<0.05);对照组治疗前后的MoCA评分没有显著变化,差异无统计学意义(P>0.05);对照组睡眠质量改善总有效率为21例(60.0%),治疗组睡眠质量改善总有效率33例(94.3%)。结论:扬刺百会穴结合舒缓音乐疗法治疗轻度认知功能障碍合并失眠,临床疗效好,安全性高,无明显不良反应,可显著改善认知功能和睡眠质量,值得临床推广。

Cell membrane-coated mesoporous silica nanorods overcome sequential drug delivery barriers against colorectal cancer

Local delivery of nanomedicines holds therapeutic promise for colorectal cancer(CRC).However,it presents tremendous challenges due to the existence of multiple physiological barriers,especially intracellular obstacles,including intracellular trafficking,subcellular accumulation,and drug release.Herein,we report a multifunctional nanoparticle(CMSNR)by wrapping the mesoporous silica nanorod with cell membrane derived from CRC cells for improved chemotherapy.Compared with their naked counterparts,the cell membrane endowed CMSNR with homotypic targeting and improved cellular uptake capacities.Due to the rod-like shape,CMSNR achieved superior colorectal mucus permeability,enhanced tumor accumulation,and boosted cellular uptake than their spherical counterparts.Moreover,the internalized CMSNR underwent robust intracellular trafficking and gained augmented motility toward the nucleus,leading to efficient perinuclear accumulation and a subsequent 5.6-fold higher nuclear accumulation of loaded drug than that of nanospheres.In the orthotopic colorectal tumor-bearing nude mice,rectally administrated mefuparib hydrochloride(MPH)-loaded CMSNR traversed the colorectal mucus,penetrated the tumor tissue,and successfully aggregated in the perinuclear region of cancer cells,thus exhibiting significantly improved antitumor outcomes.Our findings highlight the shape-based design of cell membranecoated nanoparticles that can address sequential drug delivery barriers has a promising future in cancer nanomedicine.

Equilibrium electron beam parameters of the High Energy Photon Source

Purpose The physics design of the High Energy Photon Source(HEPS)was finished after many times of iteration.Hereby,the typical equilibrium electron beam parameters corresponding to the proposed two baseline operation modes in the baseline design of HEPS are presented.Methods To compute the equilibrium parameters of the electron beam,the lattice parameters,RF parameters,and the parameters of the insertion devices(IDs)were determined first.Furthermore,it is more precise to use the full-current electron beam parameters in the estimations of the performance of the synchrotron light.Therefore,not only the single-particle dynamics but also the current-dependent collective effects need to be considered in the computations of the full-current,equilibrium parameters of the electron beam.Both analytic computations and multi-particle tracking simulations were carried out.Results The full-current,equilibrium parameters of the electron beams in the HEPS storage ring are presented in this paper.Moreover,the main beam parameters in the injector(the booster and the LINAC),corresponding to the two baseline operation modes of the storage ring,are also presented.Conclusion The typical electron beam parameters corresponding to the two baseline operation modes are given in detail in this paper.

超声心动图联合梅奥分期提高对轻链型心肌淀粉样变早期死亡高风险患者的识别

轻链型心肌淀粉样变(AL-CA)是一类预后极差的浸润性心脏病,识别高危患者并尽早开展治疗,是改善预后的关键.梅奥分期是目前最常用的危险分层体系,但相同分期患者预后存在较大差异.本研究通过连续入选2020年5月~2022年12月间在北京协和医院确诊为AL-CA患者76名,旨在探讨超声心动图常规测量指标能否在现有危险分层基础上提高对AL-CA早期死亡高风险患者的识别.本研究中位随访时间为10月(5, 20), 20名患者6个月内死亡即早期死亡,左房前后径、左室射血分数(LVEF)、E/e′比值、(E/e′)/LVEF、梅奥2004分期Ⅲb期均对AL-CA患者6个月内死亡有预测价值(P<0.05).其中(E/e′)/LVEF预测价值最佳,(E/e′)/LVEF≥0.5联合梅奥2004分期Ⅲb期预测ALCA患者早期死亡优于梅奥2004分期.研究结果显示,超声心动图常规测量指标E/e′与LVEF的比值可在梅奥2004分期Ⅲb期基础上提高对早期死亡高风险患者的预测价值.

高水平临床研究推动肺动脉高压危险分层内涵发展

肺动脉高压是一种疑难危重罕见病,一直以来被视为“心血管系统的癌症”,患者预后极差.对疾病进行危险分层可以帮助临床医生判断患者病情、指导治疗、评价疗效和预测预后,这需要大量的临床研究作为依据.高水平临床研究是解决临床实践问题的重要手段,我国肺动脉高压队列有着独特的特点,学习和借鉴国外肺动脉高压危险分层发展经验,对建立符合我国肺动脉高压人群的危险分层具有重要意义.本文以肺动脉高压危险分层发展为例,旨在深入剖析通过高水平临床研究解决临床问题的过程与方法.文章概述了肺动脉高压的发现与流行,明确了定义与深入开展临床研究的全过程;重点围绕靶向药治疗时代下肺动脉高压危险分层的建立与更新,总结临床研究推动肺动脉高压诊疗指南和治疗理念不断发展的方式方法;最后通过分析肺动脉高压危险分层在我国的应用现状和问题,希望国外研究肺动脉高压危险分层的思维方式对我国开展临床研究、解决临床实践中的问题有所启示.

Vaccination against coronavirus disease 2019 in patients with pulmonary hypertension:A national prospective cohort study

Background:Coronavirus disease 2019(COVID-19)has potential risks for both clinically worsening pulmonary hypertension(PH)and increasing mortality.However,the data regarding the protective role of vaccination in this population are still lacking.This study aimed to assess the safety of approved vaccination for patients with PH.Methods:In this national prospective cohort study,patients diagnosed with PH(World Health Organization[WHO]groups 1 and 4)were enrolled from October 2021 to April 2022.The primary outcome was the composite of PH-related major adverse events.We used an inverse probability weighting(IPW)approach to control for possible confounding factors in the baseline characteristics of patients.Results:In total,706 patients with PH participated in this study(mean age,40.3 years;mean duration after diagnosis of PH,8.2 years).All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China.Among them,278 patients did not receive vaccination,whereas 428 patients completed the vaccination series.None of the participants were infected with COVID-19 during our study period.Overall,398 patients received inactivated severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine,whereas 30 received recombinant protein subunit vaccine.After adjusting for baseline covariates using the IPW approach,the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase(27/428[6.3%]vs.24/278[8.6%],odds ratio=0.72,P=0.302).Approximately half of the vaccinated patients reported at least one post-vaccination side effects,most of which were mild,including pain at the injection site(159/428,37.1%),fever(11/428,2.6%),and fatigue(26/428,6.1%).Conclusions:COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH,although there were some tolerable side effects.A large-scale randomized controlled trial is warranted to confirm this finding.The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

Mechanism underlying the retarded nuclear translocation of androgen receptor splice variants

As shown in our previous study, two alternatively spliced androgen receptor(AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear translocation compared with wild-type AR. However, researchers have not yet determined whether these abnormalities correlate with heat shock protein 90(HSP90)and importin α(the former is a generally accepted co-chaperone of AR, and the latter is a component of classical nuclear import complexes). Here, these two variants were mainly retained in cytoplasm with HSP90 and importin α in the presence of dihydrotestosterone(DHT), and their levels in nucleus were significantly reduced, according to the immunofluorescence staining. The binding affinity of two AR variants for importin α was consistently decreased, while it was increased in WT-AR following DHT stimulation, leading to reduced nuclear import, particularly for the insertion-AR(Ins-AR). However, the binding affinities of two AR variants for HSP90 were increased in the absence of DHT compared with WT-AR, which functioned to maintain spatial structural stability, particularly for the deletion-AR(Del-AR). Therefore, the retarded nuclear translocation of two AR variants is associated with HSP90 and importin α, and the abnormal binding affinities for them play critical roles in this process.

Physics design of the HEPS LINAC

Purpose The High Energy Photon Source(HEPS)is a synchrotron radiation source with an ultrahigh brightness and under construction in China.Its accelerator system is comprised of a 6-GeV storage ring,a full energy booster,a 500-meV Linac and three transport lines.With deepening investigations on the physics designs of the storage ring and the booster,the physics scheme of the Linac has evolved through multiple versions.Methods The final version of the Linac,including the electron gun,bunching system and main accelerator,has been deter-mined.The Linac is an s-band normal conducting electron linear accelerator with a very high bunch charge and a large bunch charge range.Results Based on simulations,the Linac could provide electron bunches with charge greater than 8.5-nC,meeting the energy spread and emittance requirements.Conclusions This paper first reviews the evolution and main considerations for different design versions and then describes the physics design and dynamic simulation results of the final scheme in detail.

The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores.In this study,we demonstrate that the upregulated intestinal transporter(PCFT),which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats,mediates the uptake of the folic acid-grafted nanoparticles(FNP).Specifically,the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway,Golgi-targeting pathway and basolateral exocytosis,featuring a high oral insulin bioavailability of 14.4%in the diabetic rats.Conversely,in cells with relatively low PCFT expression,the positive surface charge contributes to the cellular uptake of FNP,and FNP are mainly degraded in the lysosomes.Overall,we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway.This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.