Copper Metabolism and Cuproptosis:Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases

Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess can adversely affect cellular function.Therefore,copper homeostasis is stringently regulated.Recent studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular copper.Cuproptosis induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster proteins.In neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper homeostasis.This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases.This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

中药配方颗粒临床应用国际专家共识

中药配方颗粒以中医药理论为指导,结合现代制剂新技术,选定最佳工艺,经现代化的制药技术提取、浓缩、干燥、制粒,精制而成。中药配方颗粒稳定、安全、便捷、有效。中药配方颗粒产业链相较于中药饮片可以实现从田间到车间的全程化、过程化控制,在药材来源、饮片炮制、加工工艺、质量检测、产品的销售流通等环节实现标准化管理。中药配方颗粒可部分替代中成药。目前中药配方颗粒仅涵盖常用的800余种中药,因此对许多临床并不常用的中药品种,中药配方颗粒并不能取代饮片。临床研究与动物实验中大量使用配方颗粒,从而使得科研人员不再对中药饮片进行提取与质量控制。应尽快从提高生产工艺、建立质量标准、完善监管制度、拓展临床应用等方面解决困扰配方颗粒发展所面临的问题。

重症急性胰腺炎微创治疗新进展与前景展望

随着内镜、介入和外科微创手术的进步,急性胰腺炎的治疗向着多学科协作诊治、有针对性的、微创的方向发展.因此,对于重症急性胰腺炎患者的局部和全身并发症干预的最佳时机、路线和治疗方案的选择需要进行重新评估.本文主要针对重症急性胰腺炎微创治疗的新进展进行总结,并提供前景展望.

International expert consensus on clinical application of traditional Chinese medicine formula granules

Guided by the theory of traditional Chinese medicine(TCM),TCM formula granules are made through the optimal process of extraction,concentration,drying,and granulation by combining modern new preparation technologies and pharmaceutical technologies.TCM formula granules are stable,safe,convenient,and effective.Compared with TCM decoction pieces,TCM formula granules can achieve the full process control of its industry chain from field to workshop and standardize the management of the origin of medicinal materials,processing of decoction pieces,processing technology,quality inspection,sales,and products distribution.TCM formula granules can partially replace Chinese patent medicines.Only available for around 800 common varieties of TCM,TCM formula granules cannot replace decoction pieces for many types which are not commonly used in clinical practice.A large number of formula granules are used in clinical and animal studies so that investigators no longer need to extract and control the quality of TCM decoction pieces.How to improve the production process,establish the quality standard,perfect the regulatory system,and expand the clinical application are the problems we need to solve as soon as possible for the better development of formula granules.

A Stable Wavelength Operation Ho:YAG Laser with Orthogonally Polarized Pump

A stable wavelength operation Ho:YAG laser dual-pumped by two orthogonally polarized Tm:YLF lasers is reported. Under the cw operation mode, a laser output power of 24 W is measured. The corresponding opticaloptical conversion efficiency is 44.75% and the slope efficiency is 50.12%. Under the Q-switched operation mode,the output maximum average power is 22.8 W at the re-frequency of 6 kHz. The corresponding optical-optical conversion efficiency and slope efficiency are 42.64% and 48.01%, respectively. The output central wavelength is 2090.73 nm, the linewidth is 0.40 nm, and the beam quality is M^2< 1.6. Moreover, the shift of the output central wavelength is less than 0.01 nm, and the linewidth shift is also less than 0.01 nm.

氧化钕在熔融氟化物中溶解过程的建模与仿真

结合氧化钕传质机制及其溶解动力学规律,提出一种针对氧化钕溶解过程的求解策略,以预测氧化钕在复杂流场条件下溶解过程中的浓度变化,并对影响氧化钕溶解过程的各个因素进行详细分析。针对工业实际中的脉冲加料和连续加料方式对比研究两种给料方式下氧化钕溶解过程的特征。仿真结果表明,与连续加料方式相比,采用脉冲加料方式时氧化钕在电解槽内达到均匀分布的时间更快。最后,将单颗粒氧化钕在静流场条件下的溶解时间与文献结果进行对比,除仅一组数据的最大误差在10%左右外,其他数据的误差均在5%以内。

Comparative study of pulsed laser diode end-pumped thulium-doped 2-µm Q-switched lasers

We report pulsed laser diode(LD)end-pumped acoustic Q-switched Tm:YAG laser,Tm:LuAG laser,and Tm:LuYAG laser and the physical properties and spectra of Tm:YAG,Tm:LuAG,and Tm:LuYAG are analyzed.The Tm:LuYAG laser is pumped by 785-nm and 788-nm pulses separately,and is compared with Tm:YAG laser.Different output energy values and output wavelengths of Tm:LuAYG lasers pumped by LDs with different wavelengths are obtained and compared with each other.When the repetition frequency is 100 Hz,the pulsed Tm:YAG laser has single pulse energy of 15.9 mJ,pulse width of 126.7 ns,and the center wavelength of 2013.36 nm,and the pulsed Tm:LuAG laser possesses single pulse energy of 11.8 mJ,pulse width of 252.4 ns,and the center wavelength of 2023.65 nm,and the pulsed Tm:LuYAG laser output energy values are 12.32 mJ and 12.25 mJ with the slope efficiencies of 12.5%and 11.85%,the center wavelengths of 2017.89 nm and 2027.11 nm,respectively,while the pump sources are 785-nm and 788-nm pulsed LDs,respectively.

False positive anti-hepatitis A virus immunoglobulin M in autoimmune hepatitis/primary biliary cholangitis overlap syndrome:A case report

BACKGROUND Autoimmune hepatitis(AIH)is an immune-mediated liver disease affecting all age groups.Associations between hepatitis A virus(HAV)and AIH have been described for many years.Herein,we report a case of an AIH/primary biliary cholangitis(PBC)overlap syndrome with anti-HAV immunoglobulin M(IgM)false positivity.CASE SUMMARY A 55-year-old man was admitted with manifestations of anorexia and jaundice along with weakness.He had marked transaminitis and hyperbilirubinemia.Viral serology was positive for HAV IgM and negative for others.Autoantibody screening was positive for anti-mitochondria antibody but negative for others.Abdominal ultrasound imaging was normal.He was diagnosed with acute hepatitis A.After symptomatic treatment,liver function tests gradually recovered.Several months later,his anti-HAV IgM positivity persisted and transaminase and bilirubin levels were also more than 10 times above of the upper limit of normal.Liver histology was prominent,and HAV RNA was negative.Therefore,AIH/primary biliary cholangitis(PBC)overlap syndrome diagnosis was made based on the“Paris Criteria”.The patient was successfully treated by immunosuppression.CONCLUSION This case highlights that autoimmune diseases or chronic or acute infections,may cause a false-positive anti-HAV IgM result because of cross-reacting antibodies.Therefore,the detection of IgM should not be the only method for the diagnosis of acute HAV infection.HAV nucleic acid amplification tests should be employed to confirm the diagnosis.

Low level of ARID1A contributes to adaptive immune resistance and sensitizes triple-negative breast cancer to immune checkpoint inhibitors

Background Immune checkpoint inhibitors(ICIs)shed new light on triple-negative breast cancer(TNBC),but only a minority of patients demonstrate response.Therefore,adaptive immune resistance(AIR)needs to be further defined to guide the development of ICI regimens.Methods Databases,including The Cancer Genome Atlas,Gene Ontology Resource,University of California Santa Cruz Genome Browser,and Pubmed,were used to screen epigenetic modulators,regulators for CD8+T cells,and transcriptional regulators of programmed cell death-ligand 1(PD-L1).Human peripheral blood mononuclear cell(Hu-PBMC)reconstruction mice were adopted for xenograft transplantation.Tumor specimens from a TNBC cohort and the clinical trial CTR20191353 were retrospectively analyzed.RNA-sequencing,Western blotting,qPCR and immunohistochemistry were used to assess gene expression.Coculture assays were performed to evaluate the regulation of TNBC cells on T cells.Chromatin immunoprecipitation and transposase-accessible chromatin sequencing were used to determine chromatin-binding and accessibility.Results The epigenetic modulator AT-rich interaction domain 1A(ARID1A)gene demonstrated the highest expression association with AIR relative to other epigenetic modulators in TNBC patients.Low ARID1A expression in TNBC,causing an immunosuppressive microenvironment,promoted AIR and inhibited CD8+T cell infiltration and activity through upregulating PD-L1.However,ARID1A did not directly regulate PD-L1 expression.We found that ARID1A directly bound the promoter of nucleophosmin 1(NPM1)and that low ARID1A expression increased NPM1 chromatin accessibility as well as gene expression,further activating PD-L1 transcription.In Hu-PBMC mice,atezolizumab demonstrated the potential to reverse ARID1A deficiency-induced AIR in TNBC by reducing tumor malignancy and activating anti-tumor immunity.In CTR20191353,ARID1A-low patients derived more benefit from pucotenlimab compared to ARID1A-high patients.Conclusions In AIR epigenetics,low ARID1A expression in TNBC contributed to AIR via the ARID1A/NPM1/PD-L1 axis,leading to poor outcome but sensitivity to ICI treatment.

PEDOT:PSS薄膜的丝网印刷、后处理改性及在染料敏化太阳能电池中的应用

运用丝网印刷的方式在导电玻璃基底表面涂覆了聚(3,4-乙烯二氧噻吩)(PEDOT):聚苯乙烯磺酸盐混合物(PSS)薄膜,并采用稀H_2SO_4加甲醇混合溶液后处理的方式对其进行了改性.使用扫描电子显微镜(SEM)和原子力显微镜(AFM)观察处理前后薄膜的表面形貌及厚度的变化,对比了处理前后薄膜的电导率,并结合X射线衍射(XRD)和X射线光电子能谱(XPS)分析探讨了导致电导率变化的原因.最后,将PEDOT:PSS薄膜作为对电极组装了染料敏化太阳能电池(DSSC),运用电化学阻抗谱(EIS)研究了对电极的催化性能,并测试了DSSC的光伏性能.结果显示,经过后处理改性后,由于PSS被部分去除,PEDOT:PSS薄膜的表面形貌发生了显著改变,厚度变薄,粗糙度升高,电导率提升至原始的3倍以上,对I_3~–还原的催化活性升高,且组装的DSSC的性能也有了显著提高,光电转换效率由5.12%提升至6.64%.

一种高强度速黏纳米杂化水凝胶“创可贴”

报道了一种制备具有高强度、高黏附性和良好生物相容性的黏合水凝胶的极其简便的方法.将N-丙烯酰-2-氨基乙酸(ACG)水溶液与纳米生物活性玻璃(BG)混合,紫外光引发自由基聚合即可快速制备PACG-BG纳米复合水凝胶.在该水凝胶体系中PACG分子链之间形成的氢键、PACG末端的羧基与BG中的金属离子形成的离子络合以及PACG分子链与BG纳米粒子之间发生的物理吸附作用共同构成了网络的多重物理交联,由此显著提高了凝胶的强度.通过调节凝胶体系中ACG和BG的含量赋予了水凝胶可调节的黏附性、机械性能以及室温自修复特性.利用搭接剪切拉伸的方式对水凝胶的黏附性能进行测试,结果显示当水凝胶中ACG的含量为25 wt%,BG占ACG含量为6 wt%时,水凝胶的表面黏附能和内聚能可达平衡,其对猪皮、铁片和陶瓷的瞬时最大黏附强度分别为120、142和125 kPa.同时,水凝胶最高拉伸强度可达0.9 MPa,撕裂能可达1500 J/m2.动物体内埋植结果显示水凝胶具有良好的生物相容性.鉴于水凝胶对生物软组织有优异的黏附性能,对其进行了体外修补胃穿孔的模拟实验,结果表明,水凝胶可以牢固地黏附在胃的穿孔处,防止模拟胃液的外泄.

A Survey on Graph Processing Accelerators:Challenges and Opportunities

Graph is a well known data structure to represent the associated relationships in a variety of applications,e.g.,data science and machine learning.Despite a wealth of existing efforts on developing graph processing systems for improving the performance and/or energy efficiency on traditional architectures,dedicated hardware solutions,also referred to as graph processing accelerators,are essential and emerging to provide the benefits significantly beyond what those pure software solutions can offer.In this paper,we conduct a systematical survey regarding the design and implementation of graph processing accelerators.Specifically,we review the relevant techniques in three core components toward a graph processing accelerator:preprocessing,parallel graph computation,and runtime scheduling.We also examine the benchmarks and results in existing studies for evaluating a graph processing accelerator.Interestingly,we find that there is not an absolute winner for all three aspects in graph acceleration due to the diverse characteristics of graph processing and the complexity of hardware configurations.We finally present and discuss several challenges in details,and further explore the opportunities for the future research.

Efficient quantum simulation of open quantum dynamics at various Hamiltonians and spectral densities

Simulation of open quantum dynamics for various Hamiltonians and spectral densities are ubiquitous for studying various quantum systems.On a quantum computer,only log2N qubits are required for the simulation of an N-dimensional quantum system,hence simulation in a quantum computer can greatly reduce the computational complexity compared with classical methods.Recently,a quantum simulation approach was proposed for studying photosynthetic light harvesting[npj Quantum Inf.4,52(2018)].In this paper,we apply the approach to simulate the open quantum dynamics of various photosynthetic systems.We show that for Drude—Lorentz spectral density,the dimerized geometries with strong couplings within the donor and acceptor clusters respectively exhibit significantly improved efficiency.We also demonstrate that the overall energy transfer can be optimized when the energy gap between the donor and acceptor clusters matches the optimum of the spectral density.The effects of different types of baths,e.g.,Ohmic,sub-Ohmic,and super-Ohmic spectral densities are also studied.The present investigations demonstrate that the proposed approach is universal for simulating the exact quantum dynamics of photosynthetic systems.

Non-Markovian Master Equation for Distant Resonators Embedded in a One-Dimensional Waveguide

We develop a master equation approach to describe the dynamics of distant resonators coupled through a one-dimensional waveguide. Our method takes into account the back-actions of the reservoirs, and enables us to calculate the exact dynamics of the complete system at all times. We show that such system can cause nonexponential and long-lived photon decay due to the existence of a relaxation effect. The physical origin of non-Markovianity in our model system is the finite propagation speed resulting in time delays in communication between the nodes, and strong decay rate of the emitters into the waveguide. When the distance satisfies the standing wave condition, we find that when the time delay is increased, the dark modes formation is no longer perfect, and the average photon number of dark mode decreases in steady time limit.

Monoclonal Antibodies Reveal Novel Localization of SPAG11E in Spermatozoa and the Antifertility Potential of SPAG11E Motifs

Objective: SPAG11E is the first β-defensin that has been reported to activate Ca;uptake and sperm motility. However, the exact subcellular localization and interaction of SPAG11E with sperm remain controversial because of the lack of qualified antibody tools. SPAG11E is also a potential male antifertility target because SPAG11E fragment conjugated with a carrier protein exhibits male contraceptive vaccine potential.However, the fine B-cell epitope motifs of SPAG11E have not been analyzed, which hampered further exploration of the potential target.Methods: Polyclonal and monoclonal antibodies（mcAbs） of mature SPAG11E were raised and qualified with Western blotting. Subcellular localization of SPAG11E was revealed by Western blotting, immunohistochemistry staining, and electron microscopy. B-cell epitopes of rat SPAG11E were mapped by Western blotting using polyclonal and mcAbs. Based on the conservation of the identified epitope motifs between rat and mouse SPAG11E, antifertility potential of the epitope motifs was evaluated by the offspring of the males compromised with specific mcAbs.Results: SPAG11E antibodies of high quality were obtained and all B-cell epitope motifs of rat SPAG 11 E were mapped, in which conserved epitope motifs of SPAG11E in various species were discovered. The epitope motifs recognized by mcAbs were identified respectively. With mcAbs, rat SPAG11E was proved to be expressed in the caput region of epididymis. A novel finding was that SPAG 11 E was located in the flagella and nuclei of sperm as revealed by immunoelectron microscopy. In addition, the males treated with mcAbs（3#-1 and 10#B4） showed apparently fewer offspring.Conclusions: SPAG11E revealed a β-defensin with novel localization in sperm flagellum and nucleus with qualified antibodies. All B-cell epitope motifs of rat SPAG11E were determined, and the antifertility potential was proved by corresponding mcAbs.