Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated.In the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated.Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy.In addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo model.Moreover,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent.Most importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice.As revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

Trametinib boosts palbociclib’s efficacy in breast cancer via autophagy inhibition

Breast cancer,a predominant global health issue,requires ongoing exploration of new therapeutic strategies.Palbociclib(PAL),a well-known cyclin-dependent kinase(CDK)inhibitor,plays a critical role in breast cancer treatment.While its efficacy is recognized,the interplay between PAL and cellular autophagy,particularly in the context of the RAF/MEK/ERK signaling pathway,remains insufficiently explored.This study investigates PAL’s inhibitory effects on breast cancer using both in vitro(MCF7 and MDA-MB-468 cells)and in vivo(tumor-bearing nude mice)models.Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib(TRA),an MEK inhibitor,our research seeks to address the challenge of PAL-induced drug resistance.Ourfindings reveal that PAL significantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A cells.However,PAL also induces protective autophagy,potentially leading to drug resistance via the RAF/MEK/ERK pathway activation.Introducing TRA effectively neutralized this autophagy,enhancing PAL’s anti-tumor efficacy.A combination of PAL and TRA synergistically reduced cell viability and proliferation,and in vivo studies showed notable tumor size reduction.In conclusion,the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance,offering a new horizon in breast cancer treatment.

反式聚异戊二烯结晶性能与分子模拟的研究进展

概述了反式-1,4-聚异戊二烯(TPI)结晶行为的研究进展,如晶型的确定、晶型的形成条件、结晶的热力学和动力学过程、晶型之间的相互转化。其中重点介绍了TPI晶型的确定、α-晶型、β-晶型的反式-CTS-反式-CTS与反式-S^-TS分子链构象研究进展。对近年来分子模拟技术在结晶方面的相关研究,如TPI晶型的构建、多相体系的结晶状态、凝聚态下晶体的相关性质、复杂体系下的结晶过程、动态环境下分子结晶的动态行为模拟研究进行了介绍,包括晶型的构建,如α-晶型、β-晶型的空间原子坐标与各向同性、各向异性之间的内在关系。

丁腈胶乳原位加氢制备氢化丁腈橡胶的研究进展

目前,氢化丁腈橡胶(HNBR)主要由贵金属溶液加氢的方法进行制备,但面临环境污染和贵金属成本高的问题,由此文中介绍了二酰亚胺原位氢化丁腈橡胶(NBR)制备HNBR的方法。选用水合肼催化剂,胶乳作为反应介质,以二酰亚胺原位的方式对NBR胶乳进行催化加氢,有效避免了贵金属催化剂及有机溶剂的使用,简化了加氢工艺,成本降低,与此同时,胶乳加氢的副产物为氮气和水,对环境无污染,是一种绿色高效的加氢方法。制备的HNBR具有优异的耐老化性能和耐油性能等综合性能,因此广泛应用于石油、汽车、航空航天及军工等领域。

Fractional Fourier domain hopped communication method based on chirp modulation for underwater acoustic channels

To improve the data rate of underwater acoustic frequency-hopped communications, frequency hopping is applied to different orders of fractional Fourier domain (FrFD), to enable non-intrusive, bandwidth-limited acoustic communications. An FrFD frequency-hopped communication method based on chirp modulation, namely multiple chirp shift keying-FrFD hopping (MCSK-FrFDH), is proposed for underwater acoustic channels. Validated by both simulations and experimental results, this method can reach a bandwidth efficiency twice more than conventional frequency-hopped methods with the same data rate and anti-multipath capability, suggesting that the proposed method achieves a better performance than the traditional frequency hopped communication in underwater acoustic communication channels. Results also show that in practical scenarios, the MCSK-FrFDH system with longer symbol length performs better at the low signal-to-noise ratio (SNR), while the system with larger frequency sweeping range performs better at a high SNR.

Autoantibodies in Alzheimer's disease:potential biomarkers,pathogenic roles,and therapeutic implications

Alzheimer＇s disease （AD） is a prevalent and debilitating neurodegenerative disorder in the elderly. The etiology of AD has not been fully defined and currently there is no cure for this devastating disease. Compelling evidence sug- gests that the immune system plays a critical role in the pathophysiology ofAD. Autoantibodies against a variety of molecules have been associated with AD. The roles of these autoantibodies in AD, however, are not well understood. This review attempts to summarize recent findings on these autoantibodies and explore their potential as diagnostic/ prognostic biomarkers for AD, their roles in the pathogenesis of AD, and their implications in the development of effective immunotherapies for AD.

The Related Research of the Genes of Gibberellin Receptor(GID1) in Plant

The hormone gibberellin(GA) plays an important role in modulating diverse processes throughout plant development.Gibberellin(GA) perception is mediated by GID1(GA-INSENSITIVE DWARF1),a receptor that shows similarity to hormone-sensitive lipases.It has been postulated that plants have two types of GA receptors,including soluble and membrane-bound forms.In recent years,significant advances have been made in the research of Gibberellin Receptor(GID1).This article highlights recent advances in the molecular structure of Gibberellin Receptor(GID1),Molecular Interactions between the Gibberellin Receptor(GID1) with DELLA,Cloning and expression of GA receptors(GID1),function identification of GA receptor gene(GID1).These discoveries open new prospects for the understanding mechanism of GA receptors(GID1) in plants.

Mitophagy and cGAS-STING crosstalk in neuroinflammation

Mitophagy,essential for mitochondrial health,selectively degrades damaged mitochondria.It is intricately linked to the cGAS-STING pathway,which is crucial for innate immunity.This pathway responds to mitochondrial DNA and is associated with cellular stress response.Our review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS-STING pathway.We critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions,primarily through the accumulation of damaged mitochondria,which activates the cGAS-STING pathway.This activation prompts the production of pro-inflammatory cytokines,exacerbating neuroinflammation.This review emphasizes the interaction between mitophagy and the cGAS-STING pathways.Effective mitophagy may suppress the cGAS-STING pathway,offering protection against neuroinflammation.Conversely,impaired mitophagy may activate the cGAS-STING pathway,leading to chronic neuroinflammation.Additionally,we explored how this interaction influences neurodegenerative disorders,suggesting a common mechanism underlying these diseases.In conclusion,there is a need for additional targeted research to unravel the complexities of mitophagy-cGAS-STING interactions and their role in neurodegeneration.This review highlights potential therapies targeting these pathways,potentially leading to new treatments for neuroinflammatory and neurodegenerative conditions.This synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.

Ononin inhibits triple-negative breast cancer lung metastasis by targeting the EGFR-mediated PI3K/Akt/mTOR pathway

The spreading of cancer cells from the primary tumor site to other parts of the body,known as metastasis,is the leading cause of cancer recurrence and mortality in patients with triple-negative breast cancer(TNBC).Overexpression of epidermal growth factor receptor(EGFR)is observed in approximately 70%of TNBC patients.EGFR is crucial for promoting tumor metastasis and associated with poor prognosis.Therefore,it is vital to identify effective therapeutic strategies targeting EGFR inhibition.Ononin,an isoflavonoid found in various plants,such as clover and soybeans,has been shown to have anticancer properties in several cancers.In the present study,we aimed to investigate the effects of ononin on TNBC lung metastasis and the associated molecular pathways.We used various assays,including cell viability,colony formation,Transwell,wound healing,ELISA,Western blotting,and staining techniques,to achieve this objective.The results demonstrated that ononin effectively suppressed cellular proliferation and induced apoptosis,as evidenced by the cell viability assay,colony formation assay,and expression of apoptosis markers,and reduced the metastatic capabilities of TNBC cells.These effects were achieved through the direct suppression of cell adhesion,invasiveness and motility.Furthermore,in TNBC xenograft lung metastatic models,ononin treatment significantly reduced tumor growth and lung metastasis.Additionally,ononin reversed the epithelial-mesenchymal transition(EMT)by downregulating the expression of EMT markers and matrix metalloproteinases,as confirmed by Western blot analysis.Furthermore,ononin treatment reduced EGFR phosphorylation and suppressed the PI3K,Akt,and m TOR signaling pathways,which was further confirmed using EGFR agonists or inhibitors.Importantly,ononin treatment did not exert any toxic effects on liver or kidney function.In conclusion,our findings suggest that ononin is a safe and potentially therapeutic treatment for TNBC metastasis that targets the EGFRmediated PI3K/Akt/m TOR pathway.Further studies are warranted to validate its efficacy and explore its potential clinical applications.

血流导向装置治疗颅内未破裂动脉瘤的疗效与影响因素分析

目的探讨单纯血流导向装置或联合弹簧圈治疗颅内未破裂动脉瘤的短中期疗效以及影响因素。方法回顾性连续纳入深圳大学第一附属医院血管神经外科2019年1月至2020年12月采用Tubridge血流导向装置治疗的未破裂颅内动脉瘤患者手术数据及3~18个月随访数据。有完整随访资料者共46例(均以最后1次随访数据为准),分析病例的临床资料、手术结果(闭塞率)、动脉瘤形态学特征情况。采用单因素结合多因素非条件Logistic回归分析方法,分析动脉瘤闭塞率的影响因素。结果46例患者根据随访结果分为完全闭塞组(28例)与不完全闭塞组(18例)。2组患者年龄、动脉瘤类型、有无侧支方面比较差异均无统计学意义(P均>0.05)。单纯使用Tubridge血流导向装置(密网支架)栓塞治疗者32例,辅助弹簧圈治疗者14例,手术成功率100%。在3~18个月术后影像学随访过程中,在完全闭塞组密网支架联合弹簧圈治疗者占12/28,而未完全闭塞组密网支架联合弹簧圈治疗者仅占2/18,2组比较差异具有统计学意义(χ^(2)=4.792,P=0.029)。进一步对照分析发现动脉瘤有无侧支发出、是否联合弹簧圈治疗、随访时间>6个月是影响动脉瘤闭塞的主要因素(OR=0.101、9.832、9.266,P=0.003、0.009、0.021)。结论血流导向装置治疗颅内未破裂动脉瘤在>6个月的时间随访时有着良好的闭塞率,且联合弹簧圈辅助治疗时闭塞率更高,但动脉瘤存在侧支血管会影响其闭塞率。

Resistance reduction of patterned surface inspired by cuticle structure of Achalinus spinalis

The crawling process of snakes is known to have fascinating tribological phenomena,whereas investigations on their frictional properties depending on patterned cuticles are insufficient.In this study,we have designed and fabricated biomimetic microstructures inspired by the geometric microunits of Achalinus spinalis cuticle using polyurethane acrylate(PUA)material and performed its tribological analysis.The micro-morphology of this Achalinus-inspired textured polymer surface(AITPS)is characterized by the closely and evenly quasi-rectangular microgrooves,periodically arranged along certain orientations.We have compared the frictional performance of our fabricated AITPS with other competitive microstructure,using a smooth steel ball and commercial clay as an interacting surface.After performing massive friction tests with steel ball and clay,AITPS still maintains good resistance reduction performed compared to the patterned surface with straight microgrooves,which is most likely due to the reduction of actual contact areas at the frictional interface.

Elucidating Structures of Complex Organic Compounds Using a Machine Learning Model Based on the 13C NMR Chemical Shifts

We present a protocol that combines the support vector machine(SVM)model with accurate 13C chemical shift calculations at the xOPBE/6-311+G(2d,p)level of theory,denoted as SVM-M(i.e.,SVM for magnetic property).We show here that this SVM-M protocol is a versatile tool for identifying the structural and stereochemical assignment of complex organic compounds with high confidence.Of particular significance is that,by utilizing the dual role of the decision values in SVM,the present SVM-M protocol provides an accurate yet efficient solution to simultaneously handle the classification issue(i.e.,“is a given structure correct or incorrect?”)and the comparison-based problem(i.e.,“which structure is more likely to be correct or wrong among several candidate structures?”).A significantly high success rate has been reached(i.e.,∼100%on a set of 760 sample molecules with 1592813C chemical shifts),which makes the SVMM protocol a powerful tool for routine applications in structural and stereochemical assignments,as well as in detecting misassignments,for complex organic compounds,including natural products.

甘蔗节间伸长过程赤霉素生物合成关键基因的表达及相关植物激素动态变化

以甘蔗(Saccharum officinarum)优良品种桂糖42号(GT42)为研究材料,分别于未伸长期(9–10叶龄以前)(Ls1)、伸长初期(12–13叶龄)(Ls2)和伸长盛期(15–16叶龄)(Ls3)取甘蔗第2片真叶(自顶部起)对应的节间组织,测定其赤霉素(GA)、生长素(IAA)、油菜素甾醇(BR)、细胞分裂素(CTK)、乙烯(ETH)和脱落酸(ABA)的含量,并通过实时荧光定量PCR(qRT-PCR)分析赤霉素合成途径关键基因GA20氧化酶基因(GA20-Oxidase1)、赤霉素受体基因(GID1)和DELLA蛋白编码基因(GAI)的差异表达。结果表明,在甘蔗伸长期间, GA和IAA含量呈现上升趋势, CTK和ABA含量呈下降趋势, ETH含量先上升后下降,BR含量则变化不明显;GA20-Oxidase1和GID1的表达呈上升趋势,而GAI的表达则呈下降趋势,这与相关植物激素的变化基本一致。综上,甘蔗节间伸长过程主要与GA和IAA相关,其次为CTK和ABA,而ETH受到IAA的调控影响节间伸长;植物激素间通过相互作用调控GA20-Oxidase1、GID1和GAI的表达,影响GA含量和GA的信号转导过程,进而影响甘蔗节间的伸长。该研究揭示了甘蔗节间伸长过程中赤霉素生物合成途径和信号转导关键基因的差异表达及植物激素含量的动态变化规律。

High-throughput screening for amyloid-β binding natural small-molecules based on the combinational use of biolayer interferometry and UHPLC−DAD-Q/TOF-MS/MS

Discovery of drugs rapidly and effectively is an important aspect for Alzheimer's disease(AD).In this study,a novel high-throughput screening(HTS)method aims at screening the small-molecules with amyloid-β(Aβ)binding affinity from natural medicines,based on the combinational use of biolayer interferometry(BLI)and ultra-high-performance liquid chromatography coupled with diode-array detector and quadrupole/time-of-flight tandem mass spectrometry(UHPLC−DAD-Q/TOF-MS/MS)has been firstly developed.Briefly,the components in natural medicines disassociated from biotinylated Aβwere collected to analyze their potential Aβbinding affinity by UHPLC−DAD-Q/TOF-MS/MS.Here,baicalein was confirmed to exhibit the highest binding affinity with Aβin Scutellaria baicalensis.Moreover,polyporenic acid C(PPAC),dehydrotumulosic acid(DTA),and tumulosic acid(TA)in Kai-Xin-San(KXS)were also identified as potent Aβinhibitors.Further bioactivity validations indicated that these compounds could inhibit Aβfibrillation,improve the viability in Aβ-induced PC-12 cells,and decrease the Aβcontent and improve the behavioral ability in Caenorhabditis elegans.The molecular docking results confirmed that PPAC,DTA,and TA possessed good binding properties with Aβ.Collectively,the present study has provided a novel and effective HTS method for the identification of natural inhibitors on Aβfibrillation,which may accelerate the process on anti-AD drugs discovery and development.

SUSTAINABLE SUGARCANE CROPPING IN CHINA

Demand for sugar is projected to grow in China for the foreseeable future.However,sugarcane production is unlikely to increase due to increasing production cost and decreasing profit margin.The persisting sugarcane yield plateau and the current cropping system with fertilizer overuse,soil acidification and pests and diseases remain the major productivity constraints.Sugarcane agriculture supports the livelihood of about 28 million farmers in South China;hence,sustaining it is a socioeconomic imperative.More compellingly,to meet the ever-increasing Chinese market demand,annual sugar production must be increased from the current 10 Mt to 16 Mt by 2030 of which 80% to 90% comes from sugarcane.Therefore,increasing sugar yield and crop productivity in an environmentally sustainable way must be a priority.This review examines the current Chinese sugarcane production system and discuss options for its transition to a green,sustainable cropping system,which is vital for the long-term viability of the industry.This analysis shows that reducing chemical inputs,preventing soil degradation,improving soil health,managing water deficit,provision of clean planting material,and consolidation of small farm holdings are critical requirements to transform the current farming practices into an economically and environmentally sustainable sugarcane cropping system.

Calculations of ionization energies and electron affinities for atoms and molecules: A comparative study with different methods

In the present work,we examined the performance of 36 density functionals,including the newly developed doubly hybrid density functional XYG3(Y.Zhang,X.Xu,and W.A.Goddard Ⅲ,Proc.Natl.Acad.Sci,USA,2009,106,4963),to calculate ionization energies(IEs)and electron affinities(EAs).We used the well-established G2-1 set as reference,which contains 14 atoms and 24 molecules for IE,along with 7 atoms and 18 molecules for EA.XYG3 leads to mean absolute deviations(MADs)of 0.057 and 0.080 eV for IEs and EAs,respectively,using the basis set of 6-311+G(3df,2p).In comparison with some other functionals,MADs for IEs are 0.109(B2PLYP),0.119(M06-2X),0.159(X3LYP),0.161(PBE),0.162(B3LYP),0.165(PBE0),0.173(TPSS),0.200(BLYP),and 0.215 eV(LC-BLYP).MADs for EAs are 0.090(X3LYP),0.090(B2PLYP),0.102(PBE),0.103(M06-2X),0.104(TPSS),0.105(BLYP),0.106(B3LYP),0.126(LC-BLYP),and 0.128 eV(PBE0).