Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(μ-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electrophoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

Recent advances and key perspectives of in-situ studies for oxygen evolution reaction in water electrolysis

Electricity-driven water splitting to produce hydrogen is one of the most efficient ways to alleviate energy crisis and environmental pollution problems,in which the anodic oxygen evolution reaction(OER)is the key half-reaction of performance-limiting in water splitting.Given the complicated reaction process and surface reconstruction of the involved catalysts under actual working conditions,unraveling the real active sites,probing multiple reaction intermediates and clarifying catalytic pathways through in-situ characterization techniques and theoretical calculations are essential.In this review,we summarize the recent advancements in understanding the catalytic process,unlocking the water oxidation active phase and elucidating catalytic mechanism of water oxidation by various in-situ characterization techniques.Firstly,we introduce conventionally proposed traditional catalytic mechanisms and novel evolutionary mechanisms of OER,and highlight the significance of optimal catalytic pathways and intrinsic stability.Next,we provide a comprehensive overview of the fundamental working principles,different detection modes,applicable scenarios,and limitations associated with the in-situ characterization techniques.Further,we exemplified the in-situ studies and discussed phase transition detection,visualization of speciation evolution,electronic structure tracking,observation of reaction active intermediates,and monitoring of catalytic products,as well as establishing catalytic structure-activity relationships and catalytic mechanism.Finally,the key challenges and future perspectives for demystifying the water oxidation process are briefly proposed.

Epistasis-aware genome-wide association studies provide insights into the efficient breeding of high-yield and high-quality rice

Marker-assisted selection(MAS)and genomic selection(GS)breeding have greatly improved the efficiency of rice breeding.Due to the influences of epistasis and gene pleiotropy,ensuring the actual breeding effect of MAS and GS is still a difficult challenge to overcome.In this study,113 indica rice varieties(V)and their 565 testcross hybrids(TC)were used as the materials to investigate the genetic basis of 12 quality traits and nine agronomic traits.The original traits and general combining ability of the parents,as well as the original traits and midparent heterosis of TC,were subjected to genome-wide association analysis.In total,381 primary significantly associated loci(SAL)and 1,759 secondary SALs that had epistatic interactions with these primary SALs were detected.Among these loci,322 candidate genes located within or nearby the SALs were screened,204 of which were cloned genes.A total of 39 MAS molecular modules that are beneficial for trait improvement were identified by pyramiding the superior haplotypes of candidate genes and desirable epistatic alleles of the secondary SALs.All the SALs were used to construct genetic networks,in which 91 pleiotropic loci were investigated.Additionally,we estimated the accuracy of genomic prediction in the parent V and TC by incorporating either no SALs,primary SALs,secondary SALs or epistatic effect SALs as covariates.Although the prediction accuracies of the four models were generally not significantly different in the TC dataset,the incorporation of primary SALs,secondary SALs,and epistatic effect SALs significantly improved the prediction accuracies of 5(26%),3(16%),and 11(58%)traits in the V dataset,respectively.These results suggested that SALs and epistatic effect SALs identified based on an additive genotype can provide considerable predictive power for the parental lines.They also provide insights into the genetic basis of complex traits and valuable information for molecular breeding in rice.

Gut microbiota changes associated with frailty in older adults:A systematic review of observational studies

BACKGROUND Frailty is a complex aging-related syndrome characterized by a cumulative loss of physiological reserve and increased vulnerability to adverse clinical outcomes,including falls,disability,incapacity and death.While an increasing number of studies suggest that the gut microbiota may play a key role in the pathophy-siology of frailty,direct evaluation of the association between gut microbiome alterations and frailty in older adults remains limited.AIM Seven electronic databases(China National Knowledge Infrastructure,VIP,SinoMed,Wanfang,PubMed,Web of Science and EMBASE)were searched for articles published before October 31,2023 to identify observational studies that compared the microbiomes of older adults with and without frailty.The diversity and composition of the gut microbiota were the main outcomes used to analyze the associations of changes in the gut microbiota with frailty in older adults.The quality of the included studies was assessed via the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality.RESULTS Eleven observational studies with 912 older adults were included in this review.Consistent results revealed a significant difference in the gut microbiota composition between frail and non-frail older adults,with a significant decrease inαdiversity and a significant increase inβdiversity in frail older adults.The pooled results revealed that at the phylum level,four microbiota(Actinobacteria,Proteo-bacteria,Verrucomicrobia and Synergistetes)were significantly enriched,and two microbiota(Firmicutes and Fusobacteria)were significantly depleted in frail older adults.At the family level,the results consistently revealed that the abundances of 6 families,most of which belong to the Actinobacteria or Proteo-bacteria phylum,were greater in frail than in non-frail older adults.At the genus or species level,consistent results from more than two studies revealed that the abundances of the genera Prevotella,Faecalibacterium,and Roseburia were significantly lower in frail older adults;individual studies revealed that the abundances of some genera or species(e.g.,Megamonas,Blautia,and Megasphaera)were significantly lower,whereas those of other genera or species(e.g.,Bifidobacterium,Oscillospira,Ruminococcus and Pyramidobacter)were significantly greater in frail older adults.CONCLUSION This systematic review suggests that changes in the gut microbiota are associated with frailty in older adults,which is commonly reflected by a reduction in beneficial species and an increase in pathogenic species.However,further studies are needed to confirm these findings.

A Research Conception on Indigenous Chinese Leadership:Based on Comparative Case Studies on Political Elites in Ancient China

Due to the complexity of leadership and its variability across situations,it is suggested that research on leadership should focus on attempts to understand leadership in specific situations or roles,and develop local knowledge about leadership in each situation or role.This paper validates the possibility and importance of building indigenous leadership theories from historical perspective.We demonstrated how to carry out research on indigenous Chinese leadership from a historical perspective by comparative case studies using historical data.Based on the principles of typicalness,representativeness,and comparativeness,we selected six counterparts of political elites in ancient China as comparative cases,which includes Guan Zhong&Shang Yang(organizational reformer),Liu Bang&Xiang Yu(entrepreneur),Li Shimin&Qin Shihuang(intergenerational transition successor),Zhuge Liang&Zeng Guofan(professional manager),Lu Su&Zhang Juzheng(mess-to-order maker),and Zuo Zongtang&Wang Anshi(national dream driver).The paper aims to develop indigenous leadership theory specific to Chinese mental states and culture.

Exploring the Path of Shantytown Renewal Based on the Theory of Environment-behavior Studies: A Case Study of the Northwest Area of Saihantala in Baotou City

The application of environment-behavior studies plays an important role in studying the renewal of shantytowns.One of the most humane ways of renewal is designing and constructing the necessary urban spatial environment from the perspective of human daily behavior.Most of the shantytown renovation projects currently carried out in China are mainly focused on demolition and reconstruction,which not only incurs high costs but also damages the original social structure and economic model.During the process of shantytown renewal,it should improve the urban landscape,living environment,and life quality of residents,and ensure the daily life of shantytown residents without increasing their economic burden,and preserve the traces of urban development.In order to achieve this goal,it should explore the renewal strategies of shantytowns from the perspective of environment-behavior studies through behavior maps,on-site research,and literature review.Updating and design from a human perspective often achieve faster and better development;the renewal of shantytowns should be a bottom-up approach and start from a grassroots perspective,completing the renovation design through the composition of the population and behavioral patterns.

Genetic Parameters and Genome-Wide Association Studies for Body Size Traits of Shuxuan Cattle in China

In domestic cattle,the body size traits have important implications in terms of breed characteristics and production performance.Shuxuan cattle is a dual-purpose breed mainly raised in Sichuan province,China,for which we have known less about the genetic parameters and underlying candidate genes in relation to the body size traits.In this study,we obtained the genome-wide single nucleotide polymorphisms(SNPs)using the Illumina Bovine BeadChip in 275 Shuxuan cattle.These SNPs were first used for estimating genetic parameters for the withers height(WH)and diagonal body length(BL).Using the bivariate animal model,the estimates(±standard error)of heritabilities were 0.71±0.22 and 0.49±0.29 for BL,and their genetic correlation was 0.64±0.37.Second,the genome-wide association study(GWAS)was performed.However,these did not result into genome-wide significant SNPs for both WH and BL traits.According to a less stringent suggestive significance,some positional candidate genes were found,and some of them(such as FAM110B,TAS1R2,PAX3,and FHIT)were previously reported in literature to be associated with body size traits in cattle.In conclusion,we estimated the genetic parameters in Shuxuan cattle using genomic information for the first time,which are required for implementing the genomic selection programs in the future.

Genome-wide and candidate gene association studies identify BnPAP17 as conferring the utilization of organic phosphorus in oilseed rape

Phosphorus(P)is essential for living plants,and P deficiency is one of the key factors limiting the yield in rapeseed production worldwide.As the most important organ for plants,root morphology traits(RMTs)play a key role in P absorption.To investigate the genetic variability of RMT under low P availability,we dissected the genetic structure of RMTs by genome-wide association studies(GWAS),linkage mapping and candidate gene association studies(CGAS).A total of 52 suggestive loci were associated with RMTs under P stress conditions in 405 oilseed rape accessions.The purple acid phosphatase gene BnPAP17 was found to control the lateral root number(LRN)and root dry weight(RDW)under low P stress.The expression of BnPAP17 was increased in shoot tissue in P-efficient cultivars compared to root tissue and P-inefficient cultivars in response to low P stress.Moreover,the haplotype of BnPAP17^(Hap3)was detected for the selective breeding of P efficiency in oilseed rape.Over-expression of the BnPAP17^(Hap3)could promote the shoot and root growth with enhanced tolerance to low P stress and organic phosphorus(Po)utilization in oilseed rape.Collectively,these findings increase our understanding of the mechanisms underlying BnPAP17-mediated low P stress tolerance in oilseed rape.

The Islamic Studies in China:Research in the Field of History

A history of the Islamic studies in China,not only includes studies on world Islam,it also includes research on Islam and Muslims in China.Before the Reform and Opening Up,China did not achieve much in this field,since then,the research field of Islam and Muslim in China has been expanding and the results have been published,forming a new trend.In this field,scholars such as Jin Yijiu,Li Xinghua,Qin Huibin,Zhou Guoli,Sha Qiuzhen,Zhou Xiefan,Wu Yungui,and Yang Huaizhong have made the most outstanding achievements.Especially in the collation of reference books and historical materials,in the past 20 years,The Encyclopedia of the history of Islam,The Chinese Encyclopedia of Islam have emerged,and the Chinese and World Encyclopedia of Islamic Law and other important historical books have been published.This paper focuses on the field of historical research and divided into academic research history at home and abroad,which is discussed from several fields such as general history,special history,national history,and regional history.

Exploration of Interdisciplinary Integration in Teaching Reform of Legal Studies and Auditing

This paper attempts to explore interdisciplinary integration from four aspects:the necessity of interdisciplinary integration between legal studies and auditing,the difficulties and challenges encountered in this integration,the ideas for teaching reform in the context of interdisciplinary integration,and the expected outcomes.The aim is to achieve an organic integration of legal studies and auditing through systematic teaching reforms,thereby providing students with comprehensive and integrated knowledge and skills training,ensuring the quality of talent cultivation,and adapting to the needs of social development.

Longitudinal Studies on Illness Perceptions in Cancer Patients: A Scoping Review

Objective:To conduct a scoping review of longitudinal studies related to disease perception in cancer patients and to provide a reference for the improvement of disease perception in cancer patients.Methods:Using the scoping method,PubMed,Web of Science,The Cochrane Library,Medline,CNKI,Wanfang Database,VIP Chinese Scientific and Technical Journals Database,and China Biomedical Literature Database were searched up to July 2023 for analysis and discussion of the included literature.Results:A total of 19 articles were included,distributed across 9 countries including China,the Netherlands,and the United Kingdom,with 8 articles published in China.The study subjects included patients with breast cancer,colorectal cancer,laryngeal cancer,lung cancer,esophageal cancer,and bladder cancer.The content covered dynamic changes in disease perception,the impact of disease perception,and the influencing factors of disease perception.Conclusion:The number of longitudinal studies on disease perception in cancer patients is gradually increasing and becoming more diverse.However,issues such as a small total number of studies,single research methods,and short observation periods persist.In the future,it is necessary to conduct in-depth longitudinal research on disease perception in cancer patients,expand the scope of research fields,and provide more comprehensive theories to guide clinical treatment and nursing practices,ultimately improving the treatment outcomes and quality of life for cancer patients.

In Vivo Studies and Flow Cytometric Investigation on Anticancer Potential of Selenium Nanoparticles Synthesized via Aqueous Extract of Clerodendron phlomidis

Nowadays,doctors and nutritionists recommend individuals incorporate selenium-rich foods such as nuts,cereals,and mushrooms into their regular diet to maintain fitness and overall health.Selenium nanoparticles(SeNPs)exhibit strong chemopreventive capabilities.The anticipations for SeNPs with enhanced and tunable bioactive activities have led to a keen interest in phytofabrication.In this study,the aqueous extract of Clerodendron phlomidis plant leaves was utilized for the synthesis of SeNPs.In traditional Indian medicine,this plant extract is recognized as a significant anti-diabetic agent.The flavonoids tetrahydroxylflavone,7-hydroxyflavanone,and 6,4’-dimethyl-7-acetoxy-scutellarein present in this plant leaf extract demonstrate excellent anticancer activity.These secondary metabolites exhibit the ability to reduce sodium selenite into SeNPs.At a concentration of 13μg/mL,the synthesized SeNPs effectively inhibited the proliferation of the HepG2 cell line.The results suggest that the SeNPs possess promising anti-cancer potential against liver cancer and can be considered as a therapeutic agent for liver cancer treatment.Additionally,the cell cycle arrest induced by SeNPs was further confirmed by the fluorescence-activated cell sorting(FACS)method,indicating that SeNPs could efficiently differentiate cancer cells from normal cells.Notably,it showed a significant improvement in diethylnitrosamine(DEN)-induced Swiss Wistar rat groups.This scientific investigation highlights the high anti-cancer potential of SeNPs,positioning them as a promising therapeutic agent for liver cancer treatment.

Overbank Flow in a Multi-Staged Open Channel: Zonal and Overall Discharge Studies

An improved divided channel method has been proposed by modelling a parameter using the function of depth ratio for a multi-stage compound channel. Experimental data suggest that as the flow depth increases over the second stage floodplain, fractional contribution of the main channel and first stage floodplain under bankfull height plays a pivotal role in shear layer and momentum distribution. Therefore, a new mathematical model has been suggested for estimating the stage-discharge relationship for staged channels of more than one floodplain using the 1D technique of overall roughness correction. .

“Blind men and an elephant”:The need for animals in research,drug safety studies,and understanding civilizational diseases

Animal-based research and drug safety studies are essential to understanding the mysteries of nature and the long-term survival of humans.Due to the rapid increase in the global human population,conflict-and economically driven human migration,tourism-related activities,densely populated metropolitan areas,and local policies,humans will be affected by a multitude of novel disease-causing microorganisms and civilizational diseases.Despite disparities among countries,recent and planned changes in regulations concerning animal research and drug safety studies could have detrimental effects on both the animal research community and nations lacking sufficient social support systems.Based on existing scientific literature,I argue that we need animal research encompassing aspects such as animal development,behavior,drug safety studies,and for the understanding of future civilizational diseases.Depending on the nature of the research questions and local challenges,a suitable animal model organism should be made mandatory.

Genome-wide association studies reveal the genetic basis of amino acid content variation in tea plants

Tea is one of the most popular non-alcoholic beverages in the world,and free amino acids,especially theanine,make a major contribution to the umami taste of tea.However,the genetic basis of the variation in amino acid content in tea plants remains largely unknown.Here,we measured the free amino acid content in fresh leaves of 174 tea accessions over two years using a targeted metabolomics approach and obtained genotype data via RNA sequencing.Genome-wide association studies were conducted to investigate loci affecting the content of free amino acids.A total of 69 quantitative trait loci(–log10(P-value)>5)were identified.Functional annotation revealed that branched-chain amino acid aminotransferase,glutamine synthetase,nitrate transporter,and glutamate decarboxylase might be important for amino acid metabolism.Two significant loci,glutamine synthetase(Glu1,P=3.71×10^(−4);Arg1,P=4.61×10^(−5))and branched-chain amino acid aminotransferase(Val1,P=4.67×10^(−5);I_Leu1,P=3.56×10^(−6)),were identified,respectively.Based on the genotyping result,two alleles of CsGS(CsGS-L and CsGS-H)and CsBCAT(CsBCAT-L and CsBCAT-H)were selected to perform function verification.Overexpression of CsGS-L and CsGS-H enhanced the contents of glutamate and arginine in transgenic plants,and overexpression of CsBCAT-L and CsBCAT-H promoted the accumulation of valine,isoleucine and leucine.Enzyme activity assay uncovered that SNP1054 is important for CsGS catalyzing glutamate into glutamine.Furthermore,CsGS-L and CsGS-H differentially regulated the accumulation of glutamine,and CsBCAT-L and CsBCAT-H differentially regulated the accumulation of branched-chain amino acids.In summary,the findings in our study would provide new insights into the genetic basis of amino acids contents variation in tea plants and facilitate the identification of elite genes to enhance amino acids content.

Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be elucidated.Here,Piezo1 channel was identified as a key iron transporter in response to mechanical stress.Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron gatekeeper.Furthermore,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical stress.Moreover,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

A review of challenges and opportunities in micropillar compression studies in Mg alloys

This review paper provides an overview of the micropillar compression technique as applied to magnesium(Mg) and its alloys. It explores the influence of various factors, such as pillar size, shape, temperature, and strain rate on the mechanical properties of Mg.Additionally, the impact of alloying elements, aging, and precipitates in Mg alloys has been extensively examined, revealing their significant influence on mechanical performance. The study highlights the strength and strain hardening improvements in Mg with decreasing pillar size in micropillar compression. Furthermore, the role of precipitates as strengthening agents, affecting deformation mechanisms and overall mechanical response, is explored. These valuable insights are crucial for designing Mg-based materials with enhanced mechanical properties for advanced engineering applications.

Lithium-Ion Charged Polymer Channels Flattening Lithium Metal Anode

The concentration difference in the near-surface region of lithium metal is the main cause of lithium dendrite growth.Resolving this issue will be key to achieving high-performance lithium metal batteries(LMBs).Herein,we construct a lithium nitrate(LiNO_(3))-implanted electroactiveβphase polyvinylidene fluoride-co-hexafluoropropylene(PVDF-HFP)crystalline polymorph layer(PHL).The electronegatively charged polymer chains attain lithium ions on the surface to form lithium-ion charged channels.These channels act as reservoirs to sustainably release Li ions to recompense the ionic flux of electrolytes,decreasing the growth of lithium dendrites.The stretched molecular channels can also accelerate the transport of Li ions.The combined effects enable a high Coulombic efficiency of 97.0%for 250 cycles in lithium(Li)||copper(Cu)cell and a stable symmetric plating/stripping behavior over 2000 h at 3 mA cm^(-2)with ultrahigh Li utilization of 50%.Furthermore,the full cell coupled with PHL-Cu@Li anode and Li Fe PO_(4) cathode exhibits long-term cycle stability with high-capacity retention of 95.9%after 900 cycles.Impressively,the full cell paired with LiNi_(0.87)Co_(0.1)Mn_(0.03)O_(2)maintains a discharge capacity of 170.0 mAh g^(-1)with a capacity retention of 84.3%after 100 cycles even under harsh condition of ultralow N/P ratio of 0.83.This facile strategy will widen the potential application of LiNO_(3)in ester-based electrolyte for practical high-voltage LMBs.

The Channel Branches & Network Vessels on the Tianhui Lacquered Meridian Figurine——Taking the Heart-Regulated Channel as an Example

Along with the surge of unearthed medical literature and cultural relics in recent years,a network of channels in the system of medical conduit vessels(meridians) during the early Western Han dynasty has become much clearer gradually.In it,the increasing number of channel branches,network vessels and needle insertion holes(acupoints) is an important feature of the development of channel medicine during the Western Han dynasty.This is not only a reflection of the expanding requirements of the theoretical system of the main trunk channels and other vessels,but also an inevitable result of the continuous enrichment and accumulation of clinical experience.This article integrates the information about channel branches,network vessels,inscriptions,dots and further relics on the Tianhui(天回) Lacquered Meridian Figurine to compare the unearthed literature of the channel genre with the transmitted classical literature about acupuncture.The “Heart-Regulated Channel” in Medical Manuscripts on Bamboo Slips from Tianhui(《天回医简》) serves as an example to explain the occurrence,development and changes of the channel branches and network vessels in the early system of medical channels.