Passive immunotherapy for Alzheimer's disease: challenges & future directions.

Passive immunotherapy with specific antibodies targeting Amyloid ß (Aß) peptide or tubulin-associated unit (tau) protein has emerged as a promising therapeutic approach in Alzheimer's disease (AD). However, in a recent phase III clinical study, Sperling et al. (N Engl J Med 10.1056/NEJMoa2305032, 2023) reported that solanezumab, a monoclonal antibody targeting Aß peptide, failed to slow cognitive decline in AD patients. Previously, three other anti-Aß antibodies, bapineuzumab, crenezumab, and gantenerumab, have also failed to show similar beneficial effects. In addition, three humanized antibodies targeting tau protein failed in their phase II trials. However, other anti-Aß antibodies, such as lecanemab (a humanized mAb binds to soluble Aß protofibrils), donanemab (a humanized mAb binds to insoluble, N-terminal truncated form of Aß peptides) and aducanumab (a human mAb binds to the aggregated form of Aß), have been shown to slow the decline of cognitive functions in early stage AD patients. The specific targets used in passive immunotherapy in these clinical trials may explain the divergent clinical outcomes. There are several challenges and limitations of passive immunotherapy using anti-Aß antibodies and long term longitudinal studies are needed to assess their efficacy, side effects and cost effectiveness in a wider spectrum of subjects, from pre-dementia to more advanced dementia. A combination therapeutic approach using both anti-Aß antibodies and other pharmaceutical agents should also be explored.

From zinc homeostasis to disease progression: Unveiling the neurodegenerative puzzle.

Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and DNA repair. The zinc transporters (ZnTs) family members are responsible for exporting intracellular zinc, while Zrt- and Irt-like proteins (ZIPs) are involved in importing extracellular zinc. These processes are essential for maintaining cellular zinc homeostasis. Imbalances in zinc metabolism have been linked to the development of neurodegenerative diseases. Disruptions in zinc levels can impact the survival and activity of neurons, thereby contributing to the progression of neurodegenerative diseases through mechanisms like cell apoptosis regulation, protein phase separation, ferroptosis, oxidative stress, and neuroinflammation. Therefore, conducting a systematic review of the regulatory network of zinc and investigating the relationship between zinc dysmetabolism and neurodegenerative diseases can enhance our understanding of the pathogenesis of these diseases. Additionally, it may offer new insights and approaches for the treatment of neurodegenerative diseases.

Molybdate-Templated Luminescent Silver Alkynyl Nanoclusters: Total Structure Determination and Optical Property Analysis.

Two novel MoO42--templated luminescent silver alkynyl nanoclusters with 20-nuclearity ([(MoO42-)@Ag20(C≡CtBu)8(Ph2PO2)7(tfa)2]·(tfa-) (1)) and 18-nuclearity ([(MoO42-)@Ag18(C≡CtBu)8(Ph2PO2)7]·(OH) (2)) (tfa = trifluoroacetate) were synthesized with the green light maximum emissions at 507 and 516 nm, respectively. The nanoclusters were investigated and characterized by single-crystal X-ray crystallography, electrospray ionization mass spectrum (ESI-MS), X-ray photoelectron spectroscopy, thermogravimetry (TG), photoluminescence (PL), ultraviolet-visible (UV-vis) spectroscopy, and density functional theory calculations (DFT). The two nanoclusters differ in their structure by a supplementary [Ag2(tfa)2] organometallic surface motif, which significantly participates in the frontier molecular orbitals of 1, resulting in similar bonding patterns but different optical properties between the two clusters. Indeed, both nanoclusters show strong temperature-dependent photoluminescence properties, which make them potential candidates in the fields of optical devices for further applications.

TP53 to mediate immune escape in tumor microenvironment: an overview of the research progress.

Increasing evidence suggests that key cancer-causing driver genes continue to exert a sustained influence on the tumor microenvironment (TME), highlighting the importance of immunotherapeutic targeting of gene mutations in governing tumor progression. TP53 is a prominent tumor suppressor that encodes the p53 protein, which controls the initiation and progression of different tumor types. Wild-type p53 maintains cell homeostasis and genomic instability through complex pathways, and mutant p53 (Mut p53) promotes tumor occurrence and development by regulating the TME. To date, it has been wildly considered that TP53 is able to mediate tumor immune escape. Herein, we summarized the relationship between TP53 gene and tumors, discussed the mechanism of Mut p53 mediated tumor immune escape, and summarized the progress of applying p53 protein in immunotherapy. This study will provide a basic basis for further exploration of therapeutic strategies targeting p53 protein.

Antifungal mechanism of rose, mustard, and their blended essential oils against Cladosporium allicinum isolated from Xinjiang naan and its storage application.

AIMS: To reveal the inhibition mechanism of rose, mustard, and blended essential oils against Cladosporium allicinum isolated from Xinjiang naan, and investigate the effect of the three essential oils on oxidative damage and energy metabolism. METHODS AND RESULTS: Rose and mustard essential oils significantly inhibited mycelial growth and spore viability in a dose-dependent relationship. After essential oil treatment, the cell membrane permeability was altered, and significant leakage of intracellular proteins and nucleic acids occurred. SEM observations further confirmed the disruption of cell structure. ROS, MDA, and SOD measurements indicated that essential oil treatment induced a redox imbalance in C. allicinum, leading to cell death. As for energy metabolism, essential oil treatment significantly reduced Na+K+-ATPase, Ca2+Mg2+-ATPase, MDH activity, and CA content, impairing metabolic functions. Finally, storage experiments showed that all three essential oils ensured better preservation of naan, with mustard essential oil having the best antifungal effect. CONCLUSIONS: Rose and mustard essential oils and their blends can inhibit C. allicinum at multiple targets and pathways, destroying cell morphological structure and disrupting metabolic processes.

Targeted inhibition of the HNF1A/SHH axis by triptolide overcomes paclitaxel resistance in non-small cell lung cancer.

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.

The Role of JAK-STAT-SOCS1 Axis in Tumorigenesis, Malignant Progression and Lymphatic Metastasis of Penile Cancer.

Background: To uncover the potential significance of JAK-STAT-SOCS1 axis in penile cancer, our study was the pioneer in exploring the altered expression processes of JAK-STAT-SOCS1 axis in tumorigenesis, malignant progression and lymphatic metastasis of penile cancer. Methods: In current study, the comprehensive analysis of JAK-STAT-SOCS1 axis in penile cancer was analyzed via multiple analysis approaches based on GSE196978 data, single-cell data (6 cancer samples) and bulk RNA data (7 cancer samples and 7 metastasis lymph nodes). Results: Our study observed an altered molecular expression of JAK-STAT-SOCS1 axis during three different stages of penile cancer, from tumorigenesis to malignant progression to lymphatic metastasis. STAT4 was an important dominant molecule in penile cancer, which mediated the immunosuppressive tumor microenvironment by driving the apoptosis of cytotoxic T cell and was also a valuable biomarker of immune checkpoint inhibitor treatment response. Conclusions: Our findings revealed that the complexity of JAK-STAT-SOCS1 axis and the predominant role of STAT4 in penile cancer, which can mediate tumorigenesis, malignant progression, and lymphatic metastasis. This insight provided valuable information for developing precise treatment strategies for patients with penile cancer.

Applications of magnetic solid-phase extraction in the sample preparation of natural product analysis (2020-2023).

Sample preparation, including extraction, separation, and purification, is a vital process for natural product analysis. As an attractive sample pretreatment method, magnetic solid-phase extraction (MSPE) has gained plenty of attention, mainly due to its simpler operation, less consumption of organic solvents, and shorter processing time than traditional SPE. This updated review is devoted to summarizing the applications of MSPE based on different magnetic nanomaterials in the analysis of various natural products in complex matrixes, such as biological samples, plants, and Chinese herbal preparations in the past four years (2020-2023). The preparation and fabrication of different materials are briefly introduced. Furthermore, the extraction mechanism and interaction forces between adsorbent and analytes are elaborated, and the advantages and disadvantages of different adsorbents coupled with various analytical methods for MSPE of different natural products are summarized. Moreover, the future trends and opportunities for MSPE in the natural product analysis are discussed. It is expected that this work can provide updated information for future research on the applications of MSPE in such fields.

Establishment and validation of a nomogram to predict postoperative anemia after total hip arthroplasty.

BACKGROUND: Anemia is a common complication of total hip arthroplasty (THA). In this study, we evaluated the preoperative risk factors for postoperative anemia after THA and developed a nomogram model based on related preoperative and intraoperative factors. METHODS: From January 2020 to May 2023, 927 THA patients at the same medical center were randomly assigned to either the training or validation cohort. The correlation between preoperative and intraoperative risk factors and postoperative anemia after THA was evaluated using univariate and multivariate logistic regression analysis. A nomogram was developed using these predictive variables. The effectiveness and validation for the clinical application of this nomogram were evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: Through univariate and multivariate logistic regression analysis, 7 independent predictive factors were identified in the training cohort: Lower body mass index (BMI), extended operation time, greater intraoperative bleeding, lower preoperative hemoglobin level, abnormally high preoperative serum amyloid A (SAA) level, history of cerebrovascular disease, and history of osteoporosis. The C-index of the model was 0.871, while the AUC indices for the training and validation cohorts were 84.4% and 87.1%, respectively. In addition, the calibration curves of both cohorts showed excellent consistency between the observed and predicted probabilities. The DCA curves of the training and validation cohorts were high, indicating the high clinical applicability of the model. CONCLUSIONS: Lower BMI, extended operation time, increased intraoperative bleeding, reduced preoperative hemoglobin level, elevated preoperative SAA level, history of cerebrovascular disease, and history of osteoporosis were seven independent preoperative risk factors associated with postoperative anemia after THA. The nomogram developed could aid in predicting postoperative anemia, facilitating advanced preparation, and enhancing blood management. Furthermore, the nomogram could assist clinicians in identifying patients most at risk for postoperative anemia.

Analysis on Foodborne Pathogen Contamination of Food Samples in Longnan City from 2013 to 2022.

The objective was to determine the prevalence of foodborne pathogens in food in Longnan City, Gansu Province, China. In this research, we conducted tests on baked foods, catering foods, meat, and fruits and vegetables sold in supermarkets, farmers' markets, restaurants, retail stores, street stalls, and school canteens from 2013 to 2022. We analyzed the variety of foodborne pathogens (Salmonella, Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, and diarrheagenic Escherichia coli) in different sites and food types. Once foodborne pathogens were detected in the sample, it was deemed unqualified. The total detection rates of foodborne pathogens were 1.559%, 3.349%, 1.980%, 1.040%, 3.383%, and 1.303% in food from supermarkets, farmers' markets, restaurants, retail stores, street stalls, and school canteens, respectively. No pathogenic bacteria were detected in baked foods. Salmonella, S. aureus, L. monocytogenes, B. cereus, and diarrheagenic E. coli were detected in catering foods, among which B. cereus had the highest detection rate. Salmonella was the most common pathogenic bacteria detected in meat, while the detection rate of pathogenic bacteria in fruits and vegetables was low, with only one positive sample for diarrheagenic E. coli. Among the six sites, street stalls (3.382%) and farmers' markets (3.349%) had higher detection rates of pathogens. In general, the detection rate of pathogens from 2013 to 2022 was not high, but there were also some hidden dangers. Catering food is vulnerable to pathogen contamination, and street stalls and farmers' markets are the main sites of pollution. According to the above findings, the regulatory authorities should continue to strengthen supervision, guarantee food safety through early warning, and reduce the risk of food contamination.

Tyrosine Hydroxylase Inhibitors and Dopamine Receptor Agonists Combination Therapy for Parkinson's Disease.

There are currently no disease-modifying therapies for Parkinson's disease (PD), a progressive neurodegenerative disorder associated with dopaminergic neuronal loss. There is increasing evidence that endogenous dopamine (DA) can be a pathological factor in neurodegeneration in PD. Tyrosine hydroxylase (TH) is the key rate-limiting enzyme for DA generation. Drugs that inhibit TH, such as alpha-methyltyrosine (α-MT), have recently been shown to protect against neurodegeneration in various PD models. DA receptor agonists can activate post-synaptic DA receptors to alleviate DA-deficiency-induced PD symptoms. However, DA receptor agonists have no therapeutic effects against neurodegeneration. Thus, a combination therapy with DA receptor agonists plus TH inhibitors may be an attractive therapeutic approach. TH inhibitors can protect and promote the survival of remaining dopaminergic neurons in PD patients' brains, whereas DA receptor agonists activate post-synaptic DA receptors to alleviate PD symptoms. Additionally, other PD drugs, such as N-acetylcysteine (NAC) and anticholinergic drugs, may be used as adjunctive medications to improve therapeutic effects. This multi-drug cocktail may represent a novel strategy to protect against progressive dopaminergic neurodegeneration and alleviate PD disease progression.

Silver Nanoparticles Encapped by Dihydromyricetin: Optimization of Green Synthesis, Characterization, Toxicity, and Anti-MRSA Infection Activities for Zebrafish (Danio rerio).

To achieve the environmentally friendly and rapid green synthesis of efficient and stable AgNPs for drug-resistant bacterial infection, this study optimized the green synthesis process of silver nanoparticles (AgNPs) using Dihydromyricetin (DMY). Then, we assessed the impact of AgNPs on zebrafish embryo development, as well as their therapeutic efficacy on zebrafish infected with Methicillin-resistant Staphylococcus aureus (MRSA). Transmission electron microscopy (TEM) and dynamic light-scattering (DLS) analyses revealed that AgNPs possessed an average size of 23.6 nm, a polymer dispersity index (PDI) of 0.197 ± 0.0196, and a zeta potential of -18.1 ± 1.18 mV. Compared to other published green synthesis products, the optimized DMY-AgNPs exhibited smaller sizes, narrower size distributions, and enhanced stability. Furthermore, the minimum concentration of DMY-AgNPs required to affect zebrafish hatching and survival was determined to be 25.0 µg/mL, indicating the low toxicity of DMY-AgNPs. Following a 5-day feeding regimen with DMY-AgNP-containing food, significant improvements were observed in the recovery of the gills, intestines, and livers in MRSA-infected zebrafish. These results suggested that optimized DMY-AgNPs hold promise for application in aquacultures and offer potential for further clinical use against drug-resistant bacteria.

An analytical overview of the composition and characteristics of China's food safety standards.

This paper discusses the framework of China's food safety standards and provides a brief overview of the problems and developmental characteristics of food safety in China. The composition and characteristics of China's food safety standards are revealed by an analysis of the changes in China's general food standards, an overview of the characteristics of the hygiene requirements in the production and operation process, and an introduction to food product and test method standards. In conclusion, Chinese food safety standards are still being improved, but they must also be effectively implemented and followed up in real time in order to continuously improve the quality of food and reduce food safety incidents. © 2024 Society of Chemical Industry.

Gas chromatography-ion mobility spectrometry (GC-IMS) technique and its recent applications in grain research.

Grains are the primary source of food for most people worldwide and constitute a major source of carbohydrates. Many novel technologies are being employed to ensure the safety and reliability of grain supply and production. Gas chromatography-ion mobility spectrometry (GC-IMS) can effectively separate and sensitively detect volatile organic compounds. It possesses advantages such as speed, convenience, high sensitivity, no pretreatment, and wide applicability. In recent years, many studies have shown that the application of GC-IMS technology for grain flavor analysis can play a crucial role in grains. This article elucidates the working principle of GC-IMS technology, reviews the application of GC-IMS in grains in the past 5 years. GC-IMS technology is mainly applied in four aspects in grains. In grain classification, it distinguishes varieties, quality, origin, production year, and processing methods based on the trace differences in volatile organic compounds, thereby fulfilling various grain classification requirements such as origin tracing, geographical indication product recognition, variety identification, production year identification, and detection of counterfeit and inferior grain samples. In optimizing the processing technology of grains and their products, it can improve food flavor, reduce undesirable flavors, and identify better processing parameters. In grain storage, it can determine the storage time, detect spoilage phenomena such as mold and discoloration during storage, eliminate pests affecting storage, and predict the vitality of seeds after storage. In aroma evaluation of grains and their processed products, it can assess the impact of new raw materials, new technologies, fermentation processes, and even oral processing on the quality of grain products. This article also summarizes the characteristics of GC-IMS technology, compiles typical grain flavor compounds, and provides prospects for the future application of GC-IMS. © 2024 Society of Chemical Industry.

Plasma extracellular vesicle circRNA signature and resistance to abiraterone in metastatic castration-resistant prostate cancer.

BACKGROUND: We aimed to develop and validate a plasma extracellular vesicle circular RNA (circRNA)-based signature that can predict overall survival (OS) in first-line abiraterone therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: In total, 582 mCRPC patients undergoing first-line abiraterone therapy from four institutions were sorted by three phases. In the discovery phase, 30 plasma samples from 30 case-matched patients with or without early progression were obtained to generate circRNA expression profiles using RNA sequencing. In the training phase, differentially expressed circRNAs were examined using digital droplet PCR in a training cohort (n = 203). The circRNA signature was constructed using a least absolute shrinkage and selection operator Cox regression to predict OS. In the validation phase, the prognostic ability of this signature was prospectively validated in two external cohorts (Cohort I, n = 183; Cohort II, n = 166). RESULTS: We developed a five-circRNA signature, based on circCEP112, circFAM13A, circBRWD1, circVPS13C and circMACROD2, which successfully stratified patients into high-risk and low-risk groups. The prognostic ability of this signature was prospectively validated in two external cohorts (P < 0.0001, P < 0.0001). Patients with high-risk scores had shorter OS than patients with low-risk scores. CONCLUSION: This five-circRNA signature is a reliable predictor of OS for mCRPC patients undergoing abiraterone.

Explore the optimal timing for administering the second dose of the varicella vaccine in China.

The prevalence of varicella in China has been increasing annually, with a relatively high incidence rate of breakthrough cases. Administering two doses of the varicella vaccine (Varv) proves to be the most effective measure. The objective of this study is to assess the immunogenicity of two doses of the Varv at varying intervals and explore the optimal timing for administering the second dose of the Varv. Utilizing a prospective cohort study design, the quantification of varicella immunoglobulin G (IgG) antibodies' geometric mean concentrations (GMC) is conducted through glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). A total of 903 infants were included in the per-protocol population. After completing the first dose of the Varv, the GMC of antibody after 1 month (Group A) was 463.8 (447.6-480.1) mIU/mL. There was a statistically significant difference in GMC and seroconversion rates among the groups (B/C/D) that received the second dose of the Varv (p < 0.05). Multiple comparisons revealed that the group with a 3-year interval between the two vaccine doses had a higher GMC of 665.2 (622.6-707.8) mIU/mL compared to the group with a 1-year interval of 611.1 (577.1-645.3) mIU/mL and the group with a 5-year interval of 564.7 (540.1-589.4) mIU/mL. To effectively prevent and control the varicella epidemic in Jiangsu Province, two dose Varv vaccination is recommended, the optimal time point for the second dose Varv is 3 years after the first vaccination.

Lung function and risk of incident dementia: A prospective cohort study of 431,834 individuals.

BACKGROUND: Whether lung function prospectively affects cognitive brain health independent of their overlapping factors remains largely unknown. This study aimed to investigate the longitudinal association between decreased lung function and cognitive brain health and to explore underlying biological and brain structural mechanisms. METHODS: This population-based cohort included 43,1834 non-demented participants with spirometry from the UK Biobank. Cox proportional hazard models were fitted to estimate the risk of incident dementia for individuals with low lung function. Mediation models were regressed to explore the underlying mechanisms driven by inflammatory markers, oxygen-carrying indices, metabolites, and brain structures. FINDINGS: During a follow-up of 3,736,181 person-years (mean follow-up 8.65 years), 5,622 participants (1.30 %) developed all-cause dementia, which consisted of 2,511 Alzheimer's dementia (AD) and 1,308 Vascular Dementia (VD) cases. Per unit decrease in lung function measure was each associated with increased risk for all-cause dementia (forced expiratory volume in 1 s [liter]: hazard ratio [HR, 95 %CI], 1.24 [1.14-1.34], P = 1.10 × 10-07; forced vital capacity [liter]: 1.16 [1.08-1.24], P = 2.04 × 10-05; peak expiratory flow [liter/min]: 1.0013 [1.0010-1.0017], P = 2.73 × 10-13). Low lung function generated similar hazard estimates for AD and VD risks. As underlying biological mechanisms, systematic inflammatory markers, oxygen-carrying indices, and specific metabolites mediated the effects of lung function on dementia risks. Besides, brain grey and white matter patterns mostly affected in dementia were substantially changed with lung function. INTERPRETATION: Life-course risk for incident dementia was modulated by individual lung function. Maintaining optimal lung function is useful for healthy aging and dementia prevention.

Correction: Surface lanthanide activator doping for constructing highly efficient energy transfer-based nanoprobes for the on-site monitoring of atmospheric sulfur dioxide.

Correction for 'Surface lanthanide activator doping for constructing highly efficient energy transfer-based nanoprobes for the on-site monitoring of atmospheric sulfur dioxide' by Cuilan Zhang et al., Analyst, 2020, 145, 537-543, https://doi.org/10.1039/C9AN01725A.

Template-Free Synthesis of Two New Luminescent One-Dimensional High-Nuclearity Silver Polyclusters.

The metallophilic properties, spherical configuration, and flexible coordination of silver ions make them prone to create various coordination modes and structural features. Therefore, with the increase of the complexities of self-assembly, the effect of various synthetic conditions in the final structure of silver compounds becomes diverse and attractive. In this study, two new silver polyclusters, 16- and 21-nuclearity, protected by multiple ligands including alkynyl, trifluoroacetate, and diphenylphosphinate, were synthesized and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, and Fourier transform infrared (FTIR) spectroscopy. The optical properties and thermal stability of the polyclusters were studied by solid-state ultraviolet-visible (UV-vis) absorption and solid UV-vis diffuse reflectance spectra and gravimetric analysis, respectively. The formation of the two polyclusters can be fine-controlled by simply adjusting the stoichiometric ratio of diphenylphosphinate ligands to silver precursors under the same synthetic condition, leading to the different coordination modes between ligands and Ag centers. This work shows a facile and template-free method to synthesize and control the silver polycluster assembly, encouraging further development of new polyclusters with the potential for various applications.

The metal ion hypothesis of Alzheimer's disease and the anti-neuroinflammatory effect of metal chelators.

Alzheimer's disease (AD), characterized by the ß-amyloid protein (Aß) deposition and tau hyperphosphorylation, is the most common dementia with uncertain etiology. The clinical trials of Aß monoclonal antibody drugs have almost failed, giving rise to great attention on the other etiologic hypothesis regarding AD such as metal ions dysmetabolism and chronic neuroinflammation. Mounting evidence revealed that the metal ions (iron, copper, and zinc) were dysregulated in the susceptible brain regions of AD patients, which was highly associated with Aß deposition, tau hyperphosphorylation, neuronal loss, as well as neuroinflammation. Further studies uncovered that iron, copper and zinc could not only enhance the production of Aß but also directly bind to Aß and tau to promote their aggregations. In addition, the accumulation of iron and copper could respectively promote ferroptosis and cuproptosis. Therefore, the metal ion chelators were recognized as promising agents for treating AD. This review comprehensively summarized the effects of metal ions on the Aß dynamics and tau phosphorylation in the progression of AD. Furthermore, taking chronic neuroinflammation contributes to the progression of AD, we also provided a summary of the mechanisms concerning metal ions on neuroinflammation and highlighted the metal ion chelators may be potential agents to alleviate neuroinflammation under the condition of AD. Nevertheless, more investigations regarding metal ions on neuroinflammation should be taken into practice, and the effects of metal ion chelators on neuroinflammation should gain more attention. Running title: Metal chelators against neuroinflammation.