First-in-human study to evaluate the safety, tolerability, and population pharmacokinetic/pharmacodynamic target attainment analysis of FL058 alone and in combination with meropenem in healthy subjects.

FL058 is a novel diazabicyclooctane ß-lactamase inhibitor. This first-in-human study evaluated the safety, tolerability, and population pharmacokinetic (PK)/pharmacodynamic target attainment analysis of FL058 alone and in combination with meropenem in healthy subjects. The results showed that the maximum tolerated dose of FL058 was 3,000 mg after single-dose infusion. FL058 in combination with meropenem did not cause any grade 3 or higher adverse event when the dose was escalated up to 1,000 mg/2,000 mg. FL058 exposure PK parameters showed dose proportionality. FL058 was excreted primarily in urine. No significant PK interaction was found between FL058 and meropenem. Population PK model analysis indicated that the PK profiles of FL058 and meropenem were consistent with the two-compartment model. The impact of covariates, creatinine clearance, concomitant use of meropenem, body weight, sex, and FL058 dose, on FL058 exposure was less than 10%. FL058/meropenem combination was safe and well tolerated up to a 1,000-mg/2,000-mg dose in healthy adults. The recommended minimum dose of FL058/meropenem combination was 500 mg/1,000 mg by intravenous infusion over 2 h every 8 h based on target attainment analysis. The good safety, tolerability, and satisfactory PK profiles of FL058 alone and in combination with meropenem in this first-in-human study will support further clinical development of FL058 in combination with meropenem in patients with target infections (ClinicalTrials.gov identifiers: NCT05055687, NCT05058118, and NCT05058105).

Effect and Potential Mechanism of Immunotherapy on Cognitive Deficits in Animal Models of Alzheimer's Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: Immunotherapy has been reported to ameliorate Alzheimer's disease (AD) in the animal model; however, the immunologic approaches and mechanisms have not been specifically described. Thus, the systematic review and meta-analysis were conducted to explore the effect and potential mechanism of immunotherapy on AD animal experiments based on behavioral indicators. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Collaboration guidelines and the inclusion/exclusion criteria of immunotherapy in animal studies, 15 studies were systematically reviewed after extraction from a collected database of 3,742 publications. Finally, the effect and mechanism of immunotherapy on AD models were described by performing multiple subgroup analyses. RESULTS: After immunotherapy, the escape latency was reduced by 18.15 seconds and the number of crossings over the platform location was increased by 1.60 times in the Morris Water Maze. Furthermore, compared to the control group, active and passive immunization could markedly ameliorate learning and memory impairment in 3 × Tg AD animal models, and active immunization could ameliorate the learning and memory ability of the APPswe/PS1ΔE9 AD animal model. Meanwhile, it could be speculated that cognitive dysfunction was improved by immunotherapy, perhaps mainly via reducing Aß40, Aß42, and Tau levels, as well as increasing IL-4 levels. CONCLUSION: Immunotherapy significantly ameliorated the cognitive dysfunction of AD animal models by assessing behavioral indicators.

Concise method for high-precision vibration recovery of Φ-OTDR based on the GF-FastICA algorithm.

To efficiently restore the vibration signals of a phase-sensitive optical time domain reflectometer (Φ-OTDR), the GF-FastICA joint algorithm is proposed, which combines guided filtering with fast independent component analysis (FastICA). The marked region of vibration is precisely located by guided filtering. FastICA deals with the optimal phase mixing matrix of the marked region to separate the vibration signals from the noise-containing phase signals. The experimental results show that the GF-FastICA achieves a correlation coefficient of 0.998 for 5-Hz vibration signal recovery from a 14.3-km sensing fiber, verifying the potency of the algorithm. Compared with the traditional method and FastICA only, GF-FastICA improves the root mean square error (RMSE) metric by an order of magnitude, which is approaching an experience value of 10-3.

Highly discriminative and adaptive feature extraction method based on NMF-MFCC for event recognition of Φ-OTDR.

To enhance the capability of phase-sensitive optical time domain reflectometers (Φ-OTDR) to recognize disturbance events, an improved adaptive feature extraction method based on NMF-MFCC is proposed, which replaces the fixed filter bank used in the traditional method to extract the mel-frequency cepstral coefficient (MFCC) features by a spectral structure obtained from the Φ-OTDR signal spectrum using nonnegative matrix factorization (NMF). Three typical events on fences are set as recognition targets in our experiments, and the results show that the NMF-MFCC features have higher distinguishability, with the corresponding recognition accuracy reaching 98.47%, which is 7% higher than that using the traditional MFCC features.

High-efficient disturbance event recognition method of ϕ-OTDR utilizing region-segmentation differential phase signals.

We demonstrate a disturbance event recognition method based on region segmentation, which utilizes differential phase signals of a phase-sensitive optical time-domain reflectometer (ϕ-OTDR) to recognize disturbance events efficiently. The long-haul sensing fiber is divided into subsensing regions; whereas the phase signals at the two end points of the subsensing regions are subtracted, unwrapped, and differenced to represent the disturbance information. Feature extraction and classification are performed separately on the subsensing regions datasets. The experimental results indicate that the average recognition accuracy of the region-segmentation-based event recognition method is up to 92.9%. Compared to the method without region segmentation, this proposed method improves the average recognition accuracy by 8%; whereas the recognition time of three disturbance events on a 14.8-km sensing system is only 0.39 s. The proposed method provides significant support for the development of disturbance event recognition of the ϕ-OTDR sensor system.

Estimation of incubation period and serial interval of COVID-19: analysis of 178 cases and 131 transmission chains in Hubei province, China.

A novel coronavirus disease, designated as COVID-19, has become a pandemic worldwide. This study aims to estimate the incubation period and serial interval of COVID-19. We collected contact tracing data in a municipality in Hubei province during a full outbreak period. The date of infection and infector-infectee pairs were inferred from the history of travel in Wuhan or exposed to confirmed cases. The incubation periods and serial intervals were estimated using parametric accelerated failure time models, accounting for interval censoring of the exposures. Our estimated median incubation period of COVID-19 is 5.4 days (bootstrapped 95% confidence interval (CI) 4.8-6.0), and the 2.5th and 97.5th percentiles are 1 and 15 days, respectively; while the estimated serial interval of COVID-19 falls within the range of -4 to 13 days with 95% confidence and has a median of 4.6 days (95% CI 3.7-5.5). Ninety-five per cent of symptomatic cases showed symptoms by 13.7 days (95% CI 12.5-14.9). The incubation periods and serial intervals were not significantly different between male and female, and among age groups. Our results suggest a considerable proportion of secondary transmission occurred prior to symptom onset. And the current practice of 14-day quarantine period in many regions is reasonable.

Clinico-Psychosocial Factors Predicting Hepatocellular Carcinoma Related Knowledge Among Patients with Chronic Liver Disease.

Regular clinical surveillance for hepatocellular carcinoma (HCC) among high-risk patients could lead to early detection and cure. Patient's knowledge and attitude are important to the uptake rate of this surveillance. This study is aimed at assessing the level of HCC-related knowledge among patients with chronic liver disease (CLD) who are at risk of HCC and determine predictors for poor knowledge. A cross-sectional study was conducted among inpatients with CLD at the Third People's Hospital of Kunming in China. Questionnaires were used to measure patient's sociodemographic characteristics, HCC-related knowledge, and patient-doctor-related psychometric factors. Factor analysis was performed to explore the underlying domains captured by the knowledge questionnaire. Univariate and multivariate analyses were performed to identify independent predictors for each domain. Three common factors were derived from the exploratory factor analysis, namely, "Surveillance," "Lifestyle," and "Prognosis." Patients with low educational background and a short period of having CLD were at a significantly low level of HCC-related knowledge of all three domains. On the other hand, surveillance and lifestyle but not prognosis, were associated with patient's communication confidence with doctors. Over two-thirds of high-risk patients had low knowledge of HCC. Medical providers should pay more attention to low educational groups and newly diagnosed CLD patients.

Clinical Diagnostic Challenge in a Case of Disseminated Talaromyces marneffei Infection Misdiagnosed Initially as Pulmonary Tuberculosis: A Case Report and Literature Review.

This case reports a middle-aged male patient who was HIV-negative and initially misdiagnosed as pulmonary tuberculosis but was eventually diagnosed with disseminated Talaromyces marneffei (T. marneffei) infection by next-generation sequencing. The patient presented with respiratory symptoms, recurrent bone pain, and subcutaneous masses as the main symptoms. After one year of antifungal treatment, the symptoms improved obviously, but the symptoms recurred after two weeks of drug withdrawal, and the symptoms were relieved after re-administration of antifungal drugs again. This report highlights the need for the rapid evaluation of fungal infections with metagenomic next-generation sequencing (mNGS) in patients with an inadequate diagnostic basis for tuberculosis infection or a poor response to antituberculosis drugs. In addition, long-term follow-up is needed to observe disease recurrence in patients with disseminated T. marneffei infection.

Corrigendum: Distribution characteristics of human herpes viruses in the lower respiratory tract and their impact on 30-day mortality in community-acquired pneumonia patients.

[This corrects the article DOI: 10.3389/fcimb.2024.1436509.].

Distribution characteristics of human herpes viruses in the lower respiratory tract and their impact on 30-day mortality in community-acquired pneumonia patients.

Human herpes viruses (HHVs) are commonly detected in community-acquired pneumonia (CAP) patients, particularly those with complex complications, attracting increased attention from clinical practitioners. However, the significance of detecting HHVs in bronchoalveolar lavage fluid (BALF) with CAP patients is still unclear. This study retrospectively analyzed BALF samples from 64 CAP patients at the Kunming Third People's Hospital between August 2021 and December 2023. Metagenomic next generation sequencing (mNGS) was conducted on BALF samples during CAP onset. Multivariate Cox regression models were used to identify independent risk factors for 30-day all-cause mortality in CAP. HHVs were found in 84.4% of CAP patients, which were the most common pathogens (45.1%), followed by bacteria (30.2%) and fungi (11.5%). Bacterial-viral co-infections were most common, occurring in 39 patients. Notably, there was no significant difference in HHV presence between severe and non-severe CAP patients (EBV: P = 0.431, CMV: P = 0.825), except for HHV-7 (P = 0.025). In addition, there was no significant difference in the 30-day mortality between HHV positive and HHV negative groups (P = 0.470), as well as between the HHV-7 positive and HHV-7 negative groups (P = 0.910). However, neither HHVs nor HHV-7 was independent risk factors for 30-day mortality in CAP patients (HHVs: HR 1.171, P = 0.888; HHV-7: HR 1.947, P = 0.382). In summary, among the prevalent presence of multiple HHVs, EBV and CMV were the most prevalent in CAP patients. Patients with sCAP were more susceptible to HHV-7 than those with non-sCAP. These results provide valuable insights for clinicians in guiding appropriate interventions for CAP treatment.

Site differentiation strategy for selective strontium uptake and elution within an all-inorganic polyoxoniobate framework.

Selective uptake and elution of trace amounts of hazardous radioactive 90Sr from large-scale high-level liquid waste (HLW) is crucial for sustainable development. Here, we propose a site differentiation strategy, based on the presence of distinct selective metal capture sites (concavity site and tweezer site) within the giant polyoxoniobate (PONb) nanoclusters of an all-inorganic PONb framework (FZU-1). Through this strategy, FZU-1 can not only effectively remove 98.9% of Sr²âº from simulated nuclear liquid waste, performing best among the reported Sr adsorbents, but also achieve desorption of adsorbed Sr²âº ions by selectively loading Na⁺ ions, thus enabling the recycling of FZU-1. Based on the well-defined single-crystal structures and theoretical studies, it can be revealed that the rapid and selective uptake of Sr²âº is attributed to the strong binding energy between the Sr²âº ions and the concavity sites. The effective elution of Sr²âº, on the other hand, stems from the preferential binding of Na⁺ ions at the tweezer sites, elevating the cluster's electrostatic potential and indirectly facilitating the elution of Sr²âº ions. The exceptional stability of FZU-1, along with its rapid and selective Sr²âº capture and elution capabilities, positions it as a promising candidate for large-scale nuclear waste treatment and groundwater remediation applications.

[Effects of Morinda officinalis polysaccharides on FN and FN-EDA of periodontal ligament fibroblasts in inflammatory microenvironment].

PURPOSE: To investigate the effect of Morinda officinalis polysaccharides(MOP) on the expression of fibronectin(FN) and fibronectin containing extra domain A(FN-EDA) in inflammatory periodontal ligament fibroblasts. METHODS: Thirty six rats were randomly divided into a control group(n=12) and a model group (n=24). The model group used orthodontic wire ligation to establish periodontitis. After three weeks, 6 rats from each group were selected and confirmed by Micro-CT to complete the modeling. The remaining rats in the model group were randomly divided into periodontitis group, normal saline(NS) group, and MOP group. In the MOP group, MOP (200 mg/kg for 3 d, 50 µL for 4 weeks) was injected into the palatal side of the left maxillary first molar of the rats. In the NS group, same volume of NS was injected, and no treatment was performed in the periodontitis group. The left maxillary tissue of rats were taken and the pathological changes of periodontal tissue were observed by H-E staining. The expression of FN and FN-EDA was detected by immunohistochemistry. Periodontal ligament fibroblasts were cultured in vitro, the effect of MOP on cell activity detected by CCK-8. The fourth generation cells were divided into control group, inflammation group (10 mg/mL lipopolysaccharide), and experimental group (12.5 µg/mL MOP, 12.5 µg/mL MOP+10 mg/mL lipopolysaccharide). The expression of FN and FN-EDA was detected by qRT-PCR and Western blot. The data were statistically analyzed using Prism 8.0 software package. RESULTS: In vivo experiments, the expression of FN-EDA in the MOP group was significantly lower than that in the periodontitis group and NS group(P＜0.05), and the infiltration of inflammatory cells was reduced. However, there was no significant difference in the expression of FN in each group. In vitro experiments, compared with the control group, the expression of FN-EDA mRNA and protein in the inflammation group was significantly increased(P＜0.000 1). MOP significantly reduced the expression of FN-EDA in inflammatory cells, but had no significant effect on FN expression. CONCLUSIONS: With increased expression of FN-EDA in inflammatory periodontal ligament tissues and cells, MOP may play a role in inhibiting inflammation by down-regulating FN-EDA.

Enhanced nitrogen removal in constructed wetlands with multivalent manganese oxides: Mechanisms underlying ammonium oxidation processes.

The ammonium (NH4+) removal efficiency in constructed wetlands (CWs) is often limited by insufficient oxygen. In this study, an extract of Eucalyptus robusta Smith leaves was used to prepare multivalent manganese oxides (MVMOs) as substrates, which were used to drive manganese oxide (MnOx) reduction coupled to anaerobic NH4+ oxidation (Mnammox). To investigate the effects and mechanisms of MVMOs on ammonium nitrogen (NH4+-N) removal, four laboratory-scale CWs (0 %/5 %/15 %/25 % volume ratios of MVMOs) were set up and operated as continuous systems. The results showed that compared to controlled C-CW (0 % MVMOs), Mn25-CW (25 % MVMOs) improved the average NH4+-N removal efficiency from 24.31 % to 80.51 %. Furthermore, N2O emissions were reduced by 81.12 % for Mn25-CW. Isotopic tracer incubations provided direct evidence of Mnammox occurrence in Mn-CWs, contributing to 18.05-43.64 % of NH4+-N removal, primarily through the N2-producing pathway (73.54-90.37 %). Notably, batch experiments indicated that Mn(III) played a predominant role in Mnammox. Finally, microbial analysis revealed the highest abundance of the nitrifying bacteria Nitrospira and Mn-cycling bacteria Pseudomonas, Geobacter, Anaeromyxobacter, Geothrix and Novosphingobium in Mn25-CW, corresponding to its superior NH4+-N removal efficiency. The enhancement of NH4+ oxidation, first to hydroxylamine and then to nitrite, in Mn25-CW was attributed to the upregulation of ammonia monooxygenase genes (amoABC and hao). This study enhanced our understanding of Mnammox and provided further support for the use of manganese oxide substrates in CWs for efficient NH4+-N removal.

Knowledge domains and emerging trends of Genome-wide association studies in Alzheimer's disease: A bibliometric analysis and visualization study from 2002 to 2022.

OBJECTIVES: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive and behavioral function. Studies have shown that genetic factors are one of the main causes of AD risk. genome-wide association study (GWAS), as a novel and effective tool for studying the genetic risk of diseases, has attracted attention from researchers in recent years and a large number of studies have been conducted. This study aims to summarize the literature on GWAS in AD by bibliometric methods, analyze the current status, research hotspots and future trends in this field. METHODS: We retrieved articles on GWAS in AD published between 2002 and 2022 from Web of Science. CiteSpace and VOSviewer software were applied to analyze the articles for the number of articles published, countries/regions and institutions of publication, authors and cited authors, highly cited literature, and research hotspots. RESULTS: We retrieved a total of 2,751 articles. The United States had the highest number of publications in this field, and Columbia University was the institution with the most published articles. The identification of AD-related susceptibility genes and their effects on AD is one of the current research hotspots. Numerous risk genes have been identified, among which APOE, CLU, CD2AP, CD33, EPHA1, PICALM, CR1, ABCA7 and TREM2 are the current genes of interest. In addition, risk prediction for AD and research on other related diseases are also popular research directions in this field. CONCLUSION: This study conducted a comprehensive analysis of GWAS in AD and identified the current research hotspots and research trends. In addition, we also pointed out the shortcomings of current research and suggested future research directions. This study can provide researchers with information about the knowledge structure and emerging trends in the field of GWAS in AD and provide guidance for future research.

Phylogenetic and mutational analysis of H10N3 avian influenza A virus in China: potential threats to human health.

In recent years, the avian influenza virus has emerged as a significant threat to both human and public health. This study focuses on a patient infected with the H10N3 subtype of avian influenza virus, admitted to the Third People's Hospital of Kunming City on March 6, 2024. Metagenomic RNA sequencing and polymerase chain reaction (PCR) analysis were conducted on the patient's sputum, confirming the H10N3 infection. The patient presented severe pneumonia symptoms such as fever, expectoration, chest tightness, shortness of breath, and cough. Phylogenetic analysis of the Haemagglutinin (HA) and neuraminidase (NA) genes of the virus showed that the virus was most closely related to a case of human infection with the H10N3 subtype of avian influenza virus found in Zhejiang Province, China. Analysis of amino acid mutation sites identified four mutations potentially hazardous to human health. Consequently, this underscores the importance of continuous and vigilant monitoring of the dynamics surrounding the H10N3 subtype of avian influenza virus, utilizing advanced genomic surveillance techniques.

Plant-microbe involvement: How manganese achieves harmonious nitrogen-removal and carbon-reduction in constructed wetlands.

Carbon deficits in inflow frequently lead to inefficient nitrogen removal in constructed wetlands (CWs) treating tailwater. Solid carbon sources, commonly employed to enhance denitrification in CWs, increase carbon emissions. In this study, MnO2 was incorporated into polycaprolactone substrates within CWs, significantly enhancing NH4+-N and NO3--N removal efficiencies by 48.26-59.78 % and 96.84-137.23 %, respectively. These improvements were attributed to enriched nitrogen-removal-related enzymes and increased plant absorption. Under high nitrogen loads (9.55 ± 0.34 g/m3/d), emissions of greenhouse gases (CO2, CH4, and N2O) decreased by 147.23-202.51 %, 14.53-86.76 %, and 63.36-87.36 %, respectively. N2O emissions were reduced through bolstered microbial nitrogen removal pathways by polycaprolactone and MnO2. CH4 accumulation was mitigated by the increased methanotrophs and dampened methanogenesis, modulated by manganese. Additionally, manganese-induced increases in photosynthetic pigment contents (21.28-64.65 %) fostered CO2 sequestration through plant photosynthesis. This research provides innovative perspectives on enhancing nitrogen removal and reducing greenhouse gas emissions in constructed wetlands with polymeric substrates.

Effect of pH on the soybean whey protein-gum arabic emulsion delivery systems for curcumin: Emulsifying, stability, and digestive properties.

A novel curcumin (CUR) delivery system was developed using soybean whey protein (SWP)-based emulsions, enhanced by pH-adjustment and gum arabic (GA) modification. Modulating electrostatic interactions between SWP and GA at oil/water interface, pH provides favorable charging conditions for stable distribution between droplets. GA facilitated the SWP form a stable interfacial layer that significantly enhanced the emulsifying properties and CUR encapsulation efficiency of the system at pH 6.0, which were 90.15 ± 0.67%, 870.53 ± 3.22 m2/g and 2157.62 ± 115.31%, respectively. Duncan's test revealed significant improvements in thermal, UV, oxidative, and storage stabilities of CUR (P < 0.05). At pH 6.0, GA effectively protected CUR by inhibiting SWP degradation during gastric digestion and promoting the release of CUR by decreasing steric hindrance with oil droplets during intestinal digestion, achieving the highest CUR bioaccessibility (69.12% ± 0.28%) based on Duncan's test. The SWP-GA-CUR emulsion delivery system would be a novel carrier for nutrients.

Different oxygen affinities of methanotrophs and Comammox Nitrospira inform an electrically induced symbiosis for nitrogen loss.

Aerobic methanotrophs establish a symbiotic association with denitrifiers to facilitate the process of aerobic methane oxidation coupled with denitrification (AME-D). However, the symbiosis has been frequently observed in hypoxic conditions continuing to pose an enigma. The present study has firstly characterized an electrically induced symbiosis primarily governed by Methylosarcina and Hyphomicrobium for the AME-D process in a hypoxic niche caused by Comammox Nitrospira. The kinetic analysis revealed that Comammox Nitrospira exhibited a higher apparent oxygen affinity compared to Methylosarcina. While the coexistence of comammox and AME-D resulted in an increase in methane oxidation and nitrogen loss rates, from 0.82 ± 0.10 to 1.72 ± 0.09 mmol CH4 d-1 and from 0.59 ± 0.04 to 1.30 ± 0.15 mmol N2 d-1, respectively. Furthermore, the constructed microbial fuel cells demonstrated a pronounced dependence of the biocurrents on AME-D due to oxygen competition, suggesting the involvement of direct interspecies electron transfer in the AME-D process under hypoxic conditions. Metagenomic and metatranscriptomic analysis revealed that Methylosarcina efficiently oxidized methane to formaldehyde, subsequently generating abundant NAD(P)H for nitrate reduction by Hyphomicrobium through the dissimilatory RuMP pathway, leading to CO2 production. This study challenges the conventional understanding of survival mechanism employed by AME-D symbionts, thereby contributing to the characterization responsible for limiting methane emissions and promoting nitrogen removal in hypoxic regions.

Water extract of moschus alleviates erastin-induced ferroptosis by regulating the Keap1/Nrf2 pathway in HT22 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Moschus, first described in the Shennong's Classic of the Materia medicine, is a scarce and precious animal medicine. Modern pharmacological researches have suggested that Moschus has neuroprotective actions, and its mechanism is related to anti-inflammatory, antioxidant, and anti-apoptosis effects. Ferroptosis is one of the major pathologies of Alzheimer's disease (AD) and is widely implicated in the pathogenesis and progression of AD. Although previous studies have suggested that Moschus possesses neuroprotective effect, whether Moschus could mitigate neuronal damages by inhibiting the onset of ferroptosis is unknown in model cells of AD. AIM OF THE STUDY: The aim of study was to explore the water extract of Moschus (WEM) on ferroptosis caused by erastin and the potential mechanism. MATERIALS AND METHODS: Erastin was used to stimulate HT22 cells to form ferroptosis model to evaluate the anti-ferroptosis effect of WEM by cell counting kit-8 and lactic dehydrogenase (LDH) tests. The malondialdehyde (MDA) and glutathione (GSH) kits are used for detection of MDA and GSH levels, and 2',7'-dichlorofluorescein diacetate and C11 BODIPY 581/591 fluorescence probe are used for evaluation of reactive oxygen species (ROS) and lipid peroxide (LOOH) levels. And Western blot was used to test nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), and ferroptosis associated proteins including glutathione peroxidase 4 (GPX4), cystine/glutamate antiporter subunit (SLC7A11), ferritin heavy chain 1 (FTH1), ferroportin1 (FPN1), transferrin receptor (TFRC). In addition, the Nrf2 inhibitor ML385 was applied to verify whether WEM prevents erastin-induced ferroptosis by activating the Keap1/Nrf2 pathway. RESULTS: After WEM treatment, erastin-induced HT22 cell survival was significantly elevated, the accumulation of intracellular MDA, ROS, and LOOH were significantly reduced, the level of GSH and expressions of ferroptosis inhibitors GPX4 and SLC7A11 were significantly increased, and iron metabolism-related proteins TFRC, FPN1, and FTH1 were regulated. These effects of WEM are implemented by activating the Keap1/Nrf2 pathway. CONCLUSIONS: This study demonstrated that WEM could perform neuroprotective effects by alleviating ferroptosis, verified that WEM treatment of AD can be mediated by the Keap1/Nrf2 pathway, and provided theoretical support for the application of WEM in the treatment of AD.

Glucagon-like peptide 1 (GLP-1) receptor agonists in experimental Alzheimer's disease models: a systematic review and meta-analysis of preclinical studies.

Alzheimer's disease (AD) is a degenerative disease of the nervous system. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a drug used to treat type 2 diabetes, have been shown to have neuroprotective effects. This systematic review and meta-analysis evaluated the effects and potential mechanisms of GLP-1 RAs in AD animal models. 26 studies were included by searching relevant studies from seven databases according to a predefined search strategy and inclusion criteria. Methodological quality was assessed using SYRCLE's risk of bias tool, and statistical analysis was performed using ReviewManger 5.3. The results showed that, in terms of behavioral tests, GLP-1 RAs could improve the learning and memory abilities of AD rodents; in terms of pathology, GLP-1 RAs could reduce Aß deposition and phosphorylated tau levels in the brains of AD rodents. The therapeutic potential of GLP-1 RAs in AD involves a range of mechanisms that work synergistically to enhance the alleviation of various pathological manifestations associated with the condition. A total of five clinical trials were retrieved from ClinicalTrials.gov. More large-scale and high-quality preclinical trials should be conducted to more accurately assess the therapeutic effects of GLP-1 RAs on AD.