All-RNA-mediated targeted gene integration in mammalian cells with rationally engineered R2 retrotransposons.

All-RNA-mediated targeted gene integration methods, rendering reduced immunogenicity, effective deliverability with non-viral vehicles, and a low risk of random mutagenesis, are urgently needed for next-generation gene addition technologies. Naturally occurring R2 retrotransposons hold promise in this context due to their site-specific integration profile. Here, we systematically analyzed the biodiversity of R2 elements and screened several R2 orthologs capable of full-length gene insertion in mammalian cells. Robust R2 system gene integration efficiency was attained using combined donor RNA and protein engineering. Importantly, the all-RNA-delivered engineered R2 system showed effective integration activity, with efficiency over 60% in mouse embryos. Unbiased high-throughput sequencing demonstrated that the engineered R2 system exhibited high on-target integration specificity (99%). In conclusion, our study provides engineered R2 tools for applications based on hit-and-run targeted DNA integration and insights for further optimization of retrotransposon systems.

Schisandrin inhibits VSMCs proliferation and migration by arresting cell cycle and targeting JAK2 to regulating the JAK2/STAT3 pathway.

Abnormal proliferation, migration, and foam cell formation of Vascular smooth muscle cells (VSMCs) each play a role in the development of atherosclerosis (AS). Schisandrin (Sch) is the active lignan ingredient with broad-spectrum pharmacological effects. However, the role of Sch in the AS process is not clear. Therefore, this study was proposed to explore the therapeutic effect and potential mechanism of Sch on VSMCs. Ox-LDL was selected to create an atherosclerosis injury environment for VSMCs and macrophages. The MTT assay, Oil red O staining, wound healing, transwell experiments and ELISA were used to investigate the phenotype effects of Sch. Network pharmacology, molecular docking, flow cytometry, and western blot were used to investigate the underlying mechanisms of Sch on AS progression. Our findings implied that Sch treatment inhibited the proliferation and migration of VSMCs, and suppressed the ROS production and inflammatory cytokines up-regulation of VSMCs and macrophages. Moreover, Sch reduced lipid uptake and foam cell formation through downregulating LOX-1. Mechanistically, we found that Sch can inhibit the activation of JAK2/STAT3 signaling by targeting JAK2, and arrest cell cycle in GO/G1 phase. In summary, Sch can inhibit VSMCs proliferation and migration by arresting cell cycle and targeting JAK2 to regulating the JAK2/STAT3 pathway. Sch may serve as a potential drug for patients with AS.

Tyrosine Kinase Inhibitor Lenvatinib Causes Cardiotoxicity by Inducing Endoplasmic Reticulum Stress and Apoptosis through Activating ATF6, IRE1α and PERK Signaling Pathways.

BACKGROUND: Lenvatinib is a tyrosine kinase inhibitor that can improve progression-free survival in patients with thyroid cancer and hepatocellular carcinoma. However, it is limited by adverse cardiovascular events, including hypertension and cardiac dysfunction. Activation of endoplasmic reticulum stress is involved in cardiomyocyte apoptosis. OBJECTIVE: This study aimed to confirm whether the cardiotoxicity of lenvatinib is associated with endoplasmic reticulum stress by targeting the activating transcription factor 6 (ATF6), inositol- requiring enzyme 1α (IRE1α) and protein kinase RNA-like ER kinase (PERK) signaling pathways. METHODS: Male C57/BL6 mice were intragastric administration with 30 mg/kg/day lenvatinib. Electrocardiography (ECG) and echocardiography were used to detect arrhythmias and cardiac function. Neonatal rat cardiomyocytes were treated with lenvatinib for 48h. Cell counting kit (CCK8), 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFHDA), Hoechst 33258 and dihydrorhodamine 123 were respectively used for evaluating cell viability, the level of reactive oxygen species (ROS), nuclear morphological changes and mitochondrial membrane potential (MMP) level. RESULTS: Lenvatinib remarkably decreased the posterior wall thickness of left ventricle during diastole and systole but caused little decrease to the left ventricular ejection fraction (LVEF, %). Furthermore, lenvatinib greatly prolonged the corrected QT interval (QTc) and altered the morphology of cardiomyocytes. No dramatic difference in fibrosis was found in mouse cardiac slices. Lenvatinib upregulates apoptosis-related protein expression. In addition, lenvatinib increased ERS-related protein expression (GRP78, CHOP, and ATF6) and enhanced PERK phosphorylation. In neonatal rat cardiac myocytes, lenvatinib markedly decreased the viability of cardiomyocytes and induced apoptosis. Furthermore, ROS production increased and MMP decreased. Similar to the mice experiment, lenvatinib caused upregulation of apoptosis-related and ERS-related proteins and increased the phosphorylation levels of PERK and IRE1α. CONCLUSION: Lenvatinib-induced cardiotoxicity is associated with ERS-induced apoptosis by targeting the ATF6, IRE1α, and PERK signaling pathways.

LncRNAs are involved in regulating ageing and age-related disease through the adenosine monophosphate-activated protein kinase signalling pathway.

A long noncoding RNA (lncRNA) is longer than 200 bp. It regulates various biological processes mainly by interacting with DNA, RNA, or protein in multiple kinds of biological processes. Adenosine monophosphate-activated protein kinase (AMPK) is activated during nutrient starvation, especially glucose starvation and oxygen deficiency (hypoxia), and exposure to toxins that inhibit mitochondrial respiratory chain complex function. AMPK is an energy switch in organisms that controls cell growth and multiple cellular processes, including lipid and glucose metabolism, thereby maintaining intracellular energy homeostasis by activating catabolism and inhibiting anabolism. The AMPK signalling pathway consists of AMPK and its upstream and downstream targets. AMPK upstream targets include proteins such as the transforming growth factor ß-activated kinase 1 (TAK1), liver kinase B1 (LKB1), and calcium/calmodulin-dependent protein kinase ß (CaMKKß), and its downstream targets include proteins such as the mechanistic/mammalian target of rapamycin (mTOR) complex 1 (mTORC1), hepatocyte nuclear factor 4α (HNF4α), and silencing information regulatory 1 (SIRT1). In general, proteins function relatively independently and cooperate. In this article, a review of the currently known lncRNAs involved in the AMPK signalling pathway is presented and insights into the regulatory mechanisms involved in human ageing and age-related diseases are provided.

The synthesis of triacylglycerol by diacylglycerol acyltransferases (CsDGAT1A and CsDGAT2D) is essential for tolerance of cucumber's resistance to low-temperature stress.

KEY MESSAGE: CsDGAT1A and CsDGAT2D play a positive regulatory role in cucumber's response to low-temperature stress and positively regulate the synthesis of triacylglycerol (TAG). Triacylglycerol (TAG), a highly abundant and significant organic compound in plants, plays crucial roles in plant growth, development, and stress responses. The final acetylation step of TAG synthesis is catalyzed by diacylglycerol acyltransferases (DGATs). However, the involvement of DGATs in cucumber's low-temperature stress response remains unexplored. This study focused on two DGAT genes, CsDGAT1A and CsDGAT2D, investigating their function in enhancing cucumber's low-temperature stress tolerance. Our results revealed that both proteins were the members of the diacylglycerol acyltransferase family and were predominantly localized in the endoplasmic reticulum. Functional analysis demonstrated that transient silencing of CsDGAT1A and CsDGAT2D significantly compromised cucumber's low-temperature stress tolerance, whereas transient overexpression enhanced it. Furthermore, the TAG content quantification indicated that CsDGAT1A and CsDGAT2D promoted TAG accumulation. In conclusion, this study elucidates the lipid metabolism mechanism in cucumber's low-temperature stress response and offers valuable insights for the cultivation of cold-tolerant cucumber plants.

An End-to-End CRSwNP Prediction with Multichannel ResNet on Computed Tomography.

Chronic rhinosinusitis (CRS) is a global disease characterized by poor treatment outcomes and high recurrence rates, significantly affecting patients' quality of life. Due to its complex pathophysiology and diverse clinical presentations, CRS is categorized into various subtypes to facilitate more precise diagnosis, treatment, and prognosis prediction. Among these, CRS with nasal polyps (CRSwNP) is further divided into eosinophilic CRSwNP (eCRSwNP) and noneosinophilic CRSwNP (non-eCRSwNP). However, there is a lack of precise predictive diagnostic and treatment methods, making research into accurate diagnostic techniques for CRSwNP endotypes crucial for achieving precision medicine in CRSwNP. This paper proposes a method using multiangle sinus computed tomography (CT) images combined with artificial intelligence (AI) to predict CRSwNP endotypes, distinguishing between patients with eCRSwNP and non-eCRSwNP. The considered dataset comprises 22,265 CT images from 192 CRSwNP patients, including 13,203 images from non-eCRSwNP patients and 9,062 images from eCRSwNP patients. Test results from the network model demonstrate that multiangle images provide more useful information for the network, achieving an accuracy of 98.43%, precision of 98.1%, recall of 98.1%, specificity of 98.7%, and an AUC value of 0.984. Compared to the limited learning capacity of single-channel neural networks, our proposed multichannel feature adaptive fusion model captures multiscale spatial features, enhancing the model's focus on crucial sinus information within the CT images to maximize detection accuracy. This deep learning-based diagnostic model for CRSwNP endotypes offers excellent classification performance, providing a noninvasive method for accurately predicting CRSwNP endotypes before treatment and paving the way for precision medicine in the new era of CRSwNP.

Design method for lens desensitization adapted to refractive index error.

The design of optical systems not only considers the imaging performance but also the manufacturing difficulty and feasibility of the system. In practice, errors in the manufacturing process of glass materials and deviations in glass material parameters introduced in complex environments can both lead to degradation in the imaging quality of optical systems. Optical systems that are sensitive to glass material errors face increased manufacturing difficulty and reduced stability. This paper, based on geometrical optics theory, establishes an evaluation function for refractive index error sensitivity and analyzes its relationship with optical parameters and glass materials. It proposes a design method to reduce the refractive index sensitivity of optical systems. Through simulation verification and analysis using examples, the validity of the desensitization design method is confirmed.

Cytotoxic and viricidal effects of human semen on mumps virus-infected lymphocytes: In vitro studies.

Viruses in human semen may be sexually transmitted via free and cell-mediated viral infection. The potential effects of semen on the infection and sexual transmission of most viruses in semen remain largely unclear. The present study elucidated the inhibitory effects of human seminal plasma (SP) on Jurkat cell (JC)-mediated mumps virus (MuV) infection. We demonstrated that MuV efficiently infected JCs and that the JCs infected by MuV (JC-MuV) mediated MuV infection of HeLa cells. Remarkably, SP was highly cytotoxic to JCs and inhibited JC-MuV infection of HeLa cells. The cytotoxic factor possessed a molecular weight of less than 3 kDa, whereas that of the viricidal factor was over 100 kDa. The cooperation of cytotoxic and viricidal factors was required for the SP inhibition of JC-MuV infection, and prostatic fluid (PF) was responsible for both the cytotoxic and viricidal effects of SP. The cytotoxic effects we observed were resistant to the treatment of PF with boiling water, proteinase K, RNase A, and DNase I. Our results provide novel insights into the antiviral properties of SP, which may limit cell-mediated sexual viral transmission.

Exploring the Impact of Online Medical Team Engagement on Patient Satisfaction: A Semantic Features Perspective.

Online medical teams (OMTs), a new mode of online healthcare service, have emerged in online health communities (OHCs) in China. This study attempts to explore the underlying mechanism of how OMTs' engagement influences patient satisfaction through the lens of semantic features. This study also scrutinizes the moderating effect of multiple specializations on the link between OMTs' engagement and semantic features. We utilized a linear model that had fixed effects controlled at the team level for analysis. A bootstrapping approach using 5000 samples was employed to test the mediation effects. The findings reveal that OMTs' engagement significantly improves language concreteness in online team consultations, which subsequently enhances patient satisfaction. OMT engagement has a negative impact on emotional intensity, ultimately decreasing patient satisfaction. Multiple specializations strengthen the impact of OMT engagement on both language concreteness and emotional intensity. This study contributes to the literature on OMTs and patient satisfaction, providing insights into patients' perceptions of OMTs' engagement during online team consultation. This study also generates several implications for the practice of OHCs and OMTs.

NF-GAT: A Node Feature-Based Graph Attention Network for ASD Classification.

Goal: The purpose of this paper is to recognize autism spectrum disorders (ASD) using graph attention network. Methods: we propose a node features graph attention network (NF-GAT) for learning functional connectivity (FC) features to achieve ASD diagnosis. Firstly, node features are modelled based on functional magnetic resonance imaging (fMRI) data, with each subject modelled as a graph. Next, we use the graph attention layer to learn the node features and gets the node information of different nodes for ASD classification. Results: Compared with other models, the NF-GAT has significant advantages in terms of classification results. Conclusions: NF-GAT can be effectively used for ASD classification.

Polygenic Score for Conscientiousness Is a Protective Factor for Reversion from Mild Cognitive Impairment to Normal Cognition.

Spontaneous reversion from mild cognitive impairment (MCI) to normal cognition (NC) is little known. Based on the data of the Genetics of Personality Consortium and MCI participants from Alzheimer's Disease Neuroimaging Initiative, the authors investigate the effect of polygenic scores (PGS) for personality traits on the reversion of MCI to NC and its underlying neurobiology. PGS analysis reveals that PGS for conscientiousness (PGS-C) is a protective factor that supports the reversion from MCI to NC. Gene ontology enrichment analysis and tissue-specific enrichment analysis indicate that the protective effect of PGS-C may be attributed to affecting the glutamatergic synapses of subcortical structures, such as hippocampus, amygdala, nucleus accumbens, and caudate nucleus. The structural covariance network (SCN) analysis suggests that the left whole hippocampus and its subfields, and the left whole amygdala and its subnuclei show significantly stronger covariance with several high-cognition relevant brain regions in the MCI reverters compared to the stable MCI participants, which may help illustrate the underlying neural mechanism of the protective effect of PGS-C.

Chern Insulator States with Tunable Chern Numbers in a Graphene Moiré Superlattice.

Moiré superlattices, constituted by two-dimensional materials, demonstrate a variety of strongly correlated and topological phenomena including correlated insulators, superconductivity, and integer/fractional Chern insulators. In the realm of topological nontrivial Chern insulators within specific moiré superlattices, previous studies usually observe a single Chern number at a given filling factor in a device. Here we present the observation of gate-tunable Chern numbers within the Chern insulator state of an ABC-stacked trilayer graphene/hexagonal boron nitride moiré superlattice device. Near quarter filling, the moiré superlattice exhibits spontaneous valley polarization and distinct ferromagnetism associated with the Chern insulator states over a range of the displacement field. Surprisingly we find a transition of the Chern number from C = 3 to 4 as the displacement field is increased. Our observation of gate-tunable correlated Chern insulators suggests new ways to control and manipulate topological states in a moiré superlattice device.

(-)-Epicatechin gallate prevented atherosclerosis by reducing abnormal proliferation of VSMCs and oxidative stress of AML 12 cells.

(-)-Epicatechin gallate (ECG) is beneficial to the treatment of cardiovascular diseases (CVDs), especially atherosclerosis (AS) through antioxidant stress, but there is a lack of detailed mechanism research. In this study, the therapeutic target of ECG was determined by crossing the drug target and disease target of CVDs and AS. The combination ability of ECG with important targets was verified by Discovery Studio software. The abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by Ang-II and the oxidative damage of AML 12 induced by H2O2 were established to verify the reliability of ECG intervention on the target protein. A total of 120 ECG targets for the treatment of CVDs-AS were predicted by network pharmacology. The results of molecular docking showed that ECG has strong binding force with VEGFA, MMP-9, CASP3 and MMP-2 domains. In vitro experiments confirmed that ECG significantly reduced the expression of VEGFA, MMP-9, CASP3 and MMP-2 in Ang-II-induced VSMCs, and also blocked the abnormal proliferation, oxidative stress and inflammatory reaction of VSMCs by inhibiting the phosphorylation of PI3K signaling pathway. At the same time, ECG also interfered with H2O2-induced oxidative damage of AML 12 cells, decreased the expression of ROS and MDA and cell foaming, and increased the activities of antioxidant enzymes such as SOD, thus playing a protective role.

Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.

ß-Cyclodextrin and Hyaluronic Acid-Modified Targeted Nanodelivery System for Atherosclerosis Prevention.

Natural products have been widely recognized in clinical treatment because of their low toxicity and high activity. It is worth paying attention to modifying the biopolymer into nanostructures to give natural active ingredients additional targeting effects. In this study, based on the multifunctional modification of ß-cyclodextrin (ß-CD), a nanoplatform encapsulating the unstable drug (-)-epicatechin gallate (ECG) was designed to deliver to atherosclerotic plaques. Acetalization cyclodextrin (PH-CD), which responds to low-pH environments, and hyaluronic acid cyclodextrin, which targets the CD44 receptor on macrophage membranes, were synthesized from ß-CD and hyaluronic acid using acetalization and transesterification, respectively. The resulting dual-carrier nanoparticles (Double-NPs) loaded with ECG were prepared using a solvent evaporation method. The Double-NPs effectively scavenged reactive oxygen species, promoted macrophage migration, inhibited macrophage apoptosis, and suppressed abnormal proliferation and migration of vascular smooth muscle cells. Furthermore, the Double-NPs actively accumulated in atherosclerotic plaques in ApoE-/- mice fed with a high-fat diet, leading to a reduced plaque area, inflammatory infiltration, and plaque instability. Our findings demonstrate that the newly developed ECG nanopreparation represents an effective and safe nanotherapy for diseases such as atherosclerosis.

Construction and application of H1R ligand screening materials based on SMA stabilization and his-tag covalent immobilization of membrane proteins.

The histamine H1 receptor (H1R) plays a pivotal role in allergy initiation and undergoes the necessity of devising a high-throughput screening approach centered on H1R to screen novel ligands effectively. This study suggests a method employing styrene maleic acid (SMA) extraction and His-tag covalent bonding to immobilize H1R membrane proteins, minimizing the interference of nonspecific proteins interference while preserving native protein structure and maximizing target exposure. This approach was utilized to develop a novel material for high-throughput ligand screening and implemented in cell membrane chromatography (CMC). An H1R-His-SMALPs/CMC model was established and its chromatographic performance (selectivity, specificity and lifespan) validated, demonstrating a significant enhancement in lifespan compared to previous CMC models. Subsequently, this model facilitated high-throughput screening of H1R ligands in the compound library and preliminary activity verification of potential H1R antagonists. Identification of a novel H1R antagonist laid the foundation for further development in this area.

Investigating the impact of a large river and its surrounding contextual conditions on pedestrians' summer thermal perceptions in a Cfa-climate city.

Thermal comfort studies are usually employed to find subjective thermal responses [indicated by neutral temperature (NT), i.e. the temperature with no thermal stress] of residents from a region towards thermal environments. According to the recently published works in the literature, NTs are affected by many factors, such as geographical location and microenvironments. To elucidate the origins of these effects, the impact of microenvironment elements around a water surface on pedestrians' thermal perceptions was systematically investigated in this work. The Fujiang River (FJR) in Mianyang City was taken as the sample site. The municipal meteorology station is located next to the site by around 2.5 km. By performing meteorology measurements combining questionnaires, it was found that the riverside NT (indicated by physiologically equivalent temperature, PET) of Mianyang in the summer of 2023 was 21.4 °C. The relationship between the distance from the water (DFW) and NT was quadratic linear. The same phenomenon took place by using either PET or Universal Thermal Climate Index (UTCI) indexes. Meanwhile, the meteorological contexts also affected NTs, including relative humidity (RH) and air velocity (Va). Regarding RH, the NPET increased from 15.2 °C (RH = 50%) to 26.9 °C (RH = 90%). In contrast, the NPET dropped from 23.0 to - 50.6 °C when the Va increased from 0.2 to 2.5 m/s, respectively. From our analysis, it was demonstrated that human thermal responses are significantly affected by both the microenvironmental and meteorological backgrounds around the water surface. Our work provides valuable insights for the proper use of water surfaces in urban design for adjusting thermal comfort.

A new multivariate index for ecological security assessment in the China-Myanmar border region.

The coordination of development efforts and ecological conservation in China's border regions is a significant challenge due to the overlap of biodiversity hotspots, ecologically fragile zones, and impoverished areas. Achieving the harmonious integration of ecological preservation and economic development relies on the fundamental assessment of ecological security (ES). However, comprehensive assessments of ES in border regions remain limited. This study introduces a new index, the multivariate ecological security index (MESI), which integrates ecosystem vigor, organization, elasticity, services and risk. Here, the MESI was utilized to assess the temporal and spatial changes in ES and its associated impact factors in the China-Myanmar border region (CMBR) from 2000 to 2020. The MESI provides a clear representation of the actual ES status in the CMBR, exhibiting a significant correlation with the eco-environmental quality index (EEQI; p < 0.01). The ES status exhibited notable spatial heterogeneity in the CMBR, consisting primarily of both relatively safe and safe levels, which accounted for approximately 85% of the total area. From 2000 to 2020, the CMBR experienced a gradual improvement in ES status, with the area experiencing an increase in the ES level accounting for 23.41% of the total area, which exceeded the proportion of the area experiencing a decrease in the ES level (4.71%). The combined impact of multiple factors exerted a greater influence on ES than did individual factors alone. Notably, human factors increasingly influenced the ES status during the study period. The results of this study provide valuable insights for ecological preservation and sustainable management in the CMBR, and the MESI can be extended to assess the ES of other regions.

Human umbilical cord-derived mesenchymal stem cell transplantation improves the long COVID.

No effective treatments can ameliorate symptoms of long COVID patients. Our study assessed the safety and efficacy of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) in the treatment of long COVID patients. Ten long COVID patients were enrolled and received intravenous infusions of UC-MSCs on Days 0, 7, and 14. Adverse events and clinical symptoms were recorded, and chest-high-resolution CT (HRCT) images and laboratory parameters were analyzed. During UC-MSCs treatment and follow-up, we did not observe serious adverse events, the symptoms of long COVID patients were significantly relieved in a short time, especially sleep difficulty, depression or anxiety, memory issues, and so forth, and the lung lesions were also repaired. The routine laboratory parameters did not exhibit any significant abnormalities following UC-MSCs transplantation (UMSCT). The proportion of regulatory T cells gradually increased, but it was not statistically significant until 12 months. The proportion of naive B cells was elevated, while memory B cells, class-switched B-cells, and nonswitched B-cells decreased at 1 month after infusion. Additionally, we observed a transient elevation in circulating interleukin (IL)-6 after UMSCT, while tumor necrosis factor (TNF)-α, IL-17A, and IL-10 showed no significant changes. The levels of circulating immunoglobulin (Ig) M increased significantly at month 2, while IgA increased significantly at month 6. Furthermore, the SARS-CoV-2 IgG levels remained consistently high in all patients at Month 6, and there was no significant decrease during the subsequent 12-month follow-up. UMSCT was safe and tolerable in long COVID patients. It showed potential in alleviating long COVID symptoms and improving interstitial lung lesions.

Hypoglycemic TCM formulas (Huangqi-Gegen drug pair) have the potential as an Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a neurological disorder. There is a considerable unmet medical need among those suffering from it. HYPOTHESIS AND PURPOSE: Given the link between type-2 diabetes mellitus (T2DM) and AD, hypoglycemic traditional Chinese medicine formulas (TCMFs) may be a treatment for AD. We investigated the possibility of identifying anti-AD medicines in hypoglycemic TCMFs and presented another option for the screening of AD medications. STUDY DESIGN AND METHODS: Paralysis of the transgenic Caenorhabditis elegans (C. elegans) strain CL4176 (caused by amyloid beta (Aß)1-42 aggregates) was used to evaluate the anti-AD effect. The toxicity and neurodegeneration induced by neuronal expression of Aß in the transgenic C. elegans strain CL2355 were determined using a 5-hydroxytryptamine (5-HT) assay. The transgenic Aß-expressing strain CL 2006 and transgenic tau-expressing strain BR5270 were used to explore the effect of TCMFs on protein expression in C. elegans using ELISAs. Then, network pharmacology was used to determine the mechanism of action. The Traditional Chinese Medicine Inheritance Support System platform was used to investigate prescription patterns, core drugs, and optimum combinations of hypoglycemic TCMFs for AD. RESULTS: Sixteen hypoglycemic TCMFs prolonged the PT50 (half paralysis time) of the CL4176 strain of C. elegans, reduced the percentage of worms paralyzed. The results of network pharmacology showed that prostaglandin-endoperoxide synthase 2 (PTGS2) and acetylcholine esterase (AChE) are main targets of hypoglycemic TCMFs. Enriched pathway analysis showed that the cholinergic receptor-related pathway was the core pathway of hypoglycemic TCMFs. According to the "four qi and five flavors" system of TCM theory, the main pharmacological qualities were "cold" and "sweet." Through the analysis by TCMISS, we found that Huangqi-Gegen drug pair as the significant Chinese herbs of hypoglycemic TCMFs. The Huangqi-Gegen pairing had the most robust therapeutic effect when delivered at a 2:1 (v/v) ratio. It reduced the paralysis caused by 5-HT, decreased protein expression of AChE and PTGS2, and reduced Aß deposition in the brain of the CL2006 strain of C. elegans. CONCLUSIONS: Huangqi-Gegen is a promising treatment of AD, and its mechanism may be induced by suppressing the protein production of AChE and PTGS2, reducing 5-HT intake, and then decreasing Aß deposition.