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Abstract Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance of METI on ST data generated from various tumor tissues, including gastric, lung, and bladder cancers, as well as premalignant tissues. We also conduct a quantitative comparison of METI with existing clustering and cell deconvolution tools, demonstrating METI’s robust and consistent performance.

Abstract Poplar trees are crucial for timber and greening, but high levels of salt in the soil have severely limited the yield of poplar. Ethylene response factor (ERF) transcription factors play an important role in growth, development, and stress response in eukaryotes. Our study focused on the PagERF021 gene from Populus alba × P. glandulosa, which was significantly upregulated in various tissues under salt stress [Correction added on October 4, 2024, after first online publication: “ETS2 reporter factor” is changed to “Ethylene response factor”.]. Both the tissue‐specific expression pattern and β‐glucuronidase (GUS) staining of proPagERF021‐GUS plants indicated that this gene was predominantly expressed in the roots and stems. The subcellular localization showed that the protein was only localized in the nucleus. The yeast assay demonstrated that this protein had transcriptional activation activity at its C‐terminal and could specifically binding to the MYB‐core cis‐element. The overexpression of PagERF021 gene could scavenge the accumulation of reactive oxygen species and reduce the degree of cellular membrane damage, indicating that this gene enhanced the salt tolerance of poplars. This finding will provide a feasible insight for future research into the regulatory mechanisms of ERF genes in resisting to abiotic stress and the development of new stress‐resistant varieties in plants.

PurposeTo explore the relationship between peripapillary atrophy (PPA) and diabetic retinopathy (DR), and to uncover potential mechanisms using swept-source optical coherence tomography (SS-OCT) angiography.MethodsThis cross-sectional study included 845 patients with type 2 diabetes (T2DM), who underwent detailed systemic and ophthalmic evaluations. A state-of-the-art deep learning method was employed to precisely identify the parapapillary beta and gamma zones. Based on PPA characteristics, eyes were categorized into four groups: without beta or gamma zone (Group A), isolated beta zone (Group B), isolated gamma zone (Group C), and with both beta and gamma zone (Group D). Digital fundus photography was utilized to diagnose and stage DR severity, while SS-OCT angiography quantified retinal and choroidal vasculature.ResultsParticipants had a mean age of 66 ± 8.8 years, with 437 (51.7%) male. Beta and gamma PPA zones were observed in 574 (67.9%) and 256 (30.3%) eyes, respectively. Beta zone PPA was associated with older age, whereas gamma zone PPA was correlated with longer axial length (AL), lower vessel density, and reduced choroidal thickness. Adjusted analyses revealed that eyes with isolated (Group C) or concurrent (Group D) gamma zone PPA conferred significantly lower DR grade, independent of known risk factors including systemic diabetes risk factors and AL.ConclusionThis study finds that gamma zone PPA is linked to a reduced risk of developing DR. These results imply that the gamma zone may reflect progressive myopia-associated thinning and microvascular depletion in posterior ocular tissues, potentially contributing to structural resilience against DR. This novel insight offers a promising avenue for understanding the interplay between PPA and DR.

Due to its small structures and high energy efficiency, the Brayton cycle using supercritical carbon dioxide (sCO2) can be implemented in various energy industries. The simulation model for a sCO2 recompression Brayton (RB) system with a two-stage compression and intercooling process (TCIP) is developed. At the design working conditions, there are minimum and optimum split ratios for the sCO2 RB with TCIP cycle. The sCO2 RB with TCIP cycle has a broader range of split ratios compared to the RB cycle. The sCO2 RB with TCIP cycle can achieve a minimum split ratio of 0.315, compared to 0.36 for the sCO2 RB cycle. The maximum efficiency of the sCO2 RB with TCIP cycle is 50.95 %, which surpasses the efficiency of the sCO2 RB cycle by 3.14 %. There exists an optimal value for the first-stage pressure ratio because the maximum efficiency of the sCO2 RB with the TCIP system tends to increase and then decrease with the increase in the first-stage pressure ratio. The pressure ratio of 1.1 for the first-stage compressor, corresponding to an interstage pressure of 8.25 MPa, maximizes the efficiency of the sCO2 RB with the TCIP cycle. The results can be used to further explore the applicability of sCO2 RB with TCIP.

BackgroundAnemia is a common complication in patients with heart failure and is associated with left ventricular systolic dysfunction. However, its role in right ventricular (RV) function has not been evaluated.MethodsWe retrospectively analyzed the electronic medical data of 1,014 Heart Failure with Preserved Ejection Fraction (HFpEF) patients to evaluate the relationship between anemia and RV dysfunction in patients with HFpEF and whether this relationship is influenced by classical risk factors such as smoking and hypertension.ResultsThe study showed that anemic patients were older and had significantly higher New York Heart Association functional class and tricuspid regurgitation (TR) than non-anemic patients. The level of hemoglobin (Hb) had a weak negative linear correlation with NT-pro-BNP (log-transform, r = 0.30, P

IntroductionAlzheimer’s disease (AD) is the leading cause of dementia, and currently, no effective treatments are available to reverse or halt its progression in clinical practice. Although a plethora of studies have highlighted the benefits of physical exercise in combating AD, elder individuals often have limited exercise capacity. Therefore, mild physical exercise and nutritional interventions represent potential strategies for preventing and mitigating neurodegenerative diseases. Our research, along with other studies, have demonstrated that platycodin D (PD) or its metabolite, platycodigenin, derived from the medicinal plant Platycodon grandiflorus, exerts neuroprotective effects against amyloid β (Aβ)-induced neuroinflammation. However, the combined effects of PD and physical exercise on alleviating AD have yet to be explored. The current study aimed to investigate whether combined therapy could synergistically ameliorate memory deficits and AD pathology in 5 × FAD mice.MethodsFive-month-old 5 × FAD mice were randomly assigned to four groups, and received either PD (5 mg/kg/day, p.o.), voluntary running, or a combination of both for 47 days. Nest building test, locomotion test, and Morris water maze test were used to evaluate the cognitive function. Immunohistochemical and ELISA analysis was performed to determine Aβ build-up, microglia and astrocytes hyperactivation, and survival neurons in the hippocampus and perirhinal cortex. Real-time quantitative PCR analysis was used to assess the polarization of microglia and astrocytes. HPLC analysis was performed to measure monoamine neurotransmitters in the hippocampus.Results and discussionThe combination of PD and voluntary running synergistically restored nest-building behavior, alleviated recognition and spatial memory deficits, and showed superior effects compared to monotherapy. In addition, the PD and voluntary running combination reduced Aβ build-up, decreased hyperactivation of microglia and astrocytes in the hippocampus and perirhinal cortex, promoted the polarization of inflammatory M1 microglia and reactive astrocytes toward beneficial phenotypes, and lowered systemic circulating pro-inflammatory cytokines while increasing anti-inflammatory cytokines in 5 × FAD mice. Furthermore, combined therapy effectively protected neurons and increased levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in the hippocampus of 5 × FAD mice. In conclusion, the combination of PD and voluntary running holds great potential as a treatment for AD, offering promise for delaying onset or progression of AD.

IntroductionShortage and high turnover intention rate of physicians are concerning problems in China. Professional identity has been shown as an influential factor for physicians’ turnover intention. Enhancing physicians’ professional identity in their early phase of career, standardized residency training program (SRTP), may help reduce the turnover rate. This study aimed to investigate the current status of professional identity and explore its associated psychosocial factors among Chinese SRTP trainees, hoping to provide evidence in strengthening the available medical human resources in China.MethodsThe final sample was comprised of 2,267 Chinese SRTP trainees in this cross-sectional survey conducted from 9 March to 20 March in 2023. Descriptive statistics were calculated. Bivariate analyses and hierarchical multiple linear regression were used to analyze potential associated factors of Chinese SRTP trainees’ professional identity.ResultsThe average score of respondents’ professional identity was 47.68 (standard deviation, SD = 8.61). Results from hierarchical multiple linear regression analysis showed that being married (β = 0.066, p

Poplar is an important greening and timber tree species in China, which has great economic and ecological values. However, the spread of Hyphantria cunea has become increasingly serious in recent years, resulting in huge economic loss of poplar production. Exploring the molecular mechanism of poplar reponse to H. cunea stress has significant implications for future development of new insect-resistant poplar varieties using genetic engineering technology. In this study, a total of 1039 differentially expressed genes (DEGs), 106 differentially expressed proteins (DEPs) and 212 differentially expressed metabolites (DEMs) were screened from Populus simonii × P. nigra leaves under H. cunea stress by transcriptome, proteomics and metabolomics analysis, respectively. GO and KEGG analysis showed that the DEGs and DEPs are associated with endopeptidase inhibitor activity, stress response, α-linolenic acid metabolism, phenylpropanoid biosynthesis and metabolic pathways, cysteine and methionine metabolism pathways and MAKP signaling pathway. Metabolomics analysis showed the most of DEMs were lipids and lipid molecules, and the pathways associated with transcriptome mainly include plant hormone signal transduction, α-linolenic acid metabolic pathway, amino sugar and nucleotide sugar metabolism, and phenylpropanoid biosynthesis. In particular, multi-omics analysis showed that several pathways such as α-linolenic acid metabolic, phenylpropanoid biosynthesis and metabolic pathway and cysteine and methionine metabolic pathway were significantly enriched in the three omics, which may play an important role in the resistance to pests in poplar.

Abstract Objectives Emerging evidence suggests a potential relationship between body composition and short-term prognosis of ulcerative colitis (UC). Early and accurate assessment of rapid remission based on conventional therapy via abdominal computed tomography (CT) images has rarely been investigated. This study aimed to build a prediction model using CT-based body composition parameters for UC risk stratification. Methods In total, 138 patients with abdominal CT images were enrolled. Eleven quantitative parameters related to body composition involving skeletal muscle mass, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured and calculated using a semi-automated segmentation method. A prediction model was established with significant parameters using a multivariable logistic regression. The receiver operating characteristic (ROC) curve was plotted to evaluate prediction performance. Subgroup analyses were implemented to evaluate the diagnostic efficiency of the prediction model between different disease locations, centers, and CT scanners. The Delong test was used for statistical comparison of ROC curves. Results VAT density, SAT density, gender, and visceral obesity were significantly statistically different between remission and invalidation groups (all p 0.05). Conclusions The predicting model constructed with CT-based body composition parameters is a potential non-invasive approach for short-term prognosis identification and risk stratification. Additionally, VAT density was an independent predictor for escalating therapeutic regimens in UC cohorts. Critical relevance statement The CT images were used for evaluating body composition and risk stratification of ulcerative colitis patients, and a potential non-invasive prediction model was constructed to identify non-responders with conventional therapy for making therapeutic regimens timely and accurately. Key points • CT-based prediction models help divide patients into invalidation and remission groups in UC. • Results of the subgroup analysis confirmed the stability of the prediction model with a high AUC (all > 0.820). • The visceral adipose tissue density was an independent predictor of bad short-term prognosis in UC. Graphical Abstract

Objective: Investigating the effects of MYB proto-oncogene like 2 (MYBL2)-mediated regulation of Cell division cycle associated 8 (CDCA8) expression on the biological activity of cutaneous malignant melanoma cells. Methods: A375 cells with MYBL2 and CDCA8 overexpression and knockdown were evaluated using migration, invasion, and proliferation assays. Besides, cell apoptosis was quantified by flow cytometry. To investigate the tumorigenic effects of MYBL2 knockdown in vivo, A375 cells with MYBL2 knockdown were injected in BALB/C nude mice. Results: The levels of MYBL2 and CDCA8 gene expression were notably elevated in A375 cells in comparison to HaCat cells (P

With China’s rapid economic development in recent years, enhancing the sense of well-being among citizens has become a critical objective. However, the interests of various stakeholder groups are often overlooked in decision-making surrounding land use. In this study, Yongsheng County, Yunnan Province serves as a case study for land use scenario simulations. The equivalent factor method is combined with Participatory Rural Appraisal (PRA) to investigate the relationship between ecosystem multifunctionality (EMF) and the equity index of multiple stakeholder groups in various land use scenarios. We also explore whether an optimal combination of land use types exists. The results indicate that (1) The current ecosystem service value in Yongsheng County is primarily driven by climate regulation and biodiversity conservation, with a relatively high functional value index but a comparatively low equity index; (2) Different stakeholder groups mainly prioritize food production and ecosystem services impacting food production, such as water resource provision and climate regulation; (3) A land use allocation pattern of 20% farmland, 4% water bodies, 21% mixed forest, 20% coniferous forest, and 35% grassland appears to provide the optimal EMF index while simultaneously achieving the optimal equity index across stakeholder groups. This research may offer valuable insights for optimizing land use planning while taking into account the well-being of diverse stakeholder groups. It also may have practical implications for the formulation of innovative land use management strategies.

The low frequency ripple of the input side current of the single-phase inverter will reduce the efficiency of the power generation system and affect the overall performance of the system. Aiming at this problem, this paper proposes a two-modal modulation method and its MPC multi-loop composite control strategy on the circuit topology of a single-stage boost inverter with a buffer unit. The control strategy achieves the balance of active power on both sides of AC and DC by controlling the stable average value of the buffer capacitor voltage, and provides a current reference for inductance current of the DC input side. At the same time, the MPC controller uses the minimum inductor current error as the cost function to control inductor current to track its reference to achieve low frequency ripple suppression of the input current. In principle, it is expounded that the inverter using the proposed control strategy has better low frequency ripple suppression effect than the multi-loop PI control strategy, and the conclusion is proved by the simulation data. Finally, an experimental device of a single-stage boost inverter using MPC multi-loop composite control strategy is designed and fabricated, and the experimental results show that the proposed research scheme has good low frequency ripple suppression effect and strong adaptability to different types of loads.

Abstract Purpose To evaluate the value of MRI T1 mapping with Gd-EOB-DTPA for assessing liver function. Methods Seventy-two patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions at Beijing Friendship Hospital from August 2020 to March 2022 were prospectively enrolled, and variable-flip-angle T1 mapping was performed before and 20 min after enhancement. The Child–Pugh (C-P) score and albumin-bilirubin (ALBI) grade of liver function were assessed using the clinical data of the patients. Correlation analysis was used to evaluate the correlation between T1 mapping parameters and liver function grading and laboratory tests. Nonparametric tests were used to compare the differences among different liver function groups. The liver function classification efficiency of each image index was evaluated with receiver operating characteristic (ROC) curves. Results T1post was positively correlated with the C-P grade and the ALBI grade (r = 0.717 and r = 0.652). ΔT1 was negatively correlated with the C-P grade and the ALBI grade (r = -0.790 and r = -0.658). T1post and ΔT1 significantly differed among different liver function grades (p

Abstract Background Prediction of locoregional treatment response is important for further therapeutic strategy in patients with hepatocellular carcinoma. This study aimed to investigate the role of MRI-based radiomics and nomogram for predicting the outcome of locoregional treatment in patients with hepatocellular carcinoma. Methods The initial postoperative MRI after locoregional treatment in 100 patients with hepatocellular carcinoma was retrospectively analysed. The outcome was evaluated according to mRECIST at 6 months. We delineated the tumour volume of interest on arterial phase, portal venous phase and T2WI. The radiomics features were selected by using the independent sample t test or nonparametric Mann‒Whitney U test and the least absolute shrinkage and selection operator. The clinical variables were selected by using univariate analysis and multivariate analysis. The radiomics model and combined model were constructed via multivariate logistic regression analysis. A nomogram was constructed that incorporated the Rad score and selected clinical variables. Results Fifty patients had an objective response, and fifty patients had a nonresponse. Nine radiomics features in the arterial phase were selected, but none of the portal venous phase or T2WI radiomics features were predictive of the treatment response. The best radiomics model showed an AUC of 0.833. Two clinical variables (hCRP and therapy method) were selected. The AUC of the combined model was 0.867. There was no significant difference in the AUC between the combined model and the best radiomics model (P = 0.573). Decision curve analysis demonstrated the nomogram has satisfactory predictive value. Conclusions MRI-based radiomics analysis may serve as a promising and noninvasive tool to predict outcome of locoregional treatment in HCC patients, which will facilitate the individualized follow-up and further therapeutic strategies guidance.

Isolated bidirectional DC–DC converters are becoming increasingly important in various applications, particularly in the electric vehicle sector, due to their ability to achieve bidirectional power flow and their safety features. This paper aims to review the switch strategies and topologies of isolated bidirectional DC–DC converters, with a specific focus on their applications in the field of electric vehicles. From the perspective of topology, PWM-type isolated bidirectional DC–DC converters, dual active bridge converters, and resonant-type isolated bidirectional DC–DC converters constitute the three main categories of these converters. The paper further examines the traditional switch strategies of these converters and discusses how specific switch technologies, such as single-phase shift, expanding-phase shift, double-phase shift, and triple-phase shift, can enhance the overall performance of isolated bidirectional DC–DC converters. The paper meticulously examines the characteristics of each topology and control scheme, as well as their typical use cases in practical applications. Particularly, the paper delves into the applications of isolated bidirectional DC–DC converters in the electric vehicle sector and draws conclusions regarding their potential and trends in future electric vehicle technology.

Background Video game play has been linked to a range of cognitive advantages, and investigations in this domain have predominantly utilized cross-sectional designs or long-term training paradigms. Nevertheless, the specific effects of engaging in a single bout of video game play remain poorly understood. Consequently, the objective of this study is to examine the influence of a single session of mobile action video game (MAVG) play on attentional networks among college students. Methods Seventy-two nonvideo game players were assigned randomly into an MAVG and a control game group. Participants in the MAVG group engaged in a 60-minute session of an action video game played on mobile phones, while the control group played a mobile card game for the same duration. All participants completed the attentional network test (ANT), which assesses alerting, orienting, and executive control network efficiencies, before and after the intervention. Results The MAVG group had significantly improved alerting network efficiency following the intervention, compared to before (p

Objectives: The main purpose of this study was to compare the surgical strategy and clinical outcomes of single-position robotic assisted laparoscopic anterograde bilateral inguinal lymphadenectomy for penile cancer. Materials and methods: 21 patients were diagnosis with squamous cell carcinoma and identified from March 2010 to December 2020 in our department. Ten patients were received single-position robotic assisted laparoscopic anterograde bilateral inguinal lymphadenectomy (robot-assisted group), and eleven patients underwent laparoscopic inguinal lymphadenectomy (laparoscopic group). Preoperative physical examination and related auxiliary examinations all indicated bilateral inguinal lymph node enlargement, and there was no distant metastasis patient presented during the follow-up period. Results: There was no intraoperative conversion to open surgery. The operation time under robot-assisted group was 104 ± 13 min which was significantly shorter than laparoscopic group (136 ± 11 min, P

Introduction Depression is the most dominant non-motor symptom of Parkinson’s disease (PD), with a prevalence of up to 50%, and can lead to a range of psychiatric and psychological problems that can affect quality of life and overall functioning. While several randomised controlled trials (RCTs) have tested the effect of certain non-pharmacological interventions on the outcome of PD depression symptoms, the comparative benefits and harms of these remain unclear. We will conduct a systematic review and network meta-analysis to compare the efficacy and safety of different non-pharmacological interventions for patients with PD depression.Methods and analysis We will search PubMed, Web of Science, Cochrane, Embase, Google Scholar, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, WanFang Data and the Chongqing VIP Database from their inception date to June 2022. The studies will be limited to results published in English or Chinese. The primary outcomes will be the changes in the depressive symptoms, while secondary outcomes will include adverse effects and the quality of life. Two researchers will screen those documents that meet the inclusion criteria, extracting data according to the preset table and evaluating the methodological quality of the included studies using the Cochrane Risk of Bias 2.0 Tool. The STATA and ADDIS statistical software will be used to conduct a systematic review and network meta-analysis. A traditional pairwise meta-analysis and a network meta-analysis will be performed to compare the efficacy and safety of different non-pharmacological interventions, ensuring the robustness of the findings. The Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the overall quality of the body of evidence associated with the main results. The publication bias assessment will be conducted using comparison-adjusted funnel plots.Ethics and dissemination All the data for this study will be extracted from published RCTs. As a literature-based systematic review, this study does not require ethical approval. The results will be disseminated through peer-reviewed journals and national/international conference presentations.PROSPERO registration number CRD42022347772.

Heat shock transcription factor (HSF) is an important TF that performs a dominant role in plant growth, development, and stress response network. In this study, we identified a total of 30 HSF members from poplar, which are unevenly distributed on 17 chromosomes. The poplar HSF family can be divided into three subfamilies, and the members of the same subfamily share relatively conserved domains and motifs. HSF family members are acidic and hydrophilic proteins that are located in the nucleus and mainly carry out gene expansion through segmental replication. In addition, they have rich collinearity across plant species. Based on RNA-Seq analysis, we explored the expression pattern of PtHSFs under salt stress. Subsequently, we cloned the significantly upregulated PtHSF21 gene and transformed it into Populus simonii × P. nigra. Under salt stress, the transgenic poplar overexpressing PtHSF21 had a better growth state and higher reactive oxygen scavenging ability. A yeast one-hybrid experiment indicated PtHSF21 could improve salt tolerance by specifically binding to the anti-stress cis-acting element HSE. This study comprehensively profiled the fundamental information of poplar HSF family members and their responses to salt stress and specifically verified the biological function of PtHSF21, which provides clues for understanding the molecular mechanism of poplar HSF members in response to salt stress.

Scale-controlling and technology-upgrading measures are considered effective for mitigating vehicle exhaust emissions. This study investigated the impacts of fuel consumption and vehicle quantities on the total factor inefficiency in China’s highway transport sector during 2011–2015, based on the Bounded Adjusted Measure Data Envelopment Analysis (BAM-DEA) model combined with natural and managerial disposability scenarios. The results showed that the average global inefficiency (GIE) score of the exhaust emissions (CO, HC, NOx, and PM) was 0.41 under the assumption of natural disposability and 0.23 in the managerial disposability situation. Moreover, the main causes of total factor inefficiency scores from the perspective of natural disposability were road length, fuel consumption, and exhaust emissions, whereas those from a managerial disposability perspective were road length and exhaust emissions. These two results suggested that environmental efficiency can be promoted by increasing the quantities of clean-energy vehicles and high-quality gasoline/diesel consumption. In terms of the spatial distribution of GIE, the scores showed a decreasing trend from China’s northwestern inland regions to its southeastern coastal regions under both natural and managerial disposability. Environmental efficiency in some provinces (such as Yunnan) demonstrated good progress under managerial disposability, but other regions did not (such as Hebei and Ningxia). Thus, each province should choose appropriate strategies regarding vehicle quantities and fuel consumption according to the technical inefficiency scores of differing disposability situations.

Abstract Given that triple-negative breast cancer (TNBC) lacks specific receptors (estrogen and progesterone receptors and human epidermal growth factor receptor 2) and cannot be treated with endocrine therapy, chemotherapy has remained the mainstay of treatment. Drug resistance is reportedly the main obstacle to the clinical use of doxorubicin (DOX) in this patient population. Accordingly, screening molecules related to chemoresistance and studying their specific mechanisms has clinical significance for improving the efficacy of chemotherapy in TNBC patients. Thioredoxin-interacting protein (TXNIP) is a metabolism-related protein that plays a tumor suppressor role in various malignant tumors; however, the specific role of TXNIP in tumor chemoresistance has not been reported. In the present study, we explored the potential molecular mechanism of TXNIP in the chemoresistance of TNBC for the first time. The results showed that TXNIP inhibited the proliferation of TNBC drug-resistant cells and promoted apoptosis in vitro and in vivo. Furthermore, TXNIP promoted the synthesis of reactive oxygen species (ROS) and the accumulation of DNA damage caused by DOX and increased γ-H2AX levels in a time and dose-dependent manner. Moreover, ROS scavenger pretreatment could block DNA damage induced by TXNIP and restore the resistance of TNBC resistant cells to DOX to a certain extent. In addition, we found that the small molecule c-Myc inhibitor 10058-F4 promoted TXNIP expression, increased ROS synthesis in cells, and could enhance the cytotoxicity of chemotherapy drugs in vitro and in vivo when combined with DOX. These results indicated that c-Myc inhibitor 10058-F4 could induce TXNIP upregulation in TNBC drug-resistant cells, and the upregulated TXNIP increased the accumulation of ROS-dependent DNA damage, thereby decreasing chemotherapy resistance of TNBC. Our findings reveal a new mechanism of mediating drug resistance and provide a new drug combination strategy to overcome DOX resistance in TNBC.

A novel magnetically-coupled energy storage inductor boost inverter circuit for renewable energy and the dual-mode control strategy with instantaneous value feedback of output voltage are proposed. In-depth research and analysis on the circuit, control strategy, voltage transmission characteristics, etc., providing the parameter design method of magnetically-coupled energy storage inductors and output filter. The circuit topology is cascaded by the input source ��in, the input filter ��in, a single-phase inverter bridge with a magnetically-coupled energy storage inductor, and a CL filter; The control strategy serves the output voltage as a reference to achieve the switch of step-down and step-up modes smoothly. The simulation results of a 1000 VA 100–200 VDC, 220 V 50 Hz AC inverter show that the proposed inverter can realize single-stage boost power conversion, which can adapt to resistive, capacitive and inductive loads, has high power density and low output waveform distortion. It has good application prospects in small and medium-capacity single-phase inverter occasions with low input voltage.

Abstract Conventional dc–dc boost converters have limited boosting capabilities, and the main switching device may suffer relatively high voltage stress and current stress. A novel transformerless dc‐dc boost converter is proposed in this paper. The proposed topology, which combines the traditional active switch‐inductor and quasi‐Z‐source network, can increase the voltage gain without limiting the duty cycle or increasing the voltage and current stresses of the power switches. The detailed analysis including working principles, steady‐state characteristics, non‐ideal element analysis and a comprehensive comparison is also presented in this paper. To verify the proposed converter's performance, a prototype circuit with 20–30 V input voltage, 200 V output voltage, and 200 W output power is implemented in the laboratory. Experiment results confirm the theoretical analysis and advantages of the proposed converter.

To investigate the protective effects of Clerodendranthus spicatus (Thunb.) C. Y. Wu extract (CSTE) on oxidative stress injury in HL-1 mouse cardiomyocytes induced by 2,2'-azo (2-methylpropamidine) dihydrochloride (AAPH, 1 mmol/L), HL-1 cells were co-cultured with different concentrations (10–100 μg/mL) of the CSTE for 24 h. A cell damage model was established by continuously culturing the cells in Dulbecco's Modified Eagle Medium plus AAPH for 4 h. Cell survival rates were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and by measuring intracellular malondialdehyde (MDA) content. MDA and total reactive oxygen species (ROS) levels were determined by thiobarbituric acid colorimetry and the 2',7'-dihydrodichlorofluorescent sodium yellow diacetate probe, respectively. Apoptosis was measured by flow cytometry. The intracellular catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione s-transferase (GST), γ-glutamylcysteine synthetase (γ-GCS), and glutathione (GSH) contents were determined by colorimetric methods. CSTE content was determined by high performance liquid chromatography. The CSTE pretreatment improved survival rates in damaged HL-1 cells, reduced total intracellular ROS and MDA levels, and reduced apoptosis. The CSTE also increased the activities of the antioxidant enzymes (CAT, SOD, GSH-Px, and GST), as well as the γ-GCS and GSH levels in damaged cells. Real-time fluorescence quantitative polymerase chain reaction analysis indicated that the CSTE upregulated CAT, SOD1, and GSH-Px mRNA expression levels. Additionally, the CSTE reduced MDA and ROS levels in HL-1 cells by improving the endogenous antioxidant system; thus, alleviating the oxidative stress damage caused by AAPH. Our compositional analyses revealed that the CSTE contained caffeic acid, isoquercetin, rosmarinic acid, luteolin, and baicalin. The CSTE demonstrates antioxidant and protective effects in myocardial cells.

Aerodynamic heating of spinning flight vehicles have critical military applications such as flight testing, location tracking, stealth, and thermal protection. Based on the numerical method which is verified to be effective in the wind tunnel tests, this article discusses the aerodynamic thermal characteristics of a spinning winged projectile. Firstly, a 6-DOF trajectory model is established to demonstrate the motional behaviors. Partial flight data in supersonic, transonic, and subsonic regimes are separately defined as the inflow conditions. After that, thermo-fluid characteristics are compared between spin and non-spin. When the spin angular velocity is considered, a striking swirling flow phenomenon in the flow field, which result in the streamlines near the tail wings interfere with each other. Meanwhile, the impacts of the shear flow, trailing vortex and turbulent fluctuation are conspicuous. Besides, demonstrating the asymmetry of the temperature due to the flow deflection on the windward and leeward sides of the tail wings. Aerodynamic thermal differences on the surface of the tail wings are remarkable, especially at the tip of the wings. Therefore, the effects of spinning process on aerodynamic heating of winged vehicles cannot be ignored, particularly in supersonic flow at high Mach number.

Introduction Currently, the first choice for the clinical treatment of static tremor in Parkinson’s disease (PD) is drug therapy, however side effects are common. In recent years, the effects of physical therapy on PD has become a serious research focus. Studies have indicated that aerobic and resistance exercises alleviate PD movement disorders and improve aerobic capacity, but the effects of Qigong on PD static tremor and aerobic capacity remain unknown.Methods and analysis Objective To observe the effects of Zhan Zhuang Qigong on upper limb static tremor and aerobic capacity in patients with PD, we established a rigorous randomised, parallel-controlled, assignment hidden, evaluator-blinded protocol.Methods Seventy-two patients with PD, at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, were recruited and randomly divided into a control (n=36) and experimental group (n=36). The intervention group received conventional medicine plus Zhan Zhuang Qigong exercises five times a week at 30 min each time, over an 8-week period. The long-term effects of Zhan Zhuang Qigong on PD was investigated after the intervention. Phyphox APP, CRST, CPET, UPDRS(II, III) were used to evaluate tremor, aerobic capacity, and motor function in groups.Discussion We are investigating the effects of Zhan Zhuang Qigong on upper limb static tremor and aerobic capacity in patients with PD. If positive are identified, they will add a new research direction and evidence for the clinical exploration of exercise therapy for PD.Ethics and dissemination This study was approved by the Ethics Committee of Shandong University of Traditional Chinese Medicine (Approval Number: 2021–025-KY). The Committee will be informed of any changes to the trial protocol, such as intervention intensity, outcome indicators and data collection. Study results will be presented as a paper at an international conference or in a journal.Trial registration number ChiCTR2100053529.

Single-phase inverters are widely employed in renewable energy applications. However, their inherent 2ω-ripple power can substantially affect system performance, leading to fluctuations in the maximum power points (MPP) of photovoltaic (PV) systems and shortening the lifespans of fuel cell (FC) systems. To alleviate input ripple, a three-leg quasi-Z-source inverter (QZSI) and its associated control strategy are proposed. The QZSI consists of a quasi-Z-source network, an H-Bridge inverter, and an active power filter (APF). The active filtering structure comprises filtering capacitors and the third bridge leg. The proposed control strategy consists of three loops: open-loop simple boost control, output voltage control, and 2ω-ripple suppression control. Open-loop simple boost control is utilized for shoot-through state modulation, output voltage control is applied to the two bridge-legs of the H-Bridge, and the additional third bridge-leg adopts a quasi-PR control (QPR) method that injects specific frequency harmonic voltage and suppresses newly generated low-frequency components of the input current. This method effectively avoids the drawbacks of utilizing passive filtering strategies, such as high-value impedance networks, low power density, and weak system stability. A simulation platform of 300W 144VDC/110VAC50Hz is constructed. The simulation results indicate that the addition of the third bridge leg under full load conditions reduces the input-side inductor current ripple ΔI from 1.89 A with passive filtering to 0.513 A, representing a reduction of 72.86%. The second harmonic ripple of the input current is reduced from 18.2% to 4.5%, and the fourth harmonic ripple is reduced from 16.5% to 2.1%. The DC bus voltage ripple ΔVPN falls from 70.75 V to 6.54 V, representing a reduction of 90.76%. The Total Harmonic Distortion (THD) of the output voltage and current are both less than 1%. The simulation results validated the feasibility of the proposed approach.

Euryale ferox Salisb. (prickly water lily) is the only extent of the genus Euryale that has been widely distributed in China, India, Korea, and Japan. The seeds of E. ferox (EFS) have been categorized as superior food for 2000 years in China, based on their abundant nutrients including polysaccharides, polyphenols, sesquineolignans, tocopherols, cyclic dipeptides, glucosylsterols, cerebrosides, and triterpenoids. These constituents exert multiple pharmacological effects, such as antioxidant, hypoglycemic, cardioprotective, antibacterial, anticancer, antidepression, and hepatoprotective properties. There are very few summarized reports on E. ferox, albeit with its high nutritional value and beneficial activities. Therefore, we collected the reported literature (since 1980), medical classics, database, and pharmacopeia of E. ferox, and summarized the botanical classification, traditional uses, phytochemicals, and pharmacological effects of E. ferox, which will provide new insights for further research and development of EFS-derived functional products.

There are limited data regarding the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) in acute heart failure (AHF). The purpose is to determine the patterns of ACEi/ARB use at the time of admission and discharge in relation to invasive hemodynamic data, mortality, and heart failure (HF) readmissions. This is a retrospective single-center study in patients with AHF who underwent right heart catheterization between January 2010 and December 2016. Patients on dialysis, evidence of shock, or incomplete follow up were excluded. Multivariate logistic regression analysis was used to analyze the factors associated with continuation of ACEi/ARB use on discharge and its relation to mortality and HF readmissions. The final sample was 626 patients. Patients on ACEi/ARB on admission were most likely continued on discharge. The most common reasons for stopping ACEi/ARB were worsening renal function (WRF), hypotension, and hyperkalemia. Patients with ACEi/ARB use on admission had a significantly higher systemic vascular resistance (SVR) and mean arterial pressure (MAP), but lower cardiac index (CI). Patients with RA pressures above the median received less ACEi/ARB (P = 0.025) and had significantly higher inpatient mortality (P = 0.048). After multivariate logistic regression, ACEi/ARB use at admission was associated with less inpatient mortality; OR 0.32 95% CI (0.11 to 0.93), and this effect extended to the subgroup of patients with HFpEF. Patients discharged on ACEi/ARB had significantly less 6-month HF readmissions OR 0.69 95% CI (0.48 to 0.98). ACEi/ARB use on admission for AHF was associated with less inpatient mortality including in those with HFpEF.

Conventional dc-dc boost converter has limited boost capacity, and its power device suffers high voltage stress. A novel hybrid Z-source dc-dc converter featured with high step-up capability and low device voltage stress is proposed in this article. Compared with the basic structure, the proposed topology can achieve higher voltage gain under the same duty ratio, and reduce the voltage stresses on the switch and diode under the same output condition. Moreover, the duty ratio is not limited. The detailed analysis and a comparison considering the proposed and other structures are also presented, which confirms its unique advantages. To verify the proposed converter performance, a prototype circuit with 40V-60V input voltage, 400V output voltage and 200W output power is built in the laboratory. Experiment results confirm the analysis and the boost capacity of the proposed converter.

Background Executive function (EF) involves a series of high-level processes, such as inhibition, switching, and updating. Aging-related cognitive decline has been shown to be strongly associated with EF worsening. The aims of this study were to perform a meta-analysis to evaluate the effects of exergaming, an emerging intervention, on EF performance in older adults and to conduct a moderator analysis of exergaming effects on EF. Methods Randomized controlled trials examining exergaming influences on EF in older adults were collated by searching the Web of Science, Elsevier Science, PubMed, and Google Scholar databases. Statistical data were quantified in Comprehensive Meta-analysis software. Overall EF and EF domains (inhibition, switching, and updating) were analyzed separately. Results A total of 15 studies were included. The meta-analysis results indicated that exergaming had a significant influence on overall EF in the older adult (standardized mean difference (SMD) = 0.349, 95% confidence interval (CI) [0.191–0.506], p < 0.001). The same effects were also found in EF domains of inhibition (SMD = 0.415, 95% CI [0.102–0.729], p = 0.009), switching (SMD = 0.243, 95% CI [0.071–0.415], p = 0.005), and updating (SMD = 0.366, 95% CI [0.140–0.592], p = 0.002). The effects of exergaming on overall EF were found to be moderated by the frequency of the intervention (Q(1) = 3.537, p = 0.06). Conclusion Exergaming was confirmed to improve overall EF, as well as in older adults, and the effect of exergaming on EF was shown to be moderated by intervention frequency.

Background: The Kocher approach is often adopted for surgical treatment of partial radial head fractures. However, anterior exposure of the radial head is limited by the Kocher approach. Radial head fractures are predisposed to be located at the anterior radius. The deviation of susceptible fracture locations against the regular operative approach imposes certain challenges on surgical procedures. This study explored whether there are any clinically significant differences in the exposure between the Henry and Kocher approaches. Materials and methods: Ten fresh-frozen cadaveric upper limbs were obtained as specimens. The radial head was exposed by both the Henry and Kocher approaches, followed by a long-axis parallel incision at the joint capsule until the capsular attachment was reached; the extracapsular ligaments and surrounding soft tissues were avoided. The 2 approaches were compared in the blind zone and in the visualized area. Results: The blind-zone arc of radial head exposure with the Henry and Kocher approaches averaged 132° ± 16° and 112° ± 21°, respectively. The supinated angle between the borderline of the blind-zone arc and the biceps tuberosity–radial medullary cavity centerline averaged 268° ± 20° and 75° ± 16°, respectively. Conclusions: The Henry approach offered optimal exposure of the anterior and lateral radial head but had a blind zone at the posteromedial radial head, whereas the Kocher approach offered optimal exposure of the posterolateral radial head but had a blind zone at the anterolateral radial head. The Henry approach could be a better option for specific management of radial head fractures based on the fracture location.

Inhibitors from lignocellulosic biomass have become the bottleneck of biorefinery development. Gluconobacter oxydans DSM2003 showed a high performance of inhibitors degradation, which had a short lag time in non-detoxified corn stover hydrolysate and could convert 90% of aldehyde inhibitors to weaker toxic acids. In this study, an aldehyde dehydrogenase gene W826-RS0111485, which plays an important function in the conversion of aldehyde inhibitors in Gluconobacter oxydans DSM2003, was identified. W826-RS0111485 was found by protein profiling, then a series of enzymatic properties were determined and were heterologously expressed in E. coli. The results indicated that NADP is the most suitable cofactor of the enzyme when aldehyde inhibitor is the substrate, and it had the highest oxidation activity to furfural among several aldehyde inhibitors. Under the optimal reaction conditions (50 °C, pH 7.5), the Km and Vmax of the enzyme under furfural stress were 2.45 and 80.97, respectively, and the Kcat was 232.22 min−1. The biodetoxification performance experiments showed that the recombinant E. coli containing the target gene completely converted 1 g/L furfural to furoic acid within 8 h, while the control E. coli only converted 18% furfural within 8 h. It was further demonstrated that W826-RS0111485 played an important role in the detoxification of furfural. The mining of this inhibitor degradation gene could provide a theoretical basis for rational modification of industrial strains to enhance its capacity of inhibitor degradation in the future.

Objective Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by inflammatory synovitis. We developed a new disease activity evaluation system using important cytokines to help doctors better evaluate disease activity in patients with RA. Methods Flow cytometry was used to detect the levels of seven cytokines. Then, the results were analyzed using an R language decision tree. Results The levels of six cytokines, namely interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ, were significantly different between the active disease and remission stages. Decision tree analysis of the six cytokines with statistical significance identified two judgment rules for the remission stage and three judgment rules for the active disease stage. Conclusion We proposed the use of the decision tree method to analyze cytokine levels in patients with RA and obtain a more intuitive and objective RA disease activity scoring system. This method revealed the relationships of IL-6 and TNF-α levels with inflammatory characteristics in patients with RA, which can help predict disease activity.

The majority of the single nucleotide variants (SNVs) identified by genome-wide association studies (GWAS) fall outside of the protein-coding regions. Elucidating the functional implications of these variants has been a major challenge. A possible mechanism for functional non-coding variants is that they disrupted the canonical transcription factor (TF) binding sites that affect the in vivo binding of the TF. However, their impact varies since many positions within a TF binding motif are not well conserved. Therefore, simply annotating all variants located in putative TF binding sites may overestimate the functional impact of these SNVs. We conducted a comprehensive survey to study the effect of SNVs on the TF binding affinity. A sequence-based machine learning method was used to estimate the change in binding affinity for each SNV located inside a putative motif site. From the results obtained on 18 TF binding motifs, we found that there is a substantial variation in terms of a SNV’s impact on TF binding affinity. We found that only about 20% of SNVs located inside putative TF binding sites would likely to have significant impact on the TF-DNA binding.

Abstract Background Investigating the factors that influence Acinetobacter baumannii(Ab) adhesion/invasion of host cells is important to understand its pathogenicity. Metal cations have been shown to play an important role in regulating the biofilm formation and increasing the virulence of Ab; however, the effect of calcium on host-bacterial interaction has yet to be clarified. Here, the dynamic process of the interaction between Ab and human respiratory epithelial cells and the effect of calcium on host-bacterial interaction were explored using microscopic imaging, quantitative PCR and real time cellular analysis (RTCA). Results The concentration of calcium, multiplicity of infection and co-culture time were all demonstrated to have effects on host-bacterial interaction. A unique “double peak” phenomenon changed to a sharp “single peak” phenomenon during the process of Ab infection under the effect of calcium was observed in the time-dependent cell response profiles. Moreover, calcium can increase Ab adhesion/invasion of epithelial cells by regulating the expression of Ab-related genes (ompA, bfmRS, abaI). Conclusions Effective control of calcium concentrations can provide new approaches for the prevention and treatment of multi-drug resistant Ab.

Objective. To investigate the prevalence of anxiety and depression in hospitalized patients in the Department of Gastroenterology and to explore the risk factors affecting psychosomatic conditions in patients with digestive disorders. Methods. Patients hospitalized with gastrointestinal diseases were enrolled by the Department of Gastroenterology of Xiangya Hospital of Central South University from November 2017 to June 2018 and completed a cross-sectional questionnaire survey. According to anxiety/nonanxiety, depression/nondepression, the subjects were divided into two groups, respectively, and the risk factors of anxiety/depression were analyzed. Results. A total of 1186 patients were included in this study. The overall detection rate was 20.74% for anxiety symptoms alone, 31.78% for depressive symptoms alone, 13.99% for both anxiety and depressive symptoms, and 38.53% for either depression or anxiety symptoms. The prevalence of anxiety symptoms was higher in female than in male patients and inversely correlated with levels of education. There was no significant difference in the detection rate of anxiety and depression between patients with functional and organic digestive diseases. Sleep quality and quality of life were inversely correlated with the severity of anxiety and depression. Notably, among the patients with abnormal psychological conditions, only 7.6% of them were willing to receive psychological treatment. Gender, sleep quality, and life quality are independent risk factors for anxiety and depression symptoms for inpatients with gastrointestinal diseases. Conclusion. Paying more attention to the education level, sleep quality, and quality of life in patients with gastrointestinal diseases will help doctors to identify the risk of psychological abnormalities and improve medical care.

Thioredoxin-interacting protein (TXNIP) is a thioredoxin-binding protein that can mediate oxidative stress, inhibit cell proliferation, and induce apoptosis by inhibiting the function of the thioredoxin system. TXNIP is important because of its wide range of functions in cardiovascular diseases, neurodegenerative diseases, cancer, diabetes, and other diseases. Increasing evidence has shown that TXNIP expression is low in tumors and that it may act as a tumor suppressor in various cancer types such as hepatocarcinoma, breast cancer, and lung cancer. TXNIP is known to inhibit the proliferation of breast cancer cells by affecting metabolic reprogramming and can affect the invasion and migration of breast cancer cells through the TXNIP-HIF1α-TWIST signaling axis. TXNIP can also prevent the occurrence of bladder cancer by inhibiting the activation of ERK, which inhibits apoptosis in bladder cancer cells. In this review, we find that TXNIP can be regulated by binding to transcription factors or other binding proteins and can also be downregulated by epigenetic changes or miRNA. In addition, we also summarize emerging insights on TXNIP expression and its functional role in different kinds of cancers, as well as clarify its participation in metabolic reprogramming and oxidative stress in cancer cells, wherein it acts as a putative tumor suppressor gene to inhibit the proliferation, invasion, and migration of different tumor cells as well as promote apoptosis in these cells. TXNIP may therefore be of basic and clinical significance for finding novel molecular targets that can facilitate the diagnosis and treatment of malignant tumors.

Background. Sepsis is a common complication of acute cholangitis (AC), which is associated with a high mortality rate. Our study is aimed at exploring the significance of white blood cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), and temperature (T) alone or combined together in early identification and curative effect monitoring of AC with or without sepsis. Methods. 65 consecutive cases with AC and 76 control cases were enrolled. They were divided into three groups: Group A (AC with sepsis), Group B (AC without sepsis), and Group C (inpatients without AC or other infections). The levels of WBC, CRP, PCT, sTREM-1, and temperature were measured dynamically. The study was carried out and reported according to STARD 2015 reporting guidelines. Results. CRP had the highest AUC to identify AC from individuals without AC or other infections (AUC 1.000, sensitivity 100.0%, specificity 100.0%, positive predictive value 100.0%, and negative predictive value 100.0%). Among various single indexes, PCT performed best (AUC 0.785, sensitivity 75.8%, specificity 72.2%, positive predictive value 68.7%, and negative predictive value 78.8%) to distinguish sepsis with AC, while different combinations of indexes did not perform better. From day 1 to day 5 of hospitalization, the levels of sTREM-1 in Group A were the highest, followed by Groups B and C (P

Multiplex quantitative polymerase chain reaction (qPCR) has found an increasing range of applications. The construction of a reliable and dynamic mathematical model for multiplex qPCR that analyzes the effects of interactions between variables is therefore especially important. This work aimed to analyze the effects of interactions between variables through response surface method (RSM) for uni- and multiplex qPCR, and further optimize the parameters by constructing two mathematical models via RSM and back-propagation neural network-genetic algorithm (BPNN-GA) respectively. The statistical analysis showed that Mg2+ was the most important factor for both uni- and multiplex qPCR. Dynamic models of uni- and multiplex qPCR could be constructed using both RSM and BPNN-GA methods. But RSM was better than BPNN-GA on prediction performance in terms of the mean absolute error (MAE), the mean square error (MSE) and the Coefficient of Determination (R2). Ultimately, optimal parameters of uni- and multiplex qPCR were determined by RSM.

Introduction: Alzheimer's disease (AD) is the leading cause of dementia, and currently, no effective treatments are available to reverse or halt its progression in clinical practice. Although a plethora of studies have highlighted the benefits of physical exercise in combating AD, elder individuals often have limited exercise capacity. Therefore, mild physical exercise and nutritional interventions represent potential strategies for preventing and mitigating neurodegenerative diseases. Our research, along with other studies, have demonstrated that platycodin D (PD) or its metabolite, platycodigenin, derived from the medicinal plant Platycodon grandiflorus, exerts neuroprotective effects against amyloid b (Ab)-induced neuroinflammation. However, the combined effects of PD and physical exercise on alleviating AD have yet to be explored. The current study aimed to investigate whether combined therapy could synergistically ameliorate memory deficits and AD pathology in 5 FAD mice. Methods: Five-month-old 5 x FAD mice were randomly assigned to four groups, and received either PD (5 mg/kg/day, p.o.), voluntary running, or a combination of both for 47 days. Nest building test, locomotion test, and Morris water maze test were used to evaluate the cognitive function. Immunohistochemical and ELISA analysis was performed to determine Ab build-up, microglia and astrocytes hyperactivation, and survival neurons in the hippocampus and perirhinal cortex. Real-time quantitative PCR analysis was used to assess the polarization of microglia and astrocytes. HPLC analysis was performed to measure monoamine neurotransmitters in the hippocampus. Results and discussion: The combination of PD and voluntary running synergistically restored nest-building behavior, alleviated recognition and spatial memory deficits, and showed superior effects compared to monotherapy. In addition, the PD and voluntary running combination reduced Ab build-up, decreased hyperactivation of microglia and astrocytes in the hippocampus and perirhinal cortex, promoted the polarization of inflammatory M1 microglia and reactive astrocytes toward beneficial phenotypes, and lowered systemic circulating pro-inflammatory cytokines while increasing anti-inflammatory cytokines in 5 FAD mice. Furthermore, combined therapy effectively protected neurons and increased levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in the hippocampus of 5 FAD mice. In conclusion, the combination of PD and voluntary running holds great potential as a treatment for AD, offering promise for delaying onset or progression of AD. [ABSTRACT FROM AUTHOR]