A comprehensive analysis of patients with cerebral arteriovenous malformation with headache: assessment of risk factors and treatment effectiveness.

BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.

Revealing sulfur-iron coupling mechanism for enhanced autotrophic denitrification in ecological floating beds.

A sulfur-iron coupled ecological floating bed (EFB-SFe) was developed to enhance the denitrification capability of sulfur-based ecological floating beds (EFB-S). The denitrification performance, kinetic process and microbial community composition were explored. Results showed that sulfur-iron coupling effectively enhanced the denitrification performance of EFB, surpassing the sum of their individual effects. The average total nitrogen removal rate ranged from 1.56 to 4.56 g·m-2·d-1, with a removal efficiency of 22-84 %. The k value for the S + Fe group increased from 0.04 to 0.18 d-1 to 0.40-0.46 d-1 relative to the S group. The sulfur-iron coupling promoted the enrichment of denitrifying bacteria (Thiobacillus and Ferritrophicum). The denitrification genes in EFB-SFe were upregulated, being 12-22 times more abundant than in EFB-S. Sulfur and iron autotrophic denitrification were identified as the main nitrogen removal processes in EFB-SFe. Overall, sulfur-iron coupling showed the potential to enhance the denitrification capacity of EFB-S for treating low-pollution water.

Coordination-Driven Self-Assembly of Metal Ion-Antisense Oligonucleotide Nanohybrids for Chronic Bacterial Infection Therapy.

Bacterial infection poses a significant challenge to wound healing and skin regeneration, leading to substantial economic burdens on patients and society. Therefore, it is crucial to promptly explore and develop effective methodologies for bacterial infections. Herein, we propose a novel approach for synthesizing nanostructures based on antisense oligonucleotides (ASOs) through the coordination-driven self-assembly of Zn2+ with ASO molecules. This approach aims to provide effective synergistic therapy for chronic wound infections caused by Staphylococcus aureus (S. aureus). The resulting hybrid nanoparticles successfully preserve the structural integrity and biological functionalities of ASOs, demonstrating excellent ASO encapsulation efficiency and bioaccessibility. In vitro antibacterial experiments reveal that Zn-ASO NPs exhibit antimicrobial properties against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. This antibacterial ability is attributed to the high concentration of metal zinc ions and the generation of high levels of reactive oxygen species. Additionally, the ftsZ-ASO effectively inhibits the expression of the ftsZ gene, further enhancing the antimicrobial effect. In vivo antibacterial assays demonstrate that the Zn-ASO NPs promote optimal skin wound healing and exhibit favorable biocompatibility against S. aureus infections, resulting in a residual infected area of less than 8%. This combined antibacterial strategy, which integrates antisense gene therapy and metal-coordination-directed self-assembly, not only achieves synergistic and augmented antibacterial outcomes but also expands the horizons of ASO coordination chemistry. Moreover, it addresses the gap in the antimicrobial application of metal-coordination ASO self-assembly, thereby advancing the field of ASO-based therapeutic approaches.

Yolk-shell FeS@N-doped carbon nanosphere as superior anode materials for sodium-ion batteries.

Iron sulfides have shown great potential as anode materials for sodium-ion batteries (SIBs) because of their high sodium storage capacity and low cost. Nevertheless, iron sulfides generally exhibit unsatisfied electrochemical performance induced by sluggish electron/ion transfer and severe pulverization upon the sodiation/desodiation process. Herein, we constructed a yolk-shell FeS@NC nanosphere with an N-doped carbon shell and FeS particle core via a simple hydrothermal method, followed by in-situ polymerization and vulcanization. The FeS particles intimately coupled with N-doped carbon can accelerate the electron transfer, avoid severe volume expansion, and maintain structural stability upon repeated sodiation/desodiation process. Furthermore, the small particle size of FeS can shorten ion-diffusion distance and facilitate ion transportation. Therefore, the FeS@NC nanosphere shows excellent cycling performance and superior rate capability that it can deliver a high capacity of 520.1 mAh g-1 over 800 cycles at 2.0 A g-1 and a remarkable capacity of 625.9 mAh g-1 at 10.0 A g-1.

Evaluation method for ecology-agriculture-urban spaces based on deep learning.

With the increasing global population and escalating ecological and farmland degradation, challenges to the environment and livelihoods have become prominent. Coordinating urban development, food security, and ecological conservation is crucial for fostering sustainable development. This study focuses on assessing the "Ecology-Agriculture-Urban" (E-A-U) space in Yulin City, China, as a representative case. Following the framework proposed by Chinese named "environmental capacity and national space development suitability evaluation" (hereinafter referred to as "Double Evaluation"), we developed a Self-Attention Residual Neural Network (SARes-NET) model to assess the E-U-A space. Spatially, the northwest region is dominated by agriculture, while the southeast is characterized by urban and ecological areas, aligning with regional development patterns. Comparative validations with five other models, including Logistic Regression (LR), Naive Bayes (NB), Gradient Boosting Decision Trees (GBDT), Random Forest (RF) and Artificial Neural Network (ANN), reveal that the SARes-NET model exhibits superior simulation performance, highlighting it's ability to capture intricate non-linear relationships and reduce human errors in data processing. This study establishes deep learning-guided E-A-U spatial evaluation as an innovative approach for national spatial planning, holding broader implications for national-level territorial assessments.

Identification and validation of a glycosyltransferase gene signature as a novel prognostic model for lung adenocarcinoma.

Background: The role of glycosyltransferase (GT) genes in lung adenocarcinoma (LUAD) needs further elucidation. Thus, our study aims to identify the prognostic gene signature of LUAD and explore its molecular functions. Methods: We initially extracted GT gene sets from the database, and obtained mRNA expression levels and clinical data from The Cancer Genome Atlas (TCGA) database. For constructing a prognostic model for GT genes, we utilized univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Using the model, patients were categorized into high- and low-risk groups. Additionally, we evaluated differences in tumor immune infiltration between these groups and identified potential therapeutic drugs. Finally, we experimentally validated the expression levels of these crucial prognostic genes. Results: We developed a risk score comprising nine GT genes (C1GALT1, FUT1, GALNT2, PLOD2, POMK, PYGB, ST3GAL6, UGT2B11, UGT3A1). Patients were then categorized into low- and high-risk groups based on this score. The low-risk group showed superior overall survival (OS) compared to the high-risk group. There were significantly distinct tumor immune microenvironment statuses observed between the two groups. We identified potential therapeutic drugs, including the MEK inhibitor (PD-184352). Finally, we verified the expression of these nine GT genes through immunohistochemistry (IHC) staining and quantitative real-time PCR (qPCR). Conclusion: We identified a distinct LUAD GT gene signature, and these differentially expressed mRNAs could serve as valuable prognostic biomarkers and therapeutic targets. Furthermore, we experimentally validated their expression levels and identified potential therapeutic agents.

Changes in Corneal Epithelial Thickness in Different Areas After Femtosecond Laser-Assisted LASIK in Patients With High Astigmatism.

PURPOSE: To explore changes in corneal epithelial thickness (CET) after femtosecond laser-assisted laser in situ keratomileusis in patients with high astigmatism. METHODS: CET was measured at every intersection of the concentric circles and specific axes using AngioVue optical coherence tomography (Angio-OCT) preoperatively and 1 month postoperatively. The average thickness of corneal central, paracentral, and peripheral regions was the mean of the points within the central 2, 2 to 5, and 5 to 7 mm areas, respectively. Correlation analysis was performed to investigate the association between CET along different axes and other preoperative and postoperative parameters. RESULTS: Forty-two eyes of 28 patients were included. CET along the astigmatic (K1) and perpendicular (K2) axes in the central and paracentral areas increased (P < .001), whereas that along the K2 axis decreased in the peripheral area 1 month postoperatively (P = .001). The amount of CET change in the peripheral area between the K1 and K2 axes was significantly different (P < .001). In the central area, the change in CET along the K2 axis was positively correlated with ablation depth (r = 0.315, P = .042) and negatively with refractive power after surgery (r = -0.347, P = .024). In the peripheral area, the changes in CET along both K1 and K2 axes were negatively correlated with ablation depth (r = -0.431, P = .004; r = -0.387, P = .011, respectively). CONCLUSIONS: Epithelial modeling differed between the different astigmatism axes after refractive surgery. The compensatory response of the corneal epithelium is more pronounced along the steeper axis. [J Refract Surg. 2024;40(4):e239-e244.].

Pathophysiology characterization of Alzheimer's disease in South China's aging population: for the Greater-Bay-Area Healthy Aging Brain Study (GHABS).

INTRODUCTION: The Guangdong-Hong Kong-Macao Greater-Bay-Area of South China has an 86 million population and faces a significant challenge of Alzheimer's disease (AD). However, the characteristics and prevalence of AD in this area are still unclear due to the rarely available community-based neuroimaging AD cohort. METHODS: Following the standard protocols of the Alzheimer's Disease Neuroimaging Initiative, the Greater-Bay-Area Healthy Aging Brain Study (GHABS) was initiated in 2021. GHABS participants completed clinical assessments, plasma biomarkers, genotyping, magnetic resonance imaging (MRI), ß-amyloid (Aß) positron emission tomography (PET) imaging, and tau PET imaging. The GHABS cohort focuses on pathophysiology characterization and early AD detection in the Guangdong-Hong Kong-Macao Greater Bay Area. In this study, we analyzed plasma Aß42/Aß40 (A), p-Tau181 (T), neurofilament light, and GFAP by Simoa in 470 Chinese older adults, and 301, 195, and 70 had MRI, Aß PET, and tau PET, respectively. Plasma biomarkers, Aß PET, tau PET, hippocampal volume, and temporal-metaROI cortical thickness were compared between normal control (NC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia groups, controlling for age, sex, and APOE-ε4. The prevalence of plasma A/T profiles and Aß PET positivity were also determined in different diagnostic groups. RESULTS: The aims, study design, data collection, and potential applications of GHABS are summarized. SCD individuals had significantly higher plasma p-Tau181 and plasma GFAP than the NC individuals. MCI and dementia patients showed more abnormal changes in all the plasma and neuroimaging biomarkers than NC and SCD individuals. The frequencies of plasma A+/T+ (NC; 5.9%, SCD: 8.2%, MCI: 25.3%, dementia: 64.9%) and Aß PET positivity (NC: 25.6%, SCD: 22.5%, MCI: 47.7%, dementia: 89.3%) were reported. DISCUSSION: The GHABS cohort may provide helpful guidance toward designing standard AD community cohorts in South China. This study, for the first time, reported the pathophysiology characterization of plasma biomarkers, Aß PET, tau PET, hippocampal atrophy, and AD-signature cortical thinning, as well as the prevalence of Aß PET positivity in the Guangdong-Hong Kong-Macao Greater Bay Area of China. These findings provide novel insights into understanding the characteristics of abnormal AD pathological changes in South China's older population.

Efficacy of oats in dyslipidemia: a systematic review and meta-analysis.

Background: In recent years, oats' effect on lowering serum cholesterol has been recognized. However, no systematic reviews summarized the effect of daily consumption of oat-based products on serum lipids in patients with dyslipidemia. Methods: We searched eight databases and two clinical trial registries from inception to July 31, 2023. We included randomized controlled trials (RCTs) evaluating the efficacy of oat-based products (≥4 weeks) on lipid levels or cardiovascular events in patients with dyslipidemia. Two authors independently screened articles, extracted data and assessed the risk of bias of included studies with Cochrane risk-of-bias tool 2.0. We used STATA 17.0 to conduct meta-analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. Results: We finally included 17 eligible trials with 1731 subjects. The oat intervention varied from oat ß-glucan-based products to oat bran-based products and wholegrain oat. Overall, the risk of bias of included trials was high or some concerns were noted because of the inadequate randomization, allocation concealment, and inappropriate data analysis method. Compared to the placebo or usual diet, one study indicated that oat-based products have no significant difference in major cardiovascular events. Pooled estimates showed that oat-based products may result in a large reduction in LDL-C (WMD, -0.24 mmol L-1; 95% CI: -0.33, -0.15) (moderate certainty) and TC (WMD, -0.32 mmol L-1; 95% CI: -0.48, -0.17) (moderate certainty). Compared to other diets (mainly other cereals), oat-based products probably reduce the level of LDL-C (WMD, -0.17 mmol L-1; 95% CI: -0.25, -0.08) (moderate certainty) and TC (WMD, -0.21 mmol L-1; 95% CI: -0.30, -0.12) (moderate certainty). Both groups showed that oat-based products had little effect on HDL-C and TG (moderate certainty). Oat-related adverse events were mostly gastrointestinal such as diarrhea, nausea, and flatulence being the most prevalent. Conclusions: Oat-based products may reduce TC and LDL-C, but have little effect on TG, HDL-C, and major cardiovascular events in patients with dyslipidemia.

Impact of a clinical care pathway developed through the action research method on the psychological well-being and quality of life in male patients with urethral stricture.

BACKGROUND: The objective of this study is to examine the development of a clinical care pathway utilizing an action research methodology for male patients with urethral stricture, and to assess the psychological and quality of life outcomes following the implementation of this pathway. METHODS: Ninety patients diagnosed with urethral stricture, admitted to our hospital between May 2021 and May 2022, were selected as the study cohort. Employing a random number method, these patients were allocated into an observation group and a control group, each comprising 45 individuals. The control cohort employs standard care protocols for individuals with urethral stenosis, while the experimental group employs an action research methodology to develop a clinical care pathway specific to the management of patients with urethral stenosis, with an intervention cycle of 3 months. The investigation evaluated the impact of the intervention by scrutinizing pre- and post-intervention data through the utilization of the WHO Quality of Life Scale (WHOQOL-BREF), in addition to the Anxiety Rating Scale and the Depression Rating Scale. RESULTS: Prior to the intervention, no significant differences were observed in WHOQOL-BREF scores across dimensions, as well as anxiety and depression scores between the 2 groups (P > .05). Subsequent to the intervention, the patients in the observation group exhibited significantly higher scores across all WHOQOL-BREF dimensions and total scores compared to the control group, with statistical significance (P < .05). Moreover, anxiety and depression scores in the observation group were markedly lower than those in the control group, demonstrating statistical significance (P < .05). CONCLUSION: The implementation of a clinical nursing pathway rooted in action research methodology proves to be an effective strategy for enhancing clinical nursing practices, elevating patient quality of life, and diminishing the prevalence of anxiety and depression.

Nanofiber-based wound dressing in wound healing of elderly patients.

Introduction: With the aging of the population, it has become a serious problem that the wounds of elderly patients are not easy to heal. Aim: To explore the application of nanofiber wound dressing in wound healing of elderly patients. Material and methods: In this article, 86 elderly patients with chronic wounds admitted to the Affiliated Hospital of Shaanxi University of Chinese Medicine from January 2023 to September 2023 were enrolled, and they were randomly divided into control and experimental groups, with 43 cases in each group. Controls used traditional wound dressings in care. The experimental group used nanofiber wound dressings. The wound healing efficacy, inflammatory factors, side effects, wound infection degree, healing time, and pain were compared between the two groups. Results: The total effective rate of the experimental group (97.67%) was higher as against controls (86.04%). Wound germiculture positive (7.14 ±2.76%) was lower in the experimental group as against controls (22.13 ±3.27%. The wound healing time of the experimental group (18.68 ±5.78 d) was shorter as against controls (30.24 ±6.19 d). The visual analogue scale (VAS) score of the experimental group (2.68 ±0.41 s) was lower as against controls (3.57 ±0.89 s) after 16 days of care (p < 0.05). Conclusions: The use of nanofiber dressings is an effective means to promote wound healing in elderly patients, which is worthy of application in practical care.

Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses.

BACKGROUND: Ginkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published. OBJECTIVE: This overview aims to assess the quality of related SRs and MAs. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022. INCLUSION CRITERIA: SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included. DATA EXTRACTION AND ANALYSIS: Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted. RESULTS: Twenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores. CONCLUSION: GBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS. Please cite this article as: Meng TT, You YP, Li M, Guo JB, Song XB, Ding JY, Xie XL, Li AQ, Li SJ, Yin XJ, Wang P, Wang Z, Wang BL, He QY. Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses. J Integr Med. 2024;22(2): 163-179.

MECOM: a bioinformatics and experimentally identified marker for the diagnosis and prognosis of lung adenocarcinoma.

Objective: We aimed to explore the clinical value of MDS1 and EVI1 complex locus (MECOM) in lung adenocarcinoma (LUAD). Methods: Bioinformatics and experimental validation confirmed MECOM expression levels in LUAD. The value of MECOM was analyzed by receiver operating characteristic (ROC) curve and Cox regression analysis. Results: Serum MECOM levels were lower in LUAD and correlated with gender, TNM stage, tumor size, lymph node metastasis and distant metastasis. The ROC curve showed that the area under the curve of MECOM was 0.804 for LUAD and, of note, could reach 0.889 for advanced LUAD; specificity was up to 90%. Conclusion: MECOM may contribute to independently identifying LUAD patients, particularly in advanced stages.

Lung adenocarcinoma is a common type of lung cancer with a high incidence and death rate. However, clinical indicators that effectively identify lung adenocarcinoma patients are still lacking. The protein encoded by the MECOM gene is a DNA-binding protein regulating gene expression, which has been found to play a cancer-promoting role in many cancers, but we found that it may play a cancer-suppressing role in lung adenocarcinoma. This study aimed to confirm whether MECOM can be a predictor for lung adenocarcinoma. Our results showed that lung adenocarcinoma patients had lower serum MECOM levels than healthy people, and patients with lower MECOM levels had a shorter survival rate. That is, patients with lower serum MECOM levels may indicate a high risk of developing lung adenocarcinoma and death. Thus, the MECOM gene is expected to be a predictor associated with the risk of developing lung adenocarcinoma and death.

Evaluation of Oxygen Consumption Rates In Situ.

An analysis of the mitochondrial respiration function represented by the oxygen consumption rate is necessary to assess mitochondrial bioenergetics and redox function. This protocol describes two alternative techniques to evaluate mitochondrial respiration function in situ: (1) measure oxygen consumption rates via an electrode; (2) measure oxygen consumption rates via a seahorse instrument. These in situ approaches provide more physiological access to mitochondria to evaluate mitochondrial respiration function in a relatively integrated cellular system.

Synergistic effect of combating air pollutants and carbon emissions in the Yangtze River Delta of China: spatial and temporal divergence analysis and key influencing factors.

Synergizing the reduction of air pollutants and carbon emissions (APCE) has become a critical tactic alternative to address the issue of climate change. Taking the Yangtze River Delta (YRD) region of China as a case study, this paper explores the spatial and temporal distribution pattern of the coupling coordination degree (CCD) of combating APCE from 2011 to 2022, analyzes the dynamic change in CCD using the convergence test, and investigates the key factors affecting CCD via the Tobit regression model. The results show that (1) from 2011 to 2022, the air pollutants (AP) and CO2 emission (CE) in the YRD region decrease at the annual rate of 10.32% and 0.85%, respectively; (2) the CCD of reducing APCE in the YRD presents a W-shaped fluctuation before 2016 and then steps into a steady increase status after 2016; (3) the order of CCD in four provincial-level units by 2022 is Shanghai > Zhejiang > Jiangsu > Anhui. The proportion of cities where the CCD of reducing APCE enters the high-coordination period has reached 87.8%; and (4) the Tobit regression results affirm that economic growth, industrial structure, and green technological innovation exacerbate the CCD of combating APCE, while opening-up level mitigates it. The findings offer policymakers valuable insights into the importance of pursuing collaborative governance over APCE and ensuring sustainable development.

Media Use Behavior Mediates the Association Between Family Health and Intention to Use Mobile Health Devices Among Older Adults: Cross-Sectional Study.

BACKGROUND: With the advent of a new era for health and medical treatment, characterized by the integration of mobile technology, a significant digital divide has surfaced, particularly in the engagement of older individuals with mobile health (mHealth). The health of a family is intricately connected to the well-being of its members, and the use of media plays a crucial role in facilitating mHealth care. Therefore, it is important to examine the mediating role of media use behavior in the connection between the family health of older individuals and their inclination to use mHealth devices. OBJECTIVE: This study aims to investigate the impact of family health and media use behavior on the intention of older individuals to use mHealth devices in China. The study aims to delve into the intricate dynamics to determine whether media use behavior serves as a mediator in the relationship between family health and the intention to use mHealth devices among older adults. The ultimate goal is to offer well-founded and practical recommendations to assist older individuals in overcoming the digital divide. METHODS: The study used data from 3712 individuals aged 60 and above, sourced from the 2022 Psychology and Behavior Investigation of Chinese Residents study. Linear regression models were used to assess the relationships between family health, media use behavior, and the intention to use mHealth devices. To investigate the mediating role of media use behavior, we used the Sobel-Goodman Mediation Test. This analysis focused on the connection between 4 dimensions of family health and the intention to use mHealth devices. RESULTS: A positive correlation was observed among family health, media use behavior, and the intention to use mHealth devices (r=0.077-0.178, P<.001). Notably, media use behavior was identified as a partial mediator in the relationship between the overall score of family health and the intention to use mHealth devices, as indicated by the Sobel test (z=5.451, P<.001). Subgroup analysis further indicated that a complete mediating effect was observed specifically between family health resources and the intention to use mHealth devices in older individuals with varying education levels. CONCLUSIONS: The study revealed the significance of family health and media use behavior in motivating older adults to adopt mHealth devices. Media use behavior was identified as a mediator in the connection between family health and the intention to use mHealth devices, with more intricate dynamics observed among older adults with lower education levels. Going forward, the critical role of home health resources must be maximized, such as initiatives to develop digital education tailored for older adults and the creation of media products specifically designed for them. These measures aim to alleviate technological challenges associated with using media devices among older adults, ultimately bolstering their inclination to adopt mHealth devices.

Discovery of WS-384, a first-in-class dual LSD1 and DCN1-UBC12 protein-protein interaction inhibitor for the treatment of non-small cell lung cancer.

Abnormally high expression of lysine-specific demethylase 1 A (LSD1) and DCN1 plays a vital role in the occurrence, development, and poor prognosis of non-small cell lung cancer (NSCLC). Accumulating evidence has shown that the development of small-molecule inhibitors dually targeting LSD1 and the DCN1-UBC12 interaction probably have therapeutic promise for cancer therapy. This work reported that WS-384 dually targeted LSD1 and DCN1-UBC12 interactions and evaluated its antitumor effects in vitro and in vivo. Specifically, WS-384 inhibited A549 and H1975 cells viability and decreased colony formation and EdU incorporation. WS-384 could also trigger cell cycle arrest, DNA damage, and apoptosis. Moreover, WS-384 significantly decreased tumor weight and volume in A549 xenograft mice. Mechanistically, WS-384 increased the gene and protein level of p21 by suppressing the neddylation of cullin 1 and decreasing H3K4 demethylation at the CDKN1A promoter. The synergetic upregulation of p21 contributed to cell cycle arrest and the proapoptotic effect of WS-384 in NSCLC cells. Taken together, our proof of concept studies demonstrated the therapeutic potential of dual inhibition of LSD1 and the DCN1-UBC12 interaction for the treatment of NSCLC. WS-384 could be used as a lead compound to develop new dual LSD1/DCN1 inhibitors for the treatment of human diseases in which LSD1 and DCN1 are dysregulated.

Microglial Reactivity Correlates with Presynaptic Loss Independent of ß-Amyloid and Tau.

OBJECTIVE: Triggering receptor expressed on myeloid cells-2 (TREM2) and progranulin (PGRN) are critical regulators of microglia activation and can be detected in cerebrospinal fluid (CSF). However, whether microglial reactivity is detrimental or neuroprotective for Alzheimer disease (AD) is still debatable. METHODS: We identified 663 participants with baseline ß-amyloid (Aß) positron emission tomography (PET) and CSF biomarker data, including phosphorylated tau181 (p-Tau181), soluble TREM2 (sTREM2), PGRN, and growth-associated protein-43 (GAP-43). Among them, 254 participants had concurrent longitudinal CSF biomarkers. We used multivariate regression analysis to study the associations of CSF microglial biomarkers with Aß PET, CSF p-Tau181, and CSF GAP-43 cross-sectionally and longitudinally. A Chinese aging cohort's independent CSF samples (n = 65) were analyzed as a validation. RESULTS: Higher baseline levels of CSF microglial biomarkers were related to faster rates of CSF sTREM2 increase and CSF PGRN decrease. Elevated CSF p-Tau181 was associated with higher levels of CSF microglial biomarkers and faster rates of CSF sTREM2 increase and CSF PGRN decrease. In both cohorts, higher Aß burden was associated with attenuated CSF p-Tau181 effects on CSF microglial biomarker increases. Independent of Aß PET and CSF p-Tau181 pathologies, higher levels of CSF sTREM2 but not CSF PGRN were related to elevated CSF GAP-43 levels and faster rates of CSF GAP-43 increase. INTERPRETATION: These findings suggest that higher Aß burden may attenuate the p-Tau-associated microglial responses, and TREM2-related microglial reactivity may independently correlate with GAP-43-related presynaptic loss. This study highlights the two-edged role of microglial reactivity in AD and other neurodegenerative diseases. ANN NEUROL 2024;95:917-928.