Effect of bending deformation on the electronic and optical properties of O atoms adsorbed by Be3N2.

CONTEXT: In this paper, the optimum coverage of 4.44% and the optimum adsorption sites were determined for the Be3N2 adsorption system of O atoms at different coverages based on density functional theory. The electronic and optical properties of the model were investigated by applying bending deformation to the model at these coverage and adsorption sites. Adsorption of O atoms disrupts the geometrical symmetry of Be3N2, resulting in orbital rehybridization and lowering its band gap. Bending deformation causes the band gap of the adsorbed O atom structure of Be3N2 to first increase and then decrease, resulting in the modulation of its band gap. With increasing bending deformation, the adsorbed system is redshifts, and the degree of redshift increases with increasing bending deformation. METHODS: All calculations in this paper were performed using the first-principles-based CASTEP module of Materials Studio (MS). The generalized gradient approximation (GGA) plane-wave pseudopotential method and the Perdew-Burke-Ernzerhof (PBE) Perdew et al. Phys Rev Lett 77:3865, 1996 generalized functional were used in the geometry optimization and calculation process to calculate the exchange-correlation potential between electrons. The effect of coverage on the electronic and optical properties of the Be3N2-adsorbed O atom system was investigated by adsorbing different numbers of O atoms on a monolayer of Be3N2. The Be3N2 protocell contains two N atoms and three Be atoms with a space community of P6/MMM (No.191). The original cell was expanded 3 times along the direction of the base vectors a and b in the Be3N2 plane to create a 3 × 3 × 1 monolayer Be3N2 supercell system. A vacuum layer of 15 Å is set in the direction of the crystal plane of the vertical monolayer Be3N2 supercell to eliminate interactions between adjacent layers. In the overall energy convergence test of the Be3N2 supercell, the plane wave truncation energy was set to 500 eV, and the energy difference between the calculations given in the literature Reyes-Serrato et al. J Phys Chem Solids 59:743-6, 1998 using 550 eV was less than 0.01 eV, verifying the reliability of the data at a truncation energy of 500 eV. The Monkhorst-Pack special k-point sampling method Monkhorst et al. Phys Rev B 13:5188, 1976 was used in the structural calculations, and the grid was set to 3 × 3 × 1. The geometric optimization parameters are set as follows: the self-consistent field iteration convergence criterion is 2.0 × 10-6 eV, and the iterative accuracy convergence value is not less than 1.0 × 10-5 eV/atom for the total force of each atom and less than 0.03 eV/Å for all atomic forces. In addition the high-symmetry k-point path is taken as Γ(0,0,0) → M(0,0.5,0) → K(- 1/3,2/3,0) → Γ(0,0,0) Chen et al, AIP Adv 8:105105, 2018.

Modulating the phenotype and function of bone marrow-derived macrophages via mandible and femur osteoblasts.

Various studies have been investigated the phenotypic and functional distinctions of craniofacial and long bone cells involved in bone regeneration. However, the process of bone tissue regeneration after bone grafting involves complicated interactions between different cell types at the donor-recipient site. Additionally, differences in alterations of the immune microenvironment at the recipient site remained to be explored. Osteoblasts (OBs) and macrophages (MØ) play essential roles in the bone restoration and regeneration processes in the bone and immune systems, respectively. The modulation of MØ on OBs has been extensively explored in the literature, whereas limited research has been conducted on the influence of OBs on the MØ phenotype and function. In the present study, OBs from the mandible and femur (MOBs and FOBs, respectively) promoted cranial defect regeneration in rats, with better outcomes noted in the MOBs-treated group. After MOBs transplantation, a significant inflammatory response was induced, accompanied by an early increase in IL-10 secretion. And then, there was an upregulation in M2-MØ-related cell markers and inflammatory factor expression. Condition media (CM) of OBs mildly inhibited apoptosis in MØ, enhanced their migration and phagocytic functions, and concurrently increased iNOS and Arg1 expression, with MOB-CM demonstrating more pronounced effects compared to FOB-CM. In conclusion, our investigation showed that MOBs and FOBs have the ability to modulate MØ phenotype and function, with MOBs exhibiting a stronger regulatory potential. These findings provide a new direction for improving therapeutic strategies for bone regeneration in autologous bone grafts from the perspective of the immune microenvironment.

Shared Decision-Making in Cardiovascular Risk Factor Management: A Systematic Review and Meta-Analysis.

Importance: The effect of shared decision-making (SDM) and the extent of its use in interventions to improve cardiovascular risk remain unclear. Objective: To assess the extent to which SDM is used in interventions aimed to enhance the management of cardiovascular risk factors and to explore the association of SDM with decisional outcomes, cardiovascular risk factors, and health behaviors. Data Sources: For this systematic review and meta-analysis, a literature search was conducted in the Medline, CINAHL, Embase, Cochrane, Web of Science, Scopus, and ClinicalTrials.gov databases for articles published from inception to June 24, 2022, without language restrictions. Study Selection: Randomized clinical trials (RCTs) comparing SDM-based interventions with standard of care for cardiovascular risk factor management were included. Data Extraction and Synthesis: The systematic search resulted in 9365 references. Duplicates were removed, and 2 independent reviewers screened the trials (title, abstract, and full text) and extracted data. Data were pooled using a random-effects model. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Decisional outcomes, cardiovascular risk factor outcomes, and health behavioral outcomes. Results: This review included 57 RCTs with 88 578 patients and 1341 clinicians. A total of 59 articles were included, as 2 RCTs were reported twice. Nearly half of the studies (29 [49.2%]) tested interventions that targeted both patients and clinicians, and an equal number (29 [49.2%]) exclusively focused on patients. More than half (32 [54.2%]) focused on diabetes management, and one-quarter focused on multiple cardiovascular risk factors (14 [23.7%]). Most studies (35 [59.3%]) assessed cardiovascular risk factors and health behaviors as well as decisional outcomes. The quality of studies reviewed was low to fair. The SDM intervention was associated with a decrease of 4.21 points (95% CI, -8.21 to -0.21) in Decisional Conflict Scale scores (9 trials; I2 = 85.6%) and a decrease of 0.20% (95% CI, -0.39% to -0.01%) in hemoglobin A1c (HbA1c) levels (18 trials; I2 = 84.2%). Conclusions and Relevance: In this systematic review and meta-analysis of the current state of research on SDM interventions for cardiovascular risk management, there was a slight reduction in decisional conflict and an improvement in HbA1c levels with substantial heterogeneity. High-quality studies are needed to inform the use of SDM to improve cardiovascular risk management.

Satisfaction with Telehealth Care in the United States: Cross-Sectional Survey.

Background: Telehealth use remains high following the COVID-19 pandemic, but patient satisfaction with telehealth care is unclear. Methods: We used cross-sectional data from the Health Information National Trends Survey (HINTS 6). 2,058 English and Spanish-speaking U.S. adults (≥18 years) with a telehealth visit in the 12 months before March-November 2022 were included in this study. The primary outcomes were telehealth visit modality and satisfaction in the 12 months before HINTS 6. We evaluated sociodemographic predictors of telehealth visit modality and satisfaction via Poisson regression. Analyses were weighted according to HINTS standards. Results: We included 2,058 participants (48.4 ± 16.8 years; 57% women; 66% White), of which 70% had an audio-video and 30% an audio-only telehealth visit. Adults with an audio-video visit were more likely to have health insurance (adjusted prevalence ratio [aPR]: 1.55, 95% confidence interval [CI]: 1.18-2.04) and have an annual household income of ≥$75,000 (aPR: 1.18, 95% CI: 1.00-1.39) and less likely to be ≥65 years (aPR: 0.79, 95% CI: 0.70-0.89), adjusting for sociodemographic characteristics. No further inequities were noted by telehealth modality. Seventy-five percent of participants felt that their telehealth visits were as good as in-person care. No significant differences in telehealth satisfaction were observed across sociodemographic characteristics, telehealth modality, or the participants' primary reason for their most recent telehealth visit in adjusted analysis. Conclusions: Among U.S. adults with a telehealth visit, the majority had an audio-video visit and were satisfied with their care. Telehealth should continue, being offered following COVID-19, as it is uniformly valued by patients.

A Group of Highly Secretory miRNAs Correlates with Lymph Node Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma.

MicroRNAs (miRNAs) in oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) play a pivotal role in modulating intercellular communications between tumor cells and other cells in the microenvironment, thereby influencing tumor progression and the efficacy of therapeutic interventions. However, a comprehensive inventory of these secretory miRNAs in sEVs and their biological and clinical implications remains elusive. This study aims to profile the miRNA content of OSCC cell line sEVs and computationally elucidate their biological and clinical relevance. We conducted miRNA sequencing to compare the miRNA profiles of OSCC cells and their corresponding sEVs. Our motif enrichment analysis identified specific sorting motifs that are implicated in either cellular retention or preferential sEV secretion. Target cell analysis suggested that the sEV miRNAs potentially interact with various immune cell types, including natural killer cells and dendritic cells. Additionally, we explored the clinical relevance of these miRNAs by correlating their expression levels with TNM stages and patient survival outcomes. Intriguingly, our findings revealed that a distinct sEV miRNA signature is associated with lymph node metastasis and poorer survival in patients in TCGA-HNSC dataset. Collectively, this research furthers our understanding of the miRNA sorting mechanisms in OSCC and underscores their clinical implications.

Supplementation of nicotinamide mononucleotide diminishes COX-2 associated inflammatory responses in macrophages by activating kynurenine/AhR signaling.

Cyclooxygenase-2 (COX-2) is an inducible enzyme responsible for prostaglandin synthesis during inflammation and immune responses. Our previous results show that NAD+ level decreased in activated macrophages while nicotinamide mononucleotide (NMN) supplementation suppressed the inflammatory responses via restoring NAD+ level and downregulating COX-2. However, whether NMN downregulates COX-2 in mouse model of inflammation, and its underlying mechanism needs to be further explored. In the present study, we established LPS- and alum-induced inflammation model and demonstrated that NMN suppressed the inflammatory responses in vivo. Quantitative proteomics in mouse peritoneal macrophages identified that NMN activated AhR signaling pathway in activated macrophages. Furthermore, we revealed that NMN supplementation led to IDO1 activation and kynurenine accumulation, which caused AhR nuclear translocation and activation. On the other hand, AhR or IDO1 knockout abolished the effects of NMN on suppressing COX-2 expression and inflammatory responses in macrophages. In summary, our results demonstrated that NMN suppresses inflammatory responses by activating IDO-kynurenine-AhR pathway, and suggested that administration of NMN in early-stage immuno-activation may cause an adverse health effect.

Heterogeneity in the Prevalence of Cardiovascular Risk Factors by Ethnicity and Birthplace Among Asian Subgroups: Evidence From the 2010 to 2018 National Health Interview Survey.

BACKGROUND: Asian people in the United States have different sociodemographic and health-related characteristics that might affect cardiovascular disease (CVD) risk by ethnicity and birthplace. However, they are often studied as a monolithic group in health care research. This study aimed to examine heterogeneity in CVD risk factors on the basis of birthplace among the 3 largest Asian subgroups (Chinese, Asian Indian, and Filipino) compared with US-born non-Hispanic White (NHW) adults. METHODS AND RESULTS: A cross-sectional analysis was conducted using the 2010 to 2018 National Health Interview Survey data from 125 008 US-born and foreign-born Chinese, Asian Indian, Filipino, and US-born NHW adults. Generalized linear models with Poisson distribution were used to examine the prevalence and prevalence ratios of self-reported hypertension, diabetes, high cholesterol, physical inactivity, smoking, and overweight/obesity among Asian subgroups compared with US-born NHW adults. The study included 118 979 US-born NHW and 6029 Asian adults who self-identified as Chinese (29%), Asian Indian (33%), and Filipino (38%). Participants' mean (±SD) age was 49±0.1 years, and 53% were females. In an adjusted analysis, foreign-born Asian Indians had significantly higher prevalence of diabetes, physical inactivity, and overweight/obesity; foreign-born Chinese had higher prevalence of physical inactivity, and foreign-born Filipinos had higher prevalence of all 5 CVD risk factors except smoking compared with NHW adults. CONCLUSIONS: This study revealed significant heterogeneity in the prevalence of CVD risk factors among Asian subgroups by ethnicity and birthplace, stressing the necessity of disaggregating Asian subgroup data. Providers should consider this heterogeneity in CVD risk factors and establish tailored CVD prevention plans for Asian subgroups.

Automatic detection method for tobacco beetles combining multi-scale global residual feature pyramid network and dual-path deformable attention.

Aiming at the problems of identifying storage pest tobacco pest beetles from images that have few object pixels and considerable image noise, and therefore suffer from lack of information and identifiable features, this paper proposes an automatic monitoring method of tobacco beetle based on Multi-scale Global residual Feature Pyramid Network and Dual-path Deformable Attention (MGrFPN-DDrGAM). Firstly, a Multi-scale Global residual Feature Pyramid Network (MGrFPN) is constructed to obtain rich high-level semantic features and more complete information on low-level features to reduce missed detection; Then, a Dual-path Deformable receptive field Guided Attention Module (DDrGAM) is designed to establish long-range channel dependence, guide the effective fusion of features and improve the localization accuracy of tobacco beetles by fitting the spatial geometric deformation features of and capturing the spatial information of feature maps with different scales to enrich the feature information in the channel and spatial. Finally, to simulate a real scene, a multi-scene tobacco beetle dataset is created. The dataset includes 28,080 images and manually labeled tobacco beetle objects. The experimental results show that under the framework of the Faster R-CNN algorithm, the detection precision and recall rate of this method can reach 91.4% and 98.4% when the intersection ratio (IoU) is 0.5. Compared with Faster R-CNN and FPN, when the intersection ratio (IoU) is 0.7, the detection precision is improved by 32.9% and 6.9%, respectively. The proposed method is superior to the current mainstream methods.

A machine learning-based ensemble model for estimating diurnal variations of nitrogen oxide concentrations in Taiwan.

Air pollution is inextricable from human activity patterns. This is especially true for nitrogen oxide (NOx), a pollutant that exists naturally and also as a result of anthropogenic factors. Assessing exposure by considering diurnal variation is a challenge that has not been widely studied. Incorporating 27 years of data, we attempted to estimate diurnal variations in NOx across Taiwan. We developed a machine learning-based ensemble model that integrated hybrid kriging-LUR, machine-learning, and an ensemble learning approach. Hybrid kriging-LUR was performed to select the most influential predictors, and machine-learning algorithms were applied to improve model performance. The three best machine-learning algorithms were suited and reassessed to develop ensemble learning that was designed to improve model performance. Our ensemble model resulted in estimates of daytime, nighttime, and daily NOx with high explanatory powers (Adj-R2) of 0.93, 0.98, and 0.94, respectively. These explanatory powers increased from the initial model that used only hybrid kriging-LUR. Additionally, the results depicted the temporal variation of NOx, with concentrations higher during the daytime than the nighttime. Regarding spatial variation, the highest NOx concentrations were identified in northern and western Taiwan. Model evaluations confirmed the reliability of the models. This study could serve as a reference for regional planning supporting emission control for environmental and human health.

The photo- and microbial degradation kinetics and pathways of sulfadoxine in seawater elucidated by liquid chromatography coupled with time-of-flight mass spectrometry.

Sulfadoxine (SDX) is a broad-spectrum veterinary antibiotic, which was used alone for the treatment of various infections in the past, and detected ubiquitously in the aqueous environment. However, understanding SDX's photo- and microbial degradation within the environment, especially in marine matrixes, remains limited. This research hones in on SDX's degradation dynamics in seawater. Photodegradation emerges as the dominant process, surpassing microbial degradation in speed and efficiency. Notably, 90% of SDX is photo-degraded within 12 h, while only 52% is removed via microbial degradation over two weeks. Time-of-flight mass spectrometry provides high-resolution molecular mass information on degradation products. The molecular structures of hydrolysis, photo-, and microbial degradation products are deduced from accurate precursor and fragment ion masses, alongside an integrated data processing workflow. Six hydrolysis products arise from the treatment, and photodegradation and microbial degradation yield nine and eighteen products, respectively. Molecular insights from these products inform plausible degradation pathways involving hydrolysis, photodegradation, and microbial degradation. Processes like bond cleavage, methylation, hydroxylation, oxidation, reduction, and methoxylation are identified and associated with degradation. This study presents a comprehensive workflow for acquiring and processing degradation product data linked to emerging organic pollutants. Moreover, it contributes to our comprehension of the environmental fate of veterinary drugs in marine ecosystems.

Blood Pressure Measurements Obtained by Community-Dwelling Adults Are Similar to Nurse-Obtained Measurements: The SMART-BP Validate Study.

BACKGROUND: Self-measured blood pressure (SMBP) is an effective strategy for managing and controlling hypertension. However, uncertainty regarding patients' ability to accurately measure their blood pressure (BP) contributes to treatment inertia. Therefore, we compared BP measurements with the Omron HEM-9210T device obtained by nurses and community-dwelling adults after training. METHODS: This cross-sectional study was conducted in a simulated home environment at an academic institution. After a 5-min rest, a trained nurse measured a participant's BP twice at a 1-min interval. The participants then ambulated at their usual pace for 2 min. Next, they were asked to rest for 5 min, during which each individual watched a 3-min video on SMBP. Following the rest, the participants obtained two readings at a 1-min interval. RESULTS: We recruited 102 community-dwelling adults with a mean age of 54 (±14) years; 59% female, 88% Black race, and 63% with a hypertension diagnosis. Half (n = 51) had a home BP monitor. Overall, there were no significant differences between nurse- and participant-obtained systolic BP (mean difference [MD]: -1.1; standard deviation [SD]: 8.0; P = 0.178) or diastolic BP (MD: -0.9; SD: 5.5; P = 0.111). Participants who used an extra-large cuff had higher self-measured diastolic BP (MD: -2.9; SD: 4.5; P = 0.010). All participants demonstrated satisfactory SMBP skills after the training. CONCLUSIONS: Community-dwelling adults can accurately measure BP after a 3-min video training. Integrating SMBP training into patient encounters may result in reliable home BP measurements, improving hypertension management and clinical decision making.

Association Between the Composite Cardiovascular Risk and mHealth Use Among Adults in the 2017-2020 Health Information National Trends Survey: Cross-Sectional Study.

BACKGROUND: Numerous studies have suggested that the relationship between cardiovascular disease (CVD) risk and the usage of mobile health (mHealth) technology may vary depending on the total number of CVD risk factors present. However, whether higher CVD risk is associated with a greater likelihood of engaging in specific mHealth use among US adults is currently unknown. OBJECTIVE: We aim to assess the associations between the composite CVD risk and each component of mHealth use among US adults regardless of whether they have a history of CVD or not. METHODS: This study used cross-sectional data from the 2017 to 2020 Health Information National Trends Survey. The exposure was CVD risk (diabetes, hypertension, smoking, physical inactivity, and overweight or obesity). We defined low, moderate, and high CVD risk as having 0-1, 2-3, and 4-5 CVD risk factors, respectively. The outcome variables of interest were each component of mHealth use, including using mHealth to make health decisions, track health progress, share health information, and discuss health decisions with health providers. We used multivariable logistic regression models to examine the association between CVD risk and mHealth use adjusted for demographic factors. RESULTS: We included 10,531 adults, with a mean age of 54 (SD 16.2) years. Among the included participants, 50.2% were men, 65.4% were non-Hispanic White, 41.9% used mHealth to make health decisions, 50.8% used mHealth to track health progress toward a health-related goal, 18.3% used mHealth to share health information with health providers, and 37.7% used mHealth to discuss health decisions with health providers (all are weighted percentages). Adults with moderate CVD risk were more likely to use mHealth to share health information with health providers (adjusted odds ratio 1.49, 95% CI 1.24-1.80) and discuss health decisions with health providers (1.22, 95% CI 1.04-1.44) compared to those with low CVD risk. Similarly, having high CVD risk was associated with higher odds of using mHealth to share health information with health providers (2.61, 95% CI 1.93-3.54) and discuss health decisions with health providers (1.56, 95% CI 1.17-2.10) compared to those with low CVD risk. Upon stratifying by age and gender, we observed age and gender disparities in the relationship between CVD risk and the usage of mHealth to discuss health decisions with health providers. CONCLUSIONS: Adults with a greater number of CVD risk factors were more likely to use mHealth to share health information with health providers and discuss health decisions with health providers. These findings suggest a promising avenue for enhancing health care communication and advancing both primary and secondary prevention efforts related to managing CVD risk factors through the effective usage of mHealth technology.

TPGS-mediated Transethosomes Enhance Transdermal Administration of Curcumin via Effects on Deformability and Stability.

BACKGROUND: Adding a suitable surfactant can enhance the transdermal permeability of transethosomes while also leveraging its functionality as a functional material. In this study, transethosomes were prepared using D-α-tocopherol acid polyethylene glycol succinate (TPGS) as edge activators for transdermal delivery of curcumin (Cur). METHODS: The TPGS-mediated curcumin-loaded transethosomes (Cur@TES) were prepared and formulated optimally, and the optimized formulations were characterized for their morphology, particle size, entrapment efficiency (EE) and drug loading (DL). The stability and deformability of Cur@TES were investigated, while the transdermal delivery of Cur@TES was investigated through in vitro transdermal assays and fluorescence imaging. A mouse ear swelling model was performed to determine the anti-inflammatory effect of Cur@TES. RESULTS: Cur@TES appeared round or elliptical in shape. The particle size, EE and DL for the optimized formulation were observed as 131.2 ± 7.2 nm, 97.68 ± 2.26%, and 6.58 ± 0.62%, respectively. X-ray diffraction analysis confirmed the formation of disordered structures in the inner core of the vesicles. Moreover, Cur@TES system demonstrated better stability and deformability compared to the curcumin-loaded ethosomes (Cur@ES). In-vitro transdermal experiments demonstrated that Cur@TES significantly increased the amount of drug retained in the skin (P＜0.05). Fluorescence imaging confirmed that the skin distribution were distinctly enhanced with the delivery by TPGS mediated transethosomes. In addition, Cur@TES showed a significant inhibitory effect on Inflammatory swelling in the mouse ear-swelling model. CONCLUSION: TPGS-mediated transethosomes exhibit significant transdermal advantages and enhanced anti-inflammatory effects, providing a new perspective for the transdermal delivery of curcumin.

Overcoming therapeutic resistance in oncolytic herpes virotherapy by targeting IGF2BP3-induced NETosis in malignant glioma.

Oncolytic virotherapy holds promise for cancer treatment, but the factors determining its oncolytic activity remain unclear. Neutrophil extracellular traps (NETs) are associated with cancer progression, yet their formation mechanism and role in oncolytic virotherapy remain elusive. In this study, we demonstrate that, in glioma, upregulation of IGF2BP3 enhances the expression of E3 ubiquitin protein ligase MIB1, promoting FTO degradation via the ubiquitin-proteasome pathway. This results in increased m6A-mediated CSF3 release and NET formation. Oncolytic herpes simplex virus (oHSV) stimulates IGF2BP3-induced NET formation in malignant glioma. In glioma models in female mice, a BET inhibitor enhances the oncolytic activity of oHSV by impeding IGF2BP3-induced NETosis, reinforcing virus replication through BRD4 recruitment with the CDK9/RPB-1 complex to HSV gene promoters. Our findings unveil the regulation of m6A-mediated NET formation, highlight oncolytic virus-induced NETosis as a critical checkpoint hindering oncolytic potential, and propose targeting NETosis as a strategy to overcome resistance in oncolytic virotherapy.

A Critical Review of Groundwater Table Fluctuation: Formation, Effects on Multifields, and Contaminant Behaviors in a Soil and Aquifer System.

The groundwater table fluctuation (GTF) zone is an important medium for the hydrologic cycle between unsaturated soil and saturated aquifers, which accelerates the migration, transformation, and redistribution of contaminants and further poses a potential environmental risk to humans. In this review, we clarify the key processes in the generation of the GTF zone and examine its links with the variation of the hydrodynamic and hydrochemistry field, colloid mobilization, and contaminant migration and transformation. Driven by groundwater recharge and discharge, GTF regulates water flow and the movement of the capillary fringe, which further control the advection and dispersion of contaminants in soil and groundwater. In addition, the formation and variation of the reactive oxygen species (ROS) waterfall are impacted by GTF. The changing ROS components partially determine the characteristic transformation of solutes and the dynamic redistribution of the microbial population. GTF facilitates the migration and transformation of contaminants (such as nitrogen, heavy metals, non-aqueous phase liquids, and volatile organic compounds) through colloid mobilization, the co-migration effect, and variation of the hydrodynamic and hydrochemistry fields. In conclusion, this review illustrates the limitations of the current literature on GTF, and the significance of GTF zones in the underground environment is underscored by expounding on the future directions and prospects.

TAT-W61 peptide attenuates neuronal injury through blocking the binding of S100b to the V-domain of Rage during ischemic stroke.

Ischemic stroke is a devastative nervous system disease associated with high mortality and morbidity rates. Unfortunately, no clinically effective neuroprotective drugs are available now. In ischemic stroke, S100 calcium-binding protein b (S100b) binds to receptor for advanced glycation end products (Rage), leading to the neurological injury. Therefore, disruption of the interaction between S100B and Rage can rescue neuronal cells. Here, we designed a peptide, termed TAT-W61, derived from the V domain of Rage which can recognize S100b. Intriguingly, TAT-W61 can reduce the inflammatory caused by ischemic stroke through the direct binding to S100b. The further investigation demonstrated that TAT-W61 can improve pathological infarct volume and reduce the apoptotic rate. Particularly, TAT-W61 significantly improved the learning ability, memory, and motor dysfunction of the mouse in the ischemic stroke model. Our study provides a mechanistic insight into the abnormal expression of S100b and Rage in ischemic stroke and yields an invaluable candidate for the development of drugs in tackling ischemic stroke. KEY MESSAGES: S100b expression is higher in ischemic stroke, in association with a high expression of many genes, especially of Rage. S100b is directly bound to the V-domain of Rage. Blocking the binding of S100b to Rage improves the injury after ischemic stroke.

FOXP2 suppresses the proliferation, invasion, and aerobic glycolysis of hepatocellular carcinoma cells by regulating the KDM5A/FBP1 axis.

The Warburg effect is the preference of cancer cells to use glycolysis rather than oxidative phosphorylation to generate energy. Accumulating evidence suggests that aerobic glycolysis is widespread in hepatocellular carcinoma (HCC) and closely related to tumorigenesis. The purpose of this study was to investigate the role and mechanism of forkhead box P2 (FOXP2) in aerobic glycolysis and tumorigenesis in HCC. Here, we found that FOXP2 was lower expressed in HCC tissues and cells than in nontumor tissues and normal hepatocytes. Overexpression of FOXP2 suppressed cell proliferation and invasion of HCC cells and promoted cell apoptosis in vitro, and hindered the growth of mouse xenograft tumors in vivo. Further researches showed that FOXP2 inhibited the Warburg effect in HCC cells. Moreover, we demonstrated that FOXP2 up-regulated the expression of fructose-1, 6-diphosphatase (FBP1), and the inhibitory effect of FOXP2 on glycolysis was dependent on FBP1. Mechanistically, as a transcription factor, FOXP2 negatively regulated the transcription of lysine-specific demethylase 5A (KDM5A), and then blocked KDM5A-induced H3K4me3 demethylation in FBP1 promoter region, thereby promoting the expression of FBP1. Consistently, overexpressing KDM5A or silencing FBP1 effectively reversed the inhibitory effect of FOXP2 on HCC progression. Together, our findings revealed the mechanistic role of the FOXP2/KDM5A/FBP1 axis in glycolysis and malignant progression of HCC cells, providing a potential molecular target for the therapy of HCC.

Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis.

Pancreatic ductal adenocarcinoma (PDAC) is a highly prevalent digestive system malignancy, with a significant impact on public health, especially in the elderly population. The advent of the Human Genome Project has opened new avenues for precision medicine, allowing researchers to explore genetic markers and molecular targets for cancer diagnosis and treatment. Despite significant advances in genomic research, early diagnosis of pancreatic cancer remains elusive due to the lack of highly sensitive and specific markers. Therefore, there is a need for in-depth research to identify more precise and reliable diagnostic markers for pancreatic cancer. In this study, we utilized a combination of public databases from different sources to meticulously screen genes associated with prognosis in pancreatic cancer. We used gene differential analysis, univariate cox regression analysis, least absolute selection and shrinkage operator (LASSO) regression, and multivariate cox regression analysis to identify genes associated with prognosis. Subsequently, we constructed a scoring system, validated its validity using survival analysis and ROC analysis, and further confirmed its reliability by nomogram and decision curve analysis (DCA). We evaluated the diagnostic value of this scoring system for pancreatic cancer prognosis and validated the function of the genes using single cell data analysis. Our analysis identifies six genes, including GABRA3, IL20RB, CDK1, GPR87, TTYH3, and KCNA2, that were strongly associated with PDAC prognosis. Clinical prognostic models based on these genes showed strong predictive power not only in the training set but also in external datasets. Functional enrichment analysis revealed significant differences between high- and low-risk groups mainly in immune-related functions. Additionally, we explored the potential of the risk score as a marker for immunotherapy response and identified key factors within the tumor microenvironment. The single-cell RNA sequencing analysis further enriched our understanding of cell clusters and six hub genes expressions. This comprehensive investigation provides valuable insights into pancreatic PDAC and its intricate immune landscape. The identified genes and their functional significance underscore the importance of continued research into improving diagnosis and treatment strategies for PDAC.

Effectiveness of health checkup with depression screening on depression treatment and outcomes in middle-aged and older adults: a target trial emulation study.

Background: Adult preventive health checkups with depression screening were launched in August 2011 in Taiwan; however, its impact has not yet been evaluated. This study aimed to use real-world data to assess the effectiveness of depression screening among middle-aged and older adults. Methods: A total of 4,972,228 adults aged 40 years and above who participated in a health checkup with depression screening between 2013 and 2019 and the same number of unscreened counterparts were included. The target trial emulation study was conducted to estimate the hazard ratios (HRs) for newly treated depression, psychiatric hospitalisation, and suicide. The changes in HRs during the study period were assessed using interval Cox models. Findings: The screening group had a higher rate of newly treated depression (HR 1.63 [95% CI 1.62, 1.64]) and a lower risk of psychiatric hospitalisation (HR 0.93 [95% CI 0.91, 0.95]). There was a null association between depression screening and suicide; however, a higher suicide risk was found in screened older adults aged 65 years and above. Only 10.8% received depression treatment during the study period among the screen-positive individuals. Interpretation: Health checkups with depression screening could potentially promote depression treatment and reduce the risk of psychiatric hospitalisation; however, there was no effect on suicide. The treatment rate for depression remained low after screening for depression. Further attention to enhance referral and treatment is required. Funding: The study was funded by the National Health Research Institutes, Taiwan.

Effect of shear strain on the electronic and optical properties of Al-doped stanane.

CONTEXT: The quasi-metallic properties of stanene limit its prospects in optoelectronic devices. Based on first-principles calculations, a systematic study is conducted on the tuning effects of surface hydrogenation and Al atom doping on the electronic and optical properties of stanene. Surface hydrogenation serves as an ideal way to open the forbidden band of stanene, and Al atom doping further increases hydrogenated stanene (stanane) band gap to 0.460 eV. Deformation has a minor impact on the stability of the stanane-Al structure, while shear strain can effectively modulate the band gap engineering of the doped system, reducing the band gap value from 0.460 to 0.170 eV. Deformation induces a redshift in the absorption peak and reflectance, also slowing down the rate of decrease in the absorption coefficient, and enhancing the peak value of light reflectance, which is positively correlated with the degree of shear strain. These findings hold promise for expanding the potential application of monolayer stanane in semiconductor devices. METHODS: All calculations are performed using CASTEP module in Materials Studio based on the density functional theory (DFT). The Perdew-Burke-Ernzerhof (PBE) generalized gradient approximation (GGA) is employed to describe the exchange-correlation energy (Perdew et al., Phys Rev Lett 77(18), 1996). We construct models for both stanene and stanane. The original unit cell of stanene has two Sn atoms, while stanane consists of two Sn atoms and two H atoms, and expand them to a 3 × 3 × 1 supercell with a vacuum layer of 20 Å in height to prevent interlayer coupling. After convergence testing, the plane-wave cutoff energy is set to 450 eV, and the energy convergence threshold is set to 1 × 10-5 eV. The maximum residual stress for each atom is set to 0.01 eV/Å. Brillouin zone sampling is performed using a 6 × 6 × 1 k-point mesh based on the Monkhorst-Pack method (Monkhorst and Pack, Phys Rev B 13(12), 1976). The k-point accuracy of the density of states and optical properties is 9 × 9 × 1. All calculations are performed using the more advanced OTFG ultrasoft pseudopotential, and structural relaxations are performed using supercells to ensure that the model is fully relaxed. We use the HSE06 functional to calculate the energy band structures of stanane-Al deformed to 0%, 4%, and 8%, resulting in band gap values of 1.465 eV, 1.368 eV, and 1.016 eV, respectively. These values are significantly higher than those obtained using the PBE functional (0.460 eV, 0.397 eV, and 0.170 eV). However, the shapes and trends of the band structures obtained from both PBE and HSE06 calculations are similar. Additionally, the calculation time needed by HSE06 is greatly longer than PBE, which exceeds the capabilities of our computer hardware, and cannot support all subsequent calculations. To investigate the influence of deformations on the variation of band gap values and to conserve computational resources, the subsequent calculations in this study use the PBE functional.