Microstate-based brain network dynamics distinguishing temporal lobe epilepsy patients: A machine learning approach.

Temporal lobe epilepsy (TLE) stands as the predominant adult focal epilepsy syndrome, characterized by dysfunctional intrinsic brain dynamics. However, the precise mechanisms underlying seizures in these patients remain elusive. Our study encompassed 116 TLE patients compared with 51 healthy controls. Employing microstate analysis, we assessed brain dynamic disparities between TLE patients and healthy controls, as well as between drug-resistant epilepsy (DRE) and drug-sensitive epilepsy (DSE) patients. We constructed dynamic functional connectivity networks based on microstates and quantified their spatial and temporal variability. Utilizing these brain network features, we developed machine learning models to discriminate between TLE patients and healthy controls, and between DRE and DSE patients. Temporal dynamics in TLE patients exhibited significant acceleration compared to healthy controls, along with heightened synchronization and instability in brain networks. Moreover, DRE patients displayed notably lower spatial variability in certain parts of microstate B, E and F dynamic functional connectivity networks, while temporal variability in certain parts of microstate E and G dynamic functional connectivity networks was markedly higher in DRE patients compared to DSE patients. The machine learning model based on these spatiotemporal metrics effectively differentiated TLE patients from healthy controls and discerned DRE from DSE patients. The accelerated microstate dynamics and disrupted microstate sequences observed in TLE patients mirror highly unstable intrinsic brain dynamics, potentially underlying abnormal discharges. Additionally, the presence of highly synchronized and unstable activities in brain networks of DRE patients signifies the establishment of stable epileptogenic networks, contributing to the poor responsiveness to antiseizure medications. The model based on spatiotemporal metrics demonstrated robust predictive performance, accurately distinguishing both TLE patients from healthy controls and DRE patients from DSE patients.

Macrophage barrier in the tumor microenvironment and potential clinical applications.

The tumor microenvironment (TME) constitutes a complex microenvironment comprising a diverse array of immune cells and stromal components. Within this intricate context, tumor-associated macrophages (TAMs) exhibit notable spatial heterogeneity. This heterogeneity contributes to various facets of tumor behavior, including immune response modulation, angiogenesis, tissue remodeling, and metastatic potential. This review summarizes the spatial distribution of macrophages in both the physiological environment and the TME. Moreover, this paper explores the intricate interactions between TAMs and diverse immune cell populations (T cells, dendritic cells, neutrophils, natural killer cells, and other immune cells) within the TME. These bidirectional exchanges form a complex network of immune interactions that influence tumor immune surveillance and evasion strategies. Investigating TAM heterogeneity and its intricate interactions with different immune cell populations offers potential avenues for therapeutic interventions. Additionally, this paper discusses therapeutic strategies targeting macrophages, aiming to uncover novel approaches for immunotherapy. Video Abstract.

Prevalence, risk factors, impact and management of pneumonia among preschool children in Chinese seven cities: a cross-sectional study with interrupted time series analysis.

BACKGROUND: Pneumonia is a common disease worldwide in preschool children. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of pneumonia among preschool children. We therefore investigated the prevalence of pneumonia among preschool children in Chinese seven representative cities, and explore the possible risk factors of pneumonia on children, with a view to calling the world's attention to childhood pneumonia to reduce the prevalence of childhood pneumonia. METHODS: Two group samples of 63,663 and 52,812 preschool children were recruited from 2011 and 2019 surveys, respectively. Which were derived from the cross-sectional China, Children, Homes, Health (CCHH) study using a multi-stage stratified sampling method. This survey was conducted in kindergartens in seven representative cities. Exclusion criteria were younger than 2 years old or older than 8 years old, non-permanent population, basic information such as gender, date of birth and breast feeding is incomplete. Pneumonia was determined on the basis of parents reported history of clearly diagnosed by the physician. All participants were assessed with a standard questionnaire. Risk factors for pneumonia, and association between pneumonia and other respiratory diseases were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was evaluated by the parents' reported history of physician diagnosis, longitudinal comparison of risk factors in 2011 and 2019. RESULTS: In 2011 and 2019, 31,277 (16,152 boys and 15,125 girls) and 32,016 (16,621 boys and 15,395 girls) preschool children aged at 2-8 of permanent population completed the questionnaire, respectively, and were thus included in the final analysis. The findings showed that the age-adjusted prevalence of pneumonia in children was 32.7% in 2011 and 26.4% in 2019. In 2011, girls (odds ratio [OR] 0.91, 95%CI [confidence interval]0.87-0.96; p = 0.0002), rural (0.85, 0.73-0.99; p = 0.0387), duration of breastfeeding ≥ 6 months(0.83, 0.79-0.88; p < 0.0001), birth weight (g) ≥ 4000 (0.88, 0.80-0.97; p = 0.0125), frequency of putting bedding to sunshine (Often) (0.82, 0.71-0.94; p = 0.0049), cooking fuel type (electricity) (0.87, 0.80-0.94; p = 0.0005), indoor use air-conditioning (0.85, 0.80-0.90; p < 0.0001) were associated with a reduced risk of childhood pneumonia. Age (4-6) (1.11, 1.03-1.20; p = 0.0052), parental smoking (one) (1.12, 1.07-1.18; p < 0.0001), used antibiotics (2.71, 2.52-2.90; p < 0.0001), history of parental allergy (one and two) (1.21, 1.12-1.32; p < 0.0001 and 1.33, 1.04-1.69; p = 0.0203), indoor dampness (1.24, 1.15-1.33; p < 0.0001), home interior decoration (1.11, 1.04-1.19; p = 0.0013), Wall painting materials (Paint) (1.16, 1.04-1.29; p = 0.0084), flooring materials (Laminate / Composite wood) (1.08, 1.02-1.16; p = 0.0126), indoor heating mode(Central heating)(1.18, 1.07-1.30, p = 0.0090), asthma (2.38, 2.17-2.61; p < 0.0001), allergic rhinitis (1.36, 1.25-1.47; p < 0.0001), wheezing (1.64, 1.55-1.74; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (2.53, 2.31-2.78; p < 0.0001), allergic rhinitis (1.41, 1.29-1.53; p < 0.0001) and wheezing (1.64, 1.55-1.74; p < 0.0001). In 2019, girls (0.92, 0.87-0.97; p = 0.0019), duration of breastfeeding ≥ 6 months (0.92, 0.87-0.97; p = 0.0031), used antibiotics (0.22, 0.21-0.24; p < 0.0001), cooking fuel type (Other) (0.40, 0.23-0.63; p = 0.0003), indoor use air-conditioning (0.89, 0.83-0.95; p = 0.0009) were associated with a reduced risk of childhood pneumonia. Urbanisation (Suburb) (1.10, 1.02-1.18; p = 0.0093), premature birth (1.29, 1.08-1.55; p = 0.0051), birth weight (g) < 2500 (1.17, 1.02-1.35; p = 0.0284), parental smoking (1.30, 1.23-1.38; p < 0.0001), history of parental asthma (One) (1.23, 1.03-1.46; p = 0.0202), history of parental allergy (one and two) (1.20, 1.13-1.27; p < 0.0001 and 1.22, 1.08-1.37; p = 0.0014), cooking fuel type (Coal) (1.58, 1.02-2.52; p = 0.0356), indoor dampness (1.16, 1.08-1.24; p < 0.0001), asthma (1.88, 1.64-2.15; p < 0.0001), allergic rhinitis (1.57, 1.45-1.69; p < 0.0001), wheezing (2.43, 2.20-2.68; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (1.96, 1.72-2.25; p < 0.0001), allergic rhinitis (1.60, 1.48-1.73; p < 0.0001) and wheezing (2.49, 2.25-2.75; p < 0.0001). CONCLUSIONS: Pneumonia is prevalent among preschool children in China, and it affects other childhood respiratory diseases. Although the prevalence of pneumonia in Chinese children shows a decreasing trend in 2019 compared to 2011, a well-established management system is still needed to further reduce the prevalence of pneumonia and reduce the burden of disease in children.

Electronic coupling and electron transfer in hydrogen-bonded mixed-valence compounds.

Electron transfer provided by hydrogen bonds represents a unique and highly significant area of research, as it has a crucial role to play in a wide variety of chemical and biological systems. The hydrogen-bonded mixed-valence system, in the form of donor-hydrogen bond-acceptor, provides an ideal platform for exploring thermally-induced electron transfer across this non-covalent unit. Over the past decades, ongoing progress has been made in this field. Here we critically assess some studies on the qualitative and quantitative evaluation of electronic coupling and thermal electron transfer across hydrogen bond interface. Additionally, selected experimental examples are discussed in terms of intervalence charge transfer, with particular attention paid to the proton-coupled and often overlooked proton-uncoupled electron transfer pathway in hydrogen-bonded mixed-valence systems. We further highlight the major limitations of this research area and suggest potential directions for future exploration.

Influence of ligand variation on the deactivation process of metal-to-ligand charge transfer excited states in quadruply bonded dimolybdenum complexes.

To explore the dynamics of metal-to-ligand charge transfer (MLCT) excited states involving covalently bonded dimetal units, a series of quadruply bonded dimolybdenum (Mo2) complexes, namely, [Mo2]-ph, [Mo2]-naph, and [Mo2]-anth, were synthesized and characterized. Our investigations reveal a non-radiative process associated with the deactivation of the MLCT state into a low-lying dimetal-centered triplet state (3Mo2-δδ*), resulting in the populated MLCT states in these molecular systems exhibiting either extremely weak emission or being non-emissive. The influence of ligand variation on the dynamics of MLCT states was examined using femtosecond transient absorption spectroscopy, with deactivation time constants determined to be 1.9 ps for [Mo2]-ph, 6.5 ps for [Mo2]-naph, and 49 ps for [Mo2]-anth. This electron transfer behaviour follows an inverse energy-gap law, contrary to the general guideline that applies to the decay of the MLCT state back to the electronic ground state. This result offers valuable insights into understanding the photochemical and photophysical properties of covalently bonded dimetal complexes.

Associations with physical activity, sedentary behavior, and premenstrual syndrome among Chinese female college students.

PURPOSE: Premenstrual syndrome refers to a set of distressing symptoms experienced before the menstrual flow, which can affect female students' behavior, cognitive abilities, mental health status, and academic performance. Identifying modifiable risk factors is essential to reduce the prevalence college students' premenstrual syndrome. We examined associations between premenstrual syndrome and physical activity and sedentary behavior in Chinese female college students. METHODS: In this cross-sectional study, 315 female college students volunteered to participate at a university in Shanghai, China. We measured physical activity and sedentary behavior using the ActiGraph GT3X-BT and assessed premenstrual syndrome using the Premenstrual Symptoms Screening Tool. The data were statistically analyzed using SPSS 24.0 software, and the primary analysis methods included Kruskal-Wallis test and logistic regression analysis. RESULTS: Among the 221 female college students who met the inclusion criteria, 148 (67.0%) had PMS while 73 (33.3%) did not. After controlling for confounding variables, moderate physical activity and moderate to vigorous intensity physical activity were significantly associated with premenstrual syndrome. There was no correlation between light-intensity physical activity, sedentary behavior, and premenstrual syndrome in the study. CONCLUSION: Premenstrual syndrome is prevalent among Chinese female college students. Moderate physical activity and moderate-to-vigorous physical activity can be effective in reducing PMS symptoms.

Global, regional and national availability of essential medicines for children, 2009-2020: a systematic review and meta-analysis.

BACKGROUND: Access to essential medicines is a vital component of universal health coverage. The low availability of essential medicines for children (EMC) has led the World Health Organization (WHO) to issue a number of resolutions calling on member states on its improvement. But its global progress has been unclear. We aimed to systematically evaluate the progress of availability of EMC over the past decade across economic regions and countries. METHODS: We searched eight databases from inception to December 2021 and reference lists to identify included studies. Two reviewers independently conducted literature screening, data extraction and quality evaluation. This study was registered with PROSPERO, CRD42022314003. RESULTS: Overall, 22 cross-sectional studies covering 17 countries, 4 income groups were included. Globally, the average availability rates of EMC were 39.0% (95%CI: 35.5-42.5%) in 2009-2015 and 43.1% (95%CI: 40.1-46.2%) in 2016-2020. Based on the World Bank classification of economic regions, income was not proportional to availability. Nationally, the availability rate of EMC was reasonable and high (> 50%) in only 4 countries, and low or very low for the rest 13 countries. The availability rates of EMC in primary healthcare centers had increased, while that for other levels of hospitals slightly declined. The availability of original medicines decreased while that of generic medicines was stable. All drug categories had not achieved the high availability rate. CONCLUSION: The availability rate of EMC was low globally, with slight increase in the last decade. Continuous monitoring and timely reporting of the availability of EMC are also needed to facilitate targets setting and inform relevant policy making.

Cognitive Aging: How the Brain Ages?

Cognitive aging refers to the cognitive changes or functional decline that comes with age. The relation between aging and functional declines involves various aspects of cognition, including memory, attention, processing speed, and executive function. In this chapter, we have introduced several dimensions about cognitive aging trajectories. Meanwhile, we have reviewed the history of the study of cognitive aging and expatiated two trends that are particularly noteworthy in the effort to elucidate the process of aging. One is that the differences between components of mental abilities have become gradually specified. The other one is a growing interest in the neural process, which relates changes in the brain structure to age-related changes in cognition. Lastly, as the basis of cognitive function, brain structures and functions change during aging, and these changes are reflected in a corresponding decline in cognitive function. We have discussed the patterns of reorganization of various structural and functional aging processes of the brain and their relationship with cognitive function.

Global trends in semen quality of young men: a systematic review and regression analysis.

PURPOSE: Many studies have reported declines in semen quality mainly focused on total sperm counts (TSC) and sperm concentration (SC), ignoring the importance of progressive motile sperm (PR), total motile sperm (TM), and normal morphological sperm (NM). Therefore, we performed a comprehensive meta-analysis to explore the trend in semen quality of young men. METHODS: We searched 3 English databases and 4 Chinese databases from January 1980 to August 2022. Random-effect meta-analyses and weighted linear regression models were conducted to perform the trend in semen quality. RESULTS: Finally, 162 eligible studies including 264,665 men from 28 countries were got between 1978 and 2021. Significant decreases were observed in TSC (- 3.06 million/year, 95% CI - 3.28 to - 2.84), SC (- 0.47 million/ml/year, 95% CI - 0.51 to - 0.43), and PR (- 0.15%/year, 95% CI - 0.20 to - 0.09), and there was an upward trend in TM (0.28%/year, 95% CI 0.24 to 0.32). The results of meta-regression analyses indicated that age, continent, income, WHO criteria, and abstinence time significantly impacted on TSC, SC, PR, and TM. Positive regression coefficients were observed in some categories suggesting that outcomes might not be declining and even increasing in these subgroups. CONCLUSIONS: Downward trends in semen quality among global young men were observed in our study, including TSC, SC, and PR. But TM did not appear to be trending down or even to be leveling off. More studies are needed to focus on the causes of the declines.

Influencing factors of self-regulated learning of medical-related students in a traditional Chinese medical university: a cross-sectional study.

BACKGROUND: In recent years, self-regulated learning (SRL) has become a hot topic in medical education. However, the factors that affect the SRL ability of medical-related specialties, such as clinical medicine, traditional Chinese medicine (TCM), and nursing specialty in TCM colleges and universities are unclear. Whether the teaching of learning strategies can help improve students' SRL also needs to be further examined. METHOD: A cross-sectional survey was distributed, and 878 medical-related students who were from a TCM university were recruited for this study. Descriptive statistics illustrated the status quo of SRL and learning strategies, and an independent t-test and analysis of variance were used to analyze the factors associated with SRL. The relationship between SRL and learning strategies was analyzed with multi-linear regression analysis. RESULTS: The scores of SRL on learning motivation, learning setting, self-regulation, and total scores were 34.76 ± 4.62, 41.14 ± 4.30, 39.26 ± 4.74, and 115.16 ± 12.42, respectively. The metacognitive, emotion, cognitive, resource management and total scores of learning strategies were 58.54 ± 12.02, 43.24 ± 8.42, 35.49 ± 7.34, 22.89 ± 4.20, 160.16 ± 29.45, and the mean was all above the midpoint. Learning strategies were positively correlated with SRL (r = 0.421, P < 0.01). Some factors can predict 32% of the variation of SRL, including whether they liked their specialty, educational system, specialty, score ranking, scholarship, whether they were taught by a tutor in middle school, gender, monthly family income, the father's educational background, metacognitive strategy, resource management strategy, and cognitive strategy. CONCLUSIONS: The SRL of medical-related students was better. Learning strategies, as well as personal or social factors, can affect SRL. Educators should pay more attention to the cultivation of learning strategies, exercising learning skills, and monitoring, adjustment, and guidance of learning time. It should adopt various methods to improve the SRL of medical-related students according to the different factors.

The effect of family structure on physical activity levels among children and adolescents in Western China in the era of COVID-19.

PURPOSE: This study aimed to examine the levels of physical activity (PA) among children and adolescents in western China, and the influence of parents on their PA, in the era of coronavirus disease 2019 (COVID-19). METHODS: This cross-sectional study used a multistage questionnaire to evaluate 4800 children and adolescents of grades 4-12 (9-17 years old) from 48 primary and secondary schools across 16 districts and counties in western China. In addition to PA, questionnaires collected data on demography, family structure, and exercise habits. Data were assessed using the International Physical Activity Questionnaire-Short Form (IPAQ-SF) and analyzed using chi-square tests, t-tests, Spearman's correlation, and logistic regression models in SPSS. RESULTS: In this study, a minority (42.1%, n = 1553) of children and adolescents met the daily exercise target (60 min) recommended by the World Health Organization (WHO). Moderate- to vigorous-intensity physical activity (MVPA) level of boys was significantly higher than that of girls. Regardless of sex, children with the highest MVPA levels were those in grades 4-6, and PA levels decreased with increasing age. Furthermore, for every hour of increase in the daily MVPA of parents, the MVPA also increased by 6.1-13.9 min in children and adolescents. Moreover, areas of higher economic development were associated with lower levels of MVPA. CONCLUSIONS: Overall, this study found a low level of MVPA in children and adolescents of western China; both family structure and parental activity have a significant influence on the children's PA levels. Besides, the impact of COVID-19 on PA levels has not been entirely negative.

One-Step Synthesis of Nitrogen-Doped Porous Biochar Based on N-Doping Co-Activation Method and Its Application in Water Pollutants Control.

In this work, birch bark (BB) was used for the first time to prepare porous biochars via different one-step methods including direct activation (BBB) and N-doping co-activation (N-BBB). The specific surface area and total pore volume of BBB and N-BBB were 2502.3 and 2292.7 m2/g, and 1.1389 and 1.0356 cm3/g, respectively. When removing synthetic methyl orange (MO) dye and heavy metal Cr6+, both BBB and N-BBB showed excellent treatment ability. The maximum adsorption capacities of BBB and N-BBB were 836.9 and 858.3 mg/g for MO, and 141.1 and 169.1 mg/g for Cr6+, respectively, which were higher than most previously reported biochar adsorbents. The probable adsorption mechanisms, including pore filling, π-π interaction, H-bond interaction, and electrostatic attraction, supported the biochars' demonstrated high performance. In addition, after five recycles, the removal rates remained above 80%, which showed the high stability of the biochars. This work verified the feasibility of the one-step N-doping co-activation method to prepare high-performance biochars, and two kinds of biochars with excellent performance (BBB and N-BBB) were prepared. More importantly, this method provides new directions and ideas for the development and utilization of other biomasses.

Improving Friend Recommendation for Online Learning with Fine-Grained Evolving Interest.

Friend recommendation plays a key role in promoting user experience in online social networks (OSNs). However, existing studies usually neglect users' fine-grained interest as well as the evolving feature of interest, which may cause unsuitable recommendation. In particular, some OSNs, such as the online learning community, even have little work on friend recommendation. To this end, we strive to improve friend recommendation with fine-grained evolving interest in this paper. We take the online learning community as an application scenario, which is a special type of OSNs for people to learn courses online. Learning partners can help improve learners' learning effect and improve the attractiveness of platforms. We propose a learning partner recommendation framework based on the evolution of fine-grained learning interest (LPRF-E for short). We extract a sequence of learning interest tags that changes over time. Then, we explore the time feature to predict evolving learning interest. Next, we recommend learning partners by fine-grained interest similarity. We also refine the learning partner recommendation framework with users' social influence (denoted as LPRF-F for differentiation). Extensive experiments on two real datasets crawled from Chinese University MOOC and Douban Book validate that the proposed LPRF-E and LPRF-F models achieve a high accuracy (i.e., approximate 50% improvements on the precision and the recall) and can recommend learning partners with high quality (e.g., more experienced and helpful). Supplementary Information: The online version contains supplementary material available at 10.1007/s11390-021-2124-z.

Cognitive profiles in adult-onset neuronal intranuclear inclusion disease: a case series from the memory clinic.

OBJECTIVE: This study aimed to analyze the characteristics of cognitive impairment in adult-onset neuronal intranuclear inclusion disease (NIID). METHODS: Seven patients with adult-onset NIID were collected consecutively from the memory clinic of Xuanwu hospital from February to December 2019. These cases were diagnosed with skin biopsy triggered by DWI high-intensity signals in corticomedullary junction on brain MRI. We used a battery of neuropsychological scales to detect the patient's performance in each cognitive domain, and made a detailed analysis on the characteristics of cognitive impairment. RESULTS: All seven cases had cognitive impairment, and four of them had met the criteria for dementia. The scores of Montreal Cognitive Assessment and Frontal Assessment Battery were abnormal in all patients. The executive dysfunction was confirmed by the abnormal scores of Trail Making Test (5/7, 71%) and Clock Drawing Test (4/7, 57%). Bad performance in Auditory Verbal Learning Test (6/7, 86%) demonstrated that the memory was also a very commonly impaired cognitive domain. The low score on the animal fluency (4/7, 57%), Boston Naming Test (3/7, 43%), and Pentagon and Cube Copying Test (4/7, 57%) indicated that the language and visuospatial skills were also impaired. Fazekas scores were significantly correlated to the global cognition, executive and language functions (r = 0.788-0.906, P < 0.05). CONCLUSIONS: There is obvious impairment in multiple cognitive domains in adult-onset NIID, and both the executive dysfunction and memory deficit are very common. Leukoencephalopathy may be the main course of cognitive impairment in adult-onset NIID.

Flexible multicamera calibration method with a rotating calibration plate.

Camera calibration is necessary for accurate image measurements, particularly in multicamera systems. The calibration process involves corresponding the coordinates of 3D calibration points with a 2D image and requires the establishment of a reliable 3D world coordinate system. This paper presents a convenient multicamera calibration method that uses a rotating calibration plate and multi-view stereo vision to calculate 3D points and their relationship with the image coordinates. Despite simple implementation, the rotation of the calibration plate presents numerous calibration points from various planes, increasing the stability of the solution and the noise reduction. The relocation accuracy and reprojection error are experimentally verified.

Association of genetic polymorphisms in chromosome 9p21 with risk of ischemic stroke.

Genome-wide association study (GWAS) has identified that rs10757278 in chromosome 9p21 was a risk loci of ischemic stroke (IS). Interferon-beta 1 (IFNB1), located on 9p21, has a protective role in IS. In this study, we aimed to investigate whether the rs10757278, rs9333358 and rs1051922 in IFNB1 were related to the risk of IS. The 3 polymorphisms were genotyped using a TaqMan allelic discrimination assay in 505 patients with IS and 652 controls with frequencies matched to cases regarding age, gender, living area, and ethnicity. The IFNB1 mRNA levels were determined using quantitative polymerase chain reaction and relative luciferase activity was measured using the Dual Luciferase reporter assay. An increased risk of IS was found for both the rs10757278 (GG vs. AA: adjusted OR = 1.80, 95% CI: 1.27-2.55, P < 0.001; GG vs. AA/AG: adjusted OR = 1.57, 95% CI: 1.18-2.10, P = 0.002; G vs. A: adjusted OR = 1.35, 95% CI: 1.13-1.61, P < 0.001) and the rs9333358 (GG vs. AA: adjusted OR = 1.91, 95% CI: 1.27-2.88, P = 0.002; GG vs. AA/AG: adjusted OR = 1.81, 95% CI: 1.23-2.68, P = 0.003; G vs. A: adjusted OR = 1.35, 95% CI: 1.12-1.64, P = 0.002). Similarly, a higher risk of IS was also observed in the combined genotypes of the rs10757278 AG/GG and rs9333358 AG/GG (95% CI: 1.34-2.83, P < 0.001). Moreover, individuals carrying the rs9333358 GG genotype exhibited lower levels of IFNB1 mRNA and the rs9333358 G allele displayed a reduced transcriptional activity. These findings suggest that 9p21 rs10757278-IFNB1 rs9333358 may have both single and joint effects on the development of IS.

The APOE ε4 exerts differential effects on familial and other subtypes of Alzheimer's disease.

INTRODUCTION: The genetic risk effects of apolipoprotein E (APOE) on familial Alzheimer's disease (FAD) with or without gene mutations, sporadic AD (SAD), and normal controls (NC) remain unclear in the Chinese population. METHODS: In total, 15 119 subjects, including 311 FAD patients without PSEN1, PSEN2, APP, TREM2, and SORL1 pathogenic mutations (FAD [unknown]); 126 FAD patients with PSENs/APP mutations (FAD [PSENs/APP]); 7234 SAD patients; and 7448 NC were enrolled. The risk effects of APOE ε4 were analyzed across groups. RESULTS: The prevalence of the APOE ε4 genotype in FAD (unknown), FAD (PSENs/APP), SAD, and NC groups was 56.27%, 26.19%, 36.23%, and 19.54%, respectively. Further, the APOE ε4 positive genotype had predictive power for FAD (unknown) risk (odds ratio: 4.51, 95% confidence interval: 3.57-5.45, P < .001). DISCUSSION: APOE ε4 positive genotype may cause familial aggregation, and the investigation of multiple interventions targeting APOE pathological function to reduce the risk for this disease warrants attention.

PDE12 disrupts mitochondrial oxidative phosphorylation and mediates mitochondrial dysfunction to induce oral mucosal epithelial barrier damage in oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic oral mucosal disease. The pathological changes of OSF include epithelial damage and subepithelial matrix fibrosis. This study aimed to reveal the epithelial injury mechanism of OSF. A histopathological method was used to analyze oral mucosal tissue from OSF patients and OSF rats. The expression of PDE12 in the oral epithelium was analyzed by immunohistochemistry. The epithelial-mesenchymal transition (EMT) and tight junction proteins in arecoline-treated HOKs were explored by western blotting. Epithelial leakage was assessed by transepithelial electrical resistance and lucifer yellow permeability. The expression of PDE12 and the mitochondrial morphology, mitochondrial permeability transition pore opening, mitochondrial membrane potential, and mitochondrial reactive oxygen species (mtROS) were evaluated in arecoline-induced HOKs. Oxidative phosphorylation (OXPHOS) complexes and ATP content were also explored in HOKs. The results showed significant overexpression of PDE12 in oral mucosal tissue from OSF patients and rats. PDE12 was also overexpressed and aggregated in mitochondria in arecoline-induced HOKs, resulting in dysfunction of OXPHOS and impaired mitochondrial function. An EMT, disruption of tight junctions with epithelial leakage, and extracellular matrix remodeling were also observed. PDE12 overexpression induced by PDE12 plasmid transfection enhanced the mtROS level and interfered with occludin protein localization in HOKs. Interestingly, knockdown of PDE12 clearly ameliorated arecoline-induced mitochondrial dysfunction and epithelial barrier dysfunction in HOKs. Therefore, we concluded that overexpression of PDE12 impaired mitochondrial OXPHOS and mitochondrial function and subsequently impaired epithelial barrier function, ultimately leading to OSF. We suggest that PDE12 may be a new potential target against OSF.

Application of high intensity focused ultrasound combined with nanomaterials in anti-tumor therapy.

High intensity focused ultrasound (HIFU) has demonstrated its safety, efficacy and noninvasiveness in the ablation of solid tumor. However, its further application is limited by its inherent deficiencies, such as postoperative recurrence caused by incomplete ablation and excessive intensity affecting surrounding healthy tissues. Recent research has indicated that the integration of nanomaterials with HIFU exhibits a promising synergistic effect in tumor ablation. The concurrent utilization of nanomaterials with HIFU can help overcome the limitations of HIFU by improving targeting and ablation efficiency, expanding operation area, increasing operation accuracy, enhancing stability and bio-safety during the process. It also provides a platform for multi-therapy and multi-mode imaging guidance. The present review comprehensively expounds upon the synergistic mechanism between nanomaterials and HIFU, summarizes the research progress of nanomaterials as cavitation nuclei and drug carriers in combination with HIFU for tumor ablation. Furthermore, this review highlights the potential for further exploration in the development of novel nanomaterials that enhance the synergistic effect with HIFU on tumor ablation.

Integrated Metabolomics and Transcriptomics Analysis Reveals New Insights into Triterpene Biosynthesis in Rosa rugosa.

Rosa rugosa is highly regarded for its aesthetic and therapeutic qualities. In particular, R. rugosa's flowers are known to produce essential oils containing a mixture of volatile terpenes, phenylpropanoids, and other compounds. Despite this, extensive research exists on volatile terpenes in flowers, while the knowledge of non-volatile terpenes in distinct tissues is still limited. Using UPLC-ESI-MS/MS, a comprehensive analysis of the terpene metabolites in five different tissues of R. rugosa was conducted. These metabolites accumulated in distinct tissues, and the majority of them were triterpenoids. Transcriptome data were collected from five tissues using RNA-seq. Transcriptomics and metabolomics were utilized to evaluate the triterpene biosynthesis pathway, resulting in new insights into its regulation and biosynthesis. The RrOSC10 was identified as a key enzyme in converting 2,3-oxidosqualene into α-amyrin, potentially contributing to the triterpene biosynthesis pathway. Furthermore, the expression of the RrOSC10 gene was upregulated by salinity for 0.5 h and 1 h, with subsequent downregulation at 2 h. This study lays a foundation for future research on the biosynthesis and accumulation of triterpenes in R. rugosa.