Serum metabolism alteration behind different etiology, diagnosis, and prognosis of disorders of consciousness.

BACKGROUND: Patients with disorders of consciousness (DoC) exhibit varied revival outcomes based on different etiologies and diagnoses, the mechanisms of which remain largely unknown. The fluctuating clinical presentations in DoC pose challenges in accurately assessing consciousness levels and prognoses, often leading to misdiagnoses. There is an urgent need for a deeper understanding of the physiological changes in DoC and the development of objective diagnostic and prognostic biomarkers to improve treatment guidance. METHODS: To explore biomarkers and understand the biological processes, we conducted a comprehensive untargeted metabolomic analysis on serum samples from 48 patients with DoC. Patients were categorized based on etiology (TBI vs. non-TBI), CRS-R scores, and prognosis. Advanced analytical techniques, including PCA and OPLS-DA models, were employed to identify differential metabolites. RESULTS: Our analysis revealed a distinct separation in metabolomic profiles among the different groups. The primary differential metabolites distinguishing patients with varying etiologies were predominantly phospholipids, with a notable decrease in glycerophospholipids observed in the TBI group. Patients with higher CRS-R scores exhibited a pattern of impaired carbohydrate metabolism coupled with enhanced lipid metabolism. Notably, serum concentrations of both LysoPE and PE were reduced in patients with improved outcomes, suggesting their potential as prognostic biomarkers. CONCLUSIONS: Our study underscores the critical role of phospholipid metabolism in the brain's metabolic alterations in patients with DoC. It identifies key biomarkers for diagnosis and prognosis, offering insights that could lead to novel therapeutic targets. These findings highlight the value of metabolomic profiling in understanding and potentially treating DoC.

Ultrafast Non-Volatile Floating-Gate Memory Based on All-2D Materials.

The explosive growth of massive-data storage and the demand for ultrafast data processing require innovative memory devices with exceptional performance. 2D materials and their van der Waal heterostructures with atomically sharp interfaces hold great promise for innovations in memory devices. Here, this work presents non-volatile, floating-gate memory devices with all functional layers made of 2D materials, achieving ultrafast programming/erasing speeds (20 ns), high extinction ratios (up to 108), and multi-bit storage capability. These devices also exhibit long-term data retention exceeding 10 years, facilitated by a high gate-coupling ratio (GCR) and atomically sharp interfaces between functional layers. Additionally, this work demonstrates the realization of an "OR" logic gate on a single-device unit by synergistic electrical and optical operations. The present results provide a solid foundation for next-generation ultrahigh-speed, ultralong lifespan, non-volatile memory devices, with a potential for scale-up manufacturing and flexible electronics applications.

Pharmacokinetics and Drug-Drug Interaction of Allisartan Isoproxil and Indapamide Sustained-Release Formulation.

Allisartan isoproxil (AI) is an angiotensin II type 1 receptor blocker and be converted into the active substance EXP3174 in vivo. We evaluated the drug-drug interactions of AI and an indapamide sustained-release (Ind SR) preparation, as well as the pharmacokinetic characteristics and safety of AI and Ind SR in healthy subjects. The trial was set up in 6 sequences and 3 cycles, and each cycle contained a 7-day washout period. Subjects received 3 different trial drugs (A, AI; B, Ind SR; C, AI + Ind SR) during 3 different cycles. Twenty-four subjects were enrolled in the clinical trial. Of these, 22 completed the study, 2 subjects dropped out due to adverse events (AEs). For subjects given AI alone or combined with Ind SR, the pharmacogenetic parameters Cmax and the geometric mean ratio of steady state (combined/single) of EXP3174 was 130%. The geometric mean ratio of area under the concentration-time curve over the dosing interval at steady state (combined/single use) was 144.5%. Therefore, the combination of Ind SR had an impact on the pharmacokinetics of AI. Then, the results indicated that the AI combination had no effect on the pharmacokinetics of Ind SR. Serious AEs did not occur. The AEs in this clinical trial were the same as those for AI and Ind SR. Combined administration resulted in 2 cases (2 subjects) of Grade 3 hypotension and 1 case of Grade 3 hypotension with AI alone. Considering that this trial included healthy volunteers, the risk of hypotension was expected to be manageable.

Untargeted Metabolomic Analyses of Body Fluids to Differentiate TBI DOC and NTBI DOC.

OBJECTIVE: To investigate the metabolomic differences between Traumatic brain injury (TBI) disorder of consciousness (DOC) patients and non-traumatic brain injury (NTBI) DOC patients by using cerebrospinal fluid (CSF), serum and urine samples beneficial to understand the pathological mechanism differences between the two etiologies, provide potential clues for the subsequent treatment and prognosis, and investigate the metabolome differences and similarities between TBI and NTBI among three different body fluids. METHODS: In total, 24 TBI DOC subjects and 29 NTBI DOC subjects were enrolled. CSF, serum and urine samples from TBI DOC and NTBI DOC patients were collected and analyzed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarkers and altered metabolic functions. RESULTS: When comparing TBI DOC and NTBI DOC, 36, 31 and 52 differential metabolites were obtained in CSF, serum and urine, respectively. The functional analysis of differential metabolites obtained in CSF, serum and urine were all related to amino acid metabolism. Except for amino acid metabolism, metabolic biomarkers in CSF, serum and urine mainly focus on central function, cognitive function, necrosis and apoptosis and neurological function, respectively. In CSF, the highest AUC was 0.864 (Isoproturon) and 0.816 (Proline betaine). Then, the AUC of NFurfurylformamide in serum was 0.941, while the AUC of Dihydronepetalactone and Doxepin N-oxide glucuronide were 1.0 in urine. CONCLUSION: CSF, serum and urine metabolomic analyses could differentiate TBI DOC from NTBI DOC and functional analyses showed a metabolic change difference between TBI DOC and NTBI DOC.

Coherent ultrafast photoemission from a single quantized state of a one-dimensional emitter.

Femtosecond laser-driven photoemission source provides an unprecedented femtosecond-resolved electron probe not only for atomic-scale ultrafast characterization but also for free-electron radiation sources. However, for conventional metallic electron source, intense lasers may induce a considerable broadening of emitting energy level, which results in large energy spread (>600 milli-electron volts) and thus limits the spatiotemporal resolution of electron probe. Here, we demonstrate the coherent ultrafast photoemission from a single quantized energy level of a carbon nanotube. Its one-dimensional body can provide a sharp quantized electronic excited state, while its zero-dimensional tip can provide a quantized energy level act as a narrow photoemission channel. Coherent resonant tunneling electron emission is evidenced by a negative differential resistance effect and a field-driven Stark splitting effect. The estimated energy spread is ~57 milli-electron volts, which suggests that the proposed carbon nanotube electron source may promote electron probe simultaneously with subangstrom spatial resolution and femtosecond temporal resolution.

Does the individual effect of resource rents imperative in the attainment of environmental sustainability? Evidence of Southeast Asian economies.

This study investigates the impact of natural resource exploitation on environmental sustainability in Southeast Asian economies, while testing the Environmental Kuznets Curve (EKC) inverted U-shaped hypothesis, a model which suggests an initial increase in environmental degradation with economic growth followed by a decrease at a certain level of income. Utilizing World Development Indicators data from 1995 to 2018, the research dissects the long-term influence of various resource rents, namely coal, oil, and forest. The research highlights the indispensable role of renewable energy in maintaining ecological balance. Results indicate that while coal rent exacerbates environmental degradation, forest and oil rents prove eco-friendly, although this is only confirmed in fully modified OLS estimation. The study underscores the importance of forest rents in achieving environmental sustainability. Renewable energy emerges as vital for promoting sustainable low-carbon practices. In line with the EKC hypothesis, the study finds that economic growth initially increases carbon emissions, but eventually reduces them. It calls for appropriate measures to manage resource exploitation, ensure renewable energy availability, alleviate energy poverty, and curb deforestation, thereby mitigating ecological damage.

Cerebrospinal fluid metabolite alterations in patients with different etiologies, diagnoses, and prognoses of disorders of consciousness.

INTRODUCTION: Medical management of disorders of consciousness (DoC) is a growing issue imposing a major burden on families and societies. Recovery rates vary widely among patients with DoC, and recovery predictions strongly influence decisions on medical care. However, the specific mechanisms underlying different etiologies, consciousness levels, and prognoses are still unclear. METHODS: We analyzed the comprehensive cerebrospinal fluid (CSF) metabolome through liquid chromatography-mass spectrometry. Metabolomic analyses were used to identify the metabolic differences between patients with different etiologies, diagnoses, and prognoses. RESULTS: We found that the CSF levels of multiple acylcarnitines were lower in patients with traumatic DoC, suggesting mitochondrial function preservation in the CNS, which might contribute to the better consciousness outcomes of these patients. Metabolites related to glutamate and GABA metabolism were altered and showed a good ability to distinguish the patients in the minimally conscious state and the vegetative state. Moreover, we identified 8 phospholipids as potential biomarkers to predict the recovery of consciousness. CONCLUSIONS: Our findings shed light on the differences in physiological activities underlying DoC with different etiologies and identified some potential biomarkers used for DoC diagnosis and prognosis.

Comprehensive analysis identifies CLEC1B as a potential prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: C-type lectin domain family 1 member B (CLEC1B, encoding the CLEC-2 protein), a member of the C-type lectin superfamily, is a type II transmembrane receptor involved in platelet activation, angiogenesis, and immune and inflammatory responses. However, data regarding its function and clinical prognostic value in hepatocellular carcinoma (HCC) remain scarce. METHODS: The expression of CLEC1B was explored using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RT-qPCR, western blot, and immunohistochemistry assays were employed to validate the downregulation of CLEC1B. Univariate Cox regression and survival analyses were used to evaluate the prognostic value of CLEC1B. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential association between cancer hallmarks and CLEC1B expression. The TISIDB database was applied to search for the correlation between immune cell infiltration levels and CLEC1B expression. The association between CLEC1B and immunomodulators was conducted by Spearman correlation analysis based on the Sangerbox platform. Annexin V-FITC/PI apoptosis kit was used for the detection of cell apoptosis. RESULTS: The expression of CLEC1B was low in various tumors and exhibited a promising clinical prognostic value for HCC patients. The expression level of CLEC1B was tightly associated with the infiltration of various immune cells in the HCC tumor microenvironment (TME) and positively correlated with a bulk of immunomodulators. In addition, CLEC1B and its related genes or interacting proteins are implicated in multiple immune-related processes and signaling pathways. Moreover, overexpression of CLEC1B significantly influenced the treatment effects of sorafenib on HCC cells. CONCLUSIONS: Our results reveal that CLEC1B could serve as a potential prognostic biomarker and may be a novel immunoregulator for HCC. However, its function in immune regulation should be further explored.

Visualizing Atomic Quantum Defects in Ultrathin 1T-PtTe2.

Defects are of significant importance to determine and improve the distinct properties of 2D materials, such as electronic, optical, and catalytic performance. In this report, we observe four types of point defects in atomically thin flakes of 1T-PtTe2 by using low-temperature scanning tunnelling microscopy and spectroscopy (STM/S). Through the combination of STM imaging and simulations, such defects are identified as a single tellurium vacancy from each side of the top PtTe2 layer and a single platinum vacancy from the topmost and next layer. The density functional theory (DFT) calculations reveal that the platinum vacancies from both the monolayer and bilayer exhibit a local magnetic moment. In bilayer PtTe2, the interlayer coulomb screening effect reduces the local magnetic momentum of the single platinum vacancy. Our research provides meaningful guidance for further experiments about the effects of intrinsic defects on potential functions of thin 1T-PtTe2, such as catalysis and spintronic applications.

Ultrafast-Programmable 2D Homojunctions Based on van der Waals Heterostructures on a Silicon Substrate.

The development of electrically ultrafast-programmable semiconductor homojunctions can lead to transformative multifunctional electronic devices. However, silicon-based homojunctions are not programmable so that alternative materials need to be explored. Here 2D, multi-functional, lateral homojunctions made of van der Waals heterostructures with a semi-floating-gate configuration on a p++ Si substrate feature atomically sharp interfaces and can be electrostatically programmed in nanoseconds, more than seven orders of magnitude faster than other 2D-based homojunctions. By applying voltage pulses with different polarities, lateral p-n, n+ -n and other types of homojunctions can be formed, varied, and reversed. The p-n homojunctions possess a high rectification ratio of up to ≈105 and can be dynamically switched between four distinct conduction states with the current spanning over nine orders of magnitude, enabling them to function as logic rectifiers, memories, and multi-valued logic inverters. Built on a p++ Si substrate, which acts as the control gate, the devices are compatible with Si technology.

Ultracoherent Single-Electron Emission of Carbon Nanotubes.

A single-electron emitter, based on a single quantized energy level, can potentially achieve ultimate temporal and spatial coherence with a large emission current, which is desirable for atomic-resolution electron probes. This is first developed by constructing a nano-object on a metal tip to form a quantized double barrier structure. However, the single-electron-emission current can only achieve a picoampere level due to the low electron tunneling rate of the heterojunction with large barrier width, which limits the practical applications. In this study, carbon nanotubes (CNTs) serve as a single-electron emitter and a current up to 1.5 nA is demonstrated. The double barrier structure formed on the CNT tip enables a high tunneling rate (≈1012  s-1 ) due to the smaller barrier width. The emitter also shows high temporal coherence (energy dispersion of ≈10 meV) and spatial coherence (effective source radius of ≈0.85 nm). This work represents a highly coherent electron source to simplify the electron optics system of atomic-resolution electron microscopy and sub-10 nm electron beam lithography.

The Relationships between Parenting Practices and Child Health-Related Behaviors in Children with Intellectual Disability: The Moderating Role of Child Body Weight Status.

This study aimed to examine the associations between parenting practices and child health-related behaviors, and the moderating role of child body weight status in children with intellectual disability (ID). A cross-sectional study was conducted among a sample of children with ID in Hong Kong; 440 participants were included in this study. All the variables investigated were collected from questionnaires, except body weight status, which was objectively measured. Logistic regression analysis was used to examine the associations between parenting practices and children's unhealthy behaviors. Interaction items were added to investigate the moderation effect of child body weight status, adjusting for significant background characteristics. Results showed that the parenting practices of "restricting access to unhealthy food and sedentary behaviors (RA)" (OR range: 0.63-0.64) and "using food or sedentary behaviors as rewards (UR)" (OR range: 1.28-1.60) were significantly associated with some eating behaviors, but not with sedentary behaviors. Body weight status significantly moderated these associations. Only RA showed favorable effects on some eating behaviors in children with overweight and obesity (OR range: 0.17-0.28), whereas the effects of UR differed by body weight status. Future research should focus on developing educational interventions which encourage parents to use practices that are tailored towards children's individual characteristics.

Effectiveness of an adapted physical activity intervention on health-related physical fitness in adolescents with intellectual disability: a randomized controlled trial.

This study aimed to examine the effects of an adapted physical activity (APA) intervention on health-related physical fitness (HRPF) in adolescents with intellectual disability (ID). With a randomized controlled trial design, adolescents aged 12-18 years, with mild and moderate ID, and being overweight and obese were recruited and randomly assigned to either an intervention or a control group. The APA intervention consisted of overall moderate intensity aerobic and resistance exercise, with a duration of 45 min/session, a frequency of 2 sessions/week, and lasting for 9 months. A negative control was involved, in which participants received no treatment. Changes in four fitness tests, including the 9-min run/walk, handgrip strength, 30-s sit-ups, and sit-and-reach tests, were assessed between the groups using general linear models. A total of 57 participants (39 in the intervention group and 18 in the control group) completed the study. Significant mean differences in changes in the 9-min run/walk test (413.6 m [95% CI 146.72 m, 680.41 m], p = 0.003) and the right-side sit-and-reach test (2.2 cm [95% CI 0.37 cm, 4.09 cm], p = 0.020) respectively were observed in the intervention group, compared to the control group. No significant between-group improvement was observed for the handgrip strength and the 30-s sit-ups tests. The APA intervention induced beneficial effects on cardiorespiratory fitness and potential beneficial effects on flexibility for adolescents with ID. However, no significant effects of this intervention on muscular strength and endurance were observed in this study. Future studies should consider involving effective exercises in interventions to improve muscular strength and endurance.

Effects of a School-Based Physical Activity Intervention for Obesity, Health-Related Physical Fitness, and Blood Pressure in Children with Intellectual Disability: A Randomized Controlled Trial.

Children with intellectual disability (ID) are more vulnerable to health conditions than their typically developing peers. Evidence of effective interventions is scarce. A randomized controlled trial was conducted in 30 overweight and obese children with intellectual disability (ID) in China to evaluate a 12-week school-based physical activity intervention for obesity, health-related physical fitness (HRPF), and blood pressure. The intervention consisted of 24 physical activity (PA) sessions (2 sessions/week, 60 min/session), with exercise intensity progressively increasing from a moderate level to a vigorous level. All participants were followed up for 12 weeks after the intervention period to evaluate sustained effects. Outcomes were repeatedly measured at baseline, after the intervention, and after follow-up. The intervention was effective in reducing some obesity-related outcomes (including weight and body mass index) and improving some HRPF-related outcomes (including the 6 min walk test and the 30 s sit-to-stand test), with the significant effects being sustained after the 12-week follow-up. No effect was observed on blood pressure. The findings of this study contribute to the development and implementation of PA interventions to reduce obesity and improve HRPF in children with ID.

Promoting Physical Activity among Workers: A Review of Literature and Future Directions on Developing Theory-Based Interventions.

Insufficient physical activity (PA) has been identified as a leading risk factor for premature and all-cause death, as well as non-communicable diseases. Employees, especially those with low occupational PA, are more vulnerable to physical inactivity, and studies in this population are scarce. However, employees may receive benefits for both health and work productivity from PA. Therefore, well-designed behavior change studies to promote PA in employees are urgently needed, especially during the COVID-19 pandemic. Literature was searched before 30 July 2022, and updated evidence was summarized. This review elaborates on the evidence related to insufficient PA and further provides an overview of theory-based interventions for promoting PA. Evidence indicates that intervention mapping (IM) was a useful tool to develop, implement, and evaluate behavior change interventions. Based on the IM framework, reviewing the theory- and evidence-based change methods and delivery modes, and further identifying the research gaps and limitations of existing interventions could provide promising suggestions and directions for development of well-founded interventions promoting PA among employees. The updated knowledge base for developing future interventions may boost efficacy and provide firm conclusions for researchers in this area.

Hypertension and Associated Risk Factors among Children with Intellectual Disability: A Cross-Sectional Study.

To investigate the prevalence of hypertension and associated risk factors in Chinese children with intellectual disability, a cross-sectional study was conducted in a sample of 558 children with intellectual disability aged 6-18 years in Hong Kong, and 452 (81.0%) with valid data were included in the data analysis. Blood pressure was measured according to a standard protocol. Hypertension was defined using the age-, gender-, and height-specific classification criteria recommended by the 2018 Chinese Guidelines for Children. Multivariate and hierarchical logistic regression was fitted to examine the associations of hypertension with potential risk factors. Overall, 31.4% of the participants were classified as having hypertension. Obese children were more likely to develop hypertension than non-obese children (adjusted OR = 2.77, 95% CI: 1.28, 5.99, p = 0.010). A paternal education of college or above and a paternal occupation of clerks, sales representatives, and workers were also associated with an increased risk of hypertension. The prevalence of hypertension is high among Chinese children with intellectual disability. Obesity was the strongest risk factor. Further longitudinal studies are warranted to confirm our findings. Nevertheless, preventions against obesity are promising to receive doubled benefits in reducing both obesity and hypertension, given its strong relationship with hypertension in this special population.

Corrigendum: TEOA inhibits proliferation and induces DNA damage of diffuse large B-cell lymphoma cells through activation of the ROS-dependent p38 MAPK signaling pathway.

[This corrects the article DOI: 10.3389/fphar.2020.554736.].

Interventions for health-related physical fitness and overweight and obesity in children with intellectual disability: Systematic review and meta-analysis.

BACKGROUND: Poor health-related physical fitness (HRPF) and overweight and obesity are common health problems for children with intellectual disability. This study aimed to review existing lifestyle intervention studies, and identify effective strategies for this population. METHODS: A systematic search was undertaken in three databases. The random-effects model was used to pool the weighted results by inverse variance methods, and the I2 statistic was applied to assess heterogeneity among the included studies. RESULTS: Most of the identified interventions (27/29) adopted physical activity (PA). For obesity-related outcomes, the results showed no significant effect of PA studies on reducing obesity. For HRPF outcomes, significant effects were found on 6-min walk distance (51.86 m, 95% CI [16.49, 87.22], p < .05). CONCLUSIONS: PA is the predominant intervention component adopted and may contribute to improving cardiopulmonary fitness; but the lack of research limits our ability to draw any confirmed conclusion on obesity-related outcomes and other HRPF outcomes.

Effectiveness of an adapted physical activity intervention for weight management in adolescents with intellectual disability: A randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a 9-month school-based adapted physical activity (APA) program for reducing weight among adolescents with intellectual disability (ID). METHODS: In this randomized controlled trial, adolescents with ID, aged 12-18 years, who were overweight/or with obesity were randomly assigned into intervention and control groups. The APA intervention consisted of aerobic and resistance exercises with an overall moderate intensity and was delivered at a frequency of two sessions per week for 9 months. Changes in body mass index (BMI, primary outcome) and changes in BMIz, weight, percent body fat, waist circumference and waist-to-height ratio (secondary outcomes) were examined using general linear models. RESULTS: In total 61 subjects (39 in the intervention and 22 in the control) completed the study and were included in the analyses. At 9 months, the intervention group exhibited a reduced BMI of -0.66 kg/m2 (95% CI -1.06 to -0.25 kg/m2 , p = 0.002), while a significant increase in BMI was observed in the control group. A significant post-intervention between-group difference in change in BMI (-1.31 kg/m2 [95% CI -1.99 to -0.63], p < 0.01) was found in favour of the intervention group. Similar results were also observed for all secondary outcomes. CONCLUSIONS: This study provides evidence that a 9-month APA intervention induced clinically meaningful effects on weight loss in adolescents with ID.

Nanocone-Shaped Carbon Nanotubes Field-Emitter Array Fabricated by Laser Ablation.

The nanocone-shaped carbon nanotubes field-emitter array (NCNA) is a near-ideal field-emitter array that combines the advantages of geometry and material. In contrast to previous methods of field-emitter array, laser ablation is a low-cost and clean method that does not require any photolithography or wet chemistry. However, nanocone shapes are hard to achieve through laser ablation due to the micrometer-scale focusing spot. Here, we develop an ultraviolet (UV) laser beam patterning technique that is capable of reliably realizing NCNA with a cone-tip radius of ≈300 nm, utilizing optimized beam focusing and unique carbon nanotube-light interaction properties. The patterned array provided smaller turn-on fields (reduced from 2.6 to 1.6 V/µm) in emitters and supported a higher (increased from 10 to 140 mA/cm2) and more stable emission than their unpatterned counterparts. The present technique may be widely applied in the fabrication of high-performance CNTs field-emitter arrays.