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1.
Nutr J ; 23(1): 59, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38834985

BACKGROUND: Given the benefits of gardening for physical and psychological health, we explored whether gardening was associated with lower risks of subjective cognitive decline (SCD), a precursor of dementia, and SCD-related functional limitations. METHODS: Included in this cross-sectional study were 136,748 participants aged 45 + years old from the Behavioral Risk Factor Surveillance System 2019 survey, who were then categorized into three groups according to self-reported exercise status: non-exercisers, gardeners, and other exercisers. SCD was assessed via a questionnaire, and SCD-related functional limitations were referred to as having difficulties in engaging in household or social activities due to SCD. The odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the associations of gardening with SCD and SCD-related functional limitations, adjusted for age, sex, socioeconomic status, lifestyle factors, and health status. Mediation analyses were conducted to examine whether the observed association between gardening and SCD was mediated by energy expenditure (MET-hours/week), depression status, and consumption of fruits and vegetables. RESULTS: Overall, 11.1% and 5.4% of participants self-reported experiencing SCD and SCD-related functional limitations, respectively. The adjusted OR for gardeners vs. non-exercisers, was 0.72 (95% CI 0.62-0.83) for SCD and 0.57 (95% CI 0.44-0.73) for SCD-related functional limitations. The observed association between gardening and SCD was explained by higher energy expenditure (39.0%), lower likelihood of having depression (21.5%), and higher consumption of fruits and vegetables (3.4%) (P<0.05 for all). Similar patterns were observed for SCD-related functional limitations. CONCLUSION: In this nationally representative sample, gardening was associated with better cognitive status, which may be mainly attributed to better depression status and energy expenditure.


Cognitive Dysfunction , Gardening , Humans , Cross-Sectional Studies , Gardening/methods , Male , Female , Cognitive Dysfunction/epidemiology , Middle Aged , Aged , Mediation Analysis , Exercise , Vegetables , Fruit , Behavioral Risk Factor Surveillance System , Depression/epidemiology , Surveys and Questionnaires
2.
BJPsych Open ; 10(4): e123, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38826027

BACKGROUND: One in 57 children are diagnosed with autism in the UK, and the estimated cost for supporting these children in education is substantial. Social Stories™ is a promising and widely used intervention for supporting children with autism in schools and families. It is believed that Social Stories™ can provide meaningful social information to children that can improve social understanding and may reduce anxiety. However, no economic evaluation of Social Stories has been conducted. AIMS: To assess the cost-effectiveness of Social Stories through Autism Spectrum Social Stories in Schools Trial 2, a multi-site, pragmatic, cluster-randomised controlled trial. METHOD: Children with autism who were aged 4-11 years were recruited and randomised (N = 249). Costs measured from the societal perspective and quality-adjusted life-years (QALYs) measured by the EQ-5D-Y-3L proxy were collected at baseline and at 6-month follow-up for primary analysis. The incremental cost-effectiveness ratio was calculated, and the uncertainty around incremental cost-effectiveness ratios was captured by non-parametric bootstrapping. Sensitivity analyses were performed to evaluate the robustness of the primary findings. RESULTS: Social Stories is likely to result in a small cost savings (-£191 per child, 95% CI -767.7 to 337.7) and maintain similar QALY improvements compared with usual care. The probability of Social Stories being a preferred option is 75% if society is willing to pay £20 000 per QALY gained. The sensitivity analysis results aligned with the main study outcomes. CONCLUSIONS: Compared with usual care, Social Stories did not lead to an increase in costs and maintained similar QALY improvements for primary-aged children with autism.

3.
J Sci Food Agric ; 2024 May 31.
Article En | MEDLINE | ID: mdl-38822542

BACKGROUND: The Songhua River Basin, a vital grain-producing area in China, faces challenges due to the uneven distribution of water resources and the intensive water demands of agriculture. To enhance agricultural development and effectively manage water scarcity, it is essential to identify the water-saving potential of major staple crops - corn, wheat, and rice. This study enhances the World Food Studies (WOFOST) model by refining the day of year for the developmental vegetative stage (DVS), thereby improving the representation of phenological stages for spring maize, spring wheat, and rice within the model. This refinement offers a detailed analysis of the potential and rainfed yields. RESULTS: The results from the modified WOFOST model show promising simulation outcomes for the biomass and yield of maize, wheat, and rice, with Nash-Sutcliffe efficiency (NS) and index of agreement (IoA) values all exceeding 0.7. An analysis of photothermal potential yields (Yp) and rainfed yields (Yr) revealed minimal differences in yields for spring maize and rice across various rainfall frequencies. Specifically, the average photothermal utilization rates (LTs) are 93.57% for maize and 85.25% for rice. In contrast, the rainfed yield for wheat is lower than its photothermal yield, with an LT of 43.66%. CONCLUSIONS: These findings suggest that in the Songhua River Basin, maize and rice offer greater potential for water conservation compared to wheat. It is recommended to judiciously reduce irrigation during the growing seasons of spring maize and rice to help alleviate agricultural water use pressures. © 2024 Society of Chemical Industry.

4.
Physiol Plant ; 176(3): e14364, 2024.
Article En | MEDLINE | ID: mdl-38837226

Phytoremediation is a promising technology for removing the high-toxic explosive 2,4,6-trinitrotoluene (TNT) pollutant from the environment. Mining dominant genes is the key research direction of this technology. Most previous studies have focused on the detoxification of TNT rather than plants' TNT tolerance. Here, we conducted a transcriptomic analysis of wild type Arabidopsis plants under TNT stress and found that the Arabidopsis cytochrome P450 gene CYP81D11 was significantly induced in TNT-treated plants. Under TNT stress, the root length was approximately 1.4 times longer in CYP81D11-overexpressing transgenic plants than in wild type plants. The half-removal time for TNT was much shorter in CYP81D11-overexpressing transgenic plants (1.1 days) than in wild type plants (t1/2 = 2.2 day). In addition, metabolic analysis showed no difference in metabolites in transgenic plants compared to wild type plants. These results suggest that the high TNT uptake rates of CYP81D11-overexpressing transgenic plants were most likely due to increased tolerance and biomass rather than TNT degradation. However, CYP81D11-overexpressing plants were not more tolerant to osmotic stresses, such as salt or drought. Taken together, our results indicate that CYP81D11 is a promising target for producing bioengineered plants with high TNT removing capability.


Arabidopsis Proteins , Arabidopsis , Biodegradation, Environmental , Cytochrome P-450 Enzyme System , Gene Expression Regulation, Plant , Plants, Genetically Modified , Trinitrotoluene , Arabidopsis/genetics , Arabidopsis/metabolism , Trinitrotoluene/metabolism , Cytochrome P-450 Enzyme System/metabolism , Cytochrome P-450 Enzyme System/genetics , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Plant Roots/genetics , Plant Roots/metabolism , Stress, Physiological/genetics
5.
Mater Horiz ; 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38842068

Intramolecular exciplex systems featuring thermally activated delayed fluorescence (TADF) have garnered significant attention in the realm of organic light-emitting diodes (OLEDs). Nonetheless, the occurrence of organic sandwich intramolecular exciplexes remains rare due to structural limitations and synthetic challenges. Herein, we present a novel rigid acceptor-donor-acceptor (A-D-A) sandwich complex, dSFQP, characterized by two sp3 C-locking moieties. This compound exhibits TADF characteristics facilitated by a multiple through-space charge-transfer process. X-ray crystallographic analysis confirms the distinctive sandwich configuration. The parallel spatial arrangement and minimized A-D-A configuration enhance electronic interactions, resulting in a high photoluminescence quantum yield, rapid reverse intersystem crossing rate, and sluggish nonradiative decay rate. OLEDs employing dSFQP as the dopant achieve a maximum external quantum efficiency (EQE) of 28.5% with a low efficiency roll-off of merely 2.8% at 1000 cd m-2. Even at a high brightness of 10 000 cd m-2, the EQE remains notably high at 17.5%. Our current results provide an effective way to further innovate the design of new organic charge-transfer complexes.

6.
Article En | MEDLINE | ID: mdl-38842617

PURPOSE OF REVIEW: The purpose of this review is to provide an updated approach to the evaluation and management of pulsatile tinnitus (PT), an uncommon but often treatable subtype of tinnitus. RECENT FINDINGS: Secondary PT can be due to either vascular or non-vascular etiologies, including, but not limited to: neoplasm, arteriovenous malformation or fistula, idiopathic intracranial hypertension, dural venous sinus stenosis, otoacoustic etiologies (e.g., otosclerosis, patulous eustachian tube) and bony defects (e.g., superior semicircular canal dehiscence). Computed tomography (CT) and magnetic resonance imaging (MRI) imaging have comparable diagnostic yield, though each may be more sensitive to specific etiologies. If initial vascular imaging is negative and a vascular etiology is strongly suspected, digital subtraction angiography (DSA) may further aid in the diagnosis. Many vascular etiologies of PT can be managed endovascularly, often leading to PT improvement or resolution. Notably, venous sinus stenting is an emerging therapy for PT secondary to idiopathic intracranial hypertension with venous sinus stenosis. Careful history and physical exam can help establish the differential diagnosis for PT and guide subsequent evaluation and management. Additional studies on the efficacy and long-term outcome of venous sinus stenting for venous stenosis are warranted.

7.
Ear Hear ; 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38831494

OBJECTIVES: To translate and validate the Chinese version of the Speech, Spatial, and Qualities of Hearing Scale (SSQ) for children with hearing impairment (C-SSQ-C) and for their parents (C-SSQ-P). DESIGN: We translated the SSQ for children into Chinese and verified its readability and comprehensibility. A total of 105 participants with moderate-to-profound hearing loss (HL) and 54 with normal hearing were enrolled in the validation process. The participants with HL were fitted with bilateral hearing aids, bimodal hearing, or bilateral cochlear implants. The C-SSQ-P was administered to the parents of participants aged 3 to 6.9 years, and the C-SSQ-C was administered to participants aged 7 to 18 years. The internal consistency, test-retest reliability, and validity were evaluated for both questionnaires. RESULTS: Both C-SSQ-P and C-SSQ-C demonstrated high internal consistency (Cronbach's α >0.8) and good validity (generalized linear model revealed significant negative relationships between the C-SSQ-P subscales with aided better-hearing threshold [ß = -0.08 to -0.12, p ≤ 0.001] and between the C-SSQ-C subscales with worse-hearing threshold [ß = -0.13 to -0.14, p < 0.001]). Among the children with HL, the participants with bilateral cochlear implants had demonstrated better performance than those with bimodal hearing and bilateral hearing aids, as evidenced by the highest mean scores in three subscales. CONCLUSIONS: Both C-SSQ-P and C-SSQ-C are reliable and valid for assessing HL in children and adolescents. The C-SSQ-P is applicable in evaluating young children aged 3 to 6.9 years after a 7-day observation period, while the C-SSQ-C is appropriate for children and adolescents aged 7 to 18 years.

8.
Breast Cancer Res ; 26(1): 94, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38844963

BACKGROUND: RNA m5C methylation has been extensively implicated in the occurrence and development of tumors. As the main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, the precise impact of NSUN2-mediated m5C modification on breast cancer (BC) remains unclear. Our study aims to elucidate the molecular mechanism underlying how NSUN2 regulates the target gene HGH1 (also known as FAM203) through m5C modification, thereby promoting BC progression. Additionally, this study targets at preliminarily clarifying the biological roles of NSUN2 and HGH1 in BC. METHODS: Tumor and adjacent tissues from 5 BC patients were collected, and the m5C modification target HGH1 in BC was screened through RNA sequencing (RNA-seq) and single-base resolution m5C methylation sequencing (RNA-BisSeq). Methylation RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA-binding protein immunoprecipitation-qPCR (RIP-qPCR) confirmed that the methylation molecules NSUN2 and YBX1 specifically recognized and bound to HGH1 through m5C modification. In addition, proteomics, co-immunoprecipitation (co-IP), and Ribosome sequencing (Ribo-Seq) were used to explore the biological role of HGH1 in BC. RESULTS: As the main m5C methylation molecule, NSUN2 is abnormally overexpressed in BC and increases the overall level of RNA m5C. Knocking down NSUN2 can inhibit BC progression in vitro or in vivo. Combined RNA-seq and RNA-BisSeq analysis identified HGH1 as a potential target of abnormal m5C modifications. We clarified the mechanism by which NSUN2 regulates HGH1 expression through m5C modification, a process that involves interactions with the YBX1 protein, which collectively impacts mRNA stability and protein synthesis. Furthermore, this study is the first to reveal the binding interaction between HGH1 and the translation elongation factor EEF2, providing a comprehensive understanding of its ability to regulate transcript translation efficiency and protein synthesis in BC cells. CONCLUSIONS: This study preliminarily clarifies the regulatory role of the NSUN2-YBX1-m5C-HGH1 axis from post-transcriptional modification to protein translation, revealing the key role of abnormal RNA m5C modification in BC and suggesting that HGH1 may be a new epigenetic biomarker and potential therapeutic target for BC.


Breast Neoplasms , Disease Progression , Gene Expression Regulation, Neoplastic , Methyltransferases , RNA Stability , Y-Box-Binding Protein 1 , Humans , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Female , Methylation , Methyltransferases/metabolism , Methyltransferases/genetics , Y-Box-Binding Protein 1/metabolism , Y-Box-Binding Protein 1/genetics , Mice , Animals , Cell Line, Tumor , RNA, Messenger/genetics , RNA, Messenger/metabolism , Cell Proliferation
9.
Psych J ; 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38845340

Social exclusion is a pervasive phenomenon that can have profound psychological consequences, including increased aggression. Self-compassion can promote psychological resilience, which helps individuals cope with challenges and may help mitigate the aggression triggered by social exclusion. This study aims to explore the relationship between self-compassion and aggression in the context of social exclusion from both state and trait perspectives. First, a cross-sectional study (Study 1) was conducted; the findings revealed that social exclusion is associated with higher levels of aggression, while self-compassion is linked to lower levels of social exclusion and aggression. Further division of self-compassion into its constituent components (self-kindness, mindfulness, and common humanity) revealed additional insights into the specific roles played by these factors. Self-kindness and mindfulness were found to moderate the relationship between social exclusion and aggression, while common humanity was observed to mediate this relationship. To determine the causal relationships among variables in further detail, an experimental study (Study 2) was designed. This study utilized a recall writing task to induce feelings of social exclusion and employed self-compassion writing tasks to elicit self-compassionate responses from participants. The results of this experiment indicated that self-compassion can significantly reduce the aggression triggered by social exclusion, thus suggesting that self-compassion may help alleviate the distress caused by individuals' experiences of social exclusion. The findings of this research have important implications for the development of clinical interventions aimed at reducing the adverse effects of social exclusion.

10.
Mitochondrial DNA B Resour ; 9(6): 687-691, 2024.
Article En | MEDLINE | ID: mdl-38835639

Arachis lutescens Krapov. & Rigoni 1958 is an important species due to their potentially extensive applications for cultivated peanut breeding. The whole chloroplast genome of A. lutescens was successfully assembled and annotated for the first time. The complete chloroplast genome of A. lutescens is a typically circular structure of 156,398 bp with a GC content of 36.3%. It comprises a large single-copy (LSC) region of 85,950 bp, a small single-copy (SSC) region of 18,800 bp, and two inverted repeat regions (IRs) of 25,824 bp, each. The plastome of A. lutescens contains a total of 125 genes, including 81 protein-coding genes, 36 tRNAs, and eight rRNAs. The phylogenetic analysis strongly supports the close relationship between A. lutescens and cultivated peanut clades. This study contributes to our understanding of the molecular characteristics and evolutionary relationships of this plant species.

11.
Front Endocrinol (Lausanne) ; 15: 1325320, 2024.
Article En | MEDLINE | ID: mdl-38836225

Background: Creatinine-cystatin C ratio (CCR) has been demonstrated as an objective marker of sarcopenia in clinical conditions but has not been evaluated as an osteoporosis marker in individuals with normal renal function. Methods: We selected 271,831 participants with normal renal function from UK Biobank cohort. Multivariable linear/logistic regression and Cox proportional hazards model were used to investigate the phenotypic relationship between CCR and osteoporosis in total subjects and gender-stratified subjects. Based on the genome-wide association study (GWAS) data, linkage disequilibrium regression (LDSC) and Mendelian randomization (MR) analysis were performed to reveal the shared genetic correlations and infer the causal effects, respectively. Results: Amongst total subjects and gender-stratified subjects, serum CCR was positively associated with eBMD after adjusting for potential risk factors (all P<0.05). The multivariable logistic regression model showed that the decrease in CCR was associated with a higher risk of osteoporosis/fracture in all models (all P<0.05). In the multivariable Cox regression analysis with adjustment for potential confounders, reduced CCR is associated with the incidence of osteoporosis and fracture in both total subjects and gender-stratified subjects (all P<0.05). A significant non-linear dose-response was observed between CCR and osteoporosis/fracture risk (P non-linearity < 0.05). LDSC found no significant shared genetic effects by them, but PLACO identified 42 pleiotropic SNPs shared by CCR and fracture (P<5×10-8). MR analyses indicated the causal effect from CCR to osteoporosis/fracture. Conclusions: Reduced CCR predicted increased risks of osteoporosis/fracture, and significant causal effects support their associations. These findings indicated that the muscle-origin serum CCR was a potential biomarker to assess the risks of osteoporosis and fracture.


Biomarkers , Creatinine , Cystatin C , Mendelian Randomization Analysis , Osteoporosis , Humans , Female , Male , Osteoporosis/genetics , Osteoporosis/blood , Osteoporosis/epidemiology , Middle Aged , Biomarkers/blood , Creatinine/blood , Cystatin C/blood , Cystatin C/genetics , Aged , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Adult , Bone Density/genetics , Risk Factors
12.
Front Immunol ; 15: 1370367, 2024.
Article En | MEDLINE | ID: mdl-38840920

Because of the considerable tumor heterogeneity in gastric cancer (GC), only a limited group of patients experiences positive outcomes from immunotherapy. Herein, we aim to develop predictive models related to glycosylation genes to provide a more comprehensive understanding of immunotherapy for GC. RNA sequencing (RNA-seq) data and corresponding clinical outcomes were obtained from GEO and TCGA databases, and glycosylation-related genes were obtained from GlycoGene DataBase. We identified 48 differentially expressed glycosylation-related genes and established a prognostic model (seven prognosis genes including GLT8D2, GALNT6, ST3GAL6, GALNT15, GBGT1, FUT2, GXYLT2) based on these glycosylation-related genes using the results from Cox regression analysis. We found that these glycosylation-related genes revealed a robust correlation with the abundance of Tumor Infiltrating Lymphocytes (TILs), especially the GLT8D2 which is associated with many TILs. Finally, we employed immunohistochemistry and Multiplex Immunohistochemical to discover that GLT8D2 serves as a valuable prognostic biomarker in GC and is closely associated with macrophage-related markers. Collectively, we established a prognostic model based on glycosylation-related genes to provide a more comprehensive understanding of prediction for GC prognosis, and identified that GLT8D2 is closely correlated with adverse prognosis and may underscore its role in regulating immune cell infiltration in GC patients.


Biomarkers, Tumor , Lymphocytes, Tumor-Infiltrating , Stomach Neoplasms , Humans , Stomach Neoplasms/immunology , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Biomarkers, Tumor/genetics , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Prognosis , Glycosylation , Female , Male , Gene Expression Regulation, Neoplastic , Middle Aged , Tumor Microenvironment/immunology
13.
PeerJ ; 12: e17494, 2024.
Article En | MEDLINE | ID: mdl-38832035

Background: Autoantibodies targeting tumor-associated antigens (TAAbs) have emerged as promising biomarkers for early cancer detection. This research aimed to assess the diagnostic capacity of anti-BIRC5 autoantibody in detecting AFP-negative hepatocellular carcinoma (ANHCC). Methods: This research was carried out in three stages (discovery phase, validation phase, and evaluation phase) and included a total of 744 participants. Firstly, the anti-BIRC5 autoantibody was discovered using protein microarray, exhibiting a higher positive rate in ANHCC samples (ANHCCs) compared to normal control samples (NCs). Secondly, the anti-BIRC5 autoantibody was validated through enzyme-linked immunosorbent assay (ELISA) in 85 ANHCCs and 85 NCs from two clinical centers (Zhengzhou and Nanchang). Lastly, the diagnostic usefulness of the anti-BIRC5 autoantibody for hepatocellular carcinoma (HCC) was evaluated by ELISA in a cohort consisting of an additional 149 AFP-positive hepatocellular carcinoma samples (APHCCs), 95 ANHCCs and 244 NCs. The association of elevated autoantibody to high expression of BIRC5 in HCC was further explored by the database from prognosis, immune infiltration, DNA methylation, and gene mutation level. Results: In the validation phase, the area under the ROC curve (AUC) of anti-BIRC5 autoantibody to distinguish ANHCCs from NCs in Zhengzhou and Nanchang centers was 0.733 and 0.745, respectively. In the evaluation phase, the AUCs of anti-BIRC5 autoantibody for identifying ANHCCs and HCCs from NCs were 0.738 and 0.726, respectively. Furthermore, when combined with AFP, the AUC for identifying HCCs from NCs increased to 0.914 with a sensitivity of 77.5% and specificity of 91.8%. High expression of BIRC5 gene is not only correlated with poor prognosis of HCCs, but also significantly associated with infiltration of immune cells, DNA methylation, and gene mutation. Conclusion: The findings suggest that the anti-BIRC5 autoantibody could serve as a potential biomarker for ANHCC, in addition to its supplementary role alongside AFP in the diagnosis of HCC. Next, we can carry out specific verification and explore the function of anti-BIRC5 autoantibody in the occurrence and development of HCC.


Autoantibodies , Biomarkers, Tumor , Carcinoma, Hepatocellular , Liver Neoplasms , Survivin , alpha-Fetoproteins , Humans , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/immunology , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Autoantibodies/blood , Autoantibodies/immunology , Biomarkers, Tumor/immunology , Biomarkers, Tumor/genetics , Male , Female , Middle Aged , Survivin/genetics , Survivin/immunology , alpha-Fetoproteins/immunology , alpha-Fetoproteins/analysis , Enzyme-Linked Immunosorbent Assay , Adult
14.
J Am Chem Soc ; 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38847788

Previous findings have suggested a close association between oxygen vacancies in SnO2 and charge carrier recombination as well as perovskite decomposition at the perovskite/SnO2 interface. Underlying the fundamental mechanism holds great significance in achieving a more favorable balance between the efficiency and stability. In this study, we prepared three SnO2 samples with different oxygen vacancy concentrations and observed that a low oxygen vacancy concentration is conducive to long-term device stability. Iodide ions were observed to easily diffuse into regions with high oxygen vacancies, thereby speeding up the deprotonation of FAI, as made evident by the detection of the decomposition product formamide. In contrast, a high oxygen vacancy concentration in SnO2 could prevent hole injection, leading to a decrease in interfacial recombination losses. To suppress this decomposition reaction and address the trade-off, we designed a bilayer SnO2 structure to ensure highly efficient carrier transport still while maintaining a chemically inert surface. As a result, an enhanced efficiency of 25.06% (certified at 24.55% with an active area of 0.09 cm2 under fast scan) was achieved, and the extended operational stability maintained 90% of their original efficiency (24.52%) after continuous operation for nearly 2000 h. Additionally, perovskite submodules with an active area of 14 cm2 were successfully assembled with a PCE of up to 22.96% (20.09% with an aperture area).

15.
Front Genet ; 15: 1393856, 2024.
Article En | MEDLINE | ID: mdl-38725481

DNA methylation indicates the individual's aging, so-called Epigenetic clocks, which will improve the research and diagnosis of aging diseases by investigating the correlation between methylation loci and human aging. Although this discovery has inspired many researchers to develop traditional computational methods to quantify the correlation and predict the chronological age, the performance bottleneck delayed access to the practical application. Since artificial intelligence technology brought great opportunities in research, we proposed a perceptron model integrating a channel attention mechanism named PerSEClock. The model was trained on 24,516 CpG loci that can utilize the samples from all types of methylation identification platforms and tested on 15 independent datasets against seven methylation-based age prediction methods. PerSEClock demonstrated the ability to assign varying weights to different CpG loci. This feature allows the model to enhance the weight of age-related loci while reducing the weight of irrelevant loci. The method is free to use for academics at www.dnamclock.com/#/original.

16.
Article En | MEDLINE | ID: mdl-38724232

BACKGROUND: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial. METHODS: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy. RESULTS: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels. CONCLUSIONS: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.

17.
Proteomics Clin Appl ; : e2300233, 2024 May 10.
Article En | MEDLINE | ID: mdl-38726756

PURPOSE: This paper is to offer insights for designing research utilizing Olink technology to identify biomarkers and potential therapeutic targets for disease treatment. EXPERIMENTAL DESIGN: We discusses the application of Olink technology in oncology, cardiovascular, respiratory and immune-related diseases, and Outlines the advantages and limitations of Olink technology. RESULTS: Olink technology simplifies the search for therapeutic targets, advances proteomics research, reveals the pathogenesis of diseases, and ultimately helps patients develop precision treatments. CONCLUSIONS: Although proteomics technology has been rapidly developed in recent years, each method has its own disadvantages, so in the future research, more methods should be selected for combined application to verify each other.

18.
Bioresour Bioprocess ; 11(1): 47, 2024 May 07.
Article En | MEDLINE | ID: mdl-38713232

Integrating hydrothermal treatment processes and anaerobic digestion (AD) is promising for maximizing resource recovery from biomass and organic waste. The process water generated during hydrothermal treatment contains high concentrations of organic matter, which can be converted into biogas using AD. However, process water also contains various compounds that inhibit the AD process. Fingerprinting these inhibitors and identifying suitable mitigation strategies and detoxification methods is necessary to optimize the integration of these two technologies. By examining the existing literature, we were able to: (1) compare the methane yields and organics removal efficiency during AD of various hydrothermal treatment process water; (2) catalog the main AD inhibitors found in hydrothermal treatment process water; (3) identify recalcitrant components limiting AD performance; and (4) evaluate approaches to detoxify specific inhibitors and degrade recalcitrant components. Common inhibitors in process water are organic acids (at high concentrations), total ammonia nitrogen (TAN), oxygenated organics, and N-heterocyclic compounds. Feedstock composition is the primary determinant of organic acid and TAN formation (carbohydrates-rich and protein-rich feedstocks, respectively). In contrast, processing conditions (e.g., temperature, pressure, reaction duration) influence the formation extent of oxygenated organics and N-heterocyclic compounds. Struvite precipitation and zeolite adsorption are the most widely used approaches to eliminate TAN inhibition. In contrast, powdered and granular activated carbon and ozonation are the preferred methods to remove toxic substances before AD treatment. Currently, ozonation is the most effective approach to reduce the toxicity and recalcitrance of N and O-heterocyclic compounds during AD. Microaeration methods, which disrupt the AD microbiome less than ozone, might be more practical for nitrifying TAN and degrading recalcitrant compounds, but further research in this area is necessary.

19.
World J Clin Oncol ; 15(4): 554-565, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38689624

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

20.
Plant Biotechnol J ; 2024 May 01.
Article En | MEDLINE | ID: mdl-38690830

Dinitrotoluene sulfonates (DNTSes) are highly toxic hazards regulated by the Resource Conservation and Recovery Act (RCRA) in the United States. The trinitrotoluene (TNT) red water formed during the TNT purification process consists mainly of DNTSes. Certain plants, including switchgrass, reed and alfalfa, can detoxify low concentrations of DNTS in TNT red water-contaminated soils. However, the precise mechanism by which these plants detoxify DNTS remains unknown. In order to aid in the development of phytoremediation resources with high DNTS removal rates, we identified and characterized 1-hydroxymethyl-2,4-dinitrobenzene sulfonic acid (HMDNBS) and its glycosylated product HMDNBS O-glucoside as the degradation products of 2,4-DNT-3-SO3Na, the major isoform of DNTS in TNT red water-contaminated soils, in switchgrass via LC-MS/MS- and NMR-based metabolite analyses. Transcriptomic analysis revealed that 15 UDP-glycosyltransferase genes were dramatically upregulated in switchgrass plants following 2,4-DNT-3-SO3Na treatment. We expressed, purified and assayed the activity of recombinant UGT proteins in vitro and identified PvUGT96C10 as the enzyme responsible for the glycosylation of HMDNBS in switchgrass. Overexpression of PvUGT96C10 in switchgrass significantly alleviated 2,4-DNT-3-SO3Na-induced plant growth inhibition. Notably, PvUGT96C10-overexpressing transgenic switchgrass plants removed 83.1% of 2,4-DNT-3-SO3Na in liquid medium after 28 days, representing a 3.2-fold higher removal rate than that of control plants. This work clarifies the DNTS detoxification mechanism in plants for the first time, suggesting that PvUGT96C10 is crucial for DNTS degradation. Our results indicate that PvUGT96C10-overexpressing plants may hold great potential for the phytoremediation of TNT red water-contaminated soils.

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