The role of circadian rhythms and sleep in the aetiology of autism spectrum disorder and attention-deficit/hyperactivity disorder: New evidence from bidirectional two-sample Mendelian randomization analysis.

LAY ABSTRACT: Research shows that people with autism spectrum disorder and attention-deficit/hyperactivity disorder often have sleep issues and problems with the body's natural daily rhythms, known as circadian rhythms. By exploring the genetic variants associated with these rhythms and the conditions, this study reveals that these rhythm changes and sleep patterns are directly linked to autism spectrum disorder and attention-deficit/hyperactivity disorder. It found that the timing of one's most active hours can increase the likelihood of having both autism spectrum disorder and attention-deficit/hyperactivity disorder. Importantly, it also shows that good sleep quality might protect against autism spectrum disorder, while disturbed sleep in people with attention-deficit/hyperactivity disorder seems to be a result rather than the cause of the condition. This understanding can help doctors and researchers develop better treatment approaches that focus on the specific ways sleep and body rhythms affect those with autism spectrum disorder and attention-deficit/hyperactivity disorder, considering their unique associations with circadian rhythms and sleep patterns. Understanding these unique links can lead to more effective, personalized care for those affected by these conditions.

Radiomic analysis based on magnetic resonance imaging for the prediction of VEGF expression in hepatocellular carcinoma patients.

OBJECTIVE: The purpose of this study was to investigate the ability of radiomic characteristics of magnetic resonance images to predict vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) patients. METHODS: One hundred and twenty-four patients with HCC who underwent fat-suppressed T2-weighted imaging (FS-T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) one week before surgical resection were enrolled in this retrospective study. Immunohistochemical analysis was used to evaluate the expression level of VEGF. Radiomic features were extracted from the axial FS-T2WI, DCE-MRI (arterial phase and portal venous phase) images of axial MRI. Least absolute shrinkage and selection operator (LASSO) and stepwise regression analyses were performed to select the best radiomic features. Multivariate logistic regression models were constructed and validated using tenfold cross-validation. Receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA) were employed to evaluate these models. RESULTS: Our results show that there were 94 patients with high VEGF expression and 30 patients with low VEGF expression among the 124 HCC patients. The FS-T2WI, DCE-MRI and combined MRI radiomics models had AUCs of 0.8713, 0.7819, and 0.9191, respectively. There was no significant difference in the AUC between the FS-T2WI radiomics model and the DCE-MRI radiomics model (p > 0.05), but the AUC for the combined model was significantly greater than the AUCs for the other two models (p < 0.05) according to the DeLong test. The combined model had the greatest net benefit according to the DCA results. CONCLUSION: The radiomic model based on multisequence MR images has the potential to predict VEGF expression in HCC patients. The combined model showed the best performance.

Prognostic relevance of ventricular arrhythmias in surgical patients with gastrointestinal tumors.

BACKGROUND: Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases. Among which, ventricular arrhythmia is a prevalent clinical concern. This suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal tumors. AIM: To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving surgery. METHODS: We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor resection. These patients were evaluated by a 24-h ambulatory electrocardiogram (ECG) at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2020. Additionally, 41 general healthy age-matched and sex-matched controls were included. Patients were categorized into survival and non-survival groups. The primary endpoint was all-cause mortality, and secondary endpoints included major adverse cardiovascular events (MACEs). RESULTS: Colorectal tumors comprised 90% of cases. Preoperative ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors, 100 (76.92%) exhibited varying degrees of premature ventricular contractions (PVCs). Ten patients (7.69%) manifested non-sustained ventricular tachycardia (NSVT). The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG [27 (21.3) vs 1 (2.5), P = 0.012] and 24-h ambulatory ECG [14 (1.0, 405) vs 1 (0, 6.5), P < 0.001]. Non-survivors had a higher PVC count than survivors [150.50 (7.25, 1690.50) vs 9 (0, 229.25), P = 0.020]. During the follow-up period, 24 patients died and 11 patients experienced MACEs. Univariate analysis linked PVC > 35/24 h to all-cause mortality, and NSVT was associated with MACE. However, neither PVC burden nor NSVT independently predicted outcomes according to multivariate analysis. CONCLUSION: Patients with gastrointestinal tumors exhibited elevated PVCs. PVCs > 35/24 h and NSVT detected by 24-h ambulatory ECG were prognostically significant but were not found to be independent predictors.

The smallest Schwarzite carbon with only heptagonal carbon rings.

Carbon materials with full sp2-hybridized buckling is a major challenge pervading fundamental nanoscience and nanotechnology research. Carbon atoms that are sp2 hybridized prefer to form hexagonal rings, such as in carbon nanotubes and graphene, which are low-dimensional materials. The incorporation of heptagonal, octagonal, and/or larger rings into a hexagonal sp2 carbon meshwork has been identified as a strategy for assembling three-dimensional (3D) sp2 carbon crystals, and one of the typical representatives are Schwarzite carbons, which possess a negative surface Gaussian curvature as well as unique physical properties. Herein, a 3D Schwarzite carbon consisting of only sp2-buckled heptagonal carbon rings, which is referred to as Hepta-carbon, is proposed based on first-principles calculations. Hepta-carbon is mechanically and thermodynamically stable, and energetically more favourable than experimental graphdiyne, fullerene C20 and most Schwarzite carbons under ambient conditions. Molecular dynamics simulations indicate that Hepta-carbon exhibits high-temperature thermostability up to 1500 K. Band structure and mechanical property simulations indicate that Hepta-carbon is a semi-metallic material with electron conduction and exhibits impressive mechanical properties such as high strength with quasi-isotropy, high incompressibility similar to diamonds, elastic deformation behaviour under uniaxial stress, and high ductility. Hepta-carbon presents a porous network with a low mass density of 1.84 g cm-3 and connected channels with diameters of 3.3-6.1 Å. Theoretical simulations of gas adsorption energy demonstrate that Hepta-carbon can effectively adsorb and stabilize greenhouse gases, including N2O, CO2, CH4, and SF6.

Association of Serum Uric Acid with Non-Valvular Atrial Fibrillation: A Retrospective Study in China.

Purpose: The association between serum uric acid (SUA) and atrial fibrillation (AF) has been widely focused on and studied in recent years. However, the exact association between SUA and AF is unclear, and the effect of gender on the association between SUA levels and AF has been controversial. This study aimed to investigate the association between SUA levels and non-valvular AF (NVAF) and the potential effect of gender on it. Patients and Methods: A total of 866 NVAF patients (463 males, age 69.44 ± 8.07 years) and 646 sex-matched control patients in sinus rhythm, with no history of arrhythmia were included in this study. t-test, ANOVA, and chi-square test were used for baseline data analysis. The receiver operating characteristic curve, logistic regression and Pearson correlation analysis were used for correlation analysis. Results: Compared to controls, NVAF patients exhibited higher SUA (P<0.001). After adjusting for confounders of NVAF, SUA remained significantly associated with NVAF, regardless of gender (OR= 1.31, 95% CI 1.18-1.43, P<0.001). SUA demonstrated higher predictability and sensitivity in predicting the occurrence of female NVAF compared to male (area under the curve was 0.68 (95% CI 0.64-0.72, P<0.001), sensitivity 87.3%), with the optimal cut-off point identified as 5.72 mg/dL. Furthermore, SUA levels correlated with APOA1, Scr and NT-proBNP in NVAF patients. SUA levels varied significantly among NVAF subtypes. Conclusion: High SUA levels were independently associated with NVAF, regardless of gender. SUA exhibited higher predictability and sensitivity in predicting the occurrence of NVAF in females compared to males. High SUA levels may affect other NVAF-related factors and participate in the pathophysiological process of NVAF.

Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models.

BACKGROUND: Acute pancreatitis (AP) encompasses a spectrum of pancreatic inflammatory conditions, ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure. Given the challenges associated with obtaining human pancreatic samples, research on AP predominantly relies on animal models. In this study, we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models. AIM: To investigate the shared molecular changes underlying the development of AP across varying severity levels. METHODS: AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide (LPS). Additionally, using Ptf1α to drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J- hM3/Ptf1α(cre) mice were administered Clozapine N-oxide to induce AP. Subsequently, we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus (GEO) database. RESULTS: Caerulein-induced AP showed severe inflammation and edema, which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis. Compared with the control group, RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway, TLR signaling pathway, and NF-κB signaling pathway, alongside elevated levels of apoptosis-related pathways, such as apoptosis, P53 pathway, and phagosome pathway. The significantly elevated genes in the TLR and NOD-like receptor signaling pathways, as well as in the apoptosis pathway, were validated through quantitative real-time PCR experiments in animal models. Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood, while TLR1, TLR7, RIPK3, and OAS2 genes exhibited marked elevation in human AP. The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP. The transgenic mouse model hM3/Ptf1α(cre) successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway, indicating that these pathways represent shared pathological processes in AP across different models. CONCLUSION: The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP, notably the MYD88 gene. Apoptosis holds a central position in the necrotic processes of AP, with TUBA1A and GADD45A genes exhibiting prominence in human AP.

Effect of oxygen-containing functional group contents on sorption of lead ions by acrylate-functionalized hydrochar.

The surface functional groups of hydrochar are crucial to its surface properties, and their contents are strongly positively correlated with the adsorption performance. In this study, acrylate-functionalized hydrochar (AHC) with varying contents of O-containing functional groups (OFGs) was synthesized via hydrothermal carbonization (HTC) of bamboo, acrylic acid and an initiator, and then deprotonated with NaOH. The AHCs were analyzed by various characterization techniques. During HTC, the higher amount of acrylic acid added led to higher carbon, oxygen and carboxyl contents, and to the larger specific surface area and pore volume of AHC. The adsorption kinetics, isotherms, thermodynamic, ionic strength and pH effects of Pb(II) on AHC were studied. Adsorption isotherms and kinetics obeyed Langmuir and pseudo-second-order models, respectively, indicating adsorption is monolayer chemical process. The adsorptive ability was well linearly related to the OFG contents of AHC. When acrylic acid was added to 25 mL during HTC, the adsorbing ability of AHC over Pb(II) reached 193.90 mg g-1. Hence, direct HTC of acrylic acid, biomass and an initiator can prepare hydrochar with controllable OFG contents, which is a prospective adsorbent for treating metal cations.

Interaction of motor practice and memory training in expressive piano performance: expanding the possibilities of improvisation.

This paper aimed to investigate the influence of motor practice and music performance experiences on musicians' auditory memory, the effect of auditory distinctiveness on melody recognition, and the differences in the working memory of classical and jazz pianists. The study was conducted among 26 jazz and 24 classical music students at Shenyang Conservatory of Music. To achieve the goal set, a melody recognition ability was analyzed after listening, performing without sound, and simultaneous listening and performing using computer recordings and pianist-taken notes. The study was conducted following repeated measures mixed design. The within-group variable was the learning condition. As the within-participant variable, the number of melody practicing trials was chosen. The type of influence on auditory memory was chosen as a between-group variable. The dependent variables were auditory recognition score, motor imagery ability, and auditory imagery ability. Students' recognition of the heard melodies was assessed by means of a 3-point Likert scale. Pearson's correlation coefficient was calculated to investigate the relationship between working memory and other student characteristics. The study outcomes unveiled that pianists are much better at recognizing tunes they generate themselves in auditory-motor practice than auditory practice alone. It was pointed out that the ability to recognize melody in auditory-motor learning is influenced by its acoustic characteristics. Hence, melodies that are slow in tempo and regular in time and intensity are easier to recognize than more variable pieces.

Environmental risks of breakdown nanoplastics from synthetic football fields.

The widespread use of synthetic turf in sports has raised health concerns due to potential risks from nanoplastic inhalation or ingestion. Our research focused on detecting nanoplastics in drainage water from a synthetic football field and evaluating the toxicity of these materials after mechanical fragmentation. We collected and analysed drainage water samples for polymer content and subjected high-density polyethylene (HDPE) straws and ethylene propylene diene monomer (EPDM) granules used on synthetic football fields, to mechanical breakdown to create nanoplastics. The results indicated the presence of trace amounts of EPDM in the water samples. Furthermore, the toxicological assessment revealed that the broken-down nanoplastics and leachate from the surface of EPDM rubber granules exhibited high toxicity to Daphnia magna, while nanoplastics from the inner material exhibited no significant toxicity. The findings highlight the urgent need for future research to identify these specific toxic agents from the surface of EPDM granules.

Addressing the long-standing limitations of double exponential and non-rectangular hyperbolic models in quantifying light-response of electron transport rates in different photosynthetic organisms under various conditions.

The models used to describe the light response of electron transport rate in photosynthesis play a crucial role in determining two key parameters i.e., the maximum electron transport rate (J max) and the saturation light intensity (I sat). However, not all models accurately fit J-I curves, and determine the values of J max and I sat. Here, three models, namely the double exponential (DE) model, the non-rectangular hyperbolic (NRH) model, and a mechanistic model developed by one of the coauthors (Z-P Ye) and his coworkers (referred to as the mechanistic model), were compared in terms of their ability to fit J-I curves and estimate J max and I sat. Here, we apply these three models to a series of previously collected Chl a fluorescence data from seven photosynthetic organisms, grown under different conditions. Our results show that the mechanistic model performed well in describing the J-I curves, regardless of whether photoinhibition/dynamic down-regulation of photosystem II (PSII) occurs. Moreover, both J max and I sat estimated by this model are in very good agreement with the measured data. On the contrary, although the DE model simulates quite well the J-I curve for the species studied, it significantly overestimates both the J max of Amaranthus hypochondriacus and the I sat of Microcystis aeruginosa grown under NH4 +-N supply. More importantly, the light intensity required to achieve the potential maximum of J (J s) estimated by this model exceeds the unexpected high value of 105 µmol photons m-2 s-1 for Triticum aestivum and A. hypochondriacus. The NRH model fails to characterize the J-I curves with dynamic down-regulation/photoinhibition for Abies alba, Oryza sativa and M. aeruginosa. In addition, this model also significantly overestimates the values of J max for T. aestivum at 21% O2 and A. hypochondriacus grown under normal condition, and significantly underestimates the values of J max for M. aeruginosa grown under NO3 -N supply. Our study provides evidence that the 'mechanistic model' is much more suitable than both the DE and NRH models in fitting the J-I curves and in estimating the photosynthetic parameters. This is a powerful tool for studying light harvesting properties and the dynamic down-regulation of PSII/photoinhibition.

Self-Feedback DNAzyme Motor for Cascade-Amplified Imaging of mRNA in Live Cells and In Vivo.

DNA motors have attracted extensive interest in biosensing and bioimaging. However, the amplification capacity of the existing DNA motor systems is limited since the products from the walking process are unable to feedback into the original DNA motor systems. As a result, the sensitivities of such systems are limited in the contexts of biosensing and bioimaging. In this study, we report a novel self-feedback DNAzyme motor for the sensitive imaging of tumor-related mRNA in live cells and in vivo with cascade signal amplification capacity. Gold nanoparticles (AuNPs) are modified with hairpin-locked DNAzyme walker and track strands formed by hybridizing Cy5-labeled DNA trigger-incorporated substrate strands with assistant strands. Hybridization of the target mRNA with the hairpin strands activates DNAzyme and promotes the autonomous walking of DNAzyme on AuNPs through DNAzyme-catalyzed substrate cleavage, resulting in the release of many Cy5-labeled substrate segments containing DNA triggers and the generation of an amplified fluorescence signal. Moreover, each released DNA trigger can also bind with the hairpin strand to activate and operate the original motor system, which induces further signal amplification via a feedback mechanism. This motor exhibits a 102-fold improvement in detection sensitivity over conventional DNAzyme motors and high selectivity for target mRNA. It has been successfully applied to distinguish cancer cells from normal cells and diagnose tumors in vivo based on mRNA imaging. The proposed DNAzyme motor provides a promising paradigm for the amplified detection and sensitive imaging of low-abundance biomolecules in vivo.

Assessing the usefulness of the Little Developmental Coordination Disorder Questionnaire-Chinese in Chinese preschoolers: a sex-and age-specific analysis.

Aim: This study evaluated the sex-and age-specific usefulness of the Little Developmental Coordination Disorder Questionnaire-Chinese (LDCDQ-CH) in Chinese preschoolers. Method: A population-based sample of 51,110 children aged 3-5 years was recruited. Internal reliability, construct validity, concurrent validity with the Ages and Stages Questionnaire-third edition (ASQ-3), and discriminant validity with the Movement Assessment Battery for Children-second edition (MABC-2) were assessed. Age and sex effects on LDCDQ-CH scores were analyzed using ANOVA and t-tests. Results: The LDCDQ-CH exhibited excellent internal consistency and reliability across ages and genders. Confirmatory factor analysis supported the 15-item model's satisfactory fit. Positive and significant correlations were observed between LDCDQ-CH and ASQ-3 scores, indicating robust concurrent validity. Significant associations were found between LDCDQ-CH and MABC-2 scores. Higher scores were observed in older children and girls, indicating age- and sex-related differences in motor functional performance. Conclusion: The LDCDQ-CH is a reliable and valid tool to support early identification of motor coordination difficulty in Chinese preschoolers, and guiding interventions. Findings support its use across ages and genders, highlighting its potential in the Chinese context. Age- and sex-specific norms are needed for enhanced clinical applicability.

Immunosuppression induces regression of fibrosis in primary biliary cholangitis with moderate-to-severe interface hepatitis.

BACKGROUND: In patients with primary biliary cholangitis (PBC) treated with ursodeoxycholic acid (UDCA), the presence of moderate-to-severe interface hepatitis is associated with a higher risk of liver transplantation and death. This highlights the need for novel treatment approaches. In this study, we aimed to investigate whether combination therapy of UDCA and immunosuppressant (IS) was more effective than UDCA monotherapy. METHODS: We conducted a multicenter study involving PBC patients with moderate-to-severe interface hepatitis who underwent paired liver biopsies. Firstly, we compared the efficacy of the combination therapy with UDCA monotherapy on improving biochemistry, histology, survival rates, and prognosis. Subsequently we investigated the predictors of a beneficial response. RESULTS: This retrospective cohort study with prospectively collected data was conducted in China from January 2009 to April 2023. Of the 198 enrolled patients, 32 underwent UDCA monotherapy, while 166 received combination therapy, consisting of UDCA combined with prednisolone, prednisolone plus mycophenolate mofetil (MMF), or prednisolone plus azathioprine (AZA). The monotherapy group was treated for a median duration of 37.6 months (IQR 27.5-58.1), and the combination therapy group had a median treatment duration of 39.3 months (IQR 34.5-48.8). The combination therapy showed a significantly greater efficacy in reducing fibrosis compared to UDCA monotherapy, with an 8.3-fold increase in the regression rate (from 6.3% to 52.4%, P < 0.001). Other parameters, including biochemistry, survival rates, and prognosis, supported its effectiveness. Baseline IgG >1.3 × ULN and ALP <2.4 × ULN were identified as predictors of regression following the combination therapy. A predictive score named FRS, combining these variables, accurately identified individuals achieving fibrosis regression with a cut-off point of ≥ -0.163. The predictive value was validated internally and externally. CONCLUSION: Combination therapy with IS improves outcomes in PBC patients with moderate-to-severe interface hepatitis compared to UDCA monotherapy. Baseline IgG and ALP are the most significant predictors of fibrosis regression. The new predictive score, FRS, incorporating baseline IgG and ALP, can effectively identify individuals who would benefit from the combination therapy.

Endothelial downregulation of nuclear m6A reader YTHDC1 promotes pulmonary vascular remodeling in sugen hypoxia model of pulmonary hypertension.

Background: Pulmonary hypertension (PH) is characterized with vascular remodeling, which is intiated by vascular endothelial dysfunction. N6-methyladenosine (m6A) modification mediates gene expression in many ways including mediating RNA degradation, splicing, nuclear export et al. m6A modification have been found to be associated with the development of PH. However, the role of m6A regulators in pulmonary artery endothelial cells (PAECs) dysfunction of PH is still under research. Methods: The expression levels of m6A regulators in PAECs were analyzed with the single-cell sequencing Data(scRNA). Next, the target differentially expressed genes (DEGs) of m6A regulators in PAECs were functionally annotated. The analysis of cellular interactions included the examination of receptor-ligand pairs regulated by m6A regulators. Pseudo-time trajectory analyses and a ceRNA network involving lncRNAs, miRNAs, and mRNAs were conducted in PAECs. Furthermore, microarray data (GSE180169) for Sugen Hypoxia PH (SuHx PH) mouse models was screened for DEGs and m6A regulators in PAECs. Moreover, the expression of YTHDC1 in the lung samples of SuHx PH models was determined using immunofluorescence. In vitro, the mRNA expression of YTHDC1 in HPAECs under hypoxia conditions was detected. The effect of YTHDC1 recombinant protein on HPAEC proliferation was detected by Cell Counting Kit-8 (CCK8). Results: Dysregulation of m6A regulators was observed in mouse PAECs. The m6A reader of YTHDC1 was decreased in PAECs in scRNA data and RNAseq data of isolated PAECs of SuHx PH models. Downregulation of YTHDC1 was caused by hypoxia in PAECs in vitro and similar results was observed in PAECs of SuHx PH mouse models. Next, YTHDC1 recombinant protein was found to inhibit HPAECs proliferation. The DEGs targeted by YTHDC1 were enriched in angiogenesis, endothelial cell migration, fluid shear stress, and stem cell maintenance. Analysis indicates that interactions among endothelial cells, smooth muscle cells, fibroblasts, and immune cells, mediated by specific YTHDC1 target genes (e.g., PTPRC-MRC1, ITBG2-ICAM1, COL4A1-CD44), contribute to PH development. Also, the YTHDC1 expression were consistent with Thioredoxin interacting protein (TXNIP). What's more, the predicted transcription factors showed that NFKB1, Foxd3 may be involved in the regulation of YTHDC1. Lastly, our data suggest that YTHDC1 may be involved in regulating PAECs dysfunction through lncRNA/miRNA/mRNA network. Conclusion: For the first time, we analyzed changes in the expression and biological functions of m6A regulators in SuHx PH mouse models. We causatively linked YTHDC1 to PAECs dysfunction, providing novel insight into and opportunities to diagnose and treat PH.

Digital PCR-based GRHL2 methylation testing in acute myeloid leukemia: diagnosis, prognosis and monitoring.

Background: Acute myeloid leukemia (AML) is a challenging disease with high rates of recurrence. The role of the cancer-related gene GRHL2 in AML has not been widely studied. Methods: Peripheral blood samples were collected from 73 AML patients and 68 healthy controls. Droplet digital PCR was used to detect GRHL2 methylation levels to explore the value of GRHL2 methylation in the diagnosis, treatment response and prognosis of AML. Result: GRHL2 methylation was significantly increased in AML patients (p < 0.01), with high diagnostic accuracy (area under the curve: 0.848; p < 0.001). GRHL2 methylation was correlated with chemotherapy response (p < 0.05) and is an independent prognostic factor for AML (p < 0.05). Conclusion: GRHL2 methylation is expected to serve as a biomarker for diagnosing AML patients and predicting prognosis.

Visualization diagnosis of acute cerebral ischemia via sulfane sulfur-activated photoacoustic imaging.

A photoacoustic (PA) imaging probe, HCy-SH, was designed and synthesized. This probe can react rapidly and specifically with sulfane sulfur to produce a strong PA signal. This probe also exhibited low cytotoxicity and biotoxicity. Thus, HCy-SH has been used for visual diagnosis of acute cerebral ischemia.

Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Invasion mechanism of Spartina alterniflora by regulating soil sulfur and iron cycling and microbial composition in the Jiuduansha Wetland.

Spartina alterniflora, an invasive plant widely distributed in China's coastal regions, has had a significant impact on the stability of wetland ecosystems and elemental biogeochemical cycles. The invasion of S. alterniflora has been found to lead to the accumulation of sulfides in the soil. The cycling of sulfur and iron in the soil is closely interconnected. Coastal estuarine wetlands are influenced by both freshwater in rivers and seawater tides, as well as the frequent variations in redox conditions caused by tidal fluctuations, which makes the cycling of sulfur and iron in the soil invaded by S. alterniflora more intricate. In this study, field surveys and laboratory experiments were conducted to explore the effects of S. alterniflora invasion and hydrological changes on the cycling of sulfur and iron as well as related functional microorganisms in the soil. The invasion of S. alterniflora showed an increase in soil reduced inorganic sulfur (RIS) components in both high and low marshes of Jiuduansha wetland, with higher content observed in summer and autumn. The tidal simulation experiments revealed abundant sulfate in seawater tidal conditions could promote the formation of acid volatile sulfides (AVS) in the soil of low marshes invaded by S. alterniflora and ensuring the continuous increase in AVS content. Diffusive gradients in-thin-films (DGT) technology indicated the existence of high-concentration soluble S2- enrichment zones in the soil of low marshes invaded by S. alterniflora, which may be related to S. alterniflora root exudates. Tidal action increased the relative abundance of sulfur-reducing bacteria (SRB) in the soil of low marshes, and under the influence of seawater tidal action, SRB exhibited higher relative abundance. However, S. alterniflora might inhibit the activity of iron-reducing bacteria (FeRB) in the soil of low marshes. In conclusion, S. alterniflora may enhance the sulfate reduction rate and promote the formation of free sulfides in tidal salt marsh ecosystems by releasing root exudates that stimulate the activity of SRB, while concurrently inhibiting the activity of FeRB and reducing their competition with SRB. This effect is particularly pronounced in low marshes under seawater tidal conditions. Thus, S. alterniflora is capable of rapidly invading tidal salt marshes by utilizing sulfides effectively.

Clinical Subtypes of Neutrophilic Asthma: A Cluster Analysis From Australasian Severe Asthma Network.

BACKGROUND: Clinical heterogeneity may exist within asthma subtypes defined by inflammatory markers. However, the heterogeneity of neutrophilic asthma (NA) remains largely unexplored. OBJECTIVE: To explore potential clusters and the stability of NA. METHODS: Participants with NA from the Australasian Severe Asthma Network underwent a multidimensional assessment. They were then asked to participate in a 12-month longitudinal cohort study. We explored potential clusters using a hierarchical cluster analysis and validated the differential future risk of asthma exacerbations in the identified clusters. A decision tree analysis was developed to predict cluster assignments. Finally, the stability of prespecified clusters was examined within 1 month. RESULTS: Three clusters were identified in 149 patients with NA. Cluster 1 (n = 99; 66.4%) was characterized by female-predominant nonsmokers with well-controlled NA, cluster 2 (n = 16; 10.7%) by individuals with comorbid anxiety/depressive symptoms with poorly controlled NA, and cluster 3 by older male smokers with late-onset NA. Cluster 2 had a greater proportion of participants with severe exacerbations (P = .005), hospitalization (P = .010), and unscheduled visits (P = .013) and a higher number of emergency room visits (P = .039) than that of the other two clusters. The decision tree assigned 92.6% of participants correctly. Most participants (87.5%; n = 7) in cluster 2 had a stable NA phenotype, whereas participants of clusters 1 and 3 had variable phenotypes. CONCLUSIONS: We identified three clinical clusters of NA, in which cluster 2 represents an uncontrolled and stable NA subtype with an elevated risk of exacerbations. These findings have clinical implications for the management of NA.

Effect of triggering receptor expressed on myeloid cells 2-associated alterations on lipid metabolism in macrophages in the development of non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Triggering receptor expressed on myeloid cells 2 (TREM2) plays crucial roles in metabolic homeostasis and inflammatory response. Altered metabolic function in macrophages could modulate their activation and immune phenotype. The present study aimed to investigate the expression of TREM2 in non-alcoholic fatty liver disease (NAFLD) and to clarify the underlying mechanism of TREM2 on macrophages lipid metabolism and oxidative stress. METHODS: Hepatic TREM2 expression and its relationship with NAFLD progression were analyzed in patients with NAFLD and mice fed a high-fat diet. Lipid metabolism and oxidative stress were investigated in macrophages from NAFLD mice or stimulated with saturated fatty acids. Knockdown and overexpression of TREM2 were further explored. RESULTS: Triggering receptor expressed on myeloid cells 2+ macrophages were increased along with NAFLD development, characterized by aggravated steatosis and liver damage in humans and mice. TREM2 expression was upregulated and lipid metabolism was changed in macrophages from NAFLD mice or metabolically activated by saturated fatty acid in vitro, as demonstrated by increased lipid uptake and catabolism, but reduced de novo synthesis of fatty acids (FAs). Regulation of TREM2 expression in lipid-laden macrophages reprogrammed lipid metabolism, especially the fatty acid oxidation capacity of mitochondria. TREM2 knockdown promoted oxidative stress by aggravating FAs deposition in mitochondria. Intervention of mitochondrial FAs transport in lipid-laden macrophages alleviated FA deposition and reactive oxygen species production induced by TREM2 knockdown. CONCLUSIONS: Triggering receptor expressed on myeloid cells 2 expression was associated with the lipid metabolic profile and reactive oxygen species production in macrophages. High expression of TREM2 in macrophages may protect the liver from oxidative stress in NAFLD.