Temporospatial hierarchy and allele-specific expression of zygotic genome activation revealed by distant interspecific urochordate hybrids.

Zygotic genome activation (ZGA) is a universal process in early embryogenesis of metazoan, when the quiescent zygotic nucleus initiates global transcription. However, the mechanisms related to massive genome activation and allele-specific expression (ASE) remain not well understood. Here, we develop hybrids from two deeply diverged (120 Mya) ascidian species to symmetrically document the dynamics of ZGA. We identify two coordinated ZGA waves represent early developmental and housekeeping gene reactivation, respectively. Single-cell RNA sequencing reveals that the major expression wave exhibits spatial heterogeneity and significantly correlates with cell fate. Moreover, allele-specific expression occurs in a species- rather than parent-related manner, demonstrating the divergence of cis-regulatory elements between the two species. These findings provide insights into ZGA in chordates.

Clinical Analysis of Lacosamide Monotherapy in the Treatment of Self-Limited Epilepsy with Centrotemporal Spikes.

Objective: To evaluate the efficacy and safety of lacosamide (LCM) monotherapy in the treatment of self-limited epilepsy with centrotemporal spikes (SeLECTS). Methods: In this study, 89 children with SeLECTS who were treated with LCM monotherapy in the Children's Hospital Affiliated to Soochow University from June 2019 to June 2021 were included. Clinical seizures and spike wave index (SWI) on video EEG during slow-wave sleep were evaluated before and after treatment. The role of LCM monotherapy in improving SWI, controlling clinical seizures and improving cognition was analyzed, and corresponding adverse reactions were documented. Results: There were 52 males and 37 females in this group, with an average age of 7.6 ± 2.1 years. The total effective rate was 93.83% and at 18 months of treatment, the cumulative control rate was 85.19%, the retention rate was 91.01% and the effective rate in terms of EEG spike index was 72.92%, all of which showed a high rate; there was no statistically significant difference in intelligence quotient before and after treatment (P > 0.05). In addition, it was found in the study that the earlier the age of onset, the less obvious the improvement in SWI after LCM treatment; the lower the baseline seizure frequency, the more significant the improvement in SWI after LCM treatment. Conclusion: LCM monotherapy had curative effect and adverse reactions for SeLECTS, with no negative impact on cognition. These significant findings indicate that LCM is likely to become a widely prescribed ASM for the treatment of SeLECTS. Meanwhile, the onset age and baseline seizure frequency had certain value in judging prognosis and predicting curative effect.

Characteristics of whole-body dynamic 18F-FDG PET/CT Patlak multi-parametric imaging in lung cancer and the influence of different delineation methods on quantitative parameters.

Background: Dynamic course of flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) Patlak muti-parametric imaging spatial distribution in the targeted tissues may reveal highly useful clinical information about the tissue's metabolic properties. The characteristics of the Patlak multi-parametric imaging in lung cancer and the influence of different delineation methods on quantitative parameters may provide reference for the clinical application of this new technology. Methods: A total of 27 patients with pathologically diagnosed lung cancer underwent whole-body dynamic 18F-FDG PET/CT examination before treatment. Parametric images of metabolic rate of FDG (MRFDG) and Patlak intercept (or distribution volume; DV) were generated using Patlak reconstruction. The values of primary lung cancer lesions, target-to-background ratio (TBR), and contrast-to-noise ratio (CNR) were investigated using contour delineation and boundary delineation. Statistical analysis was performed to analyze the relationship between multi-parametric images and clinicopathological features, and to compare the effects of contour delineation and boundary delineation on quantitative parameters. Results: MRFDG images showed higher TBR and CNR than did standardized uptake value (SUV) images. There were significant differences in MRFDG-max, MRFDG-mean, and MRFDG-peak among groups with different tumor diameters and pathology types (P<0.05). Moreover, the metabolic parameters of MRFDG were higher in patients with tumor diameters ≥3 cm and squamous carcinoma. The differences of the maximum and peak values of MRFDG and DV were not statistically significant in the different outlining method subgroups (all P>0.05). However, the difference of the mean values of MRFDG and DV were statistically significant in the different outline method groupings (all P<0.05). Conclusions: Dynamic 18F-FDG PET/CT Patlak multi-parametric imaging can obtain quantitative values for lung cancer with high TBR and CNR. Moreover, the multi-parameters are various from different pathology types to tumor size. Different delineation methods have a greater influence on the mean value of quantitative parameters.

Metabolic dysfunction-associated fatty liver disease in the elderly with diabetic foot ulcers: A longitudinal cohort study.

This study aimed to explore the association between metabolic-associated fatty liver disease (MAFLD) and ulcer recurrence risk in patients with diabetic foot ulcers (DFUs) through an ambispective longitudinal cohort. From December 2013 to December 2022, a total of 482 inpatients with DFUs (PEDIS grade 3 and above with a severe infection) were eligible for inclusion in this study. This was an ambispective longitudinal cohort study. All participants were followed up every 6 months for 9 years with a median of 36 months. According to whether having MAFLD or not, all subjects were placed into two groups: non-MAFLD (n = 351) and MAFLD (n = 131). The association between MAFLD and ulcer recurrence in patients with DFUs was then evaluated through multivariate Cox regression analysis, stratified analyses and Kaplan-Meier survival analysis. Throughout the follow-up period, out of 482 subjects with DFUs, 68 had ulcer recurrence (14.1%). Three Cox regression models were established for data analyses. In the model I (unadjusted), MAFLD was significantly associated with the ulcer recurrence rate in patients with DFUs (HR = 1.79; 95% CI = 1.097-2.92; p = 0.02). Model II (adjusted model I with gender and age) (HR = 1.781; 95% CI = 1.09-2.912; p = 0.021) and model III (adjusted model II with CVD, duration of diabetes and Cr.) (HR = 1.743; 95% CI = 1.065-2.855; p = 0.027) also showed that MAFLD was significantly related to the ulcer recurrence risk in patients with DFUs, respectively. Stratified analysis indicated that subjects aged ≥60 had a greater risk of ulcer recurrence in MAFLD than in non-MAFLD (HR = 2.31; 95% CI = 1.268-4.206; p = 0.006). Kaplan-Meier survival curve analysis showed that ulcer recurrence rate had a significant association with MAFLD (log-rank, p = 0.018). This study indicated a close association between ulcer recurrence risk and MAFLD in patients with DFUs, especially in the elderly (aged ≥60). Therefore, special attention should be paid to the elderly with both DFUs and MAFLD because they have a higher ulcer recurrence rate than other general populations in routine clinical practice.

Flowering time regulator qFT13-3 involved in soybean adaptation to high latitudes.

Soybean is a short-day plant that typically flowers earlier when exposed to short-day conditions. However, the identification of genes associated with earlier flowering time but without a yield penalty is rare. In this study, we conducted genome-wide association studies (GWAS) using two re-sequencing datasets that included 113 wild soybeans (G. soja) and 1192 cultivated soybeans (G. max), respectively, and simultaneously identified a candidate flowering gene, qFT13-3, which encodes a protein homologous to the pseudo-response regulator (PRR) transcription factor. We identified four major haplotypes of qFT13-3 in the natural population, with haplotype H4 (qFT13-3H4 ) being lost during domestication, while qFT13-3H1 underwent natural and artificial selection, increasing in proportion from 4.5% in G. soja to 43.8% in landrace and to 81.9% in improve cultivars. Notably, most cultivars harbouring qFT13-3H1 were located in high-latitude regions. Knockout of qFT13-3 accelerated flowering and maturity time under long-day conditions, indicating that qFT13-3 functions as a flowering inhibitor. Our results also showed that qFT13-3 directly downregulates the expression of GmELF3b-2 which is a component of the circadian clock evening complex. Field trials revealed that the qft13-3 mutants shorten the maturity period by 11 days without a concomitant penalty on yield. Collectively, qFT13-3 can be utilized for the breeding of high-yield cultivars with a short maturity time suitable for high latitudes.

The transcription factor HBF1 directly activates expression of multiple flowering time repressors to delay rice flowering.

Flowering time (or heading date) is an important agronomic trait that determines the environmental adaptability and yield of many crops, including rice (Oryza sativa L.). Hd3a BINDING REPRESSOR FACTOR 1 (HBF1), a basic leucine zipper transcription factor, delays flowering by decreasing the expression of Early heading date 1 (Ehd1), Heading date 3a (Hd3a), and RICE FLOWERING LOCUS T 1 (RFT1), but the underlying molecular mechanisms have not been fully elucidated. Here, we employed the hybrid transcriptional factor (HTF) strategy to enhance the transcriptional activity of HBF1 by fusing it to four copies of the activation domain from Herpes simplex virus VP16. We discovered that transgenic rice lines overexpressing HBF1-VP64 (HBF1V) show significant delays in time to flower, compared to lines overexpressing HBF1-MYC or wild-type plants, via the Ehd1-Hd3a/RFT1 pathway, under both long-day and short-day conditions. Transcriptome deep sequencing analysis indicated that 19 WRKY family genes are upregulated in the HBF1V overexpression line. We demonstrate that the previously unknown gene, OsWRKY64, is a direct downstream target of HBF1 and represses flowering in rice, whereas three known flowering repressor genes, Days to heading 7 (DTH7), CONSTANS 3 (OsCO3), and OsWRKY104, are also direct target genes of HBF1 in flowering regulation. Taking these results together, we propose detailed molecular mechanisms by which HBF1 regulates the time to flower in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00107-7.

Particle-Polymer Union with Changeable Wettability for Constructing Bijels Using a Simple Mixing Method.

Bicontinuous emulsion gels (bijels) are nonequilibrium dispersed systems with particle-stabilized continuous fluid domains, and the internal connectivity of channels brings the possibility of efficient mass transport, endowing bijels great potential in diverse applications. Different from the common method to produce bijels, the spinodal decomposition, which needs precise temperature control and is restricted by the selection of liquid pairs, in this work, a direct mixing method was performed to construct bijels, simplifying the fabrication process. The hydrophilic rod-shaped cellulose nanocrystalline (CNC) particles were in situ combined with the hydrophobic polymer, aminopropyl-terminated polydimethylsiloxane (PDMS-NH2), to acquire a controllable interfacial wettability of CNC. The CNC@mPDMS-NH2 complexes were adsorbed at the water-toluene interface and achieved a change of Pickering emulsion types, oil-in-water, bijel, and water-in-oil, through tuning the interfacial performance of CNC@mPDMS-NH2 complexes. A three-dimensional scanning image and curvature calculation were applied to verify the obtained bijel, further demonstrating the successful preparation of the bicontinuous structure. This work enriched the members of particles for stabilizing bijels and was considered to be scalable in manufacturing for applications on a large scale.

Polymerizable bijels prepared by a direct-mixing method.

A simple direct-mixing method was proposed to use a union of silica particles and amino-capped silicone oil (diNH2-PDMS) as stabilizers to form bicontinuous emulsion gels (bijels) in wide mixing proportions of silica particle/diNH2-PDMS and oil/water with a tunable channel size of the spatial continuity, which was verified by the three-dimensional reconstruction viewer and curvature analysis. By direct polymerization of the oil phase as a template, solid materials were obtained with interconnected structures.

Impact of transcranial direct current stimulation combined with motor-cognitive intervention on post-stroke cognitive impairment.

OBJECTIVE: In this study, it was explored whether the efficacy on applying transcranial direct current stimulation (tDCS) combined with motor-cognitive intervention for post-stroke cognitive impairment (PSCI) was greater than that on applying each method alone. METHODS: A total of 90 patients with PSCI admitted to Zhejiang Provincial People's Hospital, China, from April 2021 to June 2022 were randomly divided into a tDCS group (n = 30), a motor-cognitive intervention group (n = 30), and a combination group (n = 30). All three groups received conventional rehabilitation therapy. The tDCS group was given tDCS therapy. The motor-cognitive intervention group received motor-cognitive intervention, whereas the combination group received tDCS combined with motor-cognitive intervention. The treatment duration was 4 weeks. The general data of patients were recorded before treatment. The Montreal Cognitive Assessment (MoCA) Scale and the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) Scale were used to evaluate the cognitive function of patients in three groups before and after treatment. Further, within- and between-groups comparisons were performed to determine differences in cognitive function. RESULTS: Before treatment, there was no significant difference between the baseline scores of the three groups (P > 0.05). After 4 weeks of treatment, except for the score for the LOTCA motor praxis subtest of the tDCS group, the MoCA and LOTCA scores of the three groups significantly improved compared with the corresponding scores before treatment (P < 0.05), and there was no drop-out case. After treatment, the MoCA and LOTCA scores of the three groups were compared in pairs. The results showed that except for the attention domain in MoCA, the method used for the combination group had more efficacy than those used for the other two groups (P < 0.05). Further, there was no statistical difference in efficacy between the tDCS and the motor-cognitive intervention groups (P > 0.05). CONCLUSION: The combination of tDCS and motor-cognitive intervention is safe and can help improve the cognitive function of patients with PSCI.

Predictive models for sepsis in children with Staphylococcus aureus bloodstream infections: a retrospective cohort study.

BACKGROUND: The presence of Staphylococcus aureus in the bloodstream can lead to the development of sepsis; however, the severity and risk factors of the systemic inflammatory response to Staphylococcus aureus bloodstream infections were unclear. This study is aimed to build a model to predict the risk of sepsis in children with Staphylococcus aureus bloodstream infections. METHODS: A retrospective analysis of hospitalized pediatric patients diagnosed with Staphylococcus aureus bloodstream infections was performed between January 2013 and December 2019. Each patient was assessed using the pediatric version of the Sequential Organ Failure Assessment score (pSOFA) within 24 h of blood culture collection. A nomogram based on logistic regression models was constructed to predict the risk factors for sepsis in children with Staphylococcus aureus bloodstream infections. It was validated using the area under the receiver-operating characteristic curve (AUC). RESULTS: Of the 94 patients included in the study, 35 cases (37.2%) developed sepsis. The pSOFA scores ranged from 0 to 8, with 35 patients having a pSOFA score of ≥ 2. Six children (6.4%) died within 30 days, who were all from the sepsis group and had different pSOFA scores. The most common organs involved in sepsis in children with staphylococcal bloodstream infections were the neurologic system (68.6%), respiratory system (48.6%), and coagulation system (45.7%). Hospital-acquired infections (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.3-7.2), implanted catheters (aOR, 10.4; 95% CI, 3.8-28.4), procalcitonin level ≥ 1.7 ng/mL (aOR, 15.4; 95% CI, 2.7-87.1), and underlying diseases, especially gastrointestinal malformations (aOR, 14.0; 95% CI, 2.9-66.7) were associated with Staphylococcus aureus sepsis. However, methicillin-resistant Staphylococcus aureus infection was not a risk factor for sepsis. The nomogram had high predictive accuracy for the estimation of sepsis risk, with an AUC of 0.85. CONCLUSIONS: We developed a predictive model for sepsis in children with Staphylococcus aureus infection.

Voice-Related Outcomes in Deep Brain Stimulation in Patients with Vocal Tremor: A Systematic Review and Meta-Analysis.

OBJECTIVES: The effectiveness of deep brain stimulation (DBS) in treating vocal tremors is currently a subject of debate. To assess the efficacy of DBS therapy in adults with vocal tremors (VT), we analyzed its impact on voice tremor severity, voice-related quality of life, fundamental frequency, voice intensity, and emotional state. METHODS: We conducted a systematic review with meta-analysis to investigate the impact of DBS therapy on voice tremor severity, voice-related quality of life, fundamental frequency, voice intensity, and emotional state in adults with vocal tremors (PROSPERO/CRD42023420272). The PubMed, Embase, Cochrane Library, Cochrane Central Register of Controlled Trials databases were searched up to September 20, 2022. Primary outcome measures included voice tremor severity and voice-related quality of life (V-RQOL), while fundamental frequency (F0) and voice intensity, along with emotional state, were selected as secondary outcome indicators. We employed the Cochrane Collaboration's tool for assessing bias risk in randomized trials. Meta-analysis (standardized difference of means and weighted mean differences) and heterogeneity analysis (I2) were performed. RESULTS: Our search identified 1186 studies, of which nine studies involving 61 patients met the inclusion criteria. The severity of voice tremor (SMD = -1.08; 95% CI: -1.80 to 0.35; P = 0.02) and V-RQOL (SMD = -1.39; 95% CI: -2.68 to -0.09; P = 0.04) in patients with vocal tremor significantly improved after DBS "on". Subgroup analyses revealed that the stimulation site may contribute to high heterogeneity. Specifically, Vim DBS showed significant improvement in voice tremor severity (SMD = -0.97; 95% CI: -1.84 to -0.09; I2 = 51.01%), while STN DBS did not demonstrate a clear benefit in addressing vocal tremor. There was no significant difference between DBS "on" and DBS "off" in terms of F0, voice intensity, or emotional status. CONCLUSION: DBS therapy is effective in enhancing voice quality and voice-related quality of life in patients with vocal tremors. Notably, Vim DBS demonstrates a significant improvement in voice tremor severity, particularly in VT patients with ET and SD.

Surface Subsidence Monitoring of Mining Areas in Hunan Province Based on Sentinel-1A and DS-InSAR.

Monitoring the surface subsidence in mining areas is conducive to the prevention and control of geological disasters, and the prediction and early warning of accidents. Hunan Province is located in South China. The mineral resource reserves are abundant; however, large and medium-sized mines account for a low proportion of the total, and the concentration of mineral resource distribution is low, meaning that traditional mining monitoring struggles to meet the needs of large-scale monitoring of mining areas in the province. The advantages of Interferometric Synthetic Aperture Radar (InSAR) technology in large-scale deformation monitoring were applied to identify and monitor the surface subsidence of coal mining fields in Hunan Province based on a Sentinel-1A dataset of 86 images taken from 2018 to 2020, and the process of developing surface subsidence was inverted by selecting typical mining areas. The results show that there are 14 places of surface subsidence in the study area, and accidents have occurred in 2 mining areas. In addition, the railway passing through the mining area of Zhouyuan Mountain is affected by the surface subsidence, presenting a potential safety hazard.

Energy-Efficient Opportunistic Routing Algorithm for Post-Disaster Mine Internet of Things Networks.

The Mine Internet of Things (MIoT), as a key technology for reconstructing post-disaster communication networks, enables a user to monitor and control the safety of an affected roadway. However, due to the challenging underground mine environment, the MIoT suffers from severe signal attenuation, vulnerable nodes, and limited energy, which result in a low level of network reliability for the post-disaster MIoT. To improve transmission reliability and reduce energy consumption, a directional-area-forwarding-based energy-efficient opportunistic routing (DEOR) approach for the post-disaster MIoT is proposed. DEOR defines a forwarding zone (FZ) for each node to route packets toward the sink. The candidate forwarding set (CFS) is constructed by the nodes within the FZ that satisfy the energy constraint and the neighboring node degree constraint. The nodes in the CFS are prioritized based on a routing quality evaluation, which takes the local attributes of the nodes, such as the directional angle, transmission distance, and residual energy, into consideration. DEOR adopts a recovery mechanism to address the issue of void nodes. The simulation results verify that the proposed DEOR approach outperforms the ORR, OBRN and ECSOR methods in terms of energy consumption, average hop count, packet delivery rate, and network lifetime.

Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.

Inhalable mixture of polycyclic aromatic hydrocarbons and metals, DNA oxidative stress and nasal ribosomal DNA copy number amplification: Direct and indirect effect analyses among population.

The ribosomal DNA (rDNA) plays a crucial role in maintaining genome stability. So far, alterations of rDNA from airborne pollutants exposure remain unclear. Nasal epithelial cells are the earliest respiratory barrier, which has an accessible surrogate for evaluating respiratory impairment. We developed a mixture-centered biomarkers study integrated epidemiological and biological evidence among 768 subjects, a mixture of polycyclic aromatic hydrocarbons (PAHs) and metals. We identified the mixed exposure of PAHs and metals by environmental and biological monitoring, selected urinary 8-hydroxy-2'-deoxyguanosine as DNA oxidative stress marker, and measured their rDNA copy number (rDNA CN) in nasal epithelial cells. We performed linear regression, adaptive elastic net regression, BKMR, and mediation analyses to assess the direct and indirect effects. We found a 10% elevation in urinary 1-hydroxypyrene was correlated with a separate 0.31% and 0.82% amplification of nasal 5S and 45S rDNA CN, respectively (all P < 0.05). A 10% increment of urine nickel was associated with a separate 0.37% and 1.18% elevation of nasal 5S and 45S rDNA CN, respectively (all P < 0.05). BKMR results also confirmed our findings of PAHs and nickel. Our findings suggested that DNA oxidative stress might trigger rDNA instability induced by inhaled PAHs and metals.

MicroRNA-376b is involved in the pathogenesis of thyroid-associated ophthalmopathy by regulating HAS2.

PURPOSE: The aim of this study was to investigate the microRNA (miRNA) expression profile in peripheral blood mononuclear cells (PBMC) of thyroid-associated ophthalmopathy (TAO) patients and to explore the molecular mechanisms of MicroRNA-376b (miR-376b) in the pathogenesis of TAO. METHODS: PBMCs from TAO patients and healthy controls were analyzed by miRNA microarray to screen for the significantly differentially expressed miRNAs. The miR-376b expression in PBMCs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). The downstream target of miR-376b was screened by online bioinformatics, and detected by qRT-PCR and Western blotting. RESULTS: Compared with normal controls, 26 miRNAs were significantly different in PBMCs of TAO patients (14 miRNAs were down-regulated and 12 miRNAs were up-regulated). Among them, miR-376b expression was significantly decreased in PBMCs from TAO patients compared to healthy controls. Spearman correlation analysis revealed that miR-376b expression in PBMCs was significantly negatively correlated with free triiodothyronine (FT3), and positively correlated with thyroid-stimulating hormone (TSH). MiR-376b expression was obviously reduced in 6T-CEM cells after triiodothyronine (T3) stimulation compared to controls. MiR-376b mimics significantly decreased hyaluronan synthase 2 (HAS2) protein expression and the mRNA expression of intercellular cell adhesion molecule-1 (ICAM1) and tumor necrosis factor-α (TNF-α) in 6T-CEM cells, whereas miR-376b inhibitors markedly elevated HAS2 protein expression and gene expression of ICAM1 and TNF-α. CONCLUSIONS: MiR-376b expression in PBMCs was significantly decreased in PBMCs from TAO patients compared with the healthy controls. MiR-376b, regulated by T3, could modulate the expression of HAS2 and inflammatory factors. We speculate that miR-376b may be involved in the pathogenesis of TAO patients by regulating the expression of HAS2 and inflammatory factors.

Carnitine-acylcarnitine translocase deficiency caused by SLC25A20 gene heterozygous variants in twins: a case report.

The current case report describes the clinical, biochemical and genetic characteristics of carnitine-acylcarnitine translocase deficiency (CACTD) in infant male and female twins that presented with symptoms shortly after elective caesarean delivery. The clinical manifestations were neonatal hypoglycaemia, arrhythmia and sudden death. The age of onset was 1.5 days and the age of the death was 1.5-3.5 days. Dried blood filter paper analysis was used for the detection of acylcarnitine. Peripheral venous blood and skin samples were used for next-generation sequencing. The twins and their parents underwent gene analysis and whole exome sequencing analyses of the solute carrier family 25 member 20 (SLC25A20; also known as carnitine-acylcarnitine translocase) gene. Both infants carried compound heterozygous variants of the SLC25A20 gene: variant M1:c.706_707insT:p.R236L fs*12 and variant M2:c.689C>G:p.P230R. The M1 variant was paternal and had not been previously reported regarding CACTD. The M2 variant was maternal. CACTD has severe clinical manifestations and a poor prognosis, which is manifested as hypoketotic hypoglycaemia, hyperammonaemia, liver function damage and elevated creatine kinase.

N6-methyladenosine mRNA methylation is important for the light response in soybean.

N6-methyladenosine (m6A) modification of messenger RNA (mRNA) is the most prevalent and abundant modification in eukaryotic mRNA and posttranscriptionally modulates the transcriptome at almost all stages of mRNA metabolism. In plants, m6A is crucial for embryonic-phase growth, flowering time control, microspore generation and fruit maturation. However, the role of m6A in plant responses to light, the most important environmental stimulus, remains unexplored. Here, we profile the m6A transcriptome of Williams 82, a soybean cultivar, and reveal that m6A is highly conserved and plays an important role in the response to light stimuli in soybean. Similar to the case in Arabidopsis, m6A in soybean is enriched not only around the stop codon and within the 3'UTR but also around the start codon. Moreover, genes with methylation occurring in the 3'UTR have higher expression levels and are more prone to alternative splicing. The core genes in the light signaling pathway, GmSPA1a, GmPRR5e and GmBIC2b, undergo changes in methylation modification and transcription levels in response to light. KEGG pathway analysis revealed that differentially expressed genes with differential m6A peaks were involved in the "photosynthesis" and "circadian rhythm" pathways. Our results highlight the important role played by epitranscriptomic mRNA methylation in the light response in soybean and provide a solid basis for determining the functional role of light on RNA m6A modification in this plant.

Associations of Serum Antimicrobial Peptide LL-37 with Longitudinal Cognitive Decline and Neurodegeneration Among Older Adults with Memory Complaints.

BACKGROUND: A potential role of the antimicrobial peptide LL-37, which is upregulated after infection, in the pathogenesis of Alzheimer's disease (AD) was identified. However, the clinical relevance of LL-37 in AD is not clear yet. OBJECTIVE: This study aims to investigate the association of circulating LL-37 with longitudinal cognitive decline and neurodegeneration among older adults with memory complaints. METHODS: This cohort study recruited 357 older adults with memory complaints. Participants were followed-up for two years and the cognitive functions were assessed using the Mini-Mental State Examination (MMSE). Serum LL-37, pTau181, and tTau levels were determined at baseline. Associations of baseline LL-37 with longitudinal cognitive decline and change of neurodegenerative biomarkers were analyzed. RESULTS: No difference was found in the slope of longitudinal cognitive decline during follow-up between the low and high LL-37 group, adjusting for age, sex, education, body mass index, APOE ɛ4 carrier status, comorbidities, and baseline MMSE scores (difference in slope: 0.226, 95% CI: -0.169 to 0.621). Higher LL-37 levels were associated with longitudinal cognitive decline, as indicated by a decrease of MMSE scores of 3 points or above during follow-up (OR = 2.11, 95% CI: 1.32 to 3.38). The high LL-37 group had larger slopes of the increase in neurofilament light (difference in slope: 3.759, 95% CI: 2.367 to 5.152) and pTau181 (difference in slope: 0.325, 95% CI: 0.151 to 0.499) than the low LL-37 group. CONCLUSION: These findings support an association of the antimicrobial peptide LL-37 with AD from a clinical perspective.