CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche.

Rearranged during transfection (RET) rearrangement oncoprotein-mediated Ras/MAPK signaling cascade is constitutively activated in cancers. Here, we demonstrate a unique signal niche. The niche is a ternary complex based on the chimeric RET liquid-liquid phase separation. The complex comprises the rearranged kinase (RET fusion); the adaptor (GRB2), and the effector (SHC1). Together, they orchestrate the Ras/MAPK signal cascade, which is dependent on tyrosine kinase. CCDC6-RET fusion undergoes LLPS requiring its kinase domain and its fusion partner. The CCDC6-RET fusion LLPS promotes the autophosphorylation of RET fusion, with enhanced kinase activity, which is necessary for the formation of the signaling niche. Within the signal niche, the interactions among the constituent components are reinforced, and the signal transduction efficiency is amplified. The specific RET fusion-related signal niche elucidates the mechanism of the constitutive activation of the Ras/MAPK signaling pathway. Beyond just focusing on RET fusion itself, exploration of the ternary complex potentially unveils a promising avenue for devising therapeutic strategies aimed at treating RET fusion-driven diseases.

Deficiency of smooth muscle cell ILF3 alleviates intimal hyperplasia via HMGB1 mRNA degradation-mediated regulation of the STAT3/DUSP16 axis.

Intimal hyperplasia is a complicated pathophysiological phenomenon attributable to in-stent restenosis, and the underlying mechanism remains unclear. Interleukin enhancer-binding factor 3 (ILF3), a double-stranded RNA-binding protein involved in regulating mRNA stability, has been recently demonstrated to assume a crucial role in cardiovascular disease; nevertheless, its impact on intimal hyperplasia remains unknown. In current study, we used samples of human restenotic arteries and rodent models of intimal hyperplasia, we found that vascular smooth muscle cell (VSMC) ILF3 expression was markedly elevated in human restenotic arteries and murine ligated carotid arteries. SMC-specific ILF3 knockout mice significantly suppressed injury induced neointimal formation. In vitro, platelet-derived growth factor type BB (PDGF-BB) treatment elevated the level of VSMC ILF3 in a dose- and time-dependent manner. ILF3 silencing markedly inhibited PDGF-BB-induced phenotype switching, proliferation, and migration in VSMCs. Transcriptome sequencing and RNA immunoprecipitation sequencing depicted that ILF3 maintained its stability upon binding to the mRNA of the high-mobility group box 1 protein (HMGB1), thereby exerting an inhibitory effect on the transcription of dual specificity phosphatase 16 (DUSP16) through enhanced phosphorylation of signal transducer and activator of transcription 3 (STAT3). Therefore, the results both in vitro and in vivo indicated that the loss of ILF3 in VSMC ameliorated neointimal hyperplasia by regulating the STAT3/DUSP16 axis through the degradation of HMGB1 mRNA. Our findings revealed that vascular injury activates VSMC ILF3, which in turn promotes intima formation. Consequently, targeting specific VSMC ILF3 may present a potential therapeutic strategy for ameliorating cardiovascular restenosis.

Signal2signal: Pushing the Spatiotemporal Resolution to the Limit by Single Chemical Hyperspectral Imaging.

There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signal and will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.

Sextuple knockouts of a highly conserved and coexpressed AUXIN/INDOLE-3-ACETIC ACID gene set confer shade avoidance-like responses in Arabidopsis.

AUXIN/INDOLE-3-ACETIC ACIDs are transcriptional repressors for auxin signalling. Aux/IAAs of Arabidopsis thaliana display some functional redundancy. The IAA3/SHY2 clade (IAA1, IAA2, IAA3 and IAA4) show strong sequence similarity, but no higher-order mutants have been reported. Here, through CRISPR/Cas9 genome editing, we generated loss-of-function iaa1/2/3/4 mutants. The quadruple mutants only exhibited a weak phenotype. Thus, we additionally knocked out IAA7/AXR2 and IAA16, which are coexpressed with IAA1/2/3/4. Remarkably, under white light control conditions, the iaa1/2/3/4/7/16 mutants exhibited a shade avoidance-like phenotype with over-elongated hypocotyls and petioles and hyponastic leaves. The sextuple mutants were highly sensitive to low light intensity, and the hypocotyl cells of the mutants were excessively elongated. Transcriptome profiling and qRT-PCR analyses revealed that the sextuple mutation upregulated IAA19/MSG2 and IAA29, two shared shade/auxin signalling targets. Besides, genes encoding cell wall-remodelling proteins and shade-responsive transcription regulators were upregulated. Using dual-luciferase reporter assays, we verified that IAA2/IAA7 targeted the promoters of cell wall-remodelling genes to inhibit their transcription. Our work indicates that the IAA1/2/3/4/7/16 gene set is required for the optimal integration of auxin and shade signalling. The mutants generated here should be valuable for exploring the complex interactions among signal sensors, transcription activators and transcription repressors during hormone/environmental responses.

Long-term follow-up of protective effects on salivary and swallowing structures and improvement of late xerostomia and dysphagia by level IIb optimisation in clinical target volume of nasopharyngeal carcinoma.

BACKGROUND: This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). METHODS: Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. RESULTS: Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. CONCLUSIONS: Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.

Fine-Tuning Electron-Donor Capability in the Basic Anion of Poly(ionic liquid) Frameworks for Revolutionizing Catalytic Synthesis of Ethyl Methyl Carbonate with Both Ultrahigh Catalytic Activity and Selectivity.

Ethyl methyl carbonate (EMC) is a crucial solvent extensively utilized in lithium-ion battery electrolytes; the transesterification of dimethyl carbonate (DMC) with ethanol is a pivotal reaction for EMC production. However, this reaction faces challenges due to the trade-off between catalytic activity and selectivity from the basic catalysts. In this issue, we report an innovative strategy through fine-tuning the electron-donor capability of the basic phenolate anion ([PhO]) in a novel poly(ionic liquid) (PIL) framework, as synthesized via an alkylation reaction between 1,3,5-tris(bromomethyl)benzene, biphenyldiimidazole, and N,N'-carbonyldiimidazole (CDI) to trigger targeted basicity that can directionally catalyze the transesterification of DMC with ethanol, so as to achieve both ultrahigh catalytic activity and selectivity toward EMC. By varying the substituent groups with electron-withdrawing and electron-donating effects on the phenolate anion, the PILs show expected changes in the catalytic performance, following well with the trend of charge density on these substituted phenolate anions. The optimized catalyst [CPIL-CDI][MeOPhO], induced by p-methoxyphenolate anions, allows an extraordinary EMC yield of 72.19% and an EMC selectivity of 91.48% under mild conditions without any process intensifications, suppressing all of the reported catalysts reported to date. Outcomes and approaches shown in this work have the potential to expedite the systematic design of cations and anions within PILs for industrial-scale EMC production through environmentally friendly transesterification processes.

A complex metabolic network and its biomarkers regulate laccase production in white-rot fungus Cerrena unicolor 87613.

BACKGROUND: White-rot fungi are known to naturally produce high quantities of laccase, which exhibit commendable stability and catalytic efficiency. However, their laccase production does not meet the demands for industrial-scale applications. To address this limitation, it is crucial to optimize the conditions for laccase production. However, the regulatory mechanisms underlying different conditions remain unclear. This knowledge gap hinders the cost-effective application of laccases. RESULTS: In this study, we utilized transcriptomic and metabolomic data to investigate a promising laccase producer, Cerrena unicolor 87613, cultivated with fructose as the carbon source. Our comprehensive analysis of differentially expressed genes (DEGs) and differentially abundant metabolites (DAMs) aimed to identify changes in cellular processes that could affect laccase production. As a result, we discovered a complex metabolic network primarily involving carbon metabolism and amino acid metabolism, which exhibited contrasting changes between transcription and metabolic patterns. Within this network, we identified five biomarkers, including succinate, serine, methionine, glutamate and reduced glutathione, that played crucial roles in co-determining laccase production levels. CONCLUSIONS: Our study proposed a complex metabolic network and identified key biomarkers that determine the production level of laccase in the commercially promising Cerrena unicolor 87613. These findings not only shed light on the regulatory mechanisms of carbon sources in laccase production, but also provide a theoretical foundation for enhancing laccase production through strategic reprogramming of metabolic pathways, especially related to the citrate cycle and specific amino acid metabolism.

Association between gestational arsenic exposure and infant physical development: a prospective cohort study.

BACKGROUND: Arsenic pollution is widespread worldwide. The association between gestational arsenic exposure and adverse birth outcomes has been demonstrated in previous studies; however, few investigations have examined whether gestational arsenic exposure has adverse effects on infant growth and development after birth. OBJECTIVE: Our study was designed to evaluate particular associations between gestational arsenic exposure during pregnancy and newborn birth size and to investigate whether these associations continue to affect infants after birth. METHODS: An ongoing prospective cohort study of 1100 pregnant women was conducted at the Wuxi Maternity and Child Health Care Hospital. The total urinary arsenic concentrations in the 2nd and 3rd trimester were determined using atomic fluorescence spectrometry. The relationships between urinary arsenic concentration and foetal growth parameters (birth weight, head circumference, length, and ponderal index), SGA (Small for gestational age), and physical growth of infants within one year after birth were analysed. RESULTS: Urinary arsenic concentration in the 3rd trimester was associated with an increased incidence of SGA [adjusted model: OR = 2.860 (95% CI: 1.168, 7.020), P = 0.021)]. Arsenic exposure in late pregnancy had an adverse effect on the physical development of infants before the age of 1 year, and there was an interaction effect with the sex of infants. The weight and length of boys at 6 and 12 months negatively correlated with maternal urinary arsenic levels during late pregnancy. CONCLUSIONS: In addition to affecting foetal growth, exposure to arsenic in the 3rd trimester also negatively affected the growth of offspring within the first year of life.

Association of cortical morphology, white matter hyperintensity, and glymphatic function in frontotemporal dementia variants.

INTRODUCTION: Frontotemporal dementia (FTD) can be phenotypically divided into behavioral variant FTD (bvFTD), nonfluent variant primary progressive aphasia (nfvPPA), and semantic variant PPA (svPPA). However, the neural underpinnings of this phenotypic heterogeneity remain elusive. METHODS: Cortical morphology, white matter hyperintensities (WMH), diffusion tensor image analysis along the perivascular space (DTI-ALPS), and their interrelationships were assessed in subtypes of FTD. Neuroimaging-transcriptional analyses on the regional cortical morphological deviances among subtypes were also performed. RESULTS: Changes in cortical thickness, surface area, gyrification, WMH, and DTI-ALPS were subtype-specific in FTD. The three morphologic indices are related to whole-brain WMH volume and cognitive performance, while cortical thickness is related to DTI-ALPS. Neuroimaging-transcriptional analyses identified key biological pathways linked to the formation and/or spread of TDP-43/tau pathologies. DISCUSSION: We found subtype-specific changes in cortical morphology, WMH, and glymphatic function in FTD. Our findings have the potential to contribute to the development of personalized predictions and treatment strategies for this disorder. HIGHLIGHTS: Cortical morphologic changes, white matter hyperintensities (WMH), and glymphatic dysfunction are subtype-specific. Cortical morphologic changes, WMH, and glymphatic dysfunction are inter-correlated. Cortical morphologic changes and WMH burden contribute to cognitive impairments.

Structural white matter properties and cognitive resilience to tau pathology.

INTRODUCTION: We assessed whether macro- and/or micro-structural white matter properties are associated with cognitive resilience to Alzheimer's disease pathology years prior to clinical onset. METHODS: We examined whether global efficiency, an indicator of communication efficiency in brain networks, and diffusion measurements within the limbic network and default mode network moderate the association between amyloid-ß/tau pathology and cognitive decline. We also investigated whether demographic and health/risk factors are associated with white matter properties. RESULTS: Higher global efficiency of the limbic network, as well as free-water corrected diffusion measures within the tracts of both networks, attenuated the impact of tau pathology on memory decline. Education, age, sex, white matter hyperintensities, and vascular risk factors were associated with white matter properties of both networks. DISCUSSION: White matter can influence cognitive resilience against tau pathology, and promoting education and vascular health may enhance optimal white matter properties. HIGHLIGHTS: Aß and tau were associated with longitudinal memory change over ∼7.5 years. White matter properties attenuated the impact of tau pathology on memory change. Health/risk factors were associated with white matter properties.

A unique mutation in PIN-FORMED1 and a genetic pathway for reduced sensitivity of Arabidopsis roots to N-1-naphthylphthalamic acid.

The small chemical N-1-naphthylphthalamic acid (NPA) has long been used as a polar auxin transport inhibitor. Recent biochemical and structural investigations have revealed that this molecule competes with the auxin IAA (indole-3-acetic acid) inside the PIN-FORMED auxin efflux carriers. However, the existence of any mutations in PIN family proteins capable of uncoupling the docking of IAA from NPA remains unclear. We report that Arabidopsis thaliana seedlings overexpressing SMALL AUXIN UP RNA 41 were hypersensitive to NPA-induced root elongation inhibition. We mutagenized this line to improve the genetic screening efficiency for NPA hyposensitivity mutants. Using bulked segregation analysis and mapping-by-sequencing assessment of these mutants, we identified a core genetic pathway for NPA-induced root elongation inhibition, including genes required for auxin biosynthesis, transportation, and signaling. To evaluate specific changes of auxin signaling activity in mutant roots before and after NPA treatment, the DR5::GFP/DR5::YFP markers were introduced and observed. Most importantly, we discovered a unique mutation in the PIN1 protein, substituting a proline residue with leucine at position 584, leading to a loss of NPA sensitivity while keeping the auxin efflux capacity. Transforming the null mutant pin1-201 with the PIN1::PIN1P584L -GFP fusion construct rescued the PIN1 function and provided NPA hyposensitivity. The proline residue is predicted to be adjacent to a hinge in the middle region of the ninth transmembrane helix of PIN1 and is conserved from moss to higher plants. Our work may bring new insights into the engineering of NPA-resistant PINs for auxin biology studies.

Changes in the intestinal microbiota of individuals with non-alcoholic fatty liver disease based on sequencing: An updated systematic review and meta-analysis.

BACKGROUND: Alterations in the composition and abundance of the intestinal microbiota occur in non-alcoholic fatty liver disease (NAFLD). However, the results are inconsistent because of differences in the study design, subject area, and sequencing methodology. In this study, we compared the diversity and abundance of the intestinal microbiota of patients with NAFLD and healthy individuals through a systematic review and meta-analysis. METHODS: Three databases (PubMed, EMBASE, and Cochrane Library) were searched from their inception to March 20, 2023. A meta-analysis was performed using Stata software to analyze variations in the richness and abundance of the intestinal microbiota in patients with NAFLD. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used for quality assessment. RESULTS: A total of 28 articles were included. Shannon diversity was reduced in patients with NAFLD (SMD = -0.24 (95% CI -0.43-0.05, I2 = 71.7%). The relative abundance of Ruminococcus, Faecalibacterium, and Coprococcus all decreased, with total SMDs of -0.96 (95% CI -1.29 to -0.63, I2 = 4.8%), -1.13 (95% CI -2.07 to -0.19, I2 = 80.5%), and -1.66 (95% CI -3.04 to -0.28, I2 = 91.5%). Escherichia was increased in individuals with NAFLD (SMD = 1.78, 95% CI 0.12 to 3.45, I2 = 94.4%). CONCLUSION: Increasing the species diversity and altering the abundance of specific gut microbiota, including Coprococcus, Faecalibacterium, Ruminococcus, and Escherichia, may be beneficial for improving NAFLD.

Application of virtual reality to enhance therapeutic Tai Chi for depression in elderly people.

The battle against depression in the elderly is crucial due to its significant impact on their quality of life, physical and cognitive health, increased risk of social isolation and suicide, as well as the associated higher healthcare costs. This research investigates the effects of traditional and augmented reality Tai Chi, using the virtual environment "Managed Tai Chi," on depression in elderly individuals. The study involved 300 participants aged over 60 from the Beijing Medical Center, with an experimental period lasting six months and sessions held once a week. The Geriatric Depression Scale (GDS) was utilized as a diagnostic tool at the pre-test and post-test stages. The findings revealed that the VR group exhibited a more substantial reduction in depression compared to the traditional and control groups (p ≤ 0.05), indicating the enhanced efficacy of Tai Chi with VR augmentation in treating depression in the elderly.

Engineering customized nanovaccines for enhanced cancer immunotherapy.

Nanovaccines have gathered significant attention for their potential to elicit tumor-specific immunological responses. Despite notable progress in tumor immunotherapy, nanovaccines still encounter considerable challenges such as low delivery efficiency, limited targeting ability, and suboptimal efficacy. With an aim of addressing these issues, engineering customized nanovaccines through modification or functionalization has emerged as a promising approach. These tailored nanovaccines not only enhance antigen presentation, but also effectively modulate immunosuppression within the tumor microenvironment. Specifically, they are distinguished by their diverse sizes, shapes, charges, structures, and unique physicochemical properties, along with targeting ligands. These features of nanovaccines facilitate lymph node accumulation and activation/regulation of immune cells. This overview of bespoke nanovaccines underscores their potential in both prophylactic and therapeutic applications, offering insights into their future development and role in cancer immunotherapy.

ß-elemene alleviates esophageal fibrosis after endoscopic submucosal dissection via the FAP-mediated PTEN-PI3K/AKT signaling pathway.

Esophageal stricture caused by fibrosis is a serious complication after esophageal Endoscopic submucosal dissection (ESD). Myofibroblasts play a crucial role in esophageal fibrosis, so inhibiting activated myofibroblasts is a promising approach for treating esophageal fibrosis. ß-Elemene, a natural product with anti-tumor and anti-fibrotic properties, has not been thoroughly examined in esophageal fibrosis. Additionally, fibroblast activation protein (FAP) and PTEN-PI3K/AKT signaling pathway are both notably linked to fibrotic diseases. Therefore, we investigated the potential mechanisms of ß-elemene in esophageal fibrosis by treating primary human esophageal granulation fibroblasts (PHEGFs) with gradient concentrations of ß-elemene. Our findings demonstrated that ß-elemene inhibited the activity of PHEGFs in a dose-dependent manner, accompanied by downregulation of FAP, p-PI3K, and p-AKT protein expression, along with upregulation of p-PTEN protein expression. In addition, we substantiated the potential correlation between FAP and the PTEN-PI3K/AKT signaling pathway by establishing models of FAP overexpression and silencing. These results provide a new perspective on the potential mechanism of ß-elemene in relieving esophageal fibrosis and offer novel therapeutic strategies for managing post-esophageal ESD stricture in clinical practice.

The effects of a mixture of small peptide chelating minerals and inorganic minerals on the production performance and tissue deposition of broiler chickens.

Due to the limited bioavailability of inorganic trace minerals, their utilization in poultry production has led to problems such as environmental contamination and inefficient resource utilization. It was investigated whether replacing inorganic trace minerals (ITM) with a blend of organic small peptide-chelated trace minerals (MIX) would improve production performance, selected biochemical parameters, antioxidant capacity, mineral deposition in liver, heart, and tibia, as well as mineral content in feces of broilers. A total of 432 healthy 21-day-old 817 broilers were randomly divided into 4 groups with 6 replicates per group and 18 chickens per replicate. The control group received a basal diet supplemented with 1,000 mg/kg of inorganic trace minerals as sulfate. The experimental groups received basal diets supplemented with 200, 400, and 600 mg/kg of mixed trace mineral elements (50% sulfate +50% small peptide-chelate) for a trial period of 30 days, divided into two stages: 21-35 days and 36-50 days. The results indicate that on the 50th day, compared with the 1,000 mg/kg ITM group, the levels of serum cholesterol, urea nitrogen, and malondialdehyde in the 200, 400, and 600 mg/kg MIX groups decreased (p < 0.01), while the levels of serum glutathione peroxidase in the 200, 400, and 600 mg/kg MIX groups increased (p < 0.05). Compared to the ITM group, the addition of organic small peptide chelated trace minerals mixed with inorganic trace minerals can reduce the levels of zinc and manganese in feces (p < 0.01). Furthermore, the iron content in the heart and tibia of the 600 mg/kg MIX group also significantly decreased (p < 0.05). There were no differences in growth performance and slaughter performance among the groups (p > 0.05). This study shows that replacing inorganic minerals with low-dose MIX (200, 400, and 600 mg/kg) can reduce the levels of zinc and manganese in feces, with no negative impact on growth and slaughter performance.

Induction of autism-related behavior in male mice by early-life vitamin D deficiency: association with disruption of the gut microbial composition and homeostasis.

Vitamin D deficiency (VDD) during early life emerges as a potential risk factor for autism spectrum disorder (ASD). Individuals with autism commonly exhibit lower vitamin D (VD) levels compared to the general population, and VD deficiency is prevalent during pregnancy and lactation. Moreover, gastrointestinal comorbidity, prevalent in ASD patients, correlates closely with disruptions in the gut microbiota and altered intestinal permeability. Therefore, it is fascinating and significant to explore the effects of maternal VD deficiency during pregnancy and lactation on the maturation of the gut microbiota of the offspring and its relevance to autism spectrum disorders. In this study, we established maternal pregnancy and lactation VD-deficient mouse models, employed shotgun macrogenomic sequencing to unveil alterations in the gut microbiome of offspring mice, and observed autism-related behaviours. Furthermore, fecal microbial transplantation (FMT) reversed repetitive and anxious behaviours and alleviated social deficits in offspring mice by modulating the gut microbiota and increasing short-chain fatty acid levels in the cecum, along with influencing the concentrations of claudin-1 and occludin in the colon. Our findings confirm that VDD during pregnancy and lactation is a risk factor for autism in the offspring, with disturbances in the structure and function of the offspring's gut microbiota contributing at least part of the effect. The study emphasises the importance of nutrition and gut health early in life. Simultaneously, this study further demonstrates the effect of VDD on ASD and provides potential ideas for early prevention and intervention of ASD.

The role and impact of abnormal vitamin levels in autism spectrum disorders.

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental disorder with a predominance of social behavioral disorders, has increased dramatically in various countries in recent decades. The interplay between genetic and environmental factors is believed to underlie ASD pathogenesis. Recent analyses have shown that abnormal vitamin levels in early life are associated with an increased risk of autism. As essential substances for growth and development, vitamins have been shown to have significant benefits for the nervous and immune systems. However, it is unknown whether certain vitamin types influence the emergence or manifestation of ASD symptoms. Several studies have focused on vitamin levels in children with autism, and neurotypical children have provided different insights into the types of vitamins and their intake. Here, we review the mechanisms and significance of several vitamins (A, B, C, D, E, and K) that are closely associated with the development of ASD in order to prevent, mitigate, and treat ASD. Efforts have been made to discover and develop new indicators for nutritional assessment of children with ASD to play a greater role in the early detection of ASD and therapeutic remission after diagnosis.

A pretreatment multiparametric MRI-based radiomics-clinical machine learning model for predicting radiation-induced temporal lobe injury in patients with nasopharyngeal carcinoma.

BACKGROUND: To establish and validate a machine learning model using pretreatment multiparametric magnetic resonance imaging-based radiomics data with clinical data to predict radiation-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). METHODS: Data from 230 patients with NPC who received IMRT (130 with RTLI and 130 without) were randomly divided into the training (n = 161) and validation cohort (n = 69) with a ratio of 7:3. Radiomics features were extracted from pretreatment apparent diffusion coefficient (ADC) map, T2-weighted imaging (T2WI), and CE-T1-weighted imaging (CE-T1WI). T-test, spearman rank correlation, and least absolute shrinkage and selection operator (LASSO) algorithm were employed to identify significant radiomics features. Clinical features were selected with univariate and multivariate analyses. Radiomics and clinical models were constructed using multiple machine learning classifiers, and a clinical-radiomics nomogram that combined clinical with radiomics features was developed. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were drawn to compare and verify the predictive performances of the clinical model, radiomics model, and clinical-radiomics nomogram. RESULTS: A total of 5064 radiomics features were extracted, from which 52 radiomics features were selected to construct the radiomics signature. The AUC of the radiomics signature based on multiparametric MRI was 0.980 in the training cohort and 0.969 in the validation cohort, outperforming the radiomics signature only based on T2WI and CE-T1WI (p < 0.05), which highlighted the significance of the DWI sequence in the prediction of temporal lobe injury. The area under the curve (AUC) of the clinical model was 0.895 in the training cohort and 0.905 in the validation cohort. The nomogram, which integrated radiomics and clinical features, demonstrated an impressive AUC value of 0.984 in the validation set; however, no statistically significant difference was observed compared to the radiomics model. The calibration curve and decision curve analysis of the nomogram demonstrated excellent predictive performance and clinical feasibility. CONCLUSIONS: The clinical-radiomics nomogram, integrating clinical features with radiomics features derived from pretreatment multiparametric MRI, exhibits compelling predictive performance for RTLI in patients diagnosed with NPC.