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Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generate single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers. We evaluate enhancer activity for 59 elements using an in vivo transgenic assay and validate 44 (75%), demonstrating that single cell accessibility can be a strong predictor of enhancer activity. Applying our cMN atlas to 899 whole genome sequences from 270 genetically unsolved CCDD pedigrees, we achieve significant reduction in our variant search space and nominate candidate variants predicted to regulate known CCDD disease genes MAFB, PHOX2A, CHN1, and EBF3 - as well as candidates in recurrently mutated enhancers through peak- and gene-centric allelic aggregation. This work delivers non-coding variant discoveries of relevance to CCDDs and a generalizable framework for nominating non-coding variants of potentially high functional impact in other Mendelian disorders.

A decline in mitochondrial function is a hallmark of aging and neurodegenerative diseases. It has been proposed that changes in mitochondrial morphology, including fragmentation of the tubular mitochondrial network, can lead to mitochondrial dysfunction, yet the mechanism of this loss of function is unclear. Most proteins contained within mitochondria are nuclear-encoded and must be properly targeted to the mitochondria. Here, we report that sustained mRNA localization and co-translational protein delivery leads to a heterogeneous protein distribution across fragmented mitochondria. We find that age-induced mitochondrial fragmentation drives a substantial increase in protein expression noise across fragments. Using a translational kinetic and molecular diffusion model, we find that protein expression noise is explained by the nature of stochastic compartmentalization and that co-translational protein delivery is the main contributor to increased heterogeneity. We observed that cells primarily reduce the variability in protein distribution by utilizing mitochondrial fission-fusion processes rather than relying on the mitophagy pathway. Furthermore, we are able to reduce the heterogeneity of the protein distribution by inhibiting co-translational protein targeting. This research lays the framework for a better understanding of the detrimental impact of mitochondrial fragmentation on the physiology of cells in aging and disease.

Museum learning is beneficial for social inclusion, deepening partnerships between schools and museums, and increasing levels of pupil attainment. While there have been numerous empirical studies on the use of haptics in formal educational settings, few have explored the effect of haptic interaction on learning outcomes in museum learning. This study looks at an interactive 3D artifact simulation using a haptic interface and a non-haptic interface, with one group using 3D hand motions and receiving visual/haptic stimuli, and another group using a mouse and only receiving visual stimuli. Forty individuals majored in arts or social science courses were asked to perform four main interactive tasks about 3D collection. Using a triangulation of assessment scores, investing time, and satisfaction with interactions with the 3D artifact simulation, we explored the efficacy of haptic interaction in improving museum learning. The results showed that in general, the haptic interaction was more helpful in promoting learning performance in relation to 3D collections. However, significant differences only occurred in relation to the volume and material interactive tasks, and not in relation to the contour and color interactive tasks. The Findings reveal that the visual/haptic stimuli provided by haptic interaction in museum learning has a stronger modality effect on human information processing, and the effect of haptic interaction depends on the coupling of interactive tasks and sensorimotor experiences. Further, psychological immersion is more likely to occur when using haptic interaction, and haptically augmented 3D artifacts attract learners' attention, enhancing learner engagement and motivation. Explanations for these results are synthesized from the perceptual symbol, embodied cognition, and immersion theories.

Background: The number of migrant elders is increasing due to ageing of the global population and increasing life expectancy. There is accumulating evidence of the impact of internal or international migration on health. Aim: To compare the health and depression of local and migrant elders in Hainan province. Subjects and methods: Health and depression were assessed by the Self-Rated Health Measurement Scale Version 1.0 (SRHMS V1.0) and the Geriatric Depression Scale (GDS), respectively. The relationship between health and depression was investigated, along with the three sub-scales of SRHMS and the potential independent variables. Results: In total, 564 valid questionnaires were returned. Migrant elders were younger, had higher education levels and monthly income, and lower prevalence rates of chronic diseases than the local elders. The SRHMS scores were significantly higher, while the GDS scores were statistically lower in the migrant elders than the locals. Depression was negatively correlated with health (r = –0.674, p = 0.0000). Moreover, the three sub-scales of SRHMS were correlated with age, birth place, marital status, chronic diseases, GDS and/or educational level. Conclusion: Migrant elders self-reported better health and lower depression compared to the local elders. Differences in age, education, monthly income and chronic diseases might be influencing factors.

Oil content is a crucial indicator for evaluating the quality of peanuts. A rapid and non-destructive method to determine oil content of individual peanut seed can provide robust technical support for breeding high-oil-content peanut varieties. In this study, we established a rapid determination method using near-infrared hyperspectral imaging and chemometrics to assess the oil content of single peanut seed. After selecting key wavelengths through competitive adaptive reweighted sampling (CARS), uninformative variable elimination (UVE), and random frog (RF), we constructed an oil content calibration model based on partial least squares regression for single peanut seed. Validation results demonstrated that the correlation coefficient was 0.8393 with a root mean square error of 1.7771 in the calibration set, while it was 0.7915 with a root mean square error of 2.2943 in the independent prediction set. Most samples exhibited relative errors below 5%, confirming the reliability of this model in predicting oil content of single peanut seed.

Abstract Background In China, decline disease with unknown etiology appeared as an epidemic among bayberry trees in the southern area of the Yangtze River. Furthermore, the use of beneficial microbes has been reported to be able to reduce the incidence of this disease, emphasizing the association of this disease with microorganisms. Therefore, it has become critical to uncover the microbiome’s function and related metabolites in remodeling the immunity of bayberry trees under biotic or abiotic stresses. Results The amplicon sequencing data revealed that decline disease significantly altered bacterial and fungal communities, and their metabolites in the four distinct niches, especially in the rhizosphere soils and roots. Furthermore, the microbial communities in the four niches correlated with the metabolites of the corresponding niches of bayberry plants, and the fungal and bacterial networks of healthy trees were shown to be more complex than those of diseased trees. In addition, the role of microbiome in the resistance of bayberry trees to the occurrence of decline disease was justified by the isolation, identification, and characterization of important microorganisms such as significantly enriched Bacillus ASV804, Pseudomonas ASV815 in healthy plants, and significantly enriched Stenotrophomonas ASV719 in diseased plants. Conclusion Overall, our study revealed that the occurrence of decline disease altered the microbiome and its metabolites in four ecological niches in particular rhizosphere soils and roots of bayberry, which provides new insight into the control of bayberry decline disease.

Abstract Background This study explored the relationship between attention, negative emotions, empathy, mindfulness, and psychological trauma in catastrophic events to reduce psychological trauma in the public. Methods A total of 526 adults in Guangxi Province, China, were investigated using self-rating scales for post-traumatic stress disorder, emotion, and empathy, as well as a five-factor self-rating mindfulness scale and a catastrophic incident concern questionnaire. Results The results revealed the following: (1) Emotion significantly mediated attention and psychological trauma. (2) Empathy had a significant mediating effect on attention and psychological trauma. (3) Mindfulness moderated the relationship between negative emotions and psychological trauma, amplifying the impact of emotions on trauma rather than buffering it. Conclusions When people pay attention to catastrophic events, they should remain sensible and restrained, and avoid excessive emotional involvement to reduce the excessive psychological trauma caused by the event.

Abstract Background Spine grape (Vitis davidii) is a promising source of high-quality anthocyanins, with vast potential for application in food, pharmaceutical, and cosmetic industries. However, their availability is limited by resource constraints. Plant cell culture has emerged as a valuable approach for anthocyanin production and serves as an ideal model to investigate the regulation of anthocyanin biosynthesis. Elicitors are employed to achieve targeted enhancement of anthocyanin biosynthesis. The present study investigated the impact of 5-aminolevulinic acid (ALA) as an elicitor on the accumulation of anthocyanins and flavonoids during spine grape callus growth. Specifically, we examined the effects of ALA on anthocyanin and its component accumulation in callus, and biosynthetic anthocyanin gene expression. Results ALA at 25 µg/L increased the biomass of spine grape callus. ALA induction enhanced the levels of flavonoids, anthocyanins and proanthocyanidins in callus, with maximum values reaching 911.11 mg/100 g DW, 604.60 mg/100 g DW, and 5357.00 mg/100 g DW, respectively, after callus culture for 45 days. Notably, those levels were 1.47-, 1.93- and 1.83-fold higher than controls. ALA induction modulated the flavonoid profile, and among 97 differential flavonoid metabolites differing from controls, 77 were upregulated and 20 were downregulated. Six kinds of anthocyanins, namely cyanidin (8), delphinidin (6), peonidin (5), malvidin (4), petunidin (3) and pelargonidin (3), were detected in callus, with peonidin most abundant. Compared with controls, anthocyanin components were increased in ALA-treated callus. The key genes PAL1, PAL2, PAL4, CHI, CHS3, F3’H, F3H, FLS, DFR, UFGT, MYBA1, LDOX, OMT3, GT1 and ACT involved in anthocyanin biosynthesis were upregulated following ALA treatment, resulting in anthocyanin accumulation. Conclusion This study revealed a novel mode of ALA-mediated promotion of plant anthocyanin biosynthesis and accumulation at the cellular level, and a strategy for enhancing anthocyanin content in spine grape callus. The findings advance commercial-scale production of anthocyanins via spine grape callus culture. we also explored the accumulation patterns of flavonoids and anthocyanins under ALA treatment. Augmentation of anthocyanins coincided with elevated expression levels of most genes involved in anthocyanin biosynthesis within spine grape callus following ALA treatment.

Abstract To improve the sensitivity measurement of temperature sensors, a fiber optic temperature sensor structure based on the harmonic Vernier effect with two parallel fiber Sagnac interferometers (FSIs) is designed, and theoretical analysis and experimental testing are conducted. The FSI consisting of two polarization maintaining fibers (PMFs) with lengths of 13.62 m and 15.05 m respectively is used to achieve the basic Vernier effect. Then by changing the length of one PMF to approximately i times that of the others, the FSI composed of two PMFs of 7.1 m and 15.05 m is used to achieve the first-order harmonic Vernier effect. Afterward, temperature sensing tests are conducted to observe the wavelength drift during temperature changes and ultimately achieve high sensitivity. The experimental results show that the temperature sensitivity of the sensor based on the first-order harmonic Vernier effect is −28.89 nm/°C, which is 17.09 times that of a single FSI structure (−1.69 nm/°C) and 1.84 times that of the sensitivity generated by the structure based on the basic Vernier effect (−15.69 nm/°C). The experimental results are consistent with the theoretical analysis. The structure proposed in this paper achieves drift measurement of 0.1 °C variation based on 1 °C drift, making the fiber optic temperature sensor applicable to related fields that require high precision temperature. The proposed temperature sensor has the simple structure, low production cost, high sensitivity, and broad application prospects.

Abstract A decline in mitochondrial function is a hallmark of aging and neurodegenerative diseases. It has been proposed that changes in mitochondrial morphology, including fragmentation of the tubular mitochondrial network, can lead to mitochondrial dysfunction, yet the mechanism of this loss of function is unclear. Most proteins contained within mitochondria are nuclear-encoded and must be properly targeted to the mitochondria. Here, we report that sustained mRNA localization and co-translational protein delivery leads to a heterogeneous protein distribution across fragmented mitochondria. We find that age-induced mitochondrial fragmentation drives a substantial increase in protein expression noise across fragments. Using a translational kinetic and molecular diffusion model, we find that protein expression noise is explained by the nature of stochastic compartmentalization and that co-translational protein delivery is the main contributor to increased heterogeneity. We observed that cells primarily reduce the variability in protein distribution by utilizing mitochondrial fission-fusion processes rather than relying on the mitophagy pathway. Furthermore, we are able to reduce the heterogeneity of the protein distribution by inhibiting co-translational protein targeting. This research lays the framework for a better understanding of the detrimental impact of mitochondrial fragmentation on the physiology of cells in aging and disease.

Abstract Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generate single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers. We evaluate enhancer activity for 59 elements using an in vivo transgenic assay and validate 44 (75%), demonstrating that single cell accessibility can be a strong predictor of enhancer activity. Applying our cMN atlas to 899 whole genome sequences from 270 genetically unsolved CCDD pedigrees, we achieve significant reduction in our variant search space and nominate candidate variants predicted to regulate known CCDD disease genes MAFB, PHOX2A, CHN1, and EBF3 – as well as candidates in recurrently mutated enhancers through peak- and gene-centric allelic aggregation. This work delivers non-coding variant discoveries of relevance to CCDDs and a generalizable framework for nominating non-coding variants of potentially high functional impact in other Mendelian disorders.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a widespread respiratory disease. This study examines extracellular vesicles (EVs) and proteins contained in EVs in COPD. Methods Blood samples were collected from 40 COPD patients and 10 health controls. Cytokines including IFN-γ, TNF-α, IL-1β, IL-6, IL-8, and IL-17, were measured by ELISA. Small EVs samples were extracted from plasma and identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), and Western blot. Protein components contained in EVs were analyzed by Tandem Mass Tags (TMT) to identify differential proteins. Treg-derived EV was extracted and added to isolated CD8+, Treg, and Th17 subsets to assess its effect on T-lymphocytes. Results ELISA revealed higher levels of all cytokines and flow cytometry suggested a higher proportion of Treg and Th17 cells in COPD patients. After identification, TMT analysis identified 207 unique protein components, including five potential COPD biomarkers: BTRC, TRIM28, CD209, NCOA3, and SSR3. Flow cytometry revealed that Treg-derived EVs inhibited differentiation into CD8+, CD4+, and Th17 cells. Conclusion The study shows that cytokines, T-lymphocyte subsets differences in COPD and Treg-derived EVs influence T-lymphocyte differentiation. Identified biomarkers may assist in understanding COPD pathogenesis, prognosis, and therapy. The study contributes to COPD biomarker research.

Short-read genome sequencing (GS) holds the promise of becoming the primary diagnostic approach for the assessment of autism spectrum disorder (ASD) and fetal structural anomalies (FSAs). However, few studies have comprehensively evaluated its performance against current standard-of-care diagnostic tests: karyotype, chromosomal microarray (CMA), and exome sequencing (ES). To assess the clinical utility of GS, we compared its diagnostic yield against these three tests in 1,612 quartet families including an individual with ASD and in 295 prenatal families. Our GS analytic framework identified a diagnostic variant in 7.8% of ASD probands, almost 2-fold more than CMA (4.3%) and 3-fold more than ES (2.7%). However, when we systematically captured copy-number variants (CNVs) from the exome data, the diagnostic yield of ES (7.4%) was brought much closer to, but did not surpass, GS. Similarly, we estimated that GS could achieve an overall diagnostic yield of 46.1% in unselected FSAs, representing a 17.2% increased yield over karyotype, 14.1% over CMA, and 4.1% over ES with CNV calling or 36.1% increase without CNV discovery. Overall, GS provided an added diagnostic yield of 0.4% and 0.8% beyond the combination of all three standard-of-care tests in ASD and FSAs, respectively. This corresponded to nine GS unique diagnostic variants, including sequence variants in exons not captured by ES, structural variants (SVs) inaccessible to existing standard-of-care tests, and SVs where the resolution of GS changed variant classification. Overall, this large-scale evaluation demonstrated that GS significantly outperforms each individual standard-of-care test while also outperforming the combination of all three tests, thus warranting consideration as the first-tier diagnostic approach for the assessment of ASD and FSAs.