Search

Background and PurposeThe risk of skin injuries in space is increasing with longer space missions and a growing astronaut population. This highlights the importance of understanding the adverse effects of weightlessness on wound healing. The objective of this research was to examine the therapeutic potential of Low-Level Light Therapy (LLLT) on skin healing processes under simulated microgravity (SMG) conditions and uncover the underlying molecular mechanisms, thus providing innovative solutions and a sound theoretical basis for space skin injuries.MethodsHindlimb unloading (HU) mice models were used to simulate weightlessness conditions, with or without a complete management of LLLT for 14 days. A systematic testing consisting of HE, Masson and immunohistochemical staining was performed against the standardized mouse tissue specimens. In vitro assessment of cellular biological functions under SMG conditions was carried out in the rotation system of culture (RSOC) using HaCaT and NIH3T3 cell-lines.ResultsUnder SMG conditions, LLLT significantly reduced skin wound area in HU mice, especially on Days 10 (p < 0.001), accompanied by increased collagen deposition and elevated levels of Ki67 and CD31. Moreover, LLLT showed impressive anti-inflammatory effects represented by the reduced in pro-inflammatory markers including LY6G, F4/80 and CD86, as well as the decreased levels of IL-1β, IL-6 and TNF-α. Conversely, an elevation in the anti-inflammatory marker CD206 was observed. By employing bioinformatics technology, we further found the PI3K/AKT signaling was prominent in the KEGG pathway analysis and CCR2 acted as a hub gene in the interaction network. Therefore, we demonstrated that LLLT could enhance the phosphorylation of PI3K/AKT and reduce CCR2 expression under SMG conditions, while CCR2 knockdown promoted the phosphorylation of PI3K/AKT, suggesting an important role of CCR2/PI3K/AKT signal axis in LLLT-accelerated wound healing under SMG conditions.ConclusionLLLT induced activation of the PI3K/AKT signaling pathway through suppression of CCR2 expression, which significantly enhanced skin wound healing under SMG conditions.s.

BackgroundMotor coordination difficulties could contribute to social communication deficits in autistic children. However, the exploration of the mechanism implicated in these claims has been limited by the lack of potential confounders such as executive function (EF).MethodsWe investigated the role that EF plays in the relationship between motor coordination and social communication in a school-aged autistic population via a structural model in a statistically robust manner. The results of questionnaires, including the Developmental Coordination Disorder questionnaire, the Behavior Rating Inventory of Executive Function, and the Social Responsiveness Scale, were collected to measure motor coordination, social communication deficits, and EF.ResultsA total of 182 autistic children (7.61±1.31 years, 87.9% boys) were included in the final analysis. In the model with EF as a mediator, the total effect (β=-0.599, P

ABSTRACTOur previous work revealed that unbalanced dietary intake was an important independent factor associated with constipation and gastrointestinal (GI) symptoms in children with autism spectrum disorder (ASD). Growing evidence has shown the alterations in the gut microbiota and gut microbiota-derived metabolites in ASD. However, how the altered microbiota might affect the associations between unbalanced diets and GI symptoms in ASD remains unknown. We analyzed microbiome and metabolomics data in 90 ASD and 90 typically developing (TD) children based on 16S rRNA and untargeted metabolomics, together with dietary intake and GI symptoms assessment. We found that there existed 11 altered gut microbiota (FDR-corrected P-value

Abstract Visualizing polymer chain growth is always a hot topic for tailoring structure‐function properties in polymer chemistry. However, current characterization methods are limited in their ability to differentiate the degree of polymerization in real‐time without isolating the samples from the reaction vessel, let alone to detect insoluble polymers. Herein, a reliable relationship is established between polymer chain growth and fluorescence properties through polymerization induced emission. (TPE‐C2)2‐Te is used to realize in situ oxidative polymerization, leading to the aggregation of fluorophores. The relationship between polymerization degree of growing polytelluoxane (PTeO) and fluorescence intensity is constructed, enabling real‐time monitoring of the polymerization reaction. More importantly, this novel method can be further applied to the observation of the polymerization process for growing insoluble polymer via surface polymerization. Therefore, the development of visualization technology will open a new avenue for visualizing polymer chain growth in real‐time, regardless of polymer solubility.

Abstract Dysfunction of cell cycle control and defects of primary ciliogenesis are two features of many cancers. Whether these events are interconnected and the driving mechanism coordinating them remains elusive. Here, we identify an actin filament branching surveillance system that alerts cells of actin branching insufficiency and regulates cell cycle progression, cytokinesis and primary ciliogenesis. We find that Oral-Facial-Digital syndrome 1 functions as a class II Nucleation promoting factor to promote Arp2/3 complex-mediated actin branching. Perturbation of actin branching promotes OFD1 degradation and inactivation via liquid-to-gel transition. Elimination of OFD1 or disruption of OFD1-Arp2/3 interaction drives proliferating, non-transformed cells into quiescence with ciliogenesis by an RB-dependent mechanism, while it leads oncogene-transformed/cancer cells to incomplete cytokinesis and irreversible mitotic catastrophe via actomyosin ring malformation. Inhibition of OFD1 leads to suppression of multiple cancer cell growth in mouse xenograft models. Thus, targeting OFD1-mediated actin filament branching surveillance system provides a direction for cancer therapy.

Cilia project from cells to serve sensory functions, and ciliary disruption can result in multiple disorders known as ciliopathies. Here the authors show that the ciliopathy gene TCTN1 functions to regulate the ciliary transition zone and ectosome formation.

BackgroundChildren with autism spectrum disorder (ASD) are at high risk of experiencing externalizing and internalizing problems. This study aimed to reveal how maternal parenting styles and autistic traits influence behavioral problems in children with ASD.MethodsThis study recruited 70 2–5 years children with ASD and 98 typically developing (TD) children. The Parental Behavior Inventory (PBI) and Autism Spectrum Quotient (AQ) were used to collect the maternal parenting styles and autistic traits, respectively. The children’s behavioral problems were reported by the mothers using the Strengths and Difficulties Questionnaire (SDQ). Hierarchical moderated regression analyses were used to determine whether maternal autistic traits moderated the association between parenting style and behavioral problems in the children.ResultsCompared to TD children, children with ASD exhibited more severe externalizing and internalizing problems (t = 4.85, p

Idiopathic scoliosis (IS) is the most common spinal deformity diagnosed in childhood or early adolescence, while the underlying pathogenesis of this serious condition remains largely unknown. Here, we report zebrafish ccdc57 mutants exhibiting scoliosis during late development, similar to that observed in human adolescent idiopathic scoliosis (AIS). Zebrafish ccdc57 mutants developed hydrocephalus due to cerebrospinal fluid (CSF) flow defects caused by uncoordinated cilia beating in ependymal cells. Mechanistically, Ccdc57 localizes to ciliary basal bodies and controls the planar polarity of ependymal cells through regulating the organization of microtubule networks and proper positioning of basal bodies. Interestingly, ependymal cell polarity defects were first observed in ccdc57 mutants at approximately 17 days postfertilization, the same time when scoliosis became apparent and prior to multiciliated ependymal cell maturation. We further showed that mutant spinal cord exhibited altered expression pattern of the Urotensin neuropeptides, in consistent with the curvature of the spine. Strikingly, human IS patients also displayed abnormal Urotensin signaling in paraspinal muscles. Altogether, our data suggest that ependymal polarity defects are one of the earliest sign of scoliosis in zebrafish and disclose the essential and conserved roles of Urotensin signaling during scoliosis progression.

BackgroundThe evidence for associations of emotional/behavioral status with sedentary behavior (SB), physical activity (PA) and step counts is scarce in children with autism spectrum disorder (ASD). Also, ASD-related deficiencies may affect actual levels of PA. We aimed to describe accelerometer-measured SB, PA and step counts in children with ASD, and to examine the associations of emotional/behavioral problems with SB, PA and step counts after assessing associations between accelerometer-measured SB, PA and step counts and ASD-related deficiencies.MethodsA total of 93 ASD children, aged 6–9 years, were recruited from the Center for Child and Adolescent Psychology and Behavioral Development of Sun Yat-sen University in Guangzhou, China. Participants wore an accelerometer for seven consecutive days. Of the original 93, 78 participants' accelerometer-measured valid PA were obtained, and the data were shown as time spent in SB, light, moderate, moderate-to-vigorous and vigorous PA, and step counts. Participants' emotional/behavioral problems were assessed via the Strengths and Difficulties Questionnaire (SDQ), and anxiety symptoms were evaluated by the Screen for Child Anxiety Related Emotional Disorders (SCARED). ASD-associated deficiencies include restricted repetitive behaviors (Repetitive Behavior Scale-Revised), poor social competence (Social Responsiveness Scale Second Edition) and motor development restrictions (Developmental Coordination Disorder Questionnaire).ResultsOf the 78 participants, daily vigorous PA (VPA) and moderate-to-vigorous PA (MVPA) averaged 15.62 and 51.95 min, respectively. After adjustment for covariates, SDQ emotional symptoms (β = −0.060, p = 0.028) were inversely associated with the average daily minutes in VPA. Meanwhile, SDQ emotional symptoms (β = −0.033, p = 0.016) were inversely associated with the average daily MVPA minutes in the crude model. After adjustment for covariates, SCARED somatic/panic (β = −0.007, p = 0.040) and generalized anxiety (β = −0.025, p = 0.014) were negatively associated with the average daily VPA minutes; SCARED total anxiety (β = −0.006, p = 0.029) was conversely associated with daily MVPA duration. After adjustment for covariates, no significant associations between accelerometer-measured SB, PA and step counts and ASD-related deficiencies were found (p > 0.05).ConclusionsAccelerometer-measured SB, PA and step counts showed no associations with ASD-related deficiencies. On this basis, we further found that the emotional symptoms were inversely associated with VPA and MVPA. These results emphasize the importance of VPA and MVPA in children with ASD. The longitudinally investigations on the directionality of these associations between emotional symptoms with VPA and MVPA are needed in the future.

BackgroundIt is well known that children with autism spectrum disorder (ASD) had executive functions deficit. However, it is still unclear whether the poor dietary quality is related to the impairment of executive functions. The current study aimed to explore the association between dietary quality and executive functions in children with ASD.MethodsA total of 106 children with ASD (7.7 ± 1.3 years) and 207 typically developing (TD) children (7.8 ± 1.3 years) were enrolled from Guangzhou, China. The Chinese version of Behavior Rating Scale of Executive function (BRIEF), the working memory subscales of the Chinese version of Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), and the Stroop Color-Word Test (SCWT) were used to measure the participant's executive functions. The food frequency questionnaire (FFQ) was used to collect the dietary intake information, and the Chinese Diet Balance Index (DBI_16) was used to evaluate the dietary quality. Generalized linear models were used to estimate the association between dietary quality and executive functions.ResultsIn children with ASD, Low Bound Score (LBS) was positively correlated with the working memory subscale score of BRIEF (β = 0.23, 95% CI: 0.02–0.44, P < 0.05), while High Bound Score (HBS) and LBS were positively correlated with the organizable subscale score of BRIEF (β = 0.44, 95% CI: 0.11–0.77, P < 0.01; β = 0.19, 95% CI: 0.01–0.37, P < 0.05). Compared to TD children, children with ASD had a higher proportion of moderate and high levels of insufficient dietary intake (moderate level, 37.7% vs. 23.2%, high level, 4.7% vs. 1.4%) and moderate level of unbalanced dietary intake (36.8% vs.21.3%), higher scores on all subscales of BRIEF (P < 0.01), and lower score on the working memory (81.3 ± 32.3 vs. 104.6 ± 12.5, P < 0.01), while there was no difference on the SCWT.ConclusionPoor dietary quality was associated with the impairment of working memory and organizational capacity in children with ASD. This study emphasized the importance of dietary quality in executive functions among children with ASD, and attention should be paid to improving their dietary quality.

Background and ObjectivesThe relationship between brain function and sugar-sweetened beverages (SSBs) is widely explored, but the motor function was not included. We aim to explore the relationship between SSBs and motor function among children with or without autism.MethodsParticipants were a representative autism sample (ASD, n = 106) comprising ages ranging 6–9 years and their age-matched typical counterparts (TD, n = 207), recruited in the research center of Guangzhou, China. Valid questionnaires of parent-reported including weekly SSBs intake, physical activity (PA), sedentary time (ST), and motor coordination function was used to collect relevant information. SSBs intake was further classified as no intake (no habit of taking SSBs), small to medium intake (

Cantonese and Mandarin are logographic languages, and the phonology is the main difference between the two languages. It is unclear whether the long-term experience of Cantonese–Mandarin bilingualism will shape different brain white matter structures related to phonological processing. A total of 30 Cantonese–Mandarin bilinguals and 30 Mandarin monolinguals completed diffusion-weighted imaging scan and phonological processing tasks. The tractography and tract-based spatial statistics were used to investigate the structural differences in the bilateral superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), and inferior fronto–occipital fasciculus (IFOF) between Cantonese–Mandarin bilinguals and Mandarin monolinguals. The post-hoc correlation analysis was conducted to investigate the relationship between the different structures with phonological processing skills. Compared to the Mandarin monolinguals, the Cantonese–Mandarin bilinguals had higher fractional anisotropy (FA) along the left ILFs higher mean diffusivity (MD) along the right IFOF and the temporoparietal segment of SLF (tSLF), higher axial diffusivity (AD) in the right IFOF and left ILF, and lower number of streamlines in the bilateral tSLF. The mean AD of the different voxels in the right IFOF and the mean FA of the different voxels in the left ILF were positively correlated with the inverse efficiency score (IES) of the Cantonese auditory and Mandarin visual rhyming judgment tasks, respectively, within the bilingual group. The correlation between FA and IES was different among the groups. The long-term experience of Cantonese–Mandarin bilinguals shapes the different brain white matter structures in tSLF, IFOF, and ILF. Compared to the monolinguals, the bilinguals’ white matter showed higher diffusivity, especially in the axonal direction. These changes were related to bilinguals’ phonological processing.

Abstract Background Joubert syndrome (JBTS) is a rare genetic disorder that is characterized by midbrain‐hindbrain malformations. Multiple variants in genes that affect ciliary function contribute to the genetic and clinical heterogeneity of JBTS and its subtypes. However, the correlation between genotype and phenotype has not been elucidated due to the limited number of patients available. Methods In this study, we observed different clinical features in two siblings from the same family. The older sibling was classified as a pure JBTS patient, whereas her younger sibling displayed oral‐facial‐digital defects and was therefore classified as an oral‐facial‐digital syndrome type VI (OFD VI) patient. Next, we performed human genetic tests to identify the potential pathogenic variants in the two siblings. Results Genetic sequencing indicated that both siblings harbored compound heterozygous variants of a missense variant (c.1067C>T, p.S356F) and a frameshift variant (c.8377_8378del, p.E2793Lfs*24) in CPLANE1 (NM_023073.3). Conclusion This study reports that two novel CPLANE1 variants are associated with the occurrence of JBTS and OFD VI. These results help elucidate the intrafamilial phenotypic variability associated with CPLANE1 variants.

Abstract Background The relationship between sleep duration and food intake is unclear. This study aims to examine the relationship among children aged 6–17 years in China. Methods The sample consisted of 70,519 children aged 6–17 years, which were randomly selected from 7 representative areas from China, from September to November, 2013. In the structured questionnaire, children reported daily sleep hours (less than 7 h, 7–9 h and more than 9 h), weekly food intake amount (including vegetables, fruit, sugar beverages and meat), physical activity and sedentary time. The relationship of sleep duration with vegetable, sugar beverage, fruit and meat intake was evaluated by multi-nominal logistic regression and multi-variable adjusted. Results A total of 62,517 children (51.6% boys) completed the study. Short sleep duration (SSD,

Joubert syndrome (JBTS) and Meckel–Gruber syndrome (MKS) are rare recessive disorders caused by defects of cilia, and they share overlapping clinical features and allelic loci. Mutations of MKS1 contribute approximately 7% to all MKS cases and are found in some JBTS patients. Here, we describe a JBTS patient with two novel mutations of MKS1. Whole exome sequencing (WES) revealed c.191-1G > A and c.1058delG compound heterozygous variants. The patient presented with typical cerebellar vermis hypoplasia, hypotonia, and developmental delay, but without other renal/hepatic involvement or polydactyly. Functional studies showed that the c.1058delG mutation disrupts the B9 domain of MKS1, attenuates the interactions with B9D2, and impairs its ciliary localization at the transition zone (TZ), indicating that the B9 domain of MKS1 is essential for the integrity of the B9 protein complex and localization of MKS1 at the TZ. This work expands the mutation spectrum of MKS1 and elucidates the clinical heterogeneity of MKS1-related ciliopathies.

The association between sugar-sweetened beverages (SSBs) and symptom complaints among school-aged children remains unclear. Children aged 6–17 years (n = 29,028) were recruited on the basis of a national school-based study. Data collection included two waves: the exposure was the amount and frequency of SSB consumption, collected in the 2013 autumn semester, and outcomes were defined as having clinical symptom complaints after two weeks of observation, collected in the 2014 spring semester. Symptom complaints were defined as fever, cough, headache, loose bowels, vomiting, sore throat, rash, conjunctival congestion, and stomachache. The associations between the amount/frequency of SSBs and symptoms complaints were explored by a general linear model, with adjustments made for socio-demographic and other lifestyle information. Among the 12,454 children (10.32 ± 3.15 years, 48.7% male) in the final analysis, the odds ratio for having symptom complaints (1.46, 95% CI: 1.10–1.95) among children whose SSB consumption was >75 mL/day was significantly higher than that among children who had no SSB consumption. Among children with a daily SSB intake of more than 75 mL, there was a higher risk for symptom complaints. We recommend more support for decreasing SSB consumption among children to minimize negative health outcomes.

Abstract Background Joubert syndrome (JS, OMIM: 213300) is a recessive developmental disorder characterized by cerebellar vermis hypoplasia and a distinctive mid‐hindbrain malformation called the “molar tooth sign” on axial magnetic resonance imaging. To date, more than 35 ciliary genes have been identified as the causative genes of JS. Methods Whole exome sequencing was performed to detect the causative gene mutations in a Chinese patient with JS followed by Sanger sequencing. RT‐PCR and Sanger sequencing were used to confirm the abnormal transcript of centrosomal protein 104 (CEP104, OMIM: 616690). Results We identified two novel heterozygous mutations of CEP104 in the proband, which were c.2364+1G>A and c.414delC (p.Asn138Lysfs*11) (GenBank: NM_014704.3) and consistent with the autosomal recessive inheritance mode. Conclusion Our study reported the fourth case of JS patients with CEP104 mutations, which expands the mutation spectrum of CEP104 and elucidates the clinical heterogeneity of JS.

Abstract Background The relationship between sleep duration and overweight risk remains unexplored among Chinese children. This study aims to evaluate this association in a national investigation with school-aged population. Methods There were 18,302 normal weight children in this Chinese national study which conducted during 2013–2014 included in the research. Anthropometric measurements were performed both at baseline and after 6–9 month. Sleep duration, physical activity, food intake and social economic information were collected by self-report questionnaire. Overweight was defined according to the updated Chinese criterion. Cox regression was used to evaluate the relationships between sleep duration and overweight incidence with multivariable adjusted. Results In total, there were 443 new overweight cases recorded at the end of observation. Overweight incidence with greater than 9 h (long sleep duration, LSD), 7 to 9 h (middle sleep duration, MSD), and less than 7 h of sleep (short sleep duration, SSD) were 2.7, 3.1 and 3.3% respectively. Stratified by gender and compared with LSD, the hazard ratio (HR) of overweight for females with MSD was 1.60 (95% CI: 1.02–2.52). Stratified by age and gender, the HR in the group of MSD was 2.13 (1.20–3.77) in female aged 6–10 years and 0.24 (0.06–0.93) in female aged 15–17 years. Conclusion The association between short sleep duration and overweight is age- and gender dependent. In group of small age and elder age, girls’ adiposity states are independently associated with sleep duration. Sleep recommendation is a potential preventive action for overweight/obesity among girls.

Previous studies have shown that exclusive breastfeeding is associated with lower odds of having autism spectrum disorders (ASD) in children, but data are lacking in Asian countries, especially China. This cross-sectional study of seven cities in China collected data from August 2016 to March 2017 from 6049 toddlers aged 16–30 months and their parents who responded to questionnaires. The breastfeeding status was collected via questionnaires based on recommendations from the World Health Organization. The standard procedure for screening and diagnosis was applied to identify toddlers with ASD. Among the 6049 toddlers (3364 boys [55.6%]; mean [SD] age, 22.7 [4.1] months), 71 toddlers (1.2%) were identified as ASD. The prevalence of exclusive breastfeeding, partial breastfeeding, and not breastfeeding was 48.8%, 42.2%, and 9.1%, respectively. Compared to toddlers with exclusive breastfeeding, toddlers with partial breastfeeding or without breastfeeding had higher odds of having ASD (odd ratios [OR]: 1.55, 95% confidence interval [CI]: 0.90–2.74; OR: 2.34, 95% CI: 1.10–4.82). We did not find significant modification of demographic characteristics on the associations. The results remained robust in multiple sensitivity analyses. Toddlers without breastfeeding for the first six months of life had higher odds of having ASD, and our findings shed light on the necessity of strengthening public health efforts to increase exclusive breastfeeding in China.

The role of the primary cilium in key signaling pathways depends on dynamic regulation of ciliary membrane protein composition, yet we know little about the motors or membrane events that regulate ciliary membrane protein trafficking in existing organelles. Recently, we showed that cilium-generated signaling in Chlamydomonas induced rapid, anterograde IFT-independent, cytoplasmic microtubule-dependent redistribution of the membrane polypeptide, SAG1-C65, from the plasma membrane to the periciliary region and the ciliary membrane. Here, we report that the retrograde IFT motor, cytoplasmic dynein 1b, is required in the cytoplasm for this rapid redistribution. Furthermore, signaling-induced trafficking of SAG1-C65 into cilia is unidirectional and the entire complement of cellular SAG1-C65 is shed during signaling and can be recovered in the form of ciliary ectosomes that retain signal-inducing activity. Thus, during signaling, cells regulate ciliary membrane protein composition through cytoplasmic action of the retrograde IFT motor and shedding of ciliary ectosomes.

Background and aims Variants in ZFYVE19 underlie a disorder characterised by progressive portal fibrosis, portal hypertension and eventual liver decompensation. We aim to create an animal model to elucidate the pathogenic mechanism. Methods Zfyve19 knockout (Zfyve19-/-) mice were generated and exposed to different liver toxins. Their livers were characterised at the tissue, cellular and molecular levels. Findings were compared with those in wild-type mice and in ZFYVE19-deficient patients. ZFYVE19 knockout and knockdown retinal pigment epithelial-1 cells and mouse embryonic fibroblasts were generated to study cell division and cell death. Results The Zfyve19-/- mice were normal overall, particularly with respect to hepatobiliary features. However, when challenged with a-naphthyl isothiocyanate, Zfyve19-/- mice developed changes resembling those in ZFYVE19-deficient patients, including elevated serum liver injury markers, increased numbers of bile duct profiles with abnormal cholangiocyte polarity and biliary fibrosis. Failure of cell division, centriole and cilia abnormalities, and increased cell death were observed in knockdown/knockout cells. Increased cell death and altered mRNA expression of cell death-related signalling pathways was demonstrated in livers from Zfyve19-/- mice and patients. Transforming growth factor-β (TGF-β) and Janus kinase-Signal Transducer and Activator of Transcription 3 (JAK-STAT3) signalling pathways were upregulated in vivo, as were chemokines such as C-X-C motif ligands 1, 10 and 12. Conclusions Our findings demonstrated that ZFYVE19 deficiency is a ciliopathy with novel histological features. Failure of cell division with ciliary abnormalities and cell death activates macrophages and may thus lead to biliary fibrosis via TGF-β pathway in the disease. [ABSTRACT FROM AUTHOR]