Prelinguistic communication complexity predicts expressive language in initial minimally verbal autistic children.

BACKGROUND: Prelinguistic communication complexity refers to the use of different communication forms such as eye gaze, gestures and vocalisations and the degree to which these forms are coordinated and how directed to a communication partner. To date, little is known about the relationship between prelinguistic communication complexity and expressive language in minimally verbal autistic children. AIMS: To test the hypothesis that prelinguistic communication complexity predicts expressive language 12 months later in autistic children and explore whether there are any differences in specific prelinguistic intentional communicative behaviours that are related to later expressive language levels. METHODS & PROCEDURES: This longitudinal study examined 37 minimally verbal autistic children (29-71 months old). The Communication Complexity Scale (CCS) was used to measure participants' prelinguistic communication behaviours, which were extracted from a semi-structured play interaction at Time 1. The Chinese Communicative Development Inventory (CCDI) was used to examine participants' expressive language at Time 1 and Time 2 (12 months later). According to Time 2 vocabulary size, participants were divided into two groups: Low CCDI, between 0 and 62 words, and High CCDI, more than 100 words. Linear regression was used to examine the relationship between early prelinguistic communication complexity and later expressive language. Binary logistic regression was used to determine which of the early communication behaviours were uniquely significantly related to later expressive language levels. OUTCOMES & RESULTS: There was a significant positive relationship between prelinguistic communication complexity and expressive language 12 months later, even after controlling for age and concurrent language. Findings revealed a group difference in the frequency of gesture and vocalisation combinations between the Low and High CCDI groups at Time 1. Gesture-vocalisation combinations also predicted better expressive language levels at Time 2. CONCLUSIONS & IMPLICATIONS: Our findings suggest that it may be beneficial to incorporate different complex communication behaviours into prelinguistic intervention targets for minimally verbal autistic children. The CCS hierarchies can be used as a reference for the intervention goals of minimally verbal autistic children. These findings highlight the importance of targeting gesture and vocalisation combinations when autistic children transition from single prelinguistic communication behaviours to multimodal behaviours. WHAT THIS PAPER ADDS: What is already known on this subject Children use eye gaze, gestures and vocalisations to communicate with others before they learn spoken language. There is strong evidence suggest that the frequency of prelinguistic communication predicts later linguistic achievements in autistic children. However, less is known about whether prelinguistic communication complexity also predicts later language and which specific behaviours are most predictive of language outcomes. What this study adds Minimally verbal autistic children who exhibit more complex prelinguistic communication behaviours have better expressive language 12 months later. Gestures combined with vocalisations predict better expressive language in minimally verbal autistic children. What are the clinical implications of this work? When identifying intervention targets for minimally verbal autistic children, the clinicians may reference the prelinguistic communication behaviours from the CCS. The gesture and vocalisation combinations are the key behaviours when targets transit from single form to two-form behaviours.

Current Strategies for Modulating Tumor-Associated Macrophages with Biomaterials in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths in the world. However, there are currently few clinical diagnosis and treatment options available, and there is an urgent need for novel effective approaches. More research is being undertaken on immune-associated cells in the microenvironment because they play a critical role in the initiation and development of HCC. Macrophages are specialized phagocytes and antigen-presenting cells (APCs) that not only directly phagocytose and eliminate tumor cells, but also present tumor-specific antigens to T cells and initiate anticancer adaptive immunity. However, the more abundant M2-phenotype tumor-associated macrophages (TAMs) at tumor sites promote tumor evasion of immune surveillance, accelerate tumor progression, and suppress tumor-specific T-cell immune responses. Despite the great success in modulating macrophages, there are still many challenges and obstacles. Biomaterials not only target macrophages, but also modulate macrophages to enhance tumor treatment. This review systematically summarizes the regulation of tumor-associated macrophages by biomaterials, which has implications for the immunotherapy of HCC.

[Analysis of COL1A1 and COL1A2 gene variants in two fetuses with osteogenesis imperfecta].

OBJECTIVE: To explore the genetic basis of two fetuses with an osteogenesis imperfecta (OI) phenotype. METHODS: Two fetuses diagnosed at the Affiliated Hospital of Weifang Medical College respectively on June 11, 2021 and October 16, 2021 were selected as the study subjects. Clinical data of the fetuses were collected. Amniotic fluid samples of the fetuses and peripheral blood samples of their pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing (WES) and Sanger sequencing were carried out to identify the candidate variants. Minigene splicing reporter analysis was used to validate the variant which may affect the pre-mRNA splicing. RESULTS: For fetus 1, ultrasonography at 17+6 weeks of gestation had revealed shortening of bilateral humerus and femurs by more than two weeks, in addition with multiple fractures and angular deformities of long bones. WES revealed that fetus 1 had harbored a heterozygous c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in exon 49 of the COL1A1 gene (NM_000088.4). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting) for disrupting the downstream open reading frame resulting in premature translational termination, being de novo in origin, and lacking records in the population and disease databases.For fetus 2, ultrasonography at 23 weeks of gestation also revealed shortening of bilateral humerus and femurs by one and four weeks, respectively, in addition with bending of bilateral femurs, tibias and fibulas. Fetus 2 had harbored a heterozygous c.1557+3A>G variant in intron 26 of the COL1A2 gene (NM_000089.4). Minigene experiment showed that it has induced skipping of exon 26 from the COL1A2 mRNA transcript, resulting in an in-frame deletion (c.1504_1557del) of the COL1A2 mRNA transcript. The variant was inherited from its father and had been previously reported in a family with OI type 4. It was therefore classified as a pathogenic variant (PS3+PM1+PM2_Supporting+PP3+PP5). CONCLUSION: The c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in the COL1A1 gene and c.1557+3A>G variant in the COL1A2 gene probably underlay the disease in the two fetuses. Above findings not only have enriched the mutational spectrum of OI, but also shed light on the correlation between its genotype and phenotype and provided a basis for genetic counseling and prenatal diagnosis for the affected pedigrees.

Interfacial Engineering of Bi19Br3S27 Nanowires Promotes Metallic Photocatalytic CO2 Reduction Activity under Near-Infrared Light Irradiation.

Developing highly efficient photocatalysts to utilize solar radiation for converting CO2 into solar fuels is of great importance for energy sustainability and carbon neutralization. Herein, through an alkali-etching-introduced interface reconstruction strategy, a nanowire photocatalyst denoted as V-Bi19Br3S27, with rich Br and S dual-vacancies and surface Bi-O bonding introduced significant near-infrared (NIR) light response, has been developed. The as-obtained V-Bi19Br3S27 nanowires exhibit a highly efficient metallic photocatalytic reduction property for converting CO2 into CH3OH when excited solely under NIR light irradiation. Free of any cocatalyst and sacrificial agent, metallic defective V-Bi19Br3S27 shows 2.3-fold higher CH3OH generation than Bi19Br3S27 nanowires. The detailed interfacial structure evolution and reaction mechanism have been carefully illustrated down to the atomic scale. This work provides a unique interfacial engineering strategy for developing high-performance sulfur-based NIR photocatalysts for photon reducing CO2 into alcohol for achieving high-value solar fuel chemicals, which paves the way for efficiently using the solar radiation energy extending to the NIR range to achieve the carbon neutralization goal.

mTOR regulates GPVI-mediated platelet activation.

BACKGROUND: Due to mTOR (mammalian/mechanistic target of rapamycin) gene-loss mice die during embryonic development, the role of mTOR in platelets has not been evaluated using gene knockout technology. METHODS: A mouse model with megakaryocyte/platelet-specific deletion of mTOR was established, and be used to evaluate the role of mTOR in platelet activation and thrombus formation. RESULTS: mTOR-/- platelets were deficient in thrombus formation when grown on low-concentration collagen-coated surfaces; however, no deficiency in thrombus formation was observed when mTOR-/- platelets were perfused on higher concentration collagen-coated surfaces. In FeCl3-induced mouse mesenteric arteriole thrombosis models, wild-type (WT) and mTOR-/- mice displayed significantly different responses to low-extent injury with respect to the ratio of occluded mice, especially within the first 40 min. Additionally, mTOR-/- platelets displayed reduced aggregation and dense granule secretion (ATP release) in response to low doses of the glycoprotein VI (GPVI) agonist collagen related peptide (CRP) and the protease-activated receptor-4 (PAR4) agonist GYPGKF-NH2; these deficiencies were overcame by stimulation with higher concentration agonists, suggesting dose dependence of the response. At low doses of GPVI or PAR agonist, the activation of αIIbß3 in mTOR-/- platelets was reduced. Moreover, stimulation of mTOR-/- platelets with low-dose CRP attenuated the phosphorylation of S6K1, S6 and Akt Ser473, and increased the phosphorylation of PKCδ Thr505 and PKCε Ser729. Using isoform-specific inhibitors of PKCs (δ, ɛ, and α/ß), we established that PKCδ/ɛ, and especially PKCδ but not PKCα/ß or PKCθ, may be involved in low-dose GPVI-mediated/mTOR-dependent signaling. CONCLUSION: These observations indicate that mTOR plays an important role in GPVI-dependent platelet activation and thrombus formation.

Phonological acquisition and development in Putonghua-speaking children with Autism Spectrum Disorders.

Poor phonological development adversely affects language development and interpersonal communication abilities in children with Autism Spectrum Disorders (ASD). However, the characteristics of phonological development in children with ASD who speak Putonghua (the official standard spoken form of modern Mandarin Chinese) remain largely unknown. This study aims to investigate phonological acquisition and development among Putonghua-speaking children with ASD. Data were collected from participants recruited in Shanghai, China. Two experiments were conducted. In experiment I, phonological acquisition was compared between 16 children with ASD aged 3-6 years and 16 age-matched typically developing (TD) children. In experiment II, phonological acquisition was compared between 26 children with ASD over 6 years old and 26 receptive-language-age-matched TD children. Picture naming was applied to measure participants' phonology - the 21 initials, 36 finals and four tones of Putonghua. Paired-samples t-tests and Fisher's exact tests were applied. In experiment I, scores on initials, finals, tones and total phonology of children with ASD aged 3-6 years were significantly lower than those of age-matched TD children. The pronunciation accuracy rates for initials such as/x, th, l/, finals such as/jaʊ, joʊ, wo/ and Tone 3 (the low-rising tone) in the ASD group were significantly lower than in the TD group. In experiment II, there was no significant difference in overall phonological developmental level between children with ASD over 6 years old and receptive-language-age-matched TD children. Phonological development of Putonghua-speaking children with ASD was significantly lower than that of age-matched TD children but closer to that of receptive-language-age-matched TD children. Further, participants with ASD showed atypical development sequences in both initials and finals.

Separation of Alkyne Enantiomers by Chiral Column HPLC Analysis of Their Cobalt-Complexes.

Separation of the enantiomers of new chiral alkynes in strategic syntheses and bioorthogonal studies is always problematic. The chiral column high-performance liquid chromatography (HPLC) method in general could not be directly used to resolve such substrates, since the differentiation of the alkyne segment with the other alkane/alkene segment is not significant in the stationary phase, and the alkyne group is not a good UV chromophore. Usually, a pre-column derivatization reaction with a tedious workup procedure is needed. Making use of easily-prepared stable alkyne-cobalt-complexes, we developed a simple and general method by analyzing the in situ generated cobalt-complex of chiral alkynes using chiral column HPLC. This new method is especially suitable for the alkynes without chromophores and other derivable groups.

Cypermethrin Induces Macrophages Death through Cell Cycle Arrest and Oxidative Stress-Mediated JNK/ERK Signaling Regulated Apoptosis.

Cypermethrin is one of the most highly effective synthetic pyrethroid insecticides. The toxicity of cypermethrin to the reproductive and nervous systems has been well studied. However, little is known about the toxic effect of cypermethrin on immune cells such as macrophages. Here, we investigated the cytotoxicity of cypermethrin on macrophages and the underlying molecular mechanisms. We found that cypermethrin reduced cell viability and induced apoptosis in RAW 264.7 cells. Cypermethrin also increased reactive oxygen species (ROS) production and DNA damage in a dose-dependent manner. Moreover, cypermethrin-induced G1 cell cycle arrest was associated with an enhanced expression of p21, wild-type p53, and down-regulation of cyclin D1, cyclin E and CDK4. In addition, cypermethrin treatment activated MAPK signal pathways by inducing c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 ERK1/2 phosphorylation, and increased the cleaved poly ADP-ribose polymerase (PARP). Further, pretreatment with antioxidant N-acetylcysteine (NAC) effectively abrogated cypermethrin-induced cell cytotoxicity, G1 cell cycle arrest, DNA damage, PARP activity, and JNK and ERK1/2 activation. The specific JNK inhibitor (SP600125) and ERK1/2 inhibitor (PD98059) effectively reversed the phosphorylation level of JNK and ERK1/2, and attenuated the apoptosis. Taken together, these data suggested that cypermethrin caused immune cell death via inducing cell cycle arrest and apoptosis regulated by ROS-mediated JNK/ERK pathway.

Microbes translocation from oral cavity to nasopharyngeal carcinoma in patients.

The presence of oral microbes in extra-oral sites is linked to gastrointestinal cancers. However, their potential ectopically colonization in the nasopharynx and impact on local cancer development remains uncertain. Our study involving paired nasopharyngeal-oral microbial samples from nasopharyngeal carcinoma (NPC) patients and controls unveils an aberrant oral-to-nasopharyngeal microbial translocation associated with increased NPC risk (OR = 4.51, P = 0.012). Thirteen species are classified as oral-translocated and enriched in NPC patients. Among these, Fusobacterium nucleatum and Prevotella intermedia are validated through culturomics and clonal strain identification. Nasopharyngeal biopsy meta-transcriptomes confirm these microbes within tumors, influencing local microenvironment and cytokine response. These microbes correlate significantly with the Epstein-Barr virus (EBV) loads in the nasopharynx, exhibiting an increased dose-response relationship. Collectively, our study identifies oral microbes migrating to the nasopharynx, infiltrating tumors, impacting microenvironments and linking with EBV infection. These results enhance our understanding of abnormal microbial communication and their roles in carcinogenesis.

A Chinese version of the communication complexity scale (CCS): psychometric evaluation in children with minimal verbal skills.

PURPOSE: This study aimed to evaluate the reliability and validity of the translated Chinese version of the Communication Complexity Scale (C-CCS) in a Chinese sample of preschool-aged children with minimal verbal skills. METHODS: A total of 120 children with autism spectrum disorders or children with developmental delays aged 2 to 5 years with minimal verbal skills (i.e., produced less than 20 functional words) were recruited to complete the C-CCS. First, we tested the protocol with 20 children and shortened it based on their results. Second, the interrater reliability, test-retest reliability, and concurrent validity for 100 participants were examined. C-CCS scores were compared with scores from the Chinese Communicative Development Inventories (CCDI) for concurrent validity. RESULTS: Ten C-CCS interactive scripts were administered to 100 participants. Intraclass correlation coefficients (ICC) between independent observers were high. The ICCs for overall optimal scores, optimal BR scores and optimal JA scores were 0.978, 0.971 and 0.977 respectively. Agreement for scores within scripted opportunities and communication level were high-Kappa coefficients 0.869 and 1.000 respectively. The test-retest reliability was high (r = 0.911). A moderate correlation was found between the C-CCS and the CCDI (r = 0.401). CONCLUSIONS: The results indicate that C-CCS could be used as a measurement tool in research and clinical practice to describe communication levels in children with minimal verbal skills in China.

The Chinese version of the Communication Complexity Scale was developed through a rigorous cultural adaptation process.The evidence shows that the Chinese version of the Communication Complexity Scale is a reliable and valid tool for children with minimal verbal skills in China.The Chinese version of the Communication Complexity Scale can be used in research and clinical practice to assess the general level of social communication skills of Chinese children who mainly communicate using preverbal communication and develop intervention programs.

Molecular evolution and phylogenomic analysis of complete chloroplast genomes of Cotinus (Anacardiaceae).

Cotinus is an oligo-specific ornamentally valuable genus with a disjunct distribution in the Northern Hemisphere. Traditionally, the taxonomy of Cotinus was mainly based on leaf morphological characteristics. However, the limited availability of genomic information greatly hindered the study of molecular evolution and phylogeny of this genus. This study sequenced the chloroplast (cp) genomes of all currently recognized taxa of Cotinus, including three species and four varieties. A comparative analysis was performed to investigate their cp genome characteristics and evolution. Furthermore, we inferred the phylogenetic relationships of Cotinus based on whole cp genomes, protein-coding genes, and nuclear ITS data. All cp genomes exhibited a typical quadripartite structure with genome sizes ranging from 158,865 to 160,155 bp. A total of 113-114 genes were identified in the genomes. Seven non-coding and four coding regions were identified as the most divergent hotspots for potential molecular barcodes and phylogenetic markers. Selection pressure analysis showed that there had been positive selection on genes matK and rps8 in the Cotinus cp genomes. Phylogenetic results confirmed that Cotinus is a monophyletic group but the widely distributed species Cotinus coggygria is not monophyletic. The divergence-time analysis suggested that Cotinus underwent an evolutionary divergence from the middle Eocene and rapid adaptive radiation from the middle Miocene. This study revealed new insights into the cp genome evolution and phylogeny of Cotinus and related taxa.

Plastome evolution and phylogeny of the tribe Ruteae (Rutaceae).

Rutaceae is a large family, and the genus-level classification in the subfamilies or tribes of this family is not unified based on different taxonomic treatments. Until now, phylogenetic relationships of some genera in traditional tribe Ruteae have not been clearly resolved. In this study, seven new complete plastomes of this tribe were sequenced, and a comparative analysis was performed to investigate their plastome characteristics and evolution. In addition, we inferred the phylogenetic relationships of Ruteae based on complete plastome and nuclear ITS data. All plastomes exhibited a typical quadripartite structure and were relatively conserved in their structure and gene arrangement. Their genome sizes ranged from 154,656 bp to 160,677 bp, and the size variation was found to be associated with differences in IR expansion and gene loss. A total of 112 to 114 genes were identified in the genomes, including 78 to 79 protein-coding genes, 30 tRNA genes, 4 rRNA genes, and 2 pseudogenes. Sequence divergence analysis indicated that non-coding regions exhibited a higher percentage of variable characters, and nine non-coding and six coding regions were identified as divergent hotspots. Phylogenetic results based on different datasets showed that this tribe was divided into three reciprocally exclusive groups. The phylogenetic analyses between plastome and nuclear ITS data were partly incongruent with each other. This study provides new insights into plastome evolution of Ruteae as well as Rutaceae. The availability of these plastomes provides useful genomic resources for molecular DNA barcodes and phylogenetically informative markers and deepens our understanding of the phylogeny in Ruteae.

Reduced audiovisual temporal sensitivity in Chinese children with dyslexia.

Background: Temporal processing deficits regarding audiovisual cross-modal stimuli could affect children's speed and accuracy of decoding. Aim: To investigate the characteristics of audiovisual temporal sensitivity (ATS) in Chinese children, with and without developmental dyslexia and its impact on reading ability. Methods: The audiovisual simultaneity judgment and temporal order judgment tasks were performed to investigate the ATS of 106 Chinese children (53 with dyslexia) aged 8 to 12 and 37 adults without a history of dyslexia. The predictive effect of children's audiovisual time binding window on their reading ability and the effects of extra cognitive processing in the temporal order judgment task on participants' ATS were also investigated. Outcomes and results: With increasing inter-stimulus intervals, the percentage of synchronous responses in adults declined more rapidly than in children. Adults and typically developing children had significantly narrower time binding windows than children with dyslexia. The size of visual stimuli preceding auditory stimuli time binding window had a marginally significant predictive effect on children's reading fluency. Compared with the simultaneity judgment task, the extra cognitive processing of the temporal order judgment task affected children's ATS. Conclusion and implications: The ATS of 8-12-year-old Chinese children is immature. Chinese children with dyslexia have lower ATS than their peers.

Ferula sinkiangensis against gastric cancer: a network pharmacology, molecular docking and cell experiment study.

Background: Ferula sinkiangensis (F. sinkiangensis) is a traditional Chinese medicine that has been used for thousands of years to treat stomach ailments. To identify the main active compounds and explore the mechanisms underlying the therapeutic effect of F. sinkiangensis against gastric cancer (GC) by network pharmacology, molecular docking analysis and cell experiment. Methods: Based on a review of the literature and previous experiments conducted by our research group, the active compounds of F. sinkiangensis were obtained. Active compounds and their target genes were screened from SwissADME, Pubchem, and Pharmmapper databases. GC-related target genes were obtained from GeneCards. The drug-compound-target-disease (D-C-T-D) network and protein-protein interaction (PPI) network were constructed by Cytoscape 3.7.2 and STRING database, and the core target genes and core active compounds were identified. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using the R package clusterProfiler. The core genes with high expression in GC were screened, which correlated with a poor prognosis using the GEPIA, UALCAN, HPA, and KMplotter databases. KEGG signaling pathway analysis was further conducted to predict the mechanism of F. sinkiangensis during the process of GC inhibition. The AutoDock vina 1.1.2 program was used to verify the molecular docking of the core active compounds and core target genes. MTT, Transwell, and Wound healing assay were used to detect the effects of ethyl acetate extract of F. sinkiangensis on the proliferation, invasion, and apoptosis of GC cells. Results: Final results indicated that the active compounds include Farnesiferol C, Assafoetidin, Lehmannolone, Badrakemone, etc. The identified core target genes were GPI, TKT, GLYCTK, ERBB2, GAPDH, etc. The Glycolysis/Gluconeogenesis pathway and the Pentose Phosphate pathway might play important roles in the treatment of GC with F. sinkiangensis. The data from the study showed that F. sinkiangensis was able to inhibit the proliferation of GC cells. Meanwhile, F. sinkiangensis remarkedly repressed the invasion and migration of GC cells in in vitro experiment. Conclusions: This study revealed that F. sinkiangensis has an antitumor effect in in vitro experiment, and that the mechanism of F. sinkiangensis in GC treatment shows characteristics of multi-components, multi-targets, and multi-pathways, which provides a theoretical basis for its clinical application and subsequent experimental verification.

Early diagnosis of heterotopic ossification with a NIR fluorescent probe by targeting type II collagen.

Heterotopic ossification (HO) is a devastating sequela in which the pathologic extracellular matrix of the cartilage and bone forms abnormally in soft tissues following traumatic injuries or orthopaedic surgeries. Early treatment is essential for inhibiting the progression of HO but is currently limited by the absence of sensitive and specific early diagnosis. Herein, this study exploits the enrichment of type II collagen (Col2a1) in the HO cartilage formation stage towards developing a near-infrared (NIR) probe for early HO diagnosis, namely WL-808 by conjugating a Col2a1-binding peptide (WYRGRL) and a cyanine dye (IR-808). WL-808 exhibits high specificity for targeting the cartilage in vitro and in vivo with no apparent cytotoxicity. The NIR signal of WL-808 can be detected in the HO cartilage lesions as early as 1 week after injury when micro-CT cannot show any ectopic bone formation. Moreover, the probe is rarely distributed in the normal knee articular cartilage in vivo via the intravenous administration method. Taken together, WL-808 demonstrates great potential in early HO diagnosis under NIR imaging, facilitating early HO prophylaxis and treatment in the clinic.

Bioinspired strontium magnesium phosphate cement prepared utilizing the precursor method for bone tissue engineering.

Bioinspired strontium magnesium phosphate cements for bone tissue engineering were prepared using a new, facile, environmentally friendly and high yielding (98.5%) precursor method. The bioinspired SMPCs have uniform particle distributions, excellent mechanical strengths and high biocompatibilities. The in vitro responses of bone marrow stromal cells to the SMPCs, including viability, osteogenic differentiation and alkaline phosphatase activity, were evaluated. The results show that the SMPC containing 0.5 mol of strontium (referred to as SMPC-2) has a higher degradation rate and biological activity than magnesium phosphate cements and the other SMPCs. In addition, the synergistic effect of strontium and magnesium ion release from SMPC-2 creates a conducive environment for cell proliferation, mineralized calcium deposition and new bone formation. These observations demonstrate the feasibility of using the new precursor method to generate SMPCs and the utility of these biologically compatible and highly effective cements for bone tissue engineering.

Sustained notch signaling inhibition with a gamma-secretase inhibitor prevents traumatic heterotopic ossification.

Background: Traumatic heterotopic ossification (THO) is a devastating sequela following traumatic injuries and orthopedic surgeries. To date, the exact molecular mechanism of THO formation is still unclear, which hinders the development of effective treatments. The process of THO formation is believed to recapitulate a series of spatiotemporal cellular and signaling events that occur during skeletal development. The Notch signaling pathway is a critical genetic regulator in embryological bone development and fracture healing. However, few data are available concerning whether Notch signaling regulates THO development and maturation. Methods: We firstly detected the expressions of Notch target genes in both mouse and human THO samples with quantitative RT-PCR and immunohistochemistry (IHC). Then, tissue-resident mesenchymal progenitor cells (TMPCs) were isolated, and the abilities of the proliferation and osteogenic and chondrogenic differentiation of TMPCs were examined under the intervention of the gamma-secretase inhibitor-DAPT at different time points. Finally, DAPT was also administrated in THO mice by burn and Achilles tenotomy injury, and ectopic cartilage and bone formation were monitored by histology and micro-CT. Results: Several Notch target genes were upregulated in both mouse and human THO tissues. Sustained Notch signaling inhibition by DAPT reduced proliferation, osteogenic and chondrogenic differentiation of TMPCs in a time-dependent manner. Moreover, DAPT administration within 3 weeks could inhibit ectopic cartilage and bone formation in a mouse THO model without affecting the total body bone mass. Conclusions: The Notch signaling serves as an important therapeutic target during THO formation. And sustained gamma-secretase inhibition by DAPT has great potential in repressing chondrogenic and osteogenic differentiation of TMPCs, as well as inhibited ectopic cartilage and bone formation in vivo. The translational potential of this article: Sustained Notch inhibition via systemic DAPT (or other similar gamma-secretase inhibitors) administration has promising clinical utility for inhibiting THO formation, providing new insight into THO prophylaxis and treatment.

The Oral Microbiome as Mediator between Oral Hygiene and Its Impact on Nasopharyngeal Carcinoma.

Oral hygiene and the alteration of the oral microbiome have been linked to nasopharyngeal carcinoma (NPC). This study aimed to investigate whether the oral microbiome plays a mediating role in the relationship between oral hygiene and NPC, and identify differential microbial taxonomies that potentially mediated this association. We conducted a case-control study that involved 218 NPC patients and 192 healthy controls. The 16S rRNA gene sequencing of the V4 region was performed to evaluate the composition of the oral microbiome. Mediation analysis was applied to explore the relationship among oral hygiene, the oral microbiome and NPC. We found that dental fillings and poor oral hygiene score were associated with increased risks of NPC (OR = 2.51 (1.52-4.25) and OR = 1.54 (1.02-2.33)). Mediation analysis indicated that dental fillings increased the risk of NPC by altering the abundance of Erysipelotrichales, Erysipelotrichaceae, Solobacterium and Leptotrichia wadei. In addition, Leptotrichia wadei also mediated the association between oral hygiene score and the risk of NPC. Our study confirmed that poor oral hygiene increased the risk of NPC, which was partly mediated by the oral microbiome. These findings might help us to understand the potential mechanism of oral hygiene influencing the risk of NPC via the microbiome.

Complete chloroplast genome and phylogenetic analysis of Acer leipoense (Sapindaceae), a rare plant from Southwest China.

Acer leipoense is a rare and endangered species of the Sapindaceae with a very restricted distribution in Sichuan, China. In this study, the complete chloroplast genome of A. leipoense was characterized by de novo assembly using high-throughput sequencing. The chloroplast genome was 155,702 bp in length; it contained a large single copy region (85,890 bp) and a small single copy region (18,100 bp), which were separated by a pair of 25,856-bp inverted repeat regions. A total of 128 genes were predicted, including 83 protein-coding genes, 37 tRNA genes, and eight rRNA genes. A phylogenetic analysis of 23 chloroplast genome sequences from the genus Acer revealed that A. leipoense was closely related to A. yangbiense.

Chinese language teachers' dichotomous identities when teaching ingroup and outgroup students.

Research into second language teacher identity has experienced a shift in recent years from a cognitive perspective to social constructionist orientation. The existing research in Chinese language literature in relation to Foreign Language (CFL) teachers' identity shift is principally in relation to the change of social, cultural, and institutional contexts. Built on the current literature, this research asks: "How might teachers' self-images or self-conceptualizations be renegotiated when they are located within their own mainstream cultural and educational system, yet comprised of students from various cultural backgrounds?" The data were collected from a group of CFL teachers in a South China university. The research found that students' backgrounds largely impacted on, and led to, the teachers' dichotomous relational identities, but did not dramatically change the teachers' perception on what or how much subject knowledge to be possessed to make an ideal CFL teacher. This attribute of their identity was sustained even though the teaching content was modified at a practical level in response to groups' differences. Further, the CFL teachers' pedagogical identity remained stable with only minor modifications when teaching "ingroups" and "outgroups" of students.