METTL3-mediated m^(6)A RNA methylation regulates dorsal lingual epithelium homeostasis

The dorsal lingual epithelium,which is composed of taste buds and keratinocytes differentiated from K14^(+)basal cells,discriminates taste compounds and maintains the epithelial barrier.N6-methyladenosine(m^(6)A)is the most abundant mRNA modification in eukaryotic cells.How METTL3-mediated m^(6)A modification regulates K14^(+)basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear.Here we show knockout of Mettl3 in K14^(+)cells reduced the taste buds and enhanced keratinocytes.Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds.Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization,but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery.Mechanically,we revealed that the most frequent m^(6)A modifications were enriched in Hippo and Wnt signaling,and specific peaks were observed near the stop codons of Lats1 and FZD7.Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.

Magnesium promotes vascularization and osseointegration in diabetic states

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg^(2+)promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated thealveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg^(2+)promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells,thus reducing theelevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg^(2+)promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondria metabolism.

Genomic alterations in oral multiple primary cancers

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs.Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

Mapping the immune microenvironment for mandibular alveolar bone homeostasis at single-cell resolution

Alveolar bone is the thickened ridge of jaw bone that supports teeth.It is subject to constant occlusal force and pathogens invasion,and is therefore under active bone remodeling and immunomodulation.Alveolar bone holds a distinct niche from long bone considering their different developmental origin and postnatal remodeling pattern.However,a systematic explanation of alveolar bone at single-cell level is still lacking.Here,we construct a single-cell atlas of mouse mandibular alveolar bone through single-cell RNA sequencing(scRNA-seq).A more active immune microenvironment is identified in alveolar bone,with a higher proportion of mature immune cells than in long bone.Among all immune cell populations,the monocyte/macrophage subpopulation most actively interacts with mesenchymal stem cells(MSCs)subpopulation.Alveolar bone monocytes/macrophages express a higher level of Oncostatin M(Osm)compared to long bone,which promotes osteogenic differentiation and inhibits adipogenic differentiation of MSCs.In summary,our study reveals a unique immune microenvironment of alveolar bone,which may provide a more precise immune-modulatory target for therapeutic treatment of oral diseases.

Solar Thermal Application for the Dairy Industry in Taiwan

Taiwan has been developing clean energy and solar heating for hot water production is a mature technology. The subsidy program (2000-2016) for solar water heaters means that the cumulative area of solar collectors installed was approximately 2.52 million square meters at the end of 2016, in which more than 93% have been installed in the domestic sector. Industrial heat processes represent an area for solar thermal application. This study presents field measurements for solar water heaters installed for sterilization in dairy industry. Global solar radiation can be correlated with the system’s thermal efficiency reasonably well. As a pre-heating system, financial viability is validated.

Dynamic mechanical loading facilitated chondrogenic differentiation of rabbit BMSCs in collagen scaffolds

Mechanical signals have been played close attention to regulate chondrogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).In this study,dynamic mechanical loading simulation with natural frequencies and intensities were applied to the 3D cultured BMSCs–collagen scaffold constructs.We investigated the effects of dynamic mechanical loading on cell adhesion,uniform distribution,proliferation,secretion of extracellular matrix(ECM)and chondrogenic differentiation of BMSCs–collagen scaffold constructs.The results indicated that dynamic mechanical loading facilitated the BMSCs adhesion,uniform distribution,proliferation and secretion of ECM with a slight contraction,which significantly improved the mechanical strength of the BMSCs–collagen scaffold constructs for better mimicking the structure and function of a native cartilage.Gene expression results indicated that dynamic mechanical loading contributed to the chondrogenic differentiation of BMSCs with higher levels of AGG,COL2A1 and SOX9 genes,and prevented of hypertrophic process with lower levels of COL10A1,and reduced the possibility of fibrocartilage formation due to down-regulated COL1A2.In conclusion,this study emphasized the important role of dynamic mechanical loading on promoting BMSCs chondrogenic differentiation and maintaining the cartilage phenotype for in vitro reconstruction of tissue-engineered cartilage,which provided an attractive prospect and a feasibility strategy for cartilage repair.