Abnormal accumulation of collagen fibrils is a hallmark feature of oral submucous fibrosis (OSF). However, the precise characteristics and underlying mechanisms remain unclear, impeding the advancement of potential therapeutic approaches. Here, we observed that collagen I, the main component of the extracellular matrix, first accumulated in the lamina propria and subsequently in the submucosa of OSF specimens as the disease progressed. Using RNA-seq and Immunofluorescence in OSF specimens, we screened the cartilage oligomeric matrix protein (COMP) responsible for the abnormal collagen accumulation. Genetic COMP deficiency reduced arecoline-stimulated collagen I deposition significantly in vivo. In comparison, both COMP and collagen I were upregulated under arecoline stimulation in wild-type mice. Human oral buccal mucosal fibroblasts (hBMFs) also exhibited increased secretion of COMP and collagen I after stimulation in vitro. COMP knockdown in hBMFs downregulates arecoline-stimulated collagen I secretion. We further demonstrated that hBMFs present heterogeneous responses to arecoline stimulation, of which COMP-positive fibroblasts secrete more collagen I. Since COMP is a molecular bridge with Fibril-associated collagens with Interrupted Triple helices (FACIT) in the collagen network, we further screened and identified collagen XIV, a FACIT member, co-localizing with both COMP and collagen I. Collagen XIV expression increased under arecoline stimulation in wild-type mice, whereas it was hardly expressed in the Comp^-/- mice, even with under stimulation. In summary, we found that COMP may mediates abnormal collagen I deposition by functions with collagen XIV during the progression of OSF, suggesting its potential to be targeted in treating OSF.
Oral Submucous Fibrosis/pathology* ; Cartilage Oligomeric Matrix Protein/genetics* ; Animals ; Mice ; Humans ; Fibroblasts/metabolism* ; Collagen Type I/metabolism* ; Arecoline/pharmacology* ; Mouth Mucosa/metabolism* ; Cells, Cultured ; Fluorescent Antibody Technique

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

Objective To evaluate the effect of donor gender on short-term survival rate of lung transplant recipients. Methods A retrospective analysis was conducted on the data of 1 066 lung transplant recipients. The log-rank test was used to evaluate the differences in short-term fatality among different donor gender groups and donor-recipient gender combination groups. Multivariate Cox regression, propensity score (PS) regression, and propensity score matching (PSM) were employed to control for confounding factors and further assess the differences in fatality. Subgroup analyses were also performed based on donor gender. Results Multivariate Cox regression analysis showed no statistically significant differences in fatality at 30 days, 1 year, 2 years and 3 years postoperatively between male and female donor groups (all P>0.05). After PS regression and PSM, univariate Cox regression analysis indicated that recipients from female donors had a higher fatality at 2 years postoperatively compared to those from male donors, with hazard ratios (95% confidence intervals) of 1.29 (1.01-1.65) and 1.36 (1.03-1.80) respectively. Multivariate Cox regression analysis also revealed no statistically significant differences in fatality at various follow-up time points among different donor-recipient gender combination groups (all P>0.05). Subgroup analyses based on donor sex showed no statistically significant differences in fatality among recipients of different gender within either male or female donor groups (all P>0.05). Conclusions Female donors may reduce the short-term postoperative survival rate of lung transplant recipients, but this negative impact is not sustainable in the long term. At present, there is no evidence to support the inclusion of sex as a factor in lung allocation rules.

Objective: To examine the causal association and potential mechanisms between bone mineral density in different age groups and primary malignant bone tumor based on two sample Mendelian randomization (MR), so as to provide a reference for the prevention and treatment of primary malignant bone tumor. Methods: The genome-wide association study (GWAS) of bone mineral density was obtained from the GEFOS database,which included 66 628 subjects divided into five age groups (0-15, 15-30, 30-45, 45-60, and >60 years) based on the phases of human bone development. The GWAS of primary malignant bone tumor was sourced from the FinnGen database, including 648 cases and 378 749 controls. Using bone mineral density of five age groups as the exposure and primary malignant bone tumor as the outcome, an MR analysis was performed with the inverse-variance weighted (IVW) method. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO test and MR Steiger test. The potential mechanisms underlying the causal association between bone density and primary malignant bone tumors were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: The MR analysis results showed that there was a negative causal association between bone density and primary malignant bone tumors in the 30-45 age group (OR=0.301, 95%CI: 0.126-0.721). No statistically significant associations between bone density and primary malignant bone tumors were found in the 0-15, 15-30, 45-60, and >60 age groups (all P>0.05). Sensitivity analysis did not detect heterogeneity, pleiotropy (all P>0.05) and reverse causality. KEGG enrichment analysis revealed that genes highly associated with bone density and primary malignant bone tumors were enriched in the mTOR signaling pathway and the Wnt signaling pathway, among which Low Density lipoprotein Receptor Related protein 5 and Wnt Family Member 16 are key regulatory genes. Conclusion The decrease in bone mineral density among individuals aged 30-45 may increase the risk of primary malignant bone tumors through the mTOR signaling pathway and the Wnt signaling pathway.

Organ transplantation has become an effective treatment for multiple end-stage diseases. However, the recipients of organ transplantation need to take immunosuppressive drugs for a long time after operation, which leads to low immune function and relatively high incidence of bacterial, viral and fungal infections. Traditional microbial detection methods, such as pathogen culture, immunological detection and polymerase chain reaction, have been widely applied in infection detection, whereas these methods may cause problems, such as long detection time and presumed pathogens. Metagenomic next-generation sequencing has been widely adopted in infection prevention and control in organ transplantation in recent years due to high detection rate and comprehensive detection of pathogen spectrum. In this article, the application of metagenomic next-generation sequencing in the prevention and control of infection in solid organ transplantation was reviewed, aiming to provide reference for the diagnosis and treatment of transplantation-related infection.

Lung transplantation is an effective means of treating various end-stage lung diseases.However,compared with other solid organ transplants,the survival rate after lung transplantation is relatively low.The main reason is the numerous complications after lung transplantation,among which infection is one of the most common complications.Respiratory viral infections are an important type of infection after lung transplantation,which severely affect the survival time and quality of life of lung transplant recipients.Early identification,early prevention,and active diagnosis and treatment are of great significance in reducing the incidence and fatality of respiratory viral infections after lung transplantation.This article reviews the epidemiology,risk factors,prevention and treatment principles,and specific prevention and treatment progress of common viruses in respiratory viral infections after lung transplantation at home and abroad,in order to provide a reference for the prevention and treatment of respiratory viral infections after lung transplantation in clinical practice.

Objective To observe the effects of acupuncture at acupoints along the meridians on the expression of frontal lobe associated protein kinase in pchlorophenylalanine(PCPA)induced insomnia rats;To explore the mechanism of acupuncture in improving insomnia.Methods Totally 60 rats were randomly divided into blank group,model group,sham acupuncture group,acupuncture group and Western medicine group,with 12 rats in each group.An insomnia model rat was induced by intraperitoneal injection of PCPA.The acupuncture group received acupuncture at"Baihui","Shenmen"(bilateral),and"Sanyinjiao"(bilateral),while the sham acupuncture group only fixed the needle at the corresponding acupoints but did not penetrate the skin,while the model group was only fixed for 30 minutes,the Western medicine group was given a solution of estazolam by gavage for 7 consecutive days,the blank group was not treated.The pentobarbital sodium reversal experiment was used to detect the sleep latency and sleep time of rats,ELISA was used to detect the content of melatonin(MT)in plasma,RT-PCR was used to detect the mRNA expressions of calmodulin dependent protein kinase(CaMK)Ⅱ,protein kinase C(PKC)and p38 mitogen activated protein kinase(MAPK)in frontal lobe tissue,and Western blot was used to detect the protein expressions of CaMKⅡ,PKC and p38MAPK in frontal lobe tissue.Results Compared with the blank group,the sleep latency of the model group rats were significantly prolonged and the sleep time were significantly shortened(P<0.01),the content of MT in plasma was significantly reduced(P<0.01),and the mRNA and protein expressions of CaMKⅡ and PKC in frontal lobe tissue were significantly decreased(P<0.01),the mRNA and protein expressions of p38MAPK were significantly increased(P<0.01).Compared with the model group,the sleep latency were significantly shortened and the sleep time were significantly prolonged in the acupuncture group and the Western medicine group(P<0.01),the plasma MT content significantly increased(P<0.01),the mRNA and protein expressions of CaMKⅡ and PKC in frontal lobe tissue significantly increased(P<0.05),and the mRNA and protein expression of p38MAPK significantly decreased(P<0.01).Compared with the sham acupuncture group,the sleep latency shortened and sleep time were significantly prolonged in the acupuncture group and the Western medicine group(P<0.01),plasma MT content significantly increased(P<0.01),PKC mRNA expression in frontal lobe tissue significantly increased(P<0.01),and p38MAPK mRNA expression significantly decreased(P<0.01).There was no statistically difference in various indicators between the acupuncture group and the Western medicine group(P>0.05).Conclusion Acupuncture at acupoints along the meridians can shorten the sleep latency and prolong sleep time,improve sleep status by regulating the expression of associated protein kinase in frontal lobe of insomnia rats.

Objective:To explore the causes of the crosstalk in the gross α and gross β measurement using an MPC 9604 low background α/β counter.Methods:With the A4 copy paper (70 g/m 2), polyethylene (PE) films (8.7 g/m 2), and 304 stainless steel seperately as shielding materials, the gross α and gross β experiments, gamma spectrometry experiments and solid state nuclear track detection (SSNTD) experiments were conducted by using 241Am and 40K standard materials. A comprehensive analysis encompassing statistical analysis and nuclear physics analysis was performed to reveal the impact of contributing factors on the crosstalk in the gross α and gross β measurement with an MPC 9604 low background α/β counter. Results:241Am powder source experimental result: when two sheets of copy paper were used in the experiment, α-rays did not generate one count in the β channel of the low background α/β counter. The same test with the shielding material of two layers of PE films showed that the α count rate further decreased by about 36.5%, while the β count rate hardly changed. The gross α and gross β experiments and γ spectrometry with the shielding material of stainless steel demonstrated that the characteristic γ ray peaking at 59.5 keV of the 241Am powder source did not generate one count in the β channel. 40K powder source experimental result: when the source was covered with steel of total thickness of 0.965 mm in the gross α and gross β experiments, the γ rays of 40K did not generate one count in the β channel. Compared with naked 40K powder source, when source was covered with one and two sheets of copy paper, the gross α count rate decreased approximately from 3.30 × 10 -3 to 1.50 × 10 -3 and 1.75 × 10 -3, respectively. The SSNTD indicated the presence of other α nuclides in 40K powder source. Conclusions:The β counting in the β channel with the 241Am powder source using MPC 9604 low background α/β counter was, instead of α-rays, caused by the internal conversion electrons and the characteristic X rays of 11.870-22.402 keV emitted from the 241Am powder source, thus this is not a true α/β crosstalk. The α counting in α channel with the 40K powder source, except the contribution of impurity α nuclides, was mainly attributed to the α signals arising from β particles when the amplitude of the piled-up β pules exceeded the discrimination threshold of the detector, therefore it is a true crosstalk.

Reactive oxygen species (ROS)-mediated anticancer modalities, which disturb the redox balance of cancer cells through multi-pathway simulations, hold great promise for effective cancer management. Among these, cooperative physical and biochemical activation strategies have attracted increasing attention because of their spatiotemporal controllability, low toxicity, and high therapeutic efficacy. Herein, we demonstrate a nanogel complex as a multilevel ROS-producing system by integrating chloroperoxidase (CPO) into gold nanorod (AuNR)-based nanogels (ANGs) for cascade-amplifying photothermal-enzymatic synergistic tumor therapy. Benefiting from photothermal-induced hyperthermia upon near-infrared (NIR) laser exposure, the exogenous ROS (including H₂O₂) were boosted by the AuNR nanogel owing to the intercellular stress response. This ultimately promoted the efficient enzyme-catalyzed reaction of loaded CPO combined with the rich endogenous H₂O₂ in tumor cells to significantly elevate intracellular ROS levels above the threshold for improved therapeutic outcomes. Both in vitro and in vivo studies have verified the cascade-amplifying ROS-mediated antitumor effects, providing feasible multimodal synergistic tactics for tumor treatment.