Research progress on roles of iron metabolism in the occurrence and development of periodontitis. / é“ä»£è°¢åœ¨æ ¢æ€§ç‰™å‘¨ç‚Žå‘ç”Ÿå‘å±•ä¸­çš„ä½œç”¨ç ”ç©¶è¿›å±•.

Iron metabolism refers to the process of absorption, transport, excretion and storage of iron in organisms, including the biological activities of iron ions and iron-binding proteins in cells. Clinical research and animal experiments have shown that iron metabolism is associated with the progress of periodontitis. Iron metabolism can not only enhance the proliferation and toxicity of periodontal pathogens, but also activate host immune- inflammatory response mediated by macrophages, neutrophils and lymphocytes. In addition, iron metabolism is also involved in regulating the cellular death sensitivity of gingival fibroblasts and osteoblasts and promoting the differentiation of osteoclasts to play a regulatory role in the regeneration and repair of periodontal tissue. This article reviews the research progress on the pathogenesis of periodontitis from the perspective of iron metabolism, aiming to provide new ideas for the treatment of periodontitis.

Research progress on the regulatory cell death of osteoblasts in periodontitis. / ç‰™å‘¨ç— ä¸­æˆéª¨ç»†èƒžè°ƒèŠ‚æ€§ç»†èƒžæ­»äº¡çš„ç ”ç©¶è¿›å±•.

Periodontitis is a chronic inflammatory disease characterized by progressive destruction of alveolar bone. The most critical mechanism underlying alveolar bone destruction is the imbalance of bone homeostasis, where osteoblast-mediated bone matrix synthesis plays an important role in regulating bone homeostasis. Regulatory cell death is instrumental in both the inflammatory microenvironment and the regulation of bone homeostasis. Chronic inflammation, oxidative stress, and other factors can be directly involved in mitochondrial and death receptor-mediated signaling pathways, modulating B-cell lymphoma 2 (Bcl-2) family proteins and cysteine aspartic acid specific protease (caspase) activity, thereby affecting osteoblast apoptosis and alveolar bone homeostasis. Chronic inflammation and cellular damage induce osteoblast necroptosis via the RIPK1/RIPK3/MLKL signaling pathway, exacerbating the inflammatory response and accelerating alveolar bone destruction. Stimuli such as pathogenic microorganisms and cellular injury may also activate caspase-1-dependent or independent signaling pathways and gasdermin D (GSDMD) family proteins, promoting osteoblast pyroptosis and releasing pro-inflammatory cytokines to mediate alveolar bone damage. Iron overload and lipid peroxidation in periodontitis can trigger ferroptosis in osteoblasts, impacting their survival and function, ultimately leading to bone homeostasis imbalance. This article focuses on the mechanism of periodontal disease affecting bone homeostasis through regulatory cell death, aiming to provide research evidence for the treatment of periodontitis and alveolar bone homeostasis imbalance.

CircRRAS2 promotes myogenic differentiation of bovine MuSCs and is a novel regulatory molecule of muscle development.

The proliferation and myogenic differentiation of muscle stem cells (MuSCs) are important factors affecting muscle development and beef quality. There is increasing evidence that circRNAs can regulate myogenesis. We found a novel circRNA, named circRRAS2 that is significantly upregulated in the differentiation phase of bovine MuSCs. Here, we aimed to determine its roles in the proliferation and myogenic differentiation of these cells. The results showed that circRRAS2 was expressed in several bovine tissues. CircRRAS2 inhibited MuSCs proliferation and promoted myoblast differentiation. In addition, chromatin isolation by using RNA purification and mass spectrometry in differentiated muscle cells identified 52 RNA-binding proteins that could potentially bind to circRRAS2, in order to regulate their differentiation. The results suggest that circRRAS2 could be a specific regulator of myogenesis in bovine muscle.HighlightsCircRRAS2 expression is higher in DM cells than in GM cells.CircRRAS2 could significantly inhibit the proliferation and apoptosis of bovine MuSCs.CircRRAS2 promotes the differentiation of bovine MuSCs into myotubes.CircRRAS2 may exert regulatory effects through multiple RNA binding proteins.

CircUBE2Q2 promotes differentiation of cattle muscle stem cells and is a potential regulatory molecule of skeletal muscle development.

BACKGROUND: The growth and development of muscle stem cells (MuSCs) are significant events known to affect muscle plasticity, disease, meat production, and meat quality, which involves the types and functions of mRNA and non-coding RNA. Here, MuSCs were cultured from Guangxi fetal cattle. RNA sequencing was used to analyze the RNA expression of mRNA and non-coding RNAs during the cell proliferation and differentiation phases. RESULTS: Two thousand one hundred forty-eight mRNAs and 888 non-coding RNAs were differentially expressed between cell proliferation and differentiation phases, including 113 miRNAs, 662 lncRNAs, and 113 circRNAs. RT-qPCR verified the differential expression levels of mRNAs and non-coding RNAs, and the differentially expressed circUBE2Q2 was subsequently characterized. Expression profile analysis revealed that circUBE2Q2 was abundant in muscle tissues and intramuscular fat. The expression of cricUBE2Q2 was also significantly upregulated during MuSCs myogenic differentiation and SVFs adipogenic differentiation and decreased with age in cattle muscle tissue. Finally, the molecular mechanism of circUBE2Q2 regulating MuSCs function that affects skeletal muscle development was investigated. The results showed that circUBE2Q2 could serve as a sponge for miR-133a, significantly promoting differentiation and apoptosis of cultured MuSCs, and inhibiting proliferation of MuSCs. CONCLUSIONS: CircUBE2Q2 is associated with muscle growth and development and induces MuSCs myogenic differentiation through sponging miR-133a. This study will provide new clues for the mechanisms by which mRNAs and non-coding RNAs regulate skeletal muscle growth and development, affecting muscle quality and diseases.

Global burden and inequality of iron deficiency: findings from the Global Burden of Disease datasets 1990-2017.

BACKGROUND: Iron deficiency (ID) impairs patient physical activity, recognition and life quality, which is difficult to perceive but should not be underestimated. Worldwide efforts have been made to lower ID burden, however, whether it decreased equally in different regions and sexes is unclear. This study is to examine regional and sex inequalities in global ID from 1990 to 2017. METHODS: We conducted a longitudinal, comparative burden-of-disease study. Disability-adjusted life-years (DALYs) of ID were obtained from Global Burden of Disease Report 2017. Human Development Index (HDI) data were obtained from Human Development Report 2017. Gini coefficient and the concentration index were calculated to assess the equities in global burden of ID. RESULTS: A downward trend of global ID burden (from 569.3 (95% Uncertainty Interval [UI]: 387.8-815.6) to 403.0 (95% UI: 272.4-586.6), p < 0.001), age-adjusted DALYs per 100,000 population) but an uptrend of its inequalities (from 0.366 to 0.431, p < 0.001, Gini coefficients) was observed between 1990 and 2017. ID burden was heavier in women than that in men ([age-adjusted DALYs per 100,000 population from 742.2 to 514.3] vs [from 398.5 to 291.9]), but its inequalities were higher in men since 1990. The between-sex gap of ID burden was narrowed with higher HDI (ß = - 364.11, p < 0.001). East Asia & Pacific and South Asia regions made a big stride for ID control in both sexes over decades [age-adjusted DALYs per 100,000 population from 378.7 (95% UI: 255.8-551.7) in 1990 to 138.9 (95%UI: 91.8-206.5) in 2017], while a heavy burden among Sub-Saharan African men was persistent[age-adjusted DALYs per 100,000 population, 572.5 (95% UI: 385.3-815) in 1990 and 562.6 (95% UI: 367.9-833.3) in 2017]. CONCLUSIONS: Redistributing attention and resources to help countries with low HDI, especially take care of women with low socioeconomic status (SES) and men under high ID burden may help hold back the expanding ID inequality.

RANKL expression of primary osteoblasts is enhanced by an IL-17-mediated JAK2/STAT3 pathway through autophagy suppression.

Objective: Interleukin-17 (IL-17), produced by T helper (Th)-17 cells, is a potent regulator of bone homeostasis. Osteoblasts are key cells that orchestrate inflammatory bone destruction and bone remodeling. This study examines the effect of different concentrations of IL-17 on osteogenesis and receptor activator of nuclear factor-kappa B ligand (RANKL) expression of primary osteoblasts.Methods: First, the growth of primary osteoblasts was evaluated. Second, we assessed the effects of IL-17 on the level of autophagy and the related Janus activated kinase 2 (JAK2) and downstream signal transducer and activator of transcription 3 (STAT3) signaling pathway. Next, osteogenic activity in different concentrations of IL-17 was tested. Finally, the specific JAK2/STAT3 signaling pathway inhibitor AG490 and autophagy inhibitor 3-MA were used to investigate the involvement of this pathway and autophagy in IL-17-induced regulation of RANKL expression.Results: Initially, we found that IL-17 treatment promoted growth of osteoblasts in a time- and dose-dependent manner. Next, we showed that low levels of IL-17 promoted autophagy activity, whereas the opposite was observed at high levels of IL-17. Moreover, high levels of IL-17 activated the JAK2/STAT3 signaling pathway, although this effect was reversed by upregulation of autophagy. Furthermore, our findings indicated that high concentrations of IL-17 promoted the differentiation, calcification, and RANKL expression of murine osteoblasts via activation of the JAK2/STAT3 pathway. Importantly, downregulation of autophagy at high IL-17 concentrations further enhanced RANKL expression via suppressing the JAK2/STAT3 cascade.Conclusion: Overall, our findings demonstrate, for the first time, that IL-17 modulates RANKL expression of osteoblasts through an autophagy-JAK2-STAT3 signaling pathway, thus affecting bone metabolism.

Rapid and sensitive detection of rotavirus by surface-enhanced Raman scattering immunochromatography.

A surface-enhanced Raman scattering (SERS) immunochromatographic assay (ICA) has been developed for rapid, ultrasensitive, and quantitative detection of rotavirus in feces using double Raman molecule-labeled Au-core Ag-shell nanoparticles. The Raman signals are generated by 5,5'-dithiobis-(2-nitrobenzoic acid) and the intensity of the characteristic peak at 1334-1 cm was detected as the analytical signal. The Raman signals were enhanced by the SERS-enhanced effect of both Au and Ag, the large amount of Raman molecules, and the hot-spot effect in the narrow gap between the Au core and Ag shell. The SERS ICA can quantitatively detect rotavirus in a concentration range of 8- 40,000 pg/mL, with detection limits of 80 pg/mL and 8 pg/mL based on naked eye observation and SERS signal detection, respectively. No cross-reaction was observed from other common pathogens. The standard deviation of the intra- and inter-batch repetitive tests is less than 10%, and the coincidence between SERS ICA and RT-qPCR as well as commercial colloidal gold ICA is 100%. The results indicated that this SERS ICA is able to quantitatively detect rotavirus in feces in 20 min with high sensitivity, selectivity, reproducibility, and accuracy and might be a promising method for the early detection of rotavirus in clinical analysis.

Global burden of periodontal disease and its relation with socioeconomic development during 1990-2019.

To analyze the global burden of periodontal disease and its relation with socioeconomic development. Data of global disability-adjusted life year (DALY) due to periodontal disease and human development index (HDI) from 1990 to 2019 were obtained from Global Health Data Exchange (GHDx) and human development reports. The trend of the global burden of periodontal disease from 1990 to 2019 was described. The correlation between age-standardized DALY rates and HDI were examined in 2019, and between-country periodontal disease burden inequality from 1990 to 2019 was measured using health-related Gini coefficients and concentration indexes. From 1990 to 2019, the global DALY rate due to periodontal disease increased from 78.63 to 85.48, and the epidemiological burden did not increase significantly. Statistical differences were found across different HDI categories for age-standardized DALY rates of periodontal disease ( 44.315, <0.01) in 2019. Linear regression analysis also revealed a negative correlation between age-standardized DALY rate of periodontal disease and HDI ( = -0.417, <0.01) . Gini coefficients decreased from 0.361 to 0.281 and concentration indexes fell from 0.0339 to -0.0538 between 1990 and 2019. The global burden of periodontal disease did not increase between 1990 and 2019, though the socioeconomic-associated inequality still existed. The burden of periodontal disease was more concentrated in less developed countries, and the socioeconomic-associated inequality has increased since 2000.

Optimization of parthenogenetic activation of rabbit oocytes and development of rabbit embryo by somatic cell nuclear transfer.

The present study explored a suitable parthenogenetic activation (PA) procedure for rabbit oocytes and investigated the developmental potential of somatic cell nuclear transfer (SCNT) embryos using rabbit foetal fibroblasts (RFFs). The electrical activation had the optimal rate of blastocyst (14.06%) when oocytes were activated by three direct current (DC) pulses (40 V/mm, 20 µs each) followed by 6-dimethylaminopurine (6-DMAP) and cycloheximide (CHX) treatment; the blastocyst rate of ionomycin (ION) + 6-DMAP + CHX (12.07%) activation was higher than that of ION + 6-DMAP (8.6%) activation or ION + CHX (1.24%) activation; there was no significant difference in blastocyst rate between ION + 6-DMAP + CHX and DC + 6-DMAP + CHX groups. The blastocyst rate of ION + 6-DMAP + CHX-activated oocytes in the basic rabbit culture medium (M-199) + 10% foetal bovine serum (FBS; 14.28%) was higher than that in buffalo conditioned medium (5.75%) or G1/G2 medium (0), and the blastocyst rate was increased when M-199 + 10% FBS was supplemented with amino acids. Refreshing culture medium every day or every other day significantly increased the blastocyst rate. Treatment of donor cells with 0.5% FBS for 3-5 days increased blastocyst rate of SCNT embryos (33.33%) than no serum starvation (22.47%) or 0.5% FBS treatment for 6-9 days (23.61%); the blastocyst rate of SCNT embryos derived from nontransgenic RFFs was higher than that derived from transgenic RFFs by electroporation. The blastocyst development ability of SCNT embryos derived from RFFs by electroporation (32.22%) was higher than that of liposome (19.11%) or calcium phosphate (20.00%) transfection, and only the embryos from electroporation group have the EGFP expression (24.44%). In conclusion, this study for the first time systematically optimized the conditions for yield of rabbit embryo by SCNT.

Efficient generation of sFat-1 transgenic rabbits rich in n-3 polyunsaturated fatty acids by intracytoplasmic sperm injection.

N-3 polyunsaturated fatty acids (n-3 PUFAs) have their first double bond at the third carbon from the methyl end of the fatty-acid chain and had been proven to be beneficial to human health. However, mammals cannot produce n-3 PUFAs by themselves because they lack the n-3 fatty-acid desaturase (Fat-1) gene. Thus, the possibility of producing sFat-1 transgenic rabbits was explored in this study. The transgenic cassette of pPGK1-sFat-1-CMV-EGFP was constructed and transgenic rabbit embryos were produced by intracytoplasmic sperm injection (ICSI). When 123 EGFP-positive embryos at the 2-8-cell stage were transplanted into the oviduct of four oestrous-synchronised recipients, two of them became pregnant and gave birth to seven pups. However, transfer of embryos into the uterus of oestrous-synchronised recipients and oviduct or uterus of oocyte donor rabbits did not result in pregnancy. The integration of the sFat-1 gene was confirmed in six of the seven live pups by PCR and Southern blot. The expression of the sFat-1 gene in the six transgenic pups was also detected by reverse transcription polymerase chain reaction (RT-PCR). Gas chromatography-mass spectrometry analysis revealed that transgenic rabbits exhibited an ~15-fold decrease in the ratio of n-6:n-3 PUFAs in muscle compared with wild-type rabbits and non-transgenic rabbits. These results demonstrate that sFat-1 transgenic rabbits can be produced by ICSI and display a low ratio of n-6:n-3 PUFAs.

Appreciable biosafety, biocompatibility and osteogenic capability of 3D printed nonstoichiometric wollastonite scaffolds favorable for clinical translation.

Background: Alveolar bone destruction due to periodontal disease often requires a bone graft substitute to reconstruct the anatomical structures and biological functions of the bone tissue. Despite significant advances in the development of foreign ion-doped nonstoichiometric wollastonite bioceramics (CaSiO3, nCSi) for alveolar bone regeneration over the past decade, the in vivo biosafety and osteogenesis of nCSi scaffolds remain uncertain. In this study, we developed a customized porous nCSi scaffold to investigate the in vivo biocompatibility and osteogenic properties of nCSi bioceramics. Methods: Six percent Mg-doped nCSi bioceramic scaffolds were fabricated by digital light processing (DLP), and the scaffold morphology, pore architecture, compressive strength, in vitro biodegradation, and apatite-forming ability of the bioceramic scaffolds were investigated systematically. Subsequently, an alveolar bone defect rabbit model was used to evaluate the biocompatibility and osteogenic efficacy of the nCSi bioceramics. Animal weight, hematological test, blood biochemical test, wet weight of the main organs, and pathological examination of the main organs were conducted. Micro-CT and histological staining were performed to analyze the osteogenic potential of the personalized bioceramic scaffolds. Results: The nCSi scaffolds exhibited appreciable initial compressive strength (>30 MPa) and mild mechanical decay over time during in vitro biodissolution. In addition, the scaffolds induced apatite remineralization in SBF. Bioceramic scaffolds have been proven to have good biocompatibility in vivo after implantation into the alveolar bone defect of rabbits. No significant effects on the hematological indices, blood biochemical parameters, organ wet weight, or organ histopathology were detected from 3 to 180 days postoperatively. The porous scaffolds exhibited strong bone regeneration capability in the alveolar bone defect model of rabbits. Micro-CT and histological examination showed effective maintenance of bone morphology in the bioceramic scaffold group; however, depressed bone tissue was observed in the control group. Conclusions: Our results suggest that personalized nCSi bioceramic scaffolds can be fabricated using the DLP technique. These newly developed strong bioceramic scaffolds exhibit good biocompatibility and osteogenic capability in vivo and have excellent potential as next-generation oral implants. The translational potential of this article: Tissue-engineered strategies for alveolar bone repair require a bone graft substitute with appreciable biocompatibility and osteogenic capability. This article provides a systematic investigation of the in vivo biosafety and osteogenic property of nCSi to further development of a silicate-based bioceramics materials for clinical applications.

Bioceramic scaffolds with two-step internal/external modification of copper-containing polydopamine enhance antibacterial and alveolar bone regeneration capability. / å«é“œèšå¤šå·´èƒºå† å¤–åŒä¿®é¥°æ³•æž„å»ºæŠ—èŒä¿ƒéª¨å†ç”Ÿç”Ÿç‰©é™¶ç“·æ”¯æž¶.

Magnesium-doped calcium silicate (CS) bioceramic scaffolds have unique advantages in mandibular defect repair; however, they lack antibacterial properties to cope with the complex oral microbiome. Herein, for the first time, the CS scaffold was functionally modified with a novel copper-containing polydopamine (PDA(Cu2+|)) rapid deposition method, to construct internally modified (*P), externally modified (@PDA), and dually modified (*P@PDA) scaffolds. The morphology, degradation behavior, and mechanical properties of the obtained scaffolds were evaluated in vitro. The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance. During the prolonged immersion stage, the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release. The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA, while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects. Finally, the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model. Overall, it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+) modification, and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

Production of cleavage-resistant phytase transgenic pigs by handmade cloning.

With the rapid development of intensive animal husbandry in the livestock industry, large quantities of manure waste containing phytate phosphorus are being generated. Phytase can effectively solve the problem of high phosphorus pollution in the feces of monogastric animals. Enviropig, which produces phytase in the salivary glands and secretes the enzyme in the saliva, were first generated in 1999. However, phytase is easily inactivated during digestion. To address this problem, cleavage-resistant phytase transgenic pigs were generated using handmade cloning in this study. Transgene construction was improved and three cell lines carrying Cafp were obtained. In total, 810 blastocysts were generated and 712 good-quality were transferred into six recipients. Fourteen piglets were born, of which six survived after weaning. Polymerase chain reaction and sequencing results showed that seven (three live and four dead) of the fourteen piglets carried Cafp. Phytase activity in the saliva of the six live cloned pigs was tested at four months of age, and only one pig had 0.155 FTU/mL enzyme activity. The other five pigs may not have been activated in the transgenic parotid gland. Among all the transgenic pigs, the highest phosphorus digestion rate was 59.2% of intake, representing a 25.4% decrease in fecal emission compared to the average of controls. Immunohistochemical results on the three Cafp-positive pigs that died after six months of age showed that the transgene was only expressed in parotid glands, confirming tissue-specific gene expression. In conclusion, cleavage-resistant phytase transgenic pigs were successfully produced through handmade cloning. The cloned pigs offer a unique biological approach to managing phosphorus nutrition and environmental pollution in animal husbandry.

Associations of periodontitis with risk of all-cause and cause-specific mortality among us adults with chronic kidney disease.

OBJECTIVES: To investigate the associations of periodontitis with risk of all-cause and cause-specific mortality in a nationally representative sample of adults with chronic kidney disease (CKD) in the United States. METHODS: This prospective cohort study included 4,271 individuals aged ≥30 years at baseline with CKD participants in the National Health and Nutrition Examination Survey (NHANES) during 1988-1994, 1999-2004, and 2009-2014. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 and/or urinary albumin/creatinine ratio (uACR) ≥30 mg/g. Multivariate cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of all-cause and cause-specific mortality in participants with CKD according to periodontitis. The associations of the quartiles of mean clinical attachment loss (CAL) and mean periodontal probing depth (PPD) levels with mortality were examined using the first quartile as the reference group. RESULTS: During a median of 8.67 years of follow-up, 2,146 deaths were documented. After multivariate adjustments, moderate/severe periodontitis was significantly associated with all-cause (HR:1.28; 95 % CI:1.11-1.47; P = 0.001) and cardiovascular disease (CVD)-related mortality (HR:1.44; 95 % CI:1.14-1.81; P = 0.002) in participants with CKD. Compared with the reference group of mean CAL and mean PPD levels, all-cause (CAL: HR, 1.58; 95 % CI, 1.32-1.89, P <0.001; PPD: HR, 1.35, 95 % CI, 1.09-1.67, P = 0.011) and CVD-related mortality (CAL: HR, 1.70, 95 % CI, 1.21-2.40, P = 0.001) were increased for participants in the highest quartile. CONCLUSIONS: This study suggests that moderate/severe periodontitis and high levels of mean CAL and mean PPD are associated with an increased risk of all-cause mortality, and moderate/severe periodontitis and mean CAL associated with CVD-related mortality among adults with CKD in the US. CLINICAL SIGNIFICANCE: This study details the association between periodontitis and the increased risk of all-cause mortality and CVD-related mortality in a large, representative sample of adults with CKD.

Ferritin was involved in interleukin-17A enhanced osteogenesis through autophagy activation.

Periodontitis is a prevalent inflammatory immune disease that involves tissue inflammation and excessive bone loss. In murine periodontitis models and periodontitis patients, upregulated interleukin-17A (IL-17A) expression was observed, and its level seemed to correlate with the disease severity. In this study, we intended to investigate the specific role of ferritin, a critical iron storage protein, in IL-17A enhanced osteogenic differentiation as well as the underlying mechanism. Under osteogenic induction, IL-17A stimulation promoted differentiation and mineralization of murine calvarial osteoblasts. In addition, increased iron accumulation and ferritin expression were detected in osteoblasts treated with IL-17A, indicating an alteration in iron metabolism during osteogenesis. Administration of iron chelator deferoxamine (DFO) and transfection with small interfering RNA (siRNA) targeting ferritin heavy chain (FTH) further revealed that ferritin suppression consequently inhibited osteoblast differentiation. Autophagy activation was also found upon IL-17A stimulation, which played a positive role in osteogenic differentiation and was subsequently suppressed by DFO or siRNA targeting FTH. In conclusion, IL-17A induced ferritin expression in osteoblasts, which further enhanced osteogenic differentiation via autophagy activation. These findings may provide further insight into the role of IL-17A in osteoblast differentiation and demonstrate ferritin as a potential target in modulating alveolar bone homeostasis.

Behavioral assessment scale of consciousness for nonhuman primates: A Delphi study.

OBJECTIVE: Nonhuman primates (NHPs) are suitable for being model animals in the study of consciousness and loss of consciousness (LoC) with a similar brain structure and function to humans. However, there is no effective consciousness assessment scale for them. This study aimed to develop a behavioral assessment scale of consciousness for NHPs. METHODS: We constructed an initial indicator framework based on the clinical consciousness disorder assessment scales and the physiological characteristics, consciousness, and arousal behavior of NHPs. A two-round online Delphi method was conducted by a multidisciplinary expert panel to construct a behavioral assessment scale of consciousness for NHPs. The indicators and descriptions were revised according to the experts' feedback and then sent out for repeated consultations along with a summary of the results of the previous round of consultations. The accepted competencies of indicators were established with mean scores in two scoring criteria (importance and feasibility) ≥4.0, agreement rate with a rating of importance or essential ≥70.0%, and a coefficient of variation ≤0.25, as well as discussions of the research group. RESULTS: Consensus was achieved after the second round of consultations, which was completed by 28 experts who specialized in rehabilitation, neuroscience, psychology, neurosurgery, and neurology. A new behavioral assessment scale of consciousness for NHPs, including 37 items organized hierarchically within seven dimensions including visual function, auditory function, motor function, orofacial movements, arousal, brainstem reflexes, and respiration, was developed in this study. CONCLUSIONS: This study has successfully developed a behavioral assessment scale for measuring the conscious state of NHPs or NHP models with LoC. This tool is expected to facilitate future research into the underlying mechanisms of consciousness by providing a detailed and comprehensive means of measurement.

Comparative and Functional Analysis of miRNAs and mRNAs Involved in Muscle Fiber Hypertrophy of Juvenile and Adult Goats.

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate several pathway intermediates and affect the skeletal muscle development in mice, pigs, sheep, and cattle. However, to date, only a small number of miRNAs have been reported in the muscle development of goats. In this report, the longissimus dorsi transcripts of one- and ten-month-old goats were analyzed by sequencing RNAs and miRNAs. The results showed that the ten-month-old Longlin goats had 327 up- and 419 down-regulated differentially expressed genes (DEGs) compared with the one-month-old. In addition, 20 co-up-regulated and 55 co-down-regulated miRNAs involved in the muscle fiber hypertrophy of goats were identified in ten-month-old Longlin and Nubian goats compared with one-month-old. Five miRNA-mRNA pairs (chi-let-7b-3p-MIRLET7A, chi-miR193b-3p-MMP14, chi-miR-355-5p-DGAT2, novel_128-LOC102178119, novel_140-SOD3) involved in the goat skeletal muscle development were identified by miRNA-mRNA negative correlation network analysis. Our results provided new insight into the functional roles of goat muscle-associated miRNAs, allowing a deeper understanding of the transformation of miRNA roles during mammalian muscle development.

3D printed bioceramic scaffolds: Adjusting pore dimension is beneficial for mandibular bone defects repair.

Bioceramic scaffolds for repairing mandibular bone defects have considerable effects, whereas pore architecture in porous scaffolds on osteogenesis in specific structures is still controversial. Herein 6 mol% magnesium-substituted calcium silicate scaffolds were fabricated with similar porosity (∼58%) but different cylindrical pore dimensions (Ø 480, 600, and 720 µm) via digital light processing-based three-dimensional (3D) printing technique. The mechanical properties, bioactive ion release, and bio-dissolution of the bioceramic scaffolds were evaluated in vitro, and the facilitation of scaffolds on bone formation was investigated after implanting in vivo. The results showed that as the pore dimension increased, the scaffolds indicated similar surface microstructures, but their compressive strength was enhanced gradually. There was no significant difference in vitro bio-dissolution between the 480 and 600 µm groups, whereas the 720 µm group showed a much slower dissolution and ion release. Interestingly, the two-dimensional/three-dimensional (2D/3D) micro-CT reconstruction analysis of rabbits' mandibular bone defects model showed that the 600 µm group exhibited evidently higher ratio of the newly formed bone volume to total volume (BV/TV) and trabecular number (Tb. N) values and lower ratio of the scaffolds residual volume to total volume (RV/TV) compare to the other two sizes. Furthermore, the histological analysis also revealed a considerably higher new bone ingrowth rate in the 600 µm group than the other two groups at 4-12 weeks post-implantation. Totally, it is proved from these experimental studies that the DLP-based accurately fabricated calcium (Ca) silicate bioceramic scaffolds with appropriate pore dimensions (i.e., 600 µm in pore size) are promising to guide new bone ingrowth and thus accelerate the regeneration and repair of cranial maxillofacial or periodontal bone defects.

Modularized bioceramic scaffold/hydrogel membrane hierarchical architecture beneficial for periodontal tissue regeneration in dogs.

BACKGROUND: Destruction of alveolar bone and periodontal ligament due to periodontal disease often requires surgical treatment to reconstruct the biological construction and functions of periodontium. Despite significant advances in dental implants in the past two decades, it remains a major challenge to adapt bone grafts and barrier membrane in surgery due to the complicated anatomy of tooth and defect contours. Herein, we developed a novel biphasic hierarchical architecture with modularized functions and shape based on alveolar bone anatomy to achieve the ideal outcomes. METHODS: The integrated hierarchical architecture comprising of nonstoichiometric wollastonite (nCSi) scaffolds and gelatin methacrylate/silanized hydroxypropyl methylcellulose (GelMA/Si-HPMC) hydrogel membrane was fabricated by digital light processing (DLP) and photo-crosslinked hydrogel injection technique respectively. The rheological parameters, mechanical properties and degradation rates of composite hydrogels were investigated. L-929 cells were cultured on the hydrogel samples to evaluate biocompatibility and cell barrier effect. Cell scratch assay, alkaline phosphatase (ALP) staining, and alizarin red (AR) staining were used to reveal the migration and osteogenic ability of hydrogel membrane based on mouse mandible-derived osteoblasts (MOBs). Subsequently, a critical-size one-wall periodontal defect model in dogs was prepared to evaluate the periodontal tissue reconstruction potential of the biphasic hierarchical architecture. RESULTS: The personalized hydrogel membrane integrating tightly with the nCSi scaffolds exhibited favorable cell viability and osteogenic ability in vitro, while the scratch assay showed that osteoblast migration was drastically correlated with Si-HPMC content in the composite hydrogel. The equivalent composite hydrogel has proven good physiochemical properties, and its membrane exhibited potent occlusive effect in vivo; meanwhile, the hierarchical architectures exerted a strong periodontal regeneration capability in the periodontal intrabony defect models of dogs. Histological examination showed effective bone and periodontal ligament regeneration in the biomimetic architecture system; however, soft tissue invasion was observed in the control group. CONCLUSIONS: Our results suggested that such modularized hierarchical architectures have excellent potential as a next-generation oral implants, and this precisely tuned guided tissue regeneration route offer an opportunity for improving periodontal damage reconstruction and reducing operation sensitivity.