Black phosphorus quantum dot-modified ADSCs as a novel therapeutic for periodontitis bone loss coupling of osteogenesis and osteoimmunomodulation.

Alveolar bone defect repair remains a persistent clinical challenge for periodontitis treatment. The use of peripheral functional seed cells is a hot topic in periodontitis. Herein, we explored the cellular behaviors and osteogenic ability of adipose-derived mesenchymal stem cells (ADSCs) treated with black phosphorus quantum dots (BPQDs). Additionally, macrophage polarization, osteogenic effects and angiogenesis were investigated through the paracrine pathway regulated by BPQD-modified ADSCs. Our results demonstrated that BPQDs showed good biocompatibility with ADSCs and BPQD-modified ADSCs could improve the bone repair in vivo inflammatory microenvironment by regulating osteogenesis and osteoimmunomodulation. The BPQDs increased the osteogenic differentiation of ADSCs via the Wnt/ß-catenin and BMP2/SMAD5/Runx2 signaling pathway. In addition, BPQD-modified ADSCs promoted the osteogenic effect of BMSCs and facilitated the polarization of macrophages from M1 towards M2 phenotype transformation through the paracrine pathway in the periodontitis microenvironment. This strategy provides a novel idea for treatment of alveolar bone defects for periodontitis in the foreseeable future.

A novel CAF-cancer cell crosstalk-related gene prognostic index based on machine learning: prognostic significance and prediction of therapeutic response in head and neck squamous cell carcinoma.

BACKGROUND: Cancer-associated fibroblast (CAF)-cancer cell crosstalk (CCCT) plays an important role in tumor microenvironment shaping and immunotherapy response. Current prognostic indexes are insufficient to accurately assess immunotherapy response in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to develop a CCCT-related gene prognostic index (CCRGPI) for assessing the prognosis and response to immune checkpoint inhibitor (ICI) therapy of HNSCC patients. METHODS: Two cellular models, the fibroblast-cancer cell indirect coculture (FCICC) model, and the fibroblast-cancer cell organoid (FC-organoid) model, were constructed to visualize the crosstalk between fibroblasts and cancer cells. Based on a HNSCC scRNA-seq dataset, the R package CellChat was used to perform cell communication analysis to identify gene pairs involved in CCCT. Least absolute shrinkage and selection operator (LASSO) regression was then applied to further refine the selection of these gene pairs. The selected gene pairs were subsequently subjected to stepwise regression to develop CCRGPI. We further performed a comprehensive analysis to determine the molecular and immune characteristics, and prognosis associated with ICI therapy in different CCRGPI subgroups. Finally, the connectivity map (CMap) analysis and molecular docking were used to screen potential therapeutic drugs. RESULTS: FCICC and FC-organoid models showed that cancer cells promoted the activation of fibroblasts into CAFs, that CAFs enhanced the invasion of cancer cells, and that CCCT was somewhat heterogeneous. The CCRGPI was developed based on 4 gene pairs: IGF1-IGF1R, LGALS9-CD44, SEMA5A-PLXNA1, and TNXB-SDC1. Furthermore, a high CCRGPI score was identified as an adverse prognostic factor for overall survival (OS). Additionally, a high CCRGPI was positively correlated with the activation of the P53 pathway, a high TP53 mutation rate, and decreased benefit from ICI therapy but was inversely associated with the abundance of various immune cells, such as CD4+ T cells, CD8+ T cells, and B cells. Moreover, Ganetespib was identified as a potential drug for HNSCC combination therapy. CONCLUSIONS: The CCRGPI is reliable for predicting the prognosis and immunotherapy response of HSNCC patients and may be useful for guiding the individualized treatment of HNSCC patients.

Dataset of the rumen microbiota and epithelial transcriptomics and proteomics in goat affected by solid diets.

Although early solid diet supplementation is a common practice to improve the growth and development in goat kids, its biological mechanism how solid diet induces rumen microbiota and epithelial development is still unknow. In this study, rumen fermentation parameters, 16S rRNA sequencing for rumen content and epithelial microbiota, transcriptomics and proteomics of epithelium were determined to classify the effects of solid diet supplementation. Here, we classified the changes of goat phenotypes (i.e., growth performance, rumen fermentation and development) and linked them to the changes of rumen microbiota, transcriptome and expressed proteins. The mechanism of solid diet improving rumen development was elucidated preliminarily. Moreover, different roles between the rumen content and epithelial microbiota were identified. Thess datasets expands our understanding of the association between the early diet intervention and rumen development, providing the useful information how nutrient strategy affects rumen function and subsequently improves the host growth. The generated data provides insights in the importance of rumen niche microbiota and microbe-host interactions, which benefits future studies.

TNF-α-licensed exosome-integrated titaniumaccelerated T2D osseointegration by promoting autophagy-regulated M2 macrophage polarization.

Type 2 diabetes (T2D) is on a notable rise worldwide, which leads to unfavorable outcomes during implant treatments. Surface modification of implants and exosome treatment have been utilized to enhance osseointegration. However, there has been insufficient approach to improve adverse osseointegration in T2D conditions. In this study, we successfully loaded TNF-α-treated mesenchymal stem cell (MSC)-derived exosomes onto micro/nano-network titanium (Ti) surfaces. TNF-α-licensed exosome-integrated titanium (TNF-exo-Ti) effectively enhanced M2 macrophage polarization in hyperglycemic conditions, with increased secretion of anti-inflammatory cytokines and decreased secretion of pro-inflammatory cytokines. In addition, TNF-exo-Ti pretreated macrophage further enhanced angiogenesis and osteogenesis of endothelial cells and bone marrow MSCs. More importantly, TNF-exo-Ti markedly promoted osseointegration in T2D mice. Mechanistically, TNF-exo-Ti activated macrophage autophagy to promote M2 polarization through inhibition of the PI3K/AKT/mTOR pathway, which could be abolished by PI3K agonist. Thus, this study established TNF-α-licensed exosome-immobilized titanium surfaces that could rectify macrophage immune states and accelerate osseointegration in T2D conditions.

Size-Dependent Effect of Titania Nanotubes on Endoplasmic Reticulum Stress to Re-establish Diabetic Macrophages Homeostasis.

In patients with diabetes, endoplasmic reticulum stress (ERS) is a crucial disrupting factor of macrophage homeostasis surrounding implants, which remains an obstacle to oral implantation success. Notably, the ERS might be modulated by the implant surface morphology. Titania nanotubes (TNTs) may enhance diabetic osseointegration. However, a consensus has not been achieved regarding the tube-size-dependent effect and the underlying mechanism of TNTs on diabetic macrophage ERS. We manufactured TNTs with small (30 nm) and large diameters (100 nm). Next, we assessed how the different titanium surfaces affected diabetic macrophages and regulated ERS and Ca2+ homeostasis. TNTs alleviated the inflammatory response, oxidative stress, and ERS in diabetic macrophages. Furthermore, TNT30 was superior to TNT100. Inhibiting ERS abolished the positive effect of TNT30. Mechanistically, topography-induced extracellular Ca2+ influx might mitigate excessive ERS in macrophages by alleviating ER Ca2+ depletion and IP3R activation. Furthermore, TNT30 attenuated the peri-implant inflammatory response and promoted osseointegration in diabetic rats. TNTs with small nanodiameters attenuated ERS and re-established diabetic macrophage hemostasis by inhibiting IP3R-induced ER Ca2+ depletion.

A comprehensive analysis of antibiotic resistance genes in the giant panda gut.

In this study, we have successfully constructed a comprehensive database of metagenome-assembled genomes (MAGs) pertaining to the gut microbiota of the giant panda. Through our analysis, we have identified significant reservoirs of antibiotic resistance genes (ARGs), namely Escherichia coli, Citrobacter portucalensis, and Klebsiella pneumoniae. Furthermore, we have elucidated the primary contributors to ARGs, including Streptococcus alactolyticus and Clostridium SGBP116, in both captive and wild pandas. Additionally, our findings have demonstrated a higher prevalence of ARGs in the metagenome, with notable expression of the RPOB2 gene in S. alactolyticus. Crucially, 1217 ARGs shared homology with human gut ARGs, underscoring the interaction relationship between pandas and human microbiomes. These findings are instrumental in understanding the antibiotic resistance landscape in the giant panda's gut, providing a framework for developing strategies to combat antibiotic resistance and safeguard the health of this endangered species.

Single missing molar with wide mesiodistal length restored using a single or double implant-supported crown: A self-controlled case report and 3D finite element analysis.

PURPOSE: Based on a self-controlled case, this study evaluated the finite element analysis (FEA) results of a single missing molar with wide mesiodistal length (MDL) restored by a single or double implant-supported crown. METHODS: A case of a missing bilateral mandibular first molar with wide MDL was restored using a single or double implant-supported crown. The implant survival and peri-implant bone were compared. FEA was conducted in coordination with the case using eight models with different MDLs (12, 13, 14, and 15 mm). Von Mises stress was calculated in the FEA to evaluate the biomechanical responses of the implants under increasing vertical and lateral loading, including the stress values of the implant, abutment, screw, crown, and cortical bone. RESULTS: The restorations on the left and right sides supported by double implants have been used for 6 and 12 years, respectively, and so far have shown excellent osseointegration radiographically.The von Mises stress calculated in the FEA showed that when the MDL was >14 mm, both the bone and prosthetic components bore more stress in the single implant-supported strategy. The strength was 188.62-201.37 MPa and 201.85-215.9 MPa when the MDL was 14 mm and 15 mm, respectively, which significantly exceeded the allowable yield stress (180 MPa). CONCLUSIONS: Compared with the single implant-supported crown, the double implant-supported crown reduced peri-implant bone stress and produced a more appropriate stress transfer model at the implant-bone interface when the MDL of the single missing molar was ≥14 mm.

Magnetic Graphene Oxide Nanocomposites Boosts Craniomaxillofacial Bone Regeneration by Modulating circAars/miR-128-3p/SMAD5 Signaling Axis.

Background: The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism. Methods: The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites. Results: We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites. Conclusion: We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.

Unconventional Dental Implant Placement Through an Impacted Maxillary Central Incisor in Stable Contact With Enamel and Dentin: A Case Report.

When edentulism is accompanied by an impacted tooth, conventional treatment usually involves traumatic tooth extraction, which would inevitably destroy the surrounding alveolar bone and cause unfavorable esthetics, especially for anterior teeth. Recently, implant placement through the impacted tooth or residual root has been proposed as an alternative to invasive extraction. A particular type of integration has been observed between dentin/cementum and titanium implant, while enamel-implant contact has not been reported. In this article, an implant was placed through the impacted maxillary central incisor, thereby avoiding an invasive extraction surgery. The buccal section of the tooth, including crown enamel, was retained in situ for buccal alveolar ridge preservation. The follow-up results were satisfactory, and a stable enamel-implant contact was observed. Combining with previous similar studies, this technique opens intriguing possibilities and brings fresh insight for the concept of dentointegration. More histological and clinical studies with long-term follow-up are warranted before endorsing this technique in routine application.

Calcitonin gene-related peptide-modulated macrophage phenotypic alteration regulates angiogenesis in early bone healing.

OBJECTIVES: This study aimed to investigate the effect of calcitonin gene-related peptide (CGRP) on the temporal alteration of macrophage phenotypes and macrophage-regulated angiogenesis duringearlybonehealing and preliminarily elucidate the mechanism. METHODS: In vivo, the rat mandibular defect models were established with inferior alveolar nerve transection (IANT) or CGRP receptor antagonist injection. Radiographicandhistologic assessments for osteogenesis, angiogenesis, and macrophage phenotypic alteration within bone defects were performed. In vitro, the effect and mechanism of CGRP on macrophage polarization and phenotypic alteration were analyzed. Then the conditioned medium (CM) from CGRP-treated M1 or M2 macrophages was used to culture human umbilical vein endothelial cells (HUVECs), and the CGRP's effect on macrophage-regulated angiogenesis was detected. RESULTS: Comparable changes following IANT and CGRP blockade within bone defects were observed, including the suppression of early osteogenesis and angiogenesis, the prolonged M1 macrophage infiltration and the prohibited transition toward M2 macrophages around vascular endothelium. In vitro experiments showed that CGRP promoted M2 macrophage polarization while upregulating the expression of interleukin 6 (IL-6), a major cytokine that facilitates the transition from M1 to M2-dominant stage, in M1 macrophages via the activation of Yes-associated protein 1. Moreover, CGRP-treated macrophage-CM showed an anabolic effect on HUVECs angiogenesis compared with macrophage-CM and might prevail over the direct effect of CGRP on HUVECs. CONCLUSIONS: Collectively, our results reveal the effect of CGRP on M1 to M2 macrophage phenotypic alteration possibly via upregulating IL-6 in M1 macrophages, and demonstrate the macrophage-regulated pro-angiogenic potential of CGRP in early bone healing.

Mettl3­mediated m6A RNA methylation regulates osteolysis induced by titanium particles.

Peri­prosthetic osteolysis (PPO) induced by wear particles is considered the primary cause of titanium prosthesis failure and revision surgery. The specific molecular mechanisms involve titanium particles inducing multiple intracellular pathways, which impact disease prevention and the targeted therapy of PPO. Notably, N6­methyladenosine (m6A) serves critical roles in epigenetic regulation, particularly in bone metabolism and inflammatory responses. Thus, the present study aimed to determine the role of RNA methylation in titanium particle­induced osteolysis. Results of reverse transcription­quantitative PCR (RT­qPCR), western blotting, ELISA and RNA dot blot assays revealed that titanium particles induced osteogenic inhibition and proinflammatory responses, accompanied by the reduced expression of methyltransferase­like (Mettl) 3, a key component of m6A methyltransferase. Specific lentiviruses vectors were employed for Mettl3 knockdown and overexpression experiments. RT­qPCR, western blotting and ELISA revealed that the knockdown of Mettl3 induced osteogenic inhibition and proinflammatory responses comparable with that induced by titanium particle, while Mettl3 overexpression attenuated titanium particle­induced cellular reactions. Methylated RNA immunoprecipitation­qPCR results revealed that titanium particles mediated the methylation of two inhibitory molecules, namely Smad7 and SMAD specific E3 ubiquitin protein ligase 1, via Mettl3 in bone morphogenetic protein signaling, leading to osteogenic inhibition. Furthermore, titanium particles induced activation of the nucleotide binding oligomerization domain 1 signaling pathway through methylation regulation, and the subsequent activation of the MAPK and NF­κB pathways. Collectively, the results of the present study indicated that titanium particles utilized Mettl3 as an upstream regulatory molecule to induce osteogenic inhibition and inflammatory responses. Thus, the present study may provide novel insights into potential therapeutic targets for aseptic loosening in titanium prostheses.

Effect of prefabricated auxiliary devices and scanning patterns on the accuracy of complete-arch implant digital impressions.

OBJECTIVES: This study aimed to evaluate the impact of prefabricated auxiliary devices (PAD) and scanning patterns on the accuracy of complete-arch implant digital impressions. METHODS: An edentulous maxillary model was inserted with four parallel implant analogs and four PAD. The model was scanned with D2000 dental laboratory scanner as the reference scans. Test scans were obtained by 8 different scanning patterns (SP), which including SPA, SPB, SPC, SPD, SPE, SPF, SPG and SPH, with (test group) or without (control group) using the PAD by an intraoral scanner (Aoralscan 3, 3DShining). SPA was the scanning pattern recommended by the manufacturer. Each scanning time was recorded. The related files were imported into inspection software for assessment. Aligned Ranks Transformation ANOVA, Kruskal-Wallis and Mann-Whitney tests were used to evaluate the values. The level of significance was set at α = 0.05. RESULTS: The scanning patterns significantly influenced the linear accuracy in the test group and the scanning time for both groups. Lower linear trueness in the test group was found in SPF (p<0.05) and SPG (p<0.05). Longer scanning time was found in SPB and SPG for both groups. The test group demonstrated linear accuracy enhancement in all the scanning patterns; angular trueness enhancement was seen in SPA (p<0.05), SPC (p<0.01) and SPH (p<0.01). Significant longer scanning time was found in SPB (p<0.05), SPF (p<0.05), SPG (p<0.05) and SPH (p<0.05) when using PAD. CONCLUSION: The scanning patterns impact the accuracy differently depending on the PAD's existence. The scanning time can be significantly influenced by the scanning patterns and the PAD. CLINICAL SIGNIFICANCE: In daily clinical practice, selecting a suitable scanning pattern is significant in achieving accurate digital impressions. The PAD demonstrated effective linear accuracy enhancement in all the scanning patterns tested.

Effect of artificial landmarks of the prefabricated auxiliary devices located at different arch positions on the accuracy of complete-arch edentulous digital implant scanning: An in-vitro study.

OBJECTIVES: To examine the effect of artificial landmarks of prefabricated auxiliary devices (PAD) located at different arch positions on the accuracy of complete-arch edentulous digital implant scanning. METHODS: A reference model containing four analogs and PAD were fabricated by a 3D printer (AccuFab-C1s, 3DShining). 10 digital scans were performed using an intraoral scanner (Aoralscan 3, 3DShining), sv 1.0.0.3115, with artificial landmarks located at different arch positions: group I, without any artificial landmarks; group II, with artificial landmarks at the anterior region; group III, with artificial landmarks at the posterior region. group IV: with artificial landmarks at both anterior and posterior regions. For group V: Conventional open-tray splinted impressions. The reference file and conventional stone casts were digitalized by using a dental laboratory scanner. The related files were imported into inspection software for trueness and precision assessment. Statistical analysis was performed with One-way ANOVA and Kruskal-Wallis test. The level of significance was set at α=0.05. RESULTS: For the global accuracy assessment, significantly higher global trueness was seen in group II (p < 0.01), III (p < 0.001), IV (p < 0.001) and V (p < 0.001) than group I. Significantly higher global precision was seen in group III (p < 0.001), IV (p < 0.001) and V (p < 0.001) than group I. For the local accuracy assessment, the PAD primarily improved accuracy on the linear deviations. CONCLUSIONS: Artificial landmarks of PAD at different arch positions significantly influenced the scanning accuracy. Applying the PAD in group IV could achieve comparable outcomes to conventional open-tray splinted impressions. Artificial landmarks on the posterior region may be more pivotal than those on the anterior region. CLINICAL SIGNIFICANCE: Group IV could achieve comparable accuracy to conventional open-tray splinted impressions.

Magnetic graphene oxide nanocomposites induce cytotoxicity in ADSCs via GPX4 regulating ferroptosis.

Magnetic graphene oxide nanocomposites (MGO NPs) have been widely studied in biomedical applications. However, their cytotoxicity and underlying mechanisms remain unclear. In this study, the biosafety of MGO NPs was investigated, and the mechanism involved in ferroptosis was further explored. MGO can produce cytotoxicity in ADSCs, which is dependent on their concentration. Ferroptosis was involved in MGO NP-induced ADSC survival inhibition by increasing total ROS and lipid ROS accumulation as well as regulating the expression levels of ferroptosis-related genes and proteins. GPX4 played a critical role in the MGO NP-induced ADSC ferroptosis process, and overexpressing GPX4 suppressed ferroptosis to increase cell survival. This study provides a theoretical basis for the biosafety management of MGO NPs used in the field of biomedical treatment.

Screening and evaluation of skin potential probiotic from high-altitude Tibetans to repair ultraviolet radiation damage.

Human skin microbes play critical roles in skin health and diseases. Microbes colonizing on the skin of Tibetans living in the high-altitude area for generations may have a stronger ability to resist the harsh environment, such as high ultraviolet radiation (UV). Isolation of a potential probiotic from Tibetans skin is beneficial for resistance of skin disease for humans in the world. In this study, the signature microbiota for Tibetan skin were characterized compared to low-altitude humans. Next, using culture-omics, 118 species were isolated. The culturability of high-altitude of Tibetan skin microbiome reached approximate 66.8%. Next, we found that one strain, Pantoea eucrina, had the greatest ability to repair UV damage to the skin as the lowest pathological score was observed in this group. Interestingly, another animal trial found this bacterium resisted UV rather than its metabolites. Using whole genome sequencing, this strain P. eucrina KBFS172 was confirmed, and its functions were annotated. It might involve in the metabolic pathway of carotenoid biosynthesis with anti-oxidative stress properties, which plays critical roles in UV-damage repair. In conclusion, we characterized the signature microbes of skin in high-altitude Tibetans, isolated a skin bacterium of Pantoea eucrina KBFS172 which could repair UV damage via involving the metabolic pathway of carotenoid biosynthesis. Our results provide a new potential skin probiotic for skin disease prevention or sunburn.

The spatial dissimilarities and connections of the microbiota in the upper and lower respiratory tract of beef cattle.

Bovine respiratory disease (BRD) causes morbidity and mortality in cattle. The critical roles of the respiratory microbiota in BRD have been widely studied. The nasopharynx was the most popular sampling niche for BRD pathogen studies. The oral cavity and other niches within the respiratory tract, such as nostrils and lung, are less assessed. In this study, oropharyngeal swabs (OS), nasal swabs (NS), nasopharyngeal swabs (NP), and bronchoalveolar lavage (BAL) were collected from calves located in four countries and analyzed for investigation of the dissimilarities and connections of the respiratory microbiota. The results showed that the microbial diversity, structure, and composition in the upper and lower respiratory tract in beef cattle from China, the USA, Canada, and Italy were significantly different. The microbial taxa for each sampling niche were specific and associated with their local physiology and geography. The signature microbiota for OS, NS, NP, and BAL were identified using the LEfSe algorithm. Although the spatial dissimilarities among the respiratory niches existed, the microbial connections were observed in beef cattle regardless of geography. Notably, the nostril and nasopharynx had more similar microbiomes compared to lung communities. The major bacterial immigration patterns in the bovine respiratory tract were estimated and some of them were associated with geography. In addition, the contribution of oral microbiota to the nasal and lung ecosystems was confirmed. Lastly, microbial interactions were characterized to reveal the correlation between the commercial microbiota and BRD-associated pathogens. In conclusion, shared airway microbiota among niches and geography provides the possibility to investigate the common knowledge for bovine respiratory health and diseases. In spite of the dissimilarities of the respiratory microbiota in cattle, the spatial connections among these sampling niches not only allow us to deeply understand the airway ecosystem but also benefit the research and development of probiotics for BRD.

Osseointegration of functionally graded Ti6Al4V porous implants: Histology of the pore network.

The additive manufacturing of titanium into porous geometries offers a means to generate low-stiffness endosseous implants with a greater surface area available for osseointegration. In this work, selective laser melting was used to produce gyroid-based scaffolds with a uniform pore size of 300 µm or functionally graded pore size from 600 µm to 300 µm. Initial in vitro assessment with Saos-2 cells showed favourable cell proliferation at pore sizes of 300 and 600 µm. Following implantation into rabbit tibiae, early histological observations at four weeks indicated some residual inflammation alongside neovessel infiltration into the scaffold interior and some early apposition of mineralized bone tissue. At twelve weeks, both scaffolds were filled with a mixture of adipocyte-rich marrow, micro-capillaries, and mineralized bone tissue. X-ray microcomputed tomography showed a higher bone volume fraction (BV/TV) and percentage of bone-implant contact (BIC) in the implants with 300 µm pores than in the functionally graded specimens. In functionally graded specimens, localized BV/TV measurement was observed to be higher in the innermost region containing smaller pores (estimated at 300-400 µm) than in larger pores at the implant exterior. The unit cell topology of the porous implant was also observed to guide the direction of bone ingrowth by conducting along the implant struts. These results suggest that in vivo experimentation is necessary alongside parametric optimization of functionally graded porous implants to predict short-term and long-term bone apposition.

ATG7-mediated autophagy protects human gingival myofibroblasts from irradiation-induced apoptosis.

BACKGROUND: Apoptosis resistance of myofibroblasts is critical in pathology of irradiation-induced fibrosis and osteoradionecrosis of the jaw (ORNJ). However, molecular mechanism of apoptosis resistance induced by irradiation in oral myofibroblasts remains largely obscure. METHODS: Matched ORNJ fibroblasts and normal fibroblasts pairs from gingival were primarily cultured, and myofibroblast markers of α-SMA and FAP were evaluated by qRT-PCR and western blot. CCK8 assay and flow cytometric analysis were performed to investigate the cell viability and apoptosis under irradiation treatment. Autophagy-related protein LC3 and ATG7, and punctate distribution of LC3 localization were further detected. After inhibition of autophagy with inhibitor CQ and 3-MA, as well as transfected ATG7-siRNA, cell viability and apoptosis of ORNJ and normal fibroblasts were further assessed. RESULTS: Compared with normal fibroblasts, ORNJ fibroblasts exhibited significantly higher α-SMA and FAP expression, increased cell, viability and decreased apoptosis under irradiation treatment. LC3-II and ATG7 were up-regulated in ORNJ fibroblasts with irradiation stimulation. After inhibition of irradiation-induced autophagic flux with lysosome inhibitor CQ, LC3-II protein was accumulated and punctate distribution of LC3 localization was increased in ORNJ fibroblasts. Moreover, autophagy inhibitor CQ and 3-MA enhanced the irradiation-induced apoptosis but inhibited viability of ORNJ fibroblasts. Silencing ATG7 with siRNA could obviously weaken irradiation-induced LC3-II expression, and promoted irradiation-induced apoptosis of ORNJ fibroblasts. After knockdown of ATG7, finally, p-AKT(Ser473) and p-mTOR(Ser2448) levels of ORNJ fibroblasts were significantly increased under irradiation. CONCLUSION: Compared with normal fibroblasts, human gingival myofibroblasts are resistant to irradiation-induced apoptosis via autophagy activation. Silencing ATG7 may evidently inhibit activation of autophagy, and promote apoptosis of gingival myofibroblasts via Akt/mTOR pathway.

The role of gut archaea in the pig gut microbiome: a mini-review.

The gastrointestinal microbiota of swine harbors an essential but often overlooked component: the gut archaea. These enigmatic microorganisms play pivotal roles in swine growth, health, and yield quality. Recent insights indicate that the diversity of gut archaea is influenced by various factors including breed, age, and diet. Such factors orchestrate the metabolic interactions within the porcine gastrointestinal environment. Through symbiotic relationships with bacteria, these archaea modulate the host's energy metabolism and digestive processes. Contemporary research elucidates a strong association between the abundance of these archaea and economically significant traits in swine. This review elucidates the multifaceted roles of gut archaea in swine and underscores the imperative for strategic interventions to modulate their population and functionality. By exploring the probiotic potential of gut archaea, we envisage novel avenues to enhance swine growth, health, and product excellence. By spotlighting this crucial, yet under-investigated, facet of the swine gut microbiome, we aim to galvanize further scientific exploration into harnessing their myriad benefits.