Ecological water diversion activity changes the fate of carbon in a eutrophic lake.

Lake eutrophication mitigation measures have been implemented by ecological water diversion, however, the responses of carbon cycle to the human-derived hydrologic process still remains unclear. With a famous river-to-lake water diversion activity at eutrophic Lake Taihu, we attempted to fill the knowledge gap with integrative field measurements (2011-2017) of gas carbon (CO2 and CH4) flux, including CO2-equivalent, and dissolved carbon (DOC and DIC) at water-receiving zone and reference zone. Overall, results showed the artificial water diversion activity increased gas carbon emissions. At water-receiving zone, total gas carbon (expressed as CO2-equivalent) emissions increased significantly due to the occurring of water diversion, with CO2 flux increasing from 9.31 ± 16.28 to 18.16 ± 12.96 mmol C m-2 d-1. Meanwhile, CH4 emissions at water-receiving zone (0.06 ± 0.05 mmol C m-2 d-1) was double of that at reference zone. Water diversion decreased DOC but increased DIC especially at inflowing river mouth. Temporal variability of carbon emissions and dissolved carbon were linked to water temperature, chlorophyll a, and nutrient, but less or negligible dependency on these environment variables were found with diversion occurring. Water diversion may increase gas carbon production via stimulating DOC mineralization with nutrient enrichment, which potentially contribute to increasing carbon emissions and decreasing DOC at the same time and the significant correlation between CO2 flux and CH4 flux. Our study provided new insights into carbon biogeochemical processes, which may help to predict carbon fate under hydrologic changes of lakes.

Occlusal disharmony promotes anxiety-like behaviours by suppressing Sirt1.

BACKGROUND: Previous studies have indicated that occlusal disharmony (OD) can promote anxiety-like behaviours. However, the specific molecules involved in the development of anxiety-like behaviours and their underlying mechanisms remain unknown. METHODS: OD was produced by anterior crossbite of female mice. We measured the anxiety levels of mice in each group and screened the hippocampal mRNA expression profiles of mice in the control group and OD group. The role of target mRNA in OD-induced anxiety-like behaviours was evaluated and we preliminarily explored the possible downstream pathways. RESULTS: The results suggested that OD can induce and promote anxiety-like behaviours with/without chronic unpredictable mild stress. We found that Sirt1 was significantly downregulated within the hippocampus in OD mice. In addition, the downregulation of Sirt1 within the hippocampus in OD and control mice promoted anxiety-like behaviours, increased acetylated histone H3 expression and decreased Dnah12 transcription levels. In contrast, in OD mice subjected to an injection of resveratrol, there was a remission of anxiety-like behaviours and an upregulation of Sirt1 in the hippocampus, the effects of which were accompanied by decreased acetylated histone H3 expression and increased Dnah12 transcription levels. CONCLUSIONS: OD leads to increased sensitivity to chronic stress in mice, resulting in anxiety-like behaviours. During this process, Sirt1 acts as an effective factor in the regulation of OD-induced anxiety-like behaviours. CLINICAL RELEVANCE: OD, as a stressor, could induce anxiety-like behaviours. It investigates the impact of OD (a stressor) on the molecular genetic of the pathophysiology of major neuropsychiatric disorders.

GhMYB52 Like: A Key Factor That Enhances Lint Yield by Negatively Regulating the Lignin Biosynthesis Pathway in Fibers of Upland Cotton (Gossypium hirsutum L.).

In the context of sustainable agriculture and biomaterial development, understanding and enhancing plant secondary cell wall formation are crucial for improving crop fiber quality and biomass conversion efficiency. This is especially critical for economically important crops like upland cotton (Gossypium hirsutum L.), for which fiber quality and its processing properties are essential. Through comprehensive genome-wide screening and analysis of expression patterns, we identified a particularly high expression of an R2R3 MYB transcription factor, GhMYB52 Like, in the development of the secondary cell wall in cotton fiber cells. Utilizing gene-editing technology to generate a loss-of-function mutant to clarify the role of GhMYB52 Like, we revealed that GhMYB52 Like does not directly contribute to cellulose synthesis in cotton fibers but instead represses a subset of lignin biosynthesis genes, establishing it as a lignin biosynthesis inhibitor. Concurrently, a substantial decrease in the lint index, a critical measure of cotton yield, was noted in parallel with an elevation in lignin levels. This study not only deepens our understanding of the molecular mechanisms underlying cotton fiber development but also offers new perspectives for the molecular improvement of other economically important crops and the enhancement of biomass energy utilization.

Azithromycin cationic non-lecithoid nano/microparticles improve bioavailability and targeting efficiency.

PURPOSE: The purpose of this study was to develop and evaluate the azithromycin cationic non-lecithoid nano/microparticles with high bioavailability and lung targeting efficiency. METHODS: The cationic niosomes with different sizes (AMCNS-S and AMCNS-L) along with varied built-in characteristics were produced to achieve high bioavailability and lung targeting efficiency of azithromycin (AM) via two administration routes widely used in clinical practice, i.e., oral and intravenous routes, instead of transdermal route (by which the only marketed niosome-based drug delivery dermatologic products were given). The possible explanations for improved bioavailability and lung targeting efficacy were put forward here. RESULTS: AMCNS-S (or AMCNS-L) had high bioavailability, for example, the oral (or intravenous) relative bioavailability of AMCNS-S (or AMCNS-L) to free AM increased to 273.19% (or 163.50%). After intravenous administration, AMCNS-S (or AMCNS-L) had obvious lung targeting efficiency, for example, the lung AM concentration of AMCNS-S (or AMCNS-L) increased 16 (or 28) times that of free AM at 12 h; the AM concentration of AMCNS-S (or AMCNS-L) in lung was higher than that in heart and kidney all the time. CONCLUSIONS: The development of niosome-based AM nanocarriers provides valuable tactics in antibacterial therapy and in non-lecithoid niosomal application.

Electrospun multifunctional nanofibrous mats loaded with bioactive anemoside B4 for accelerated wound healing in diabetic mice.

With the worldwide prevalence of diabetes and considering the complicated microenvironment of diabetic wounds, the design and development of innovative multifunctional wound dressing materials are much wanted for the treatment of hard-to-heal wounds in diabetic patients. In the present study, anti-inflammatory ingredients loaded with nanofibrous wound dressing materials were manufactured by a promising blend-electrospinning strategy, and their capability for treating the diabetic wound was also systematically explored. A polymer blend consisting of Chitosan (CS) and polyvinyl alcohol (PVA) was electrospun into CS-PVA nanofibrous mats as control groups. In the meanwhile, a bioactive ingredient of Chinese medicine Pulsatilla, anemoside B4(ANE), with different contents were loaded into the electrospinning solution to construct CS-PVA-ANE nanofibrous mats. The developed CS-PVA-ANE wound dressing materials exhibited multifunctional properties including prominent water absorption, biomimetic elastic mechanical properties, and sustained ANE releasing behavior, as well as outstanding hemostatic properties. The in vitro studies showed that the CS-PVA-ANE nanofiber mats could significantly suppress lipopolysaccharide (LPS)-stimulated differentiation of pro-inflammatory (M1) macrophage subsets, and notably reduce the reactive oxygen species (ROS) generation, as well as obviously decrease inflammatory cytokine release. The in vivo animal studies showed that the CS-PVA-ANE nanofiber mats promoted the healing of diabetic wounds by significantly enhancing wound closure rates, accelerating excellent angiogenesis, promoting re-epithelization and collagen matrix deposition throughout all stages of wound healing. The present study demonstrated that CS-PVA-ANE nanofiber mats could effectively shorten the wound-healing time by inhibiting inflammatory activity, which makes them promising candidates for the treatment of hard-to-heal wounds caused by diabetes.

Effect of Different Membranes on Vertical Bone Regeneration: A Systematic Review and Network Meta-Analysis.

This study is aimed at performing a systematic review and a network meta-analysis of the effects of several membranes on vertical bone regeneration and clinical complications in guided bone regeneration (GBR) or guided tissue regeneration (GTR). We compared the effects of the following membranes: high-density polytetrafluoroethylene (d-PTFE), expanded polytetrafluoroethylene (e-PTFE), crosslinked collagen membrane (CCM), noncrosslinked collagen membrane (CM), titanium mesh (TM), titanium mesh plus noncrosslinked (TM + CM), titanium mesh plus crosslinked (TM + CCM), titanium-reinforced d-PTFE, titanium-reinforced e-PTFE, polylactic acid (PLA), polyethylene glycol (PEG), and polylactic acid 910 (PLA910). Using the PICOS principles to help determine inclusion criteria, articles are collected using PubMed, Web of Science, and other databases. Assess the risk of deviation and the quality of evidence using the Cochrane Evaluation Manual, and GRADE. 27 articles were finally included. 19 articles were included in a network meta-analysis with vertical bone increment as an outcome measure. The network meta-analysis includes network diagrams, paired-comparison forest diagrams, funnel diagrams, surface under the cumulative ranking curve (SUCRA) diagrams, and sensitivity analysis diagrams. SUCRA indicated that titanium-reinforced d-PTFE exhibited the highest vertical bone increment effect. Meanwhile, we analyzed the complications of 19 studies and found that soft tissue injury and membrane exposure were the most common complications.

Effects of Physical Stimulation in the Field of Oral Health.

Physical stimulation has been widely used in clinical medicine and healthcare due to its noninvasiveness. The main applications of physical stimulation in the oral cavity include laser, ultrasound, magnetic field, and vibration, which have photothermal, cavitation, magnetocaloric, and mechanical effects, respectively. In addition, the above four stimulations with their unique biological effects, which can play a role at the gene, protein, and cell levels, can provide new methods for the treatment and prevention of common oral diseases. These four physical stimulations have been used as important auxiliary treatment methods in the field of orthodontics, implants, periodontal, dental pulp, maxillofacial surgery, and oral mucosa. This paper systematically describes the application of physical stimulation as a therapeutic method in the field of stomatology to provide guidance for clinicians. In addition, some applications of physical stimulation in specific directions are still at the research stage, and the specific mechanism has not been fully elucidated. To encourage further research on the oral applications of physical stimulation, we elaborate the research results and development history of various physical stimuli in the field of oral health.

A Multifunctional Antibacterial and Osteogenic Nanomedicine: QAS-Modified Core-Shell Mesoporous Silica Containing Ag Nanoparticles.

Treatments for infectious bone defects such as periodontitis require antibacterial and osteogenic differentiation capabilities. Nanotechnology has prompted the development of multifunctional material. In this research, we aim to synthesize a nanoparticle that can eliminate periodontal pathogenic microorganisms and simultaneously stimulate new bone tissue regeneration and mineralization. QAS-modified core-shell mesoporous silica containing Ag nanoparticles (Ag@QHMS) was successfully synthesized through the classic hydrothermal method and surface quaternary ammonium salt functionalization. The Ag@QHMS in vitro antibacterial activity was explored via coculture with Staphylococcus aureus, Escherichia coli, and Porphyromonas gingivalis biofilms. Bone mesenchymal stem cells (BMSCs) were selected for observing cytotoxicity, apoptosis, and osteogenic differentiation. Ag@QHMS showed a good sustained release profile of Ag+ and a QAS-grafted mesoporous structure. Compared with the single-contact antibacterial activity of QHMS, Ag@QHMS exhibited a more efficient and stable concentration-dependent antimicrobial efficacy; the minimum inhibitory concentration was within 100 µg/ml, which was below the BMSC biocompatibility concentration (200 µg/ml). Thus, apoptosis would not occur while promoting the increased expression of osteogenic-associated factors, such as runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN), bone sialoprotein (BSP), and collagen type 1 (COL-1). A safe concentration of particles can stimulate cell alkaline phosphatase and matrix calcium salt deposition. The dual antibacterial effect from the direct contact killing of QAS and the sustained release of Ag nanoparticles, along with the Ag-promoted osteogenic differentiation, had been verified and utilized in Ag@QHMS. This system demonstrates the potential for utilizing pluripotent biomaterials to treat complex lesions.

Fabrication and evaluation of modified poly(ethylene terephthalate) microfibrous scaffolds for hepatocyte growth and functionality maintenance.

For hepatocyte culture in vitro, the surface feature of utilized scaffolds exerts a direct impact on cell adhesion, growth and differentiated functionality. Herein, to regulate hepatocyte growth and differentiated functionality, modified microfibrous scaffolds were fabricated by surface grafting monoamine terminated lactobionic lactone (L-NH2) and gelatin onto non-woven poly(ethylene terephthalate) (PET) fibrous substrate (PET-Gal and PET-Gel), respectively. The physicochemical properties of PET scaffolds before and after modification were characterized. Upon 15-day culture, the effects of modified PET scaffolds on growth and differentiated functionality of human induced hepatocytes (hiHeps) were evaluated, compared with that of control without modification. Results demonstrated that both L-NH2 and gelatin modifications improved scaffold properties including hydrophilicity, water uptake ratio, stiffness and roughness, resulting in efficient cell adhesion, ~20-fold cell expansion and enhanced differentiated functionality. After culture for 15 days, PET-Gal cultured cells formed aggregates, displaying better cell viability and significantly higher differentiated functionality regarding albumin secretion, urea synthesis, phases I (cytochrome P450, CYP1A1/2 and CYP3A4) and II (uridine 5'-diphosphate glucuronosyltransferases, UGT) enzyme activity, biliary excretion and detoxification ability (ammonia elimination and bilirubin conjugation), compared with PET and PET-Gel cultured ones. Hence, as a three-dimensional (3D) microfibrous scaffold, PET-Gal promotes hiHeps growth and differentiated functionality maintenance, which is promisingly utilized in bioartificial liver (BAL) bioreactors.

Design, synthesis and anti-cancer activity of pyrrole-imidazole polyamides through target-downregulation of c-kit gene expression.

Pyrrole-imidazole polyamide (PIP) can specifically bind in the B-DNA minor groove that has been used in several biological applications, such as anti-cancer activity, gene expression and translation control, and visualization of complex genomic areas. c-kit is a family member of the Tyrosine Kinase (RTK) type III receptor and plays a vital role in tumor growth, proliferation, differentiation, and cell apoptosis; however, its mutations and overexpression induce tumor dysfunction. Here, we designed and synthesized five matched PIPs that can recognize and bind to the DNA sequence in the oncogene c-kit promoter region, and evaluated their anti-cancer activity. The RTCA assay findings revealed that the PIPs would prevent the proliferation of cancer cells A549 and SGC-7901. EMSA assay showed that the PIPs were actively interacting with the c-kit gene target DNA. RT-PCR and Western blot assays have an effect on expression levels of the c-kit gene in the presence of PIPs. Flow cytometry and wound-healing assays showed that PIPs 4, 5 would cause apoptosis of cancer cells and inhibit the migration of cells, respectively. Overall findings indicate that PIP 5 has a relatively significant intracellular and extracellular impact on the target, contributing to migration and proliferation reduction, and cancer cell apoptosis. In addition, PIP has a certain ability to evolve into c-kit gene-targeting drugs.

Biological Modification of Montan Resin from Lignite by Bacillus benzoevorans.

The montan resin (MR) is a solid waste produced during the industrial process of refined montan wax from lignite, and usually disposed by landfill and incineration, which easily cause environmental pollution and resource waste. Based its physicochemical properties, our study attempted to modify MR by Bacillus benzoevorans to achieve ecological utilization of MR. As results, the weight loss rate of MR, expressed as modification degree, was found to increase with the increase of B. benzoevorans-incubated time. The apparent oil-water partition coefficient (Kow), used to evaluate the improvement on hydrophilicity of MR, significantly increased (P < 0.01) after modification. IR analysis showed the functional groups of -OH and C=O in modified MR were more than those in MR. Meanwhile, comparison of the chemical changes between MR and modified MR by relatively quantitative analysis of gas chromatography-mass spectrometry (GC-MS) revealed that the content of some chemical components in the latter decreased, and the newly appeared chemical components all had more oxygen-containing functional groups. The bioactivity of the modified MR in agricultural application was evaluated regarding germination and seedling growth of maize seed preliminarly. Compared with the original MR-treated group, the modified MR showed an obvious effect on promoting the growth and germination of maize.

Hepatocyte culture on 3D porous scaffolds of PCL/PMCL.

The development of three-dimensional (3D) porous scaffolds for soft tissue engineering mainly focused on manipulation of scaffold properties with cell behaviors. By emulsion freeze-drying method, four types of porous scaffolds were prepared from amorphous poly(4-methy-ε-caprolactone) (PMCL) and semi-crystalline poly(ε-caprolactone) (PCL) at different weight ratios, named as PMCL0, PMCL30, PMCL50 and PMCL70, respectively. Visual observation on cross-sectional images of the scaffolds appeared as sponge-like materials with three-dimensional and highly porous morphologies. However, the pore size, porosity and wettability of blends were not decreased linearly with increasing amorphous PMCL. Distinguished from PMCL30 or PMCL70, PMCL50 preserved intact PCL crystals distributed in amorphous matrix, resulting in the lowest Young's modulus (E) and relatively high wettability. From in vitro cell culture, it was observed that PMCL50 scaffold supported human induced hepatocytes (hiHeps) proliferation and function preservation best among all scaffolds. hiHeps on PMCL50 inclined to adopt fibroblastic morphology, whereas formed spheroidal morphology on PMCL0. It was suggested that our bare scaffolds with tailored properties have shown remarkable capability towards hiHep proliferation and function expression.

Tooth loss and risk of cardiovascular disease and stroke: A dose-response meta analysis of prospective cohort studies.

Conflicting results identifying the association between tooth loss and cardiovascular disease and stroke have been reported. Therefore, a dose-response meta-analysis was performed to clarify and quantitatively assess the correlation between tooth loss and cardiovascular disease and stroke risk. Up to March 2017, seventeen cohort studies were included in current meta-analysis, involving a total of 879084 participants with 43750 incident cases. Our results showed statistically significant increment association between tooth loss and cardiovascular disease and stroke risk. Subgroups analysis indicated that tooth loss was associated with a significant risk of cardiovascular disease and stroke in Asia and Caucasian. Furthermore, tooth loss was associated with a significant risk of cardiovascular disease and stroke in fatal cases and nonfatal cases. Additionally, a significant dose-response relationship was observed between tooth loss and cardiovascular disease and stroke risk. Increasing per 2 of tooth loss was associated with a 3% increment of coronary heart disease risk; increasing per 2 of tooth loss was associated with a 3% increment of stroke risk. Subgroup meta-analyses in study design, study quality, number of participants and number of cases showed consistent findings. No publication bias was observed in this meta-analysis. Considering these promising results, tooth loss might provide harmful health benefits.

Uricase alkaline enzymosomes with enhanced stabilities and anti-hyperuricemia effects induced by favorable microenvironmental changes.

Enzyme therapy is an effective strategy to treat diseases. Three strategies were pursued to provide the favorable microenvironments for uricase (UCU) to eventually improve its features: using the right type of buffer to constitute the liquid media where catalyze reactions take place; entrapping UCU inside the selectively permeable lipid vesicle membranes; and entrapping catalase together with UCU inside the membranes. The nanosized alkaline enzymosomes containing UCU/(UCU and catalase) (ESU/ESUC) in bicine buffer had better thermal, hypothermal, acid-base and proteolytic stabilities, in vitro and in vivo kinetic characteristics, and uric acid lowering effects. The favorable microenvironments were conducive to the establishment of the enzymosomes with superior properties. It was the first time that two therapeutic enzymes were simultaneously entrapped into one enzymosome having the right type of buffer to achieve added treatment efficacy. The development of ESU/ESUC in bicine buffer provides valuable tactics in hypouricemic therapy and enzymosomal application.

A comparative study of high-viscosity cement percutaneous vertebroplasty vs. low-viscosity cement percutaneous kyphoplasty for treatment of osteoporotic vertebral compression fractures.

The clinical effects of two different methods-high-viscosity cement percutaneous vertebroplasty (PVP) and low-viscosity cement percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCFs) were investigated. From June 2010 to August 2013, 98 cases of OVCFs were included in our study. Forty-six patients underwent high-viscosity PVP and 52 patients underwent low-viscosity PKP. The occurrence of cement leakage was observed. Pain relief and functional activity were evaluated using the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI), respectively. Restoration of the vertebral body height and angle of kyphosis were assessed by comparing preoperative and postoperative measurements of the anterior heights, middle heights and the kyphotic angle of the fractured vertebra. Nine out of the 54 vertebra bodies and 11 out of the 60 vertebra bodies were observed to have cement leakage in the high-viscosity PVP and low-viscosity PKP groups, respectively. The rate of cement leakage, correction of anterior vertebral height and kyphotic angles showed no significant differences between the two groups (P>0.05). Low-viscosity PKP had significant advantage in terms of the restoration of middle vertebral height as compared with the high-viscosity PVP (P<0.05). Both groups showed significant improvements in pain relief and functional capacity status after surgery (P<0.05). It was concluded that high-viscosity PVP and low-viscosity PKP have similar clinical effects in terms of the rate of cement leakage, restoration of the anterior vertebral body height, changes of kyphotic angles, functional activity, and pain relief. Low-viscosity PKP is better than high-viscosity PVP in restoring the height of the middle vertebra.

Cross-linked collagen-chondroitin sulfate-hyaluronic acid imitating extracellular matrix as scaffold for dermal tissue engineering.

The objective of this study was to develop a novel scaffold imitating the ingredients and their ratios of natural dermal matrix and to evaluate its biological activity. We applied different ratios and different synthetic methods to fabricate nine kinds of cross-linked (CL) collagen/chondroitin sulfate/hyaluronic acid (Co/CS/HA) scaffolds for dermal tissue engineering. On the basis of comparison among the morphology, mechanical properties, and biodegradation rates of scaffolds, we selected the novel scaffold that was fabricated under unique procedures. In the procedures, Co, CS, and HA were firstly synthesized together in the ratio of 9:1:1 to form a membrane that was then CL with 5 mM of 1-ethyl-3-3-dimethylaminopropylcarbodiimide hydrochloride (EDC) (Co-CS-HA/CL 9:1:1). From the results of comparison, we also found that the ratio of 9:1:1 was better than other ratios. So the scaffold of Co-CS-HA/CL 9:1:1 was used as experimental group with the scaffolds of Co-HA/CS CL 9:1:1 and Co-CS/HA CL 9:1:1 as control groups to evaluate their characteristics in vitro. A control group of an open wound without scaffold was supplemented to evaluate their effects on promoting wound healing in vivo. Morphological observation showed that the novel Co-CS-HA/CL 9:1:1 scaffold had uniform and widely interconnected pores with mean diameters of 109 +/- 11 microm and adequate porosity of about 94%. Mechanical property and biodegradation assessment indicated that it had more degradation-resistant and higher elastic modulus than other scaffolds. Metabolic activity assay showed that it could more strongly promote cellular attachment and proliferation. When scaffolds were seeded with allogenic skin fibroblasts and implanted on the dorsum of Sprague-Dawley rats for 6 weeks, the novel Co-CS-HA/CL 9:1:1 skin equivalent could more successfully repair full thickness skin defects in Sprague-Dawley rats. The histology was more approximate to normal skin than those of the controls within 6 weeks. These results demonstrated that the novel CoCS-HA/CL 9:1:1 tri-copolymer has the potential to be used as a scaffold for dermal tissue engineering.

Effect of age and extrinsic microenvironment on the proliferation and osteogenic differentiation of rat dental pulp stem cells in vitro.

INTRODUCTION: It is suggested that dental pulp stem cells (DPSCs) possess pluripotent differentiation and self-renewal capacity and play a crucial role in maintaining dental pulp homeostasis. However, little is known about the age-related changes of DPSCs, and whether aging and its microenvironment are associated with DPSCs remains a question. In this study, age-related changes in proliferation and osteogenic differentiation ability of rat DPSCs were assessed. METHODS: To examine the influence of microenvironment factors on different ages of DPSCs, we exposed adult rat DPSCs to juvenile rat dental pulp cell-conditioned medium (DPC-CM), and juvenile DPSCs were exposed to adult DPC-CM. Morphologic appearance, colony-forming assay, cell cycle analysis, 3-(4,5-dimethyl-thyazol-2-yl)-2,5-diphenyltetrazolium, gene expression, and mineralization assay after osteogenic induction of DPSCs were evaluated. RESULTS: DPSCs isolated from the juvenile donors displayed increased proliferation and decreased osteogenic differentiation ability compared with the adult DPSCs. Interestingly, adult DPSCs induced by juvenile DPC-CM demonstrated enhanced proliferation but decreased osteogenic differentiation ability, whereas DPSCs from juvenile donors induced by adult DPC-CM showed decreased proliferation but enhanced osteogenic differentiation ability. CONCLUSIONS: Our data suggest that age-related changes of DPSCs should be taken into account when DPSCs are intended to be used for investigations and application. Furthermore, the activity of DPSCs can be modulated by the extrinsic microenvironment.