A Janus Microsphere Delivery System Orchestrates Immunomodulation and Osteoinduction by Fine-tuning Release Profiles.

Bone regeneration is a well-orchestrated process synergistically involving inflammation, angiogenesis, and osteogenesis. Therefore, an effective bone graft should be designed to target multiple molecular events and biological demands during the bone healing process. In this study, a biodegradable gelatin methacryloyl (GelMA)-based Janus microsphere delivery system containing calcium phosphate oligomer (CPO) and bone morphogenetic protein-2 (BMP-2) is developed based on natural biological events. The exceptional adjustability of GelMA facilitates the controlled release and on-demand application of biomolecules, and optimized delivery profiles of CPO and BMP-2 are explored. The sustained release of CPO during the initial healing stages contributes to early immunomodulation and promotes mineralization in the late stage. Meanwhile, the administration of BMP-2 at a relatively high concentration within the therapeutic range enhances the osteoinductive property. This delivery system, with fine-tuned release patterns, induces M2 macrophage polarization and creates a conducive immuno-microenvironment, which in turn facilitates effective bone regeneration in vivo. Collectively, this study proposes a bottom-up concept, aiming to develop a user-friendly and easily controlled delivery system targeting individual biological events, which may offer a new perspective on developing function-optimized biomaterials for clinical use.

L-Theanine Inhibits Chemoresistance of Lung Cancer Cells to Cisplatin by Regulating STAT3/NOTCH1-BMAL1 Signaling.

BACKGROUND: L-Theanine, a nonproteinogenic amino acid derived from green tea, is being recognized as an anti-cancer candidate. However, it's roles in the development of cancer chemoresistance is still unknown and the molecular mechanism is urgently to be explored. METHODS: The effects of L-Theanine on lung cancer chemoresistance were validated by Cell Counting Kit-8 (CCK-8) assay, transwell assay, and in vitro tumor spheroid formation assay; the expression of proteins was detected by using polymerase chain reaction (PCR) and western blotting. RNA-sequencing (RNA-seq) and bioinformatics analysis were used to identify differentially expressed genes induced by L-Theanine. BMAL1 knockdown and overexpression were constructed by using a lentivirus-mediated transfection system. RESULTS: L-Theanine improved the chemoresistance to cis-diamminedichloroplatinum (DDP) and inhibited stemness of DDP-resistant lung cancer cells but not non-resistant lung cancer cells. The results from RNA-seq analysis showed that STAT3/NOTCH1 pathway was a potential dominant signaling involved in L-Theanine improving the chemoresistance in DDP-resistant lung cancer. Mechanistically, L-Theanine impeded migration and stemness activation of DDP-resistant lung cancer cells via regulating the expression of STAT3/NOTCH1/BMAL1 signaling-induced stemness markers as well as inhibiting the expression levels of drug resistance-related genes. In addition, a combination of L-Theanine and Stat3 blockade synergistically improved the chemoresistance in DDP-resistant lung cancer. CONCLUSION: L-Theanine improves the chemoresistance by regulating STAT3/NOTCH1/BMAL1 signaling, reducing stemness, and inhibiting the migration of DDP-resistant lung cancer cells. The finding might provide some evidence for therapeutic options in overcoming the chemoresistance in cancers, including lung cancer.

CNPY2 governs PDGF­BB­treated vascular smooth muscle cell proliferation, migration and phenotypic transformation via the Akt/mTOR/GSK­3ß signaling pathway.

Phenotype switching of vascular smooth muscle cells (VSMCs) is a pathological process in various vascular diseases. Canopy FGF signaling regulator 2 (CNPY2) has previously been found to be abnormally expressed in ApoE-/- mice and aortic endothelial cells, indicating it may have an important role in vascular diseases. The present study aimed to determine the role and mechanism of CNPY2 in VSMC phenotype switching. Following stimulation with platelet-derived growth factor type BB (PDGF-BB), the expression of CNPY2 in VSMCs was detected using reverse transcription-quantitative PCR and western blot analysis. Subsequently, to explore the regulatory effects of CNPY2 on VSMCs, CNPY2 expression was knocked down by transfection with short hairpin RNA and cell viability, proliferation, migration and phenotypic transformation indicators were detected. Western blot analysis was also used to detect the phosphorylation of Akt/mTOR/GSK-3ß pathway-associated proteins downstream of CNPY2. In addition, pretreatment with the Akt pathway activator SC79 was performed to further explore the regulatory mechanisms of CNPY2. The results revealed that CNPY2 expression was upregulated in PDGF-BB-stimulated VSMCs. In addition, the knockdown of CNPY2 inhibited PDGF-BB-induced VSMC hyperproliferation, cell cycle arrest, migration and phenotypic transformation, as well the activation of Akt/mTOR/GSK-3ß pathway-associated proteins. Pretreatment with SC79 significantly reversed the inhibitory effects of CNPY2 knockdown on the proliferation, cell cycle arrest, migration and phenotypic transformation of the model cells. In summary, the present study indicates that CNPY2 regulates the abnormal proliferation, migration and phenotypic transformation of PDGF-BB-stimulated VSMCs via activation of the Akt/mTOR/GSK-3ß signaling pathway.

A review of quantification methods for light absorption enhancement of black carbon aerosol.

Black carbon (BC) is a distinct type of carbonaceous aerosol that has a significant impact on the environment, human health, and climate. A non-BC material coating on BC can alter the mixing state of the BC particles, which considerably enhances the mass absorption efficiency of BC by directing more energy toward the BC cores (lensing effect). A lot of methods have been reported for quantifying the enhancement factor (Eabs), with diverse results. However, to the best of our knowledge, a comprehensive review specific to the quantification methods for Eabs has not been systematically performed, which is unfavorable for the evaluation of obtained results and subsequent radiative forcing. In this review, quantification methods are divided into two broad categories, direct and indirect, depending on whether experimental removal of the coating layer from an aged carbonaceous particle is required. The direct methods described include thermal peeling, solvent dissolution, and optical virtual exfoliation, while the indirect methods include intercept-linear regression fitting, minimum R squared, numerical simulation, and empirical value. We summarized the principles, procedures, virtues, and limitations of the major Eabs quantification methods and analyzed the current problems in the determination of Eabs. We pointed out what breakthroughs are needed to improve or innovate Eabs quantification methods, particularly regarding the need to avoid the influence of brown carbon, develop a broadband Eabs quantification scheme, quantify the Eabs values for the emissions of low-efficiency combustions, measure the Eabs of particles in a high-humidity environment, design a real-time monitor of Eabs by a proper combination of mature techniques, and make more use of artificial intelligence for better Eabs quantification. This review deepens the understanding of Eabs quantification methods and benefits the estimation of the contribution of BC to radiative forcing using climate models.

Social appearance anxiety among the dark tetrad and self-concealment.

This study analyzed the effects of the Dark Tetrad (narcissism, Machiavellianism, psychopathy, sadism) and self-concealment on social appearance anxiety. Empirical investigations on which personality traits influence social appearance anxiety are yet missing. In this study, a sample of N = 1186 Chinese students performed a questionnaire-based survey assessing different personality facets and social appearance anxiety tendencies. Measures included the Narcissistic Personality Inventory, the Levenson Self-Report Psychopathy Scale, the Machiavellian Personality Scale, the Short Sadistic Impulse Scale, the Self-concealment Scale, and the Social Appearance Anxiety Scale. The results of the multiple regression analysis showed that psychopathy, Machiavellianism, sadism, and self-concealment positively predicted social appearance anxiety and narcissism negatively predicted social appearance anxiety. Machiavellianism, psychopathy, sadism, and self-concealment were positive predictors of social appearance anxiety, whereas narcissism was a negative predictor. These findings provide insight into the complex nature of the Dark Tetrad and their influence on social appearance anxiety.

ACP-Mediated Phase Transformation for Collagen Mineralization: A New Understanding of the Mechanism.

Despite significant efforts utilizing advanced technologies, the contentious debate surrounding the intricate mechanism underlying collagen fibril mineralization, particularly with regard to amorphous precursor infiltration and phase transformation, persists. This work proposes an amorphous calcium phosphate (ACP)-mediated pathway for collagen fibril mineralization and utilizing stochastic optical reconstruction microscopy technology, and has experimentally confirmed for the first time that the ACP nanoparticles can infiltrate inside collagen fibrils. Subsequently, the ACP-mediated phase transformation occurs within collagen fibrils to form HAP crystallites, and significantly enhances the mechanical properties of the mineralized collagen fibrils compared to those achieved by the calcium phosphate ion (CPI)-mediated mineralization and resembles the natural counterpart. Furthermore, demineralized dentin can be effectively remineralized through ACP-mediated mineralization, leading to complete restoration of its mechanical properties. This work provides a new paradigm of collagen mineralization via particle-mediated phase transformation, deepens the understanding of the mechanism behind the mineralization of collagen fibrils, and offers a new strategy for hard tissue repair.

KRAS G12V neoantigen specific T cell receptor for adoptive T cell therapy against tumors.

KRAS mutations are broadly recognized as promising targets for tumor therapy. T cell receptors (TCRs) can specifically recognize KRAS mutant neoantigens presented by human lymphocyte antigen (HLA) and mediate T cell responses to eliminate tumor cells. In the present study, we identify two TCRs specific for the 9-mer KRAS-G12V mutant neoantigen in the context of HLA-A*11:01. The TCR-T cells are constructed and display cytokine secretion and cytotoxicity upon co-culturing with varied tumor cells expressing the KRAS-G12V mutation. Moreover, 1-2C TCR-T cells show anti-tumor activity in preclinical models in female mice. The 9-mer KRAS-G12V mutant peptide exhibits a distinct conformation from the 9-mer wildtype peptide and its 10-mer counterparts. Specific recognition of the G12V mutant by TCR depends both on distinct conformation from wildtype peptide and on direct interaction with residues from TCRs. Our study reveals the mechanisms of presentation and TCR recognition of KRAS-G12V mutant peptide and describes TCRs with therapeutic potency for tumor immunotherapy.

Hyaluronic acid-mediated collagen intrafibrillar mineralization and enhancement of dentin remineralization.

Non-collagenous proteins (NCPs) in the extracellular matrix (ECM) of bone and dentin are known to play a critical regulatory role in the induction of collagen fibril mineralization and are embedded in hyaluronic acid (HA), which acts as a water-retaining glycosaminoglycan and provides necessary biochemical and biomechanical cues. Our previous study demonstrated that HA could regulate the mineralization degree and mechanical properties of collagen fibrils, yet its kinetics dynamic mechanism on mineralization is under debate. Here, we further investigated the role of HA on collagen fibril mineralization and the possible mechanism. The HA modification can significantly promote intrafibrillar collagen mineralization by reducing the electronegativity of the collagen surface to enhance calcium ions (Ca2+) binding capacity to create a local higher supersaturation. In addition, the HA also provides additional nucleation sites and shortens the induction time of amorphous calcium phosphate (ACP)-mediated hydroxyapatite (HAP) crystallization, which benefits mineralization. The acceleration effect of HA on intrafibrillar collagen mineralization is also confirmed in collagen hydrogel and in vitro dentin remineralization. These findings offer a physicochemical view of the regulation effect of carbohydrate polymers in the body on biomineralization, the fine prospect for an ideal biomaterial to repair collagen-mineralized tissues.

An injectable photopolymerizable chitosan hydrogel doped anti-inflammatory peptide for long-lasting periodontal pocket delivery and periodontitis therapy.

Periodontitis is a common chronic inflammatory disease caused by plaque that leads to alveolar bone resorption and tooth loss. Inflammation control and achieving better tissue repair are the key to periodontitis treatment. In this study, human ß-Defensin 1 short motif Pep-B with inflammation inhibition and differentiation regulation properties, is firstly used in the treatment of periodontitis, and an injectable photopolymerizable Pep-B/chitosan methacryloyl composite hydrogel (CMSA/Pep-B) is constructed. We confirm that Pep-B improves inflammation, and restores osteogenic behavior and function of injured stem cells. CMSA/Pep-B has good injectability, fluidity and photopolymerizability, and can sustainably release Pep-B to maintain drug concentration in periodontal pockets. Furthermore, animal experiments showed that CMSA/Pep-B significantly ameliorated the inflammation of the periodontium and reduced the alveolar bone loss by decreasing inflammatory infiltration, osteoclast formation and collagen destruction. In conclusion, CMSA/Pep-B is envisaged to be a novel bioactive material or therapeutic drug for treating periodontitis.

A Novel Metabolic Score for Predicting the Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) has higher mortality when developing to acute exacerbation (AECOPD); hence, the early intervention of COPD is critical for preventing AECOPD. Exploring the serum metabolites associated with acute exacerbation in patients with COPD will contribute to the early intervention of COPD. Methods: In the study, a non-targeted metabolomics strategy combined with multivariate statistical methods was performed to explore the metabolic profiling of COPD developing acute exacerbation, to screen the potential metabolites associated with AECOPD and to analyze the potential value of these metabolites in predicting the development of COPD. Results: Serum lysine, glutamine, 3-hydroxybutyrate, pyruvate and glutamate levels were significantly higher, while 1-methylhistidine, isoleucine, choline, valine, alanine, histidine and leucine levels were significantly lower in AECOPD patients, compared with stable COPD patients after normalization based on the healthy controls. Moreover, eight metabolic pathways were significantly altered (P<0.05) in the serum of AECOPD patients compared with the stable COPD population, including purine metabolism, glutamine and glutamate metabolism, arginine biosynthesis, butyrate metabolism, ketone body synthesis and degradation, and linoleic acid metabolism. In addition, the correlation analysis between metabolites and AECOPD patients demonstrated that an M-score based on a weighted sum of concentrations of four metabolites including pyruvate, isoleucine, 1-methylhistidine and glutamine were significantly associated with the acute exacerbation of pulmonary ventilation function in COPD patients. Conclusion: Altogether, the metabolite score based on a weighted sum of concentrations of four serum metabolites was associated with an increased risk of COPD developing acute exacerbation, which will provide a new insight for the understanding of COPD development.

The integrating sphere system plus in-situ absorption monitoring: A new scheme to study absorption enhancement of black carbon in ambient aerosols.

Black carbon (BC) is the strongest light-absorbing aerosol in the atmosphere. The coating process causes lensing effects to enhance the BC absorption. The reported BC absorption enhancement values (Eabs) significantly differ partly due to the measurement methods used. The biggest difficulty in measuring the Eabs values is how to denude the coated particles so that the true value of absorption without coatings can be distinguished from lensing effects. In this study, we proposed a new approach based on an integrating sphere (IS) system plus in-situ absorption monitoring instrument to study Eabs in ambient aerosols. This approach is capable of (i) "de-lensing through solvent dissolution and solvent de-refraction", by which the absorption coefficient of denuded BC is acquired, and (ii) monitoring in-situ absorption with photoacoustic spectroscopy. With the help of the EC concentration measured by a thermal/optical carbon analyser, the Eabs values were calculated as the quotient of in-situ mass absorption efficiency divided by denude mass absorption efficiency. We applied this new approach to measure the Eabs values of four seasons in Beijing and found an annual mean of 1.90 ± 0.41 in 2019. More importantly, a previous assumption that BC absorption efficiency may be progressively enhanced by increased air pollution was validated and quantified using a logarithmic relationship of Eabs = 0.6 ln (PM2.5 ̶ 3.59) ̶ 0.43 (R2 = 0.99). This signals a continued drop of Eabs for future ambient aerosols with the sustained improvement in local air quality in China, meriting serious attention to its influences in climate, air quality, and atmospheric chemistry.

Intrafibrillar Mineralization and Immunomodulatory for Synergetic Enhancement of Bone Regeneration via Calcium Phosphate Nanocluster Scaffold.

Inspired by the bionic mineralization theory, organic-inorganic composites with hydroxyapatite nanorods orderly arranged along collagen fibrils have attracted extensive attention. Planted with an ideal bone scaffold will contribute greatly to the osteogenic microenvironment; however, it remains challenging to develop a biomimetic scaffold with the ability to promote intrafibrillar mineralization and simultaneous regulation of immune microenvironment in situ. To overcome these challenges, a scaffold containing ultra-small particle size calcium phosphate nanocluster (UsCCP) is prepared, which can enhance bone regeneration through the synergetic effect of intrafibrillar mineralization and immunomodulatory. By efficient infiltration into collagen fibrils, the UsCCP released from the scaffold achieves intrafibrillar mineralization. It also promotes the M2-type polarization of macrophages, leading to an immune microenvironment with both osteogenic and angiogenic potential. The results confirm that the UsCCP scaffold has both intrafibrillar mineralization and immunomodulatory effects, making it a promising candidate for bone regeneration.

Oriented Crystallization of Hydroxyapatite in Self-Assembled Peptide Fibrils as a Bonelike Material.

Controlling oriented crystallization is key to producing bonelike composite materials with a well-organized structure. However, producing this type of composite material using synthetic biopolymers as scaffolds is challenging. Inspired by the molecular structure of collagen-I, a collagenlike peptide─(Pro-Hyp-Gly)10 (POG10)─was designed to produce self-assembled fibrils that resemble the structure of collagen-I fibrils. In addition, the oriented mineralization of HAP crystals is formed in the fibrils that reproduces a bonelike material similar to collagen-I fibril mineralization. Unlike collagen-I fibrils, POG10 fibrils do not contain gap spaces. The molecular simulation results indicate that in addition to space confinement, the molecular field generated by POG10 can also confine the orientation of HAP, enriching our understanding of physical confinement and shedding light on the design of synthetic biopolymer scaffolds for bonelike material fabrication.

Upregulation of CDGSH iron sulfur domain 2 attenuates cerebral ischemia/reperfusion injury.

CDGSH iron sulfur domain 2 can inhibit ferroptosis, which has been associated with cerebral ischemia/reperfusion, in individuals with head and neck cancer. Therefore, CDGSH iron sulfur domain 2 may be implicated in cerebral ischemia/reperfusion injury. To validate this hypothesis in the present study, we established mouse models of occlusion of the middle cerebral artery and HT22 cell models of oxygen-glucose deprivation and reoxygenation to mimic cerebral ischemia/reperfusion injury in vivo and in vitro, respectively. We found remarkably decreased CDGSH iron sulfur domain 2 expression in the mouse brain tissue and HT22 cells. When we used adeno-associated virus and plasmid to up-regulate CDGSH iron sulfur domain 2 expression in the brain tissue and HT22 cell models separately, mouse neurological dysfunction was greatly improved; the cerebral infarct volume was reduced; the survival rate of HT22 cells was increased; HT22 cell injury was alleviated; the expression of ferroptosis-related glutathione peroxidase 4, cystine-glutamate antiporter, and glutathione was increased; the levels of malondialdehyde, iron ions, and the expression of transferrin receptor 1 were decreased; and the expression of nuclear-factor E2-related factor 2/heme oxygenase 1 was increased. Inhibition of CDGSH iron sulfur domain 2 upregulation via the nuclear-factor E2-related factor 2 inhibitor ML385 in oxygen-glucose deprived and reoxygenated HT22 cells blocked the neuroprotective effects of CDGSH iron sulfur domain 2 up-regulation and the activation of the nuclear-factor E2-related factor 2/heme oxygenase 1 pathway. Our data indicate that the up-regulation of CDGSH iron sulfur domain 2 can attenuate cerebral ischemia/reperfusion injury, thus providing theoretical support from the perspectives of cytology and experimental zoology for the use of this protein as a therapeutic target in patients with cerebral ischemia/reperfusion injury.

Identifying the fundamental drives behind the 10-year evolution of northern China's rural household energy and emission: Implications for 2030 and beyond.

Rural household energy, particularly solid fuels, in northern China is thought to be a major source of air pollution. However, there is no complete, systematic, and reliable dataset for northern China's rural areas owing to the diversity of energy types used and the difficulty in acquiring data, particularly for solid fuels. Here we assessed existing progress in estimating solid fuels and proposed a practical route for deriving the information on rural household energy consumption and structure in northern China spanning 2010-2020, with important findings. (i) In 2010, the total rural household energy consumption for northern China was 287.51 million tons standard coal equivalent (TCE), while for 2020, it decreased to 205.14 million TCE, showing a 29 % decrease and an annual down 3.3 % averagely. Among a number of underlying reasons, China's urbanization process, which made the rural population shrink year by year, was primarily responsible. (ii) The share of clean energy in northern rural areas began at 4.2 % in 2010 and grew to 15.6 % in 2020, displaying a sustained improvement in energy structure. Particularly in the second 5 years, the clean energy share of policy priority areas grew by 20.0 percentage points (from 15.0 % in 2010 to 35.0 % in 2020), which is more than 18 percentage points higher than the growth of non-priority areas (from 2.9 % in 2010 to 4.5 % in 2020). Clean air policy, particularly the "two replacements" (replace coal with gas and electricity), in priority areas played a core role in changing the energy structure. (iii) Although both air pollutants and CO2 are predicted to decrease in 2030, there is a large gap between expected 2030 emissions and hoped 2060 carbon neutrality in northern rural households. It is thus necessary to gradually boost the share of green electricity (non-fossil) and to reverse the trend of "biomass fuel curtailment" in rural residential sector. This calls for the improvement in biomass style (e.g., biomass pellets) and in stove efficiency (e.g., complete combustion).

Circ_0000520 interacts with miR-512-5p to upregulate KIAA0100 to promote malignant behaviors in lung cancer.

BACKGROUND: CircRNAs function as pivotal molecules to regulate the malignant development of lung cancer. This study was designed to research the functional role and how it acted in lung cancer progression. METHODS: Circ_0000520, microRNA-512-5p (miR-512-5p) and Breast cancer-overexpressed gene 1 (KIAA0100) levels were measured through reverse transcription-quantitative polymerase chain reaction assay. Cell Counting Kit-8 assay and EdU assay were used to examine cell proliferation. Cell cycle and apoptosis were evaluated via flow cytometry. The protein levels were determined using western blot. Cell migration and invasion were assessed by wound healing assay and transwell assay. The circ_0000520 function in vivo was explored by tumor xenograft assay. The molecular interaction was analyzed via Dual-luciferase reporter assay. RESULTS: Circ_0000520 was obviously upregulated in lung cancer tissues and cells. Silence of circ_0000520 inhibited proliferation, cell cycle progression, migration, invasion and angiogenesis but promoted cell apoptosis. Circ_0000520 downregulation reduced tumor growth of lung cancer in vivo. Circ_0000520 served as a miR-512-5p sponge. The oncogenic function of circ_0000520 was partly achieved by sponging miR-512-5p in lung cancer. KIAA0100 was a target of miR-512-5p and miR-512-5p inhibited the malignant behaviors of lung cancer cells via downregulating KIAA0100. Circ_0000520 targeted miR-512-5p to regulate the level of KIAA0100. CONCLUSION: All these data demonstrated that circ_0000520 was able to drive the progression of lung cancer via the mediation of miR-512-5p/KIAA0100 axis. Circ_0000520 might be a potential biomarker for lung cancer.

Struggling or Liberating? The Effects of Machiavellianism on Break-Up Distress.

Negative emotions caused by break-up are the key work of university students' psychological intervention. It is important to explore the specific factors of break-up distress for university students' psychological intervention. Therefore, we investigated 869 university students to examine the effect of Machiavellianism and psychological capital on break-up distress, as well as its gender difference. The results indicated that high Machiavellians experience more break-up distress. Moreover, through structural equation models, we found that as for female university students, psychological capital mediated the relationship between Machiavellianism and break-up distress. However, as for male university students, the mediation effect was not significant. It means that for female university students, psychological capital acted as the mechanism to connect Machiavellianism and break-up distress.

Health-Related Quality of Life in Children: The Roles of Age, Gender and Interpersonal Trust.

Health-related quality of life (HRQoL) is an interesting topic in health care sciences and psychology. Deeper insight into the internal mechanism of this effect through large samples is crucial to further understanding HRQoL and making targeted suggestions to improve HRQoL. The present study aims to investigate the mediating role of interpersonal trust between age and HRQoL from a developmental lens. The purpose of this study was to profile the Pediatric Quality of Life Inventory 4.0 generic scale in China and test the relationship between age and health-related quality of life, as well as the mediating role of interpersonal trust and the moderating role of gender. A sample of 6248 children completed measures of demography, health-related quality of life, and interpersonal trust. Regression analyses were performed to test the mediating role of interpersonal trust and the moderating role of gender. Age was associated with lower health-related quality of life and lower interpersonal trust. Similarly, gender differences were also noted, with boys reporting higher health-related quality of life and lower interpersonal trust than girls. Additionally, the health-related quality of life of girls declined more than that of boys with increasing age. Regression analyses revealed that age could predict decreased health-related quality of life via lower levels of interpersonal trust. What is more, the mediation effect was moderated by gender, with the observed mediation effect being stronger among boys than girls. The current study replicates age and gender differences in health-related quality of life and interpersonal trust. Moreover, this study explained how and when age affected the health-related quality of life of children, and provided a deeper understanding of the relation between age and health-related quality of life.

Promotion of collagen mineralization and dentin repair by succinates.

Biomineralization of collagen fibers is regulated by non-collagenous proteins and small biomolecules, which are essential in bone and teeth formation. In particular, small biomolecules such as succinic acid (SA) exist at a high level in hard tissues, but their role is yet unclear. Here, our work demonstrated that SA could significantly promote intrafibrillar mineralization in two- and three-dimensional collagen models, where the relative mineralization rate was 16 times faster than the control group. Furthermore, the FTIR spectra and isothermal experimental results showed that collagen molecules could interact with SA via a hydrogen bond and that the interaction energy was about 4.35 kJ mol-1. As expected, the SA-pretreated demineralized dentin obtained full remineralization within two days, whereas it took more than four days in the control group, and their mechanical properties were considerably enhanced compared with those of the demineralized one. The possible mechanism of the promotion effect of SA was ultimately illustrated, with SA modification strengthening the capacity of the collagen matrix to attract more calcium ions, which might create a higher local concentration that could accelerate the mineralization of collagen fibers. These findings not only advance the understanding of the vital role of small biomolecules in collagen biomineralization but also facilitate the development of an effective strategy to repair hard tissues.

Therapeutic Potential of Synthetic Human ß-Defensin 1 Short Motif Pep-B on Lipopolysaccharide-Stimulated Human Dental Pulp Stem Cells.

Dental pulp inflammation is a widespread public problem usually caused by caries or trauma. Alleviating inflammation is critical to inflamed pulp repair. Human ß-defensin 1 short motif Pep-B is a cationic peptide that has anti-inflammatory, antibacterial, and immunoregulation properties, but its repair effect on human dental pulp stem cells (hDPSCs) under inflammation remains unclear. In this study, we aimed to investigate anti-inflammatory function of Pep-B and explore its therapeutic potential in lipopolysaccharide-(LPS-) induced hDPSCs. CCK-8 assay and transwell assay evaluated effects of Pep-B on hDPSC proliferation and chemotaxis. Inflammatory response in hDPSCs was induced by LPS; after Pep-B application, lactate dehydrogenase release, intracellular ROS, inflammatory factor genes expression and possible signaling pathway were measured. Then, osteo-/odontoblast differentiation effect of Pep-B on LPS-induced hDPSCs was detected. The results showed that Pep-B promoted hDPSC proliferation and reduced LPS-induced proinflammatory marker expression, and western blot result indicated that Pep-B inhibited inflammatory activation mediated by NF-κB and MAPK pathways. Pep-B also enhanced the expression of the osteo-/odontogenic genes and proteins, alkaline phosphatase activity, and nodule mineralization in LPS-stimulated hDPSCs. These findings indicate that Pep-B has anti-inflammatory activity and promote osteo-/odontoblastic differentiation in LPS-induced inflammatory environment and may have a potential role of hDPSCs for repair and regeneration.