Apoptotic Vesicles Derived from Dental Pulp Stem Cells Promote Bone Formation through the ERK1/2 Signaling Pathway.

Osteoporosis is a common degenerative bone disease. The treatment of osteoporosis remains a clinical challenge in light of the increasing aging population. Human dental pulp stem cells (DPSCs), a type of mesenchymal stem cells (MSCs), are easy to obtain and have a high proliferation ability, playing an important role in the treatment of osteoporosis. However, MSCs undergo apoptosis within a short time when used in vivo; therefore, apoptotic vesicles (apoVs) have attracted increasing attention. Currently, the osteogenic effect of DPSC-derived apoVs is unknown; therefore, this study aimed to determine the role of DPSC-derived apoVs and their potential mechanisms in bone regeneration. We found that MSCs could take up DPSC-derived apoVs, which then promoted MSC osteogenesis in vitro. Moreover, apoVs could increase the trabecular bone count and bone mineral density in the mouse osteoporosis model and could promote bone formation in rat cranial defects in vivo. Mechanistically, apoVs promoted MSC osteogenesis by activating the extracellular regulated kinase (ERK)1/2 signaling pathway. Consequently, we propose a novel therapy comprising DPSC-derived apoVs, representing a promising approach to treat bone loss and bone defects.

Apoptotic vesicles derived from human red blood cells promote bone regeneration via carbonic anhydrase 1.

Apoptotic vesicles (apoVs) are nanoscale vesicles derived from billions of apoptotic cells involved in the maintenance of the human body's homeostasis. Previous researches have shown that some apoVs, such as those derived from mesenchymal stem cells, contribute to bone formation. However, those apoVs cannot be extracted from patients in large quantities, and cell expansion is needed before apoV isolation, which limits their clinical translation. Mature RBCs, which have no nuclei or genetic material, are easy to obtain, showing high biological safety as a source of extracellular vesicles (EVs). Previous studies have demonstrated that RBC-derived EVs have multiple biological functions, but it is unknown whether RBCs produce apoVs and what effect these apoVs have on bone regeneration. In this study, we isolated and characterized RBC-derived apoVs (RBC-apoVs) from human venous blood and investigated their role in the osteogenesis of human bone mesenchymal stem cells (hBMSCs). We showed that RBCs could produce RBC-apoVs that expressed both general apoVs markers and RBC markers. RBC-apoVs significantly promoted osteogenesis of hBMSCs and enhanced bone regeneration in rat calvarial defects. Mechanistically, RBC-apoVs regulated osteogenesis by transferring carbonic anhydrase 1 (CA1) into hBMSCs and activating the P38 MAPK pathway. Our results indicated that RBC-apoVs could deliver functional molecules from RBCs to hBMSCs and promote bone regeneration, pointing to possible therapeutic use in bone tissue engineering.

Platelet-Derived Apoptotic Vesicles Promote Bone Regeneration via Golgi Phosphoprotein 2 (GOLPH2)-AKT Signaling Axis.

Apoptotic vesicles (apoVs) are apoptotic-cell-derived nanosized vesicles that take on dominant roles in regulating bone homeostasis. We have demonstrated that mesenchymal stem cell (MSC)-derived apoVs are promising therapeutic agents for bone regeneration. However, clinical translation of MSC-derived apoVs has been hindered due to cell expansion and nuclear substance. As another appealing source for apoV therapy, blood cells could potentially eliminate these limitations. However, whether blood cells can release apoVs during apoptosis is uncertain, and the detailed characteristics and biological properties of respective apoVs are not elucidated. In this study, we showed that platelets (PLTs) could rapidly release abundant apoVs during apoptosis in a short time. To recognize the different protein expressions between PLT-derived apoVs and PLTs, we established their precise protein landscape. Furthermore, we identified six proteins specifically enriched in PLT-derived apoVs, which could be considered as specific biomarkers. More importantly, PLT-derived apoVs promoted osteogenesis of MSCs and rescued bone loss via Golgi phosphoprotein 2 (GOLPH2)-induced AKT phosphorylation, therefore, leading to the emergence of their potential in bone regeneration. In summary, we comprehensively determined characteristics of PLT-derived apoVs and confirmed their roles in bone metabolism through previously unrecognized GOPLH2-dependent AKT signaling, providing more understanding for exploring apoV-based therapy in bone tissue engineering.

Robust and rapid partitioning in thermoplastic.

Partitioning is the core technology supporting digital assays. It divides a sample into thousands of individual reactors prior to amplification and absolute quantification of target molecules. Thermoplastics are attractive materials for large scale manufacturing, however they have been seldomly used for fabricating partitioning arrays. Patitioning in thermoplastic devices has proven difficult due to the challenge of efficiently displacing the air trapped in the nanoliter structures during priming of thousands of chambers. Here, we report the design of an array of chambers made of thermoplastics where the progression of the liquid-air interface is controlled by capillary effects. Our device performs robust partitioning over a wide range of pressures and can be actuated at low pressure by a simple micropipette. Our thermoplastic device lays the foundation to cost-effective and instrument-free partitioning platforms, which could be deployed in low-resource settings.

Strong Biopolymer-Based Nanocomposite Hydrogel Adhesives with Removability and Reusability for Damaged Tissue Closure and Healing.

Bioadhesives are widely used in a variety of medical settings due to their ease of use and efficient wound closure and repair. However, achieving both strong adhesion and removability/reusability is highly needed but challenging. Here, we reported an injectable mesoporous bioactive glass nanoparticle (MBGN)-incorporated biopolymer hydrogel bioadhesive that demonstrates a strong adhesion strength (up to 107.55 kPa) at physiological temperatures that is also removable and reusable. The incorporation of MBGNs in the biopolymer hydrogel significantly enhances the tissue adhesive strength due to an increased cohesive and adhesive property compared to the hydrogel adhesive alone. The detachment of bioadhesive results from temperature-induced weakening of interfacial adhesive strength. Moreover, the bioadhesive displays injectability, self-healing, and excellent biocompatibility. We demonstrate potential applications of the bioadhesive in vitro, ex vivo, and in vivo for hemostasis and intestinal leakage closure and accelerated skin wound healing compared to surgical wound closures. This work provides a novel design of strong and removable bioadhesives.

Obesity-Associated Anxiety Is Prevalent among College Students and Alleviated by Calorie Restriction.

Anxiety is a common disorder among college students, especially those with obesity. Obesity contributes to metabolic disorders and disturbs the neural functions, further leading to anxiety. In this cross-sectional study, we aimed to determine the association between obesity and anxiety among college students and identified the potential factors for obesity-associated anxiety. We evaluated the intervention effects of calorie restriction on anxiety. Self-reported questionnaires were distributed to 1381 college students from January to March in 2021. Anxiety was measured by the State-Trait Anxiety Inventory (STAI). Participants were classified into anxiety and non-anxiety groups according to their STAI scores. Chi-squared test and logistic regression were used to analyze the potential factors. We found that 383 college students exhibited anxiety, accounting for 30.1% among all included college students, which was higher than the global average. The association between anxiety and obesity was observed among college students (p = 0.009), especially in males (p = 0.007). We identified that pre-obesity (p = 0.012), unhealthy calorie intake (p = 0.001), dieting (p = 0.003) and high academic year (p = 0.006) as the risk factors for anxiety and found that the long sleep duration was a protective factor for anxiety (p < 0.001). We found that more obese students showed an improvement of anxiety than the underweight students after calorie restriction (p < 0.001). Collectively, our findings suggest that obesity-associated anxiety is prevalent among the college students and could be alleviated by moderate calorie restriction. It is necessary for students to receive anxiety management in their college life. Additionally, the proper calorie restriction should be promoted to help students protect against obesity and obesity-associated anxiety.

Proteomic analysis of MSC-derived apoptotic vesicles identifies Fas inheritance to ameliorate haemophilia a via activating platelet functions.

Apoptotic vesicles (apoVs) are apoptotic cell-derived nanosized vesicles that play a crucial role in multiple pathophysiological settings. However, their detailed characteristics, specific surface markers, and biological properties are not fully elucidated. In this study, we compared mesenchymal stem cell (MSC)-derived apoVs and exosomes from three different types of MSCs including human bone marrow MSCs (hBMSCs), human adipose MSCs (hASCs), and mouse bone marrow MSCs (mBMSCs). We established a unique protein map of MSC-derived apoVs and identified the differences between apoVs and exosomes in terms of functional protein cargo and surface markers. Furthermore, we identified 13 proteins specifically enriched in apoVs compared to exosomes, which can be used as apoV-specific biomarkers. In addition, we showed that apoVs inherited apoptotic imprints such as Fas to ameliorate haemophilia A in factor VIII knockout mice via binding to the platelets' FasL to activate platelet functions, and therefore rescuing the blood clotting disorder. In summary, we systemically characterized MSC-derived apoVs and identified their therapeutic role in haemophilia A treatment through a previously unknown Fas/FasL linkage mechanism.

Combination multi-nitrogen with high heat of formation: theoretical studies on the performance of bridged 1,2,4,5-tetrazine derivatives.

A series of bridged tetrazine derivatives (BDDT) were designed by using different bridges to connect two molecules of 1,2,4, 5-tetrazine oxides and then combining different substituents. At the same time, we used DFT-wB97/6-31 + G** method to regularly predict the HOMO-LUMO, heats of formation (HOF), detonation properties, thermal stability, and thermodynamic property orbitals of BDDT compounds. By studying the comprehensive relationship between different substituents and bridging and performance, it is shown that -N(NO2)2 and -C(NO2)3 are not only excellent groups to improve the heat of formation and detonation properties, but also can cause the compound to have a superior oxygen balance. And that the incorporation of the -N = N- and -NH-N = N- is helpful to enhance their thermal stabilities and HOF. -CH2-CH2- and -CH2-NH- are good for improving the HOMO-LUMO energy gaps. Performances with positive HOF (1170-1590 kJ mol-1), remarkable density (1.88-1.93 g cm-3), outstanding detonation properties (D = 9.15-9.80 km s-1, P = 38.24-44.40 GPa), and acceptable impact sensitivity lead C5, D8, E5, E7, F5, and F7 to be the potential candidates of HEDMs.

Chemical study of fused ring tetrazine derivatives as possible high energy density materials (HEDMs).

Using density functional theory (DFT), enthalpy of formation (HOF), thermodynamic properties, and detonation properties of a series of tetrazine fused ring derivatives are calculated. The results show that the introduction of coordinated oxygen is beneficial to increase the HOF value. The effects of different substituents on HOF are as follows: -C(NO2)3 > -N3 > -CH(NO2)2 > -NHNO2 > -NO2 > -NHNH2 > -H > -OH. Introduction of -H, -NH2, and -NHNH2 on the parent is not conducive to improving the detonation performance, while the introduction of -C(NO2)3 is conducive to improving the detonation performance of the designed compound. The explosion velocity of the newly designed compounds varies between 8.96 and 10.48 km·s-1. The explosion pressure varies between 35.97 and 51.80 GPa, and the density varies between 1.83 and 2.00 g·cm-3. Considering the thermal stability, density, and detonation properties, most of these compounds designed this time can be used as potential candidates for high energy density compounds.

Hybrid gelatin/oxidized chondroitin sulfate hydrogels incorporating bioactive glass nanoparticles with enhanced mechanical properties, mineralization, and osteogenic differentiation.

Biopolymer based hydrogels are characteristic of their biocompatibility and capability of mimicking extracellular matrix structure to support cellular behavior. However, these hydrogels suffer from low mechanical properties, uncontrolled degradation, and insufficient osteogenic activity, which limits their applications in bone regeneration. In this study, we developed hybrid gelatin (Gel)/oxidized chondroitin sulfate (OCS) hydrogels that incorporated mesoporous bioactive glass nanoparticles (MBGNs) as bioactive fillers for bone regeneration. Gel-OCS hydrogels could be self-crosslinked in situ under physiological conditions in the presence of borax. The incorporation of MBGNs enhanced the crosslinking and accelerated the gelation. The gelation time decreased with increasing the concentration of MBGNs added. Incorporation of MBGNs in the hydrogels significantly improved the mechanical properties in terms of enhanced storage modulus and compressive strength. The injectability of the hydrogels was not significantly affected by the MBGN incorporation. Also, the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro and rat cranial defect restoration in vivo were significantly promoted by the hydrogels in the presence of MBGNs. The hybrid Gel-OCS/MBGN hydrogels show promising potential as injectable biomaterials or scaffolds for bone regeneration/repair applications given their tunable degradation and gelation behavior as well as favorable mechanical behavior and osteogenic activities.

Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis.

Osteoporosis is a systemic metabolic bone disease with characteristics of bone loss and microstructural degeneration. The personal and societal costs of osteoporosis are increasing year by year as the ageing of population, posing challenges to public health care. Homing disorders, impaired capability of osteogenic differentiation, senescence of mesenchymal stem cells (MSCs), an imbalanced microenvironment, and disordered immunoregulation play important roles during the pathogenesis of osteoporosis. The MSC transplantation promises to increase osteoblast differentiation and block osteoclast activation, and to rebalance bone formation and resorption. Preclinical investigations on MSC transplantation in the osteoporosis treatment provide evidences of enhancing osteogenic differentiation, increasing bone mineral density, and halting the deterioration of osteoporosis. Meanwhile, the latest techniques, such as gene modification, targeted modification and co-transplantation, are promising approaches to enhance the therapeutic effect and efficacy of MSCs. In addition, clinical trials of MSC therapy to treat osteoporosis are underway, which will fill the gap of clinical data. Although MSCs tend to be effective to treat osteoporosis, the urgent issues of safety, transplant efficiency and standardization of the manufacturing process have to be settled. Moreover, a comprehensive evaluation of clinical trials, including safety and efficacy, is still needed as an important basis for clinical translation.

Association between Take-Out Food Consumption and Obesity among Chinese University Students: A Cross-Sectional Study.

BACKGROUND: The frequency of take-out food consumption has increased rapidly among Chinese college students, which has contributed to high obesity prevalence. However, the relationships between take-out food consumption, body mass index (BMI), and other individual factors influencing eating behavior among college students are still unclear. This study explored the association of take-out food consumption with gender, BMI, physical activity, preference for high-fat and high-sugar (HFHS) food, major category, and degree level among Chinese college students. METHODS: Cross-sectional data were collected from 1220 college students in Beijing, China, regarding information about take-out food consumption, physical activity, and preference for HFHS food using a self-reported questionnaire. The logistic linear regression model was used to analyze the association between take-out food consumption and personal and lifestyle characteristics. RESULTS: Out of 1220 college students, 11.6% of college students were overweight or obese. Among the personal and lifestyle characteristics, high frequency of take-out food consumption was significantly associated with a non-medical major, high preference for HFHS food, degree level, and higher BMI, but not physical activity. CONCLUSION: Among Chinese college students, consumption of take-out food may be affected by major category, preference for HFHS food, degree level, and BMI. This could provide guidance on restrictions of high take-out food consumption, which contributes to high obesity prevalence and high risk for metabolic diseases.

Inactivation of Escherichia coli O157:H7 and Bacillus cereus by power ultrasound during the curing processing in brining liquid and beef.

The objective of this study was to evaluate the effects of ultrasound on the number of Escherichia coli O157:H7 and vegetative cells of Bacillus cereus in brining and beef during the curing processing. The mechanisms of the inactivation for the pathogens were preliminarily explored. The ultrasound intensity (2.39, 6.23, 11.32 and 20.96Wcm-2) and sonication time (30, 60, 90 and 120min) at 10°C were assessed in brine and meat. Plate count data indicated that 20.96Wcm-2 for 120min was the optimal treatment for bacterial reductions. E. coli O157:H7 was more susceptible to ultrasonic treatment in the first 30min than B. cereus in brine. However, a similar reduction percentage with around 40% in both cultures could be achieved when sonicated for 120min. Good fitness of Weibull model (R2>0.98; RMSE<0.12) was obtained with the distinct shape of the curves which predicted microbial inactivation by ultrasound in salt solution (6%). The production of hydrogen peroxide in brine by ultrasound confirmed the effects of ultrasound on the inactivation of microorganisms during the curing processing. The particle size distribution of bacterial and cell fluorescence staining analysis showed that ultrasound could result in the formation of cell fragments through destroying the integrality of the membrane of E. coli O157:H7 and B. cereus. However, the promoting effect of ultrasound on the number of bacteria in beef suggested that the sanitation conditions of equipment and raw meat must be paid attention when applying ultrasound for curing procedure.

Interfacial Engineering with Cross-Linkable Fullerene Derivatives for High-Performance Perovskite Solar Cells.

Two fullerene derivatives with styryl and oxetane cross-linking groups served as interfacial materials to modify an electron-transporting layer (ETL) of TiO2, doped with Au nanoparticles, processed under low-temperature conditions to improve the performance of perovskite solar cells (PSC). The cross-linkable [6,6]-phenyl-C61-butyric styryl dendron ester was produced via thermal treatment at 160 °C for 20 min, whereas the cross-linkable [6,6]-phenyl-C61-butyric oxetane dendron ester (C-PCBOD) was obtained via UV-curing treatment for 45 s. Both cross-linked fullerenes can passivate surface-trap states of TiO2 and have also excellent surface coverage on the TiO2 layer shown in the corresponding atomic force microscopy images. To improve the crystallinity of perovskite, we propose a simple co-solvent method involving mixing dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) in a specific ratio (DMF/DMSO = 90/10). The fullerene derivative layer between the ETL and perovskite layers significantly improved electron extraction and suppressed charge recombination by decreasing the density of traps at the ETL surface. A planar PSC device was fabricated with the configuration indium tin oxide/TiO2 (Au)/C-PCBOD/perovskite/spiro-OMeTAD/Au to attain a power conversion efficiency (PCE) of 15.9%. The device performance was optimized with C-PCBOD as an interfacial mediate to modify the surface of the mesoporous TiO2 ETL; the C-PCBOD-treated device attained a significantly enhanced performance, PCE 18.3%. Electrochemical impedance spectral and photoluminescence decay measurements were carried out to understand the characteristics of electron transfer and charge recombination of the perovskite/TiO2 samples with and without a fullerene interfacial layer.