Application of Bioactive Materials for Osteogenic Function in Bone Tissue Engineering.

Bone tissue defects present a major challenge in orthopedic surgery. Bone tissue engineering using multiple versatile bioactive materials is a potential strategy for bone-defect repair and regeneration. Due to their unique physicochemical and mechanical properties, biofunctional materials can enhance cellular adhesion, proliferation, and osteogenic differentiation, thereby supporting and stimulating the formation of new bone tissue. 3D bioprinting and physical stimuli-responsive strategies have been employed in various studies on bone regeneration for the fabrication of desired multifunctional biomaterials with integrated bone tissue repair and regeneration properties. In this review, biomaterials applied to bone tissue engineering, emerging 3D bioprinting techniques, and physical stimuli-responsive strategies for the rational manufacturing of novel biomaterials with bone therapeutic and regenerative functions are summarized. Furthermore, the impact of biomaterials on the osteogenic differentiation of stem cells and the potential pathways associated with biomaterial-induced osteogenesis are discussed.

Moulting behaviour in the trilobite Oryctocephalus indicus (Reed, 1910) from the Cambrian Miaolingian Series (Wuliuan Stage) of Jianhe, South China.

The accurate interpretation of trilobite moulting behaviour relies on a comprehensive understanding of their moult configurations, yet the focus has commonly been limited to a brief description of the exuviae, and how differences in moulting behaviour further impact the preservation of exuviae is often ignored. This study investigates the configuration, style, and process of moulting in Oryctocephalus indicus through analysis of 88 exuviae collected from the Kaili Formation (Cambrian, Wuliuan) in Guizhou Province, South China. The moult configurations of O. indicus are typically characterised by the lower cephalic unit (LCU), which comprises the librigenae and rostral-hypostomal plate connected as a whole, detached from the cephalon and positioned anterior to the thoracopygon, while the cranidium is mostly absent. From detailed observation and description of the available material, we believe that O. indicus completes its moult through an exuvial gape formed by disarticulation of the facial sutures, rostral sutures and/or sutures of the cephalothoracic joints. Although many exuviae exhibited an opening at the cephalothoracic joint-disjunction of which is usually accompanied by disarticulation of both the facial and rostral sutures-the Salter's configuration produced by the 'Salterian' mode of moulting was not observed. Additionally, the structural characteristics of Henningsmoen's configuration, Harrington's configuration, and Somersault's configuration are discussed based on the exuviae of O. indicus, and Henningsmoen's configuration has been categorised into three types according to the different states of fossil preservation. In this article, apart from promoting further research on moulting behaviour in O. indicus, we also provide a supplement for moult configuration based on the exuviae, which offers new materials for studying moulting behaviour in oryctocephalid trilobites.

Life cycle evolution in the trilobites Balangia and Duyunaspis from the Cambrian Series 2 (Stage 4) of South China.

The evolution process can be reconstructed by tracking the changes in the dynamic characters of life cycles. A number of related trilobites from the Cambrian of South China provide additional information for the study of trilobite evolutionary patterns, which has been hampered by previous incomplete fossil record though. Here, Balangia and Duyunaspis represent related Cambrian oryctocephalid trilobites from South China, are comprehensively discussed over the ontogeny, and the results show that, from B. balangensis via D. duyunensis to D. jianheensis, their exoskeletal morphology shows a directional evolution. Based on the direction of evolutionary changes in the development of Balangia and Duyunaspis, we speculate that Duyunaspis likely evolved from Balangia instead of Balangia evolved from Duyunaspis, as was previously assumed. This inference is also supported by the phylogenetic tree. This research provides not only a better understanding of the mechanisms of evolution in trilobites, but also new insights for the relationship between developmental evolutionary changes and phylogeny in trilobites.

The mediating effect of resilience on mental health literacy and positive coping style among Chinese empty nesters: A cross-sectional study.

Objectives: Empty nesters in China have limited mental health literacy (MHL), which may lead to poorer health outcomes. Studies demonstrate that MHL is associated with both resilience and positive coping style. However, the potential mechanism of MHL, resilience and positive coping style remain unclear. Therefore, the study aims to investigate the possible mediating role of resilience in the relationship between MHL and positive coping style. Method: In this cross-sectional study, a total of 363 empty nesters from Huzhou, China were surveyed in 2022. The Chinese version of Mental Health Literacy Scale (C-MHLS), the Chinese version of 10-item Connor-Davidson Resilience Scale (CD-RISC-10) and the Simplified Coping Style Questionnaire (SCSQ-19) were used to assess MHL, resilience, and positive coping style, respectively. Results: Positive coping style was significantly correlated with MHL and resilience, and MHL was positively correlated with resilience (p < 0.01). MHL can significantly and positively predict the positive coping style, and resilience played a partial intermediary role between MHL and positive coping style, with the intermediary effect of 77.36%. Conclusion: This study indicates that MHL not only directly affected positive coping style, but also indirectly influences positive coping style by increasing the resilience of empty nesters. The results provide an empirical evidence for the development of intervention programs to improve positive coping style directly and indirectly. Consequently, community health servicers should take targeted measures which focus on MHL and resilience as breakthrough points to stimulate positive coping style of empty nesters, and ultimately achieve their overall well-being.

Reliability and validity of the Chinese version of the instrument of health literacy competencies for health professionals.

AIMS: This study aimed to evaluate the reliability and validity of the Chinese version of an instrument of health literacy competencies for health professionals. DESIGN: This study utilized a cross-sectional design. METHODS: Authorization was obtained from the authors of the original scale to translate the scale and perform cross-cultural debugging. From August 2020 to November 2020, 573 health professionals were randomly selected from primary, secondary and tertiary hospitals in Huzhou to examine the reliability and validity of the Chinese version of an instrument of health literacy competencies for health professionals. RESULTS: The Chinese version of the scale contains 49 items. The internal consistency Cronbach's α was 0.958 for the total scale and 0.791-0.956 for each dimension. The test-retest reliability was 0.973. Confirmatory factor analysis showed that the fitness degree of the model is good (χ2 /df = 1.347, IFI = 0.924, TLI = 0.913, CFI = 0.922, GFI = 0.841, AGFI = 0.815, RMR = 0.011, RMSEA = 0.035). CONCLUSION: The Chinese version of an instrument of health literacy competencies is reliable and valid, which is a credible and effective tool to assess the level of health literacy competencies in Chinese health professionals. PATIENT OR PUBLIC CONTRIBUTION: Health professionals with good health literacy competencies can provide patient-specific treatment and guidance to promote healthy outcomes for patients.

Research on the Expression Level of Matrin-Type Zinc Finger Protein 4 Gene in T Cells of Thyroid Carcinoma Tissue.

In order to analyze the expression level of zinc finger matrin-type protein 4 (ZMAT4) gene in T cells of thyroid carcinoma (TC) tissue and its clinical significance to prognosis of patients based on bioinformatics and reverse transcription polymerase chain reaction (RT-PCR), 389 TC patients with ZMAT4 gene and its corresponding survival and prognosis are searched by the Cancer Genome Atlas database. The expression of ZMAT4 gene is compared between normal thyroid tissue and TC tissue by RT-PCR. The relationship between ZMAT4 expression levels and clinicopathological parameters and baseline data is analyzed. The experimental results show that the low expression of ZMAT4 gene has an important relationship with the development of thyroid cancer, and real-time monitoring of ZMAT4 gene in TC patients can effectively evaluate the prognosis of patients.

Facile synthesis by a covalent binding reaction for pH-responsive drug release of carboxylated chitosan coated hollow mesoporous silica nanoparticles.

In this study, a promising drug nano-carrier system consisting of mono-dispersed and pH sensitive carboxylated chitosan-hollow mesoporous silica nanoparticles (Ccs-HMSNs) suitable for the treatment of malignant cells was synthesised and investigated. At neutral pH, the Ccs molecules are orderly aggregated state, which could effectively hinder the release of loaded drug molecules. However, in slightly acidic environment, Ccs chains are heavily and flexibly entangled in gel state, which would enhance the subsequent controlled release of the loaded drug. Using doxorubicin hydrochloride (DOX•HCl) as the drug model, their results demonstrated that the system had an excellent loading efficiency (64.74 µg/mg Ccs-HMSNs) and exhibited a pH-sensitive release behaviour. Furthermore, confocal laser scanning microscopy revealed that the Ccs-HMSNs nanocomposite could effectively deliver and release DOX•HCl to the nucleus of HeLa cells, thereby inducing apoptosis. In addition, MTT assay also confirmed that DOX•HCl loaded Ccs-HMSNs (DOX•HCl@Ccs-HMSNs) exhibited a good anticancer effect on HeLa cells with a time-dependent manner. Finally, haemolysis experiment showed Ccs-HMSNs had no haemolytic activity at all the tested concentrations (5-320 µg/mL). Thus, this biocompatible and effective nano-carrier system will have potential applications in controllable drug delivery and cancer therapy.

PM2.5 exposure decreases viability, migration and angiogenesis in human umbilical vein endothelial cells and human microvascular endothelial cells.

Previous studies have confirmed that exposure to particulate matter with a diameter of ≤2.5 µm (PM2.5) is associated with inflammation. PM2.5 decreases cardiac cell viability and increases apoptosis through overproduction of reactive oxygen species (ROS). In the present study, the role of PM2.5 in ECs was investigated in vitro. Human umbilical vein endothelial cells and human microvascular endothelial cells (ECs) were incubated with PM2.5 (100­800 µg/ml) to investigate the effects of PM2.5 on EC viability, migration, tube formation and intracellular levels of ROS. Cell viability and cell apoptosis were determined by MTT assay and flow cytometry analysis. Cell migration was assessed using a Boyden chamber assay, and tube formation was determined by matrigel assay. Tumor necrosis factor­α and interleukin­8 levels were measured by ELISA, and ROS levels were assessed with 2',7'­dichlorofluorescin diacetate. The results indicated that PM2.5 decreases EC viability and increases EC apoptosis in a concentration­dependent manner. PM2.5 also decreased EC tube formation in a dose­dependent manner. The results also demonstrated that PM2.5 suppresses adhesion to EC extracellular matrix proteins. Furthermore, PM2.5 exposure significantly induced ROS generation, indicative of oxidative stress. Finally, it was demonstrated that PM2.5 decreased angiogenesis in vivo. These results suggested that repeated exposure to PM2.5 induces vascular inflammation.

Curcumin-Loaded TPGS/F127/P123 Mixed Polymeric Micelles for Cervical Cancer Therapy: Formulation, Characterization, and InVitro and InVivo Evaluation.

Cervical cancer is the fourth most common cancer in women worldwide, and existing treatments cause severe side effects and great burdens. Thus, the development of safe, inexpensive therapeutic agents is necessary. Curcumin (Cur), a well-known natural product, exerts promising anti-cancer activities against various cancer types. However, its therapeutic efficacy is severely restrained due to rapid degradation, poor aqueous solubility, and low bioavailability. The objective of this study was to investigate the therapeutic potential of novel curcumin-loaded TPGS/F127/P123 mixed polymeric micelles (Cur@NPT100) for cervical cancer treatment. The Cur@NPT100 exhibited an average size of approximately 19 nm, a zeta potential of around -4 mV, a drug loading of 8.18 ± 0.36%, and an encapsulation efficiency of 79.38 ± 4.65%. Unlike free Cur, Cur@NPT100 are readily dispersed in aqueous medium, showing enhanced stability and a sustained release profile over a 6-day period. In vitro cell culture experiments revealed that TPGS/F127/P123 mixed polymeric micelles (NPT100) based nanocarriers substantially promoted the selective cellular uptake of Cur into HeLa cells rather than by non-cancerous NIH3T3 cells, inducing higher cytotoxicity and greater apoptosis and significantly increasing the percentage of cells arrested at the G2/M phase of the cell cycle. Additionally, the Cur@NPT100 facilitated more Cur accumulation in the mitochondria and decreased the mitochondrial membrane potential. In addition, western blot assays demonstrated that Cur@NPT100 were more potent than free Cur at activating the mitochondria-mediated apoptosis pathway. In vivo results further confirmed that Cur@NPT100 exhibited a much higher antitumor efficacy than free Cur and had excellent biocompatibility. In conclusion, Cur@NPT100 might be an effective therapeutic agent for cervical cancer.

Association of depression with pre-diabetes, undiagnosed diabetes, and previously diagnosed diabetes: a meta-analysis.

We performed a meta-analysis to analyze the associations of depression with pre-diabetes (PreDM), undiagnosed diabetes (UDM), and previously diagnosed diabetes (PDM), and whether the association was affected by important study characteristics. We searched relevant articles published in PubMed and EMBASE up to August, 2015. Studies reporting cross-sectional associations of depression with PreDM, UDM, or PDM compared with normal glucose metabolism (NGM) were included. Odds ratios (ORs) were pooled with random-effect and fixed-effect models. Subgroup analyses by sex, study mean age, different degrees of adjustment, publication year, quality score, and depression assessment scales were also performed. Twenty studies were eligible and included in current analysis. Summary estimates showed that compared with NGM individuals, prevalence of depression was moderately increased in PreDM (random-effect odds ratio (OR) 1.11, 95 % confidence interval (CI) 1.03-1.19) and UDM (OR 1.27, 95 % CI 1.02-1.59), and markedly increased in PDM (OR 1.80, 95 % CI 1.40-2.31). Subgroup analyses showed that the positive association remained only among studies with mean age <60 years old but not among those with mean age ≥60 years old. Summary estimates of ORs with cardiovascular disease adjustment substantially attenuated the association. Our findings suggested that risk of prevalent depression was gradually increased with the deterioration of glucose metabolism among younger age groups but not among older age groups. Comorbid cardiovascular diseases might be an important intermediate factor underlying the association between depression and diabetes.

Discovery of Xuebijing Injection Exhibiting Protective Efficacy on Sepsis by Inhibiting the Expression of HMGB1 in Septic Rat Model Designed by Cecal Ligation and Puncture.

Xuebijing (XBJ) injection is a complex traditional Chinese prescription that has been widely used to treat sepsis in China. However, its underlying mechanisms on sepsis still remain uninvestigated. In this study, 150 male Sprague Dawley rats were randomly divided into a normal control group, cecal ligation and puncture (CLP) group, CLP+XBJ group, and CLP+gibberellic acid group. Each of them contained 3 subgroups of different treatment periods (12, 24, and 48 hours after injection, respectively). The mRNA expression of HMGB1 in liver tissue of the 4 groups was calculated by the semiquantitative reverse-transcription polymerase chain reaction. The level of IL-6, IL-10, and TNF-α was determined by an enzyme-linked immunosorbent assay. Immunohistochemical analysis for HMGB1 showed the effect of XBJ on infiltration of inflammatory cells. The mRNA expression of HMGB1 in liver tissue in CLP+XBJ and CLP+gibberellic acid groups was lower than that in the CLP group. The levels of IL-6, IL-10, and TNF-α were decreased at the each monitored time point. All these results indicated that XBJ exhibits protective efficacy on sepsis by inhibiting the expression of HMGB1.

The skeletal effects of thiazolidinedione and metformin on insulin-resistant mice.

To explore the skeletal effects and the potential underlying mechanisms of treatment with two thiazolidinediones (rosiglitazone and pioglitazone) or metformin in insulin-resistant mice, 24 female, 12-week-old C57BL6J ob/ob mice were evaluated according to the following treatment groups for 6 weeks: placebo group, pioglitazone group (Pio), rosiglitazone group (Rosi), and metformin group (Met). Bone mineral density (BMD), bone microarchitecture, bone histomorphometry, and expression of three phenotype-specific gene markers, including bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), and fatty acid-binding protein 4 (Fabp4), were compared across the four groups. At the femur, the Met group had the highest BMD (0.084 ± 0.001 g/cm(2)) and trabecular bone volume/total volume (0.644 ± 0.018 %) and the lowest trabecular spacing (Tb.Sp.) (0.143 ± 0.008 µm), whereas the Rosi group had lower BMD (0.076 ± 0.003 g/cm(2)) and a relatively higher degree of Tb.Sp. (0.173 ± 0.024 µm). A histomorphometric analysis revealed that in the Rosi group the number of adipocytes was fourfold higher than in the placebo group and fivefold higher than in the Met group, whereas the highest osteoid width and mineral apposition rate were found in the Met group (49.88 ± 48.53 µm and 4.46 ± 1.72 µm/day). Furthermore, the Rosi group displayed the highest level of Fabp4 gene expression, which was accompanied by normal expression levels of Bmp2 and Runx2. Seemingly, metformin is a bone-friendly antidiabetic drug. Rosiglitazone had adverse effects on the skeleton at the trabecular bone even in insulin-resistant mice, whereas no evidence of adverse effects was found for pioglitazone.