The influence of phosphorus precursor on the structure and properties of SiO2-P2O5-CaO bioactive glass

Bioactive glasses (BGs) are one of the most promising bone regeneration materials because they can bond to bone and simulate new bone growth. Sol-gel methods for producing BG are well established, however challenges still remain in selecting and optimizing the precursors. Even for BGs with the same final composition, different precursors may lead to different structures and properties of the gel derived BG. In this work, three different phosphorus precursors, phytic acid (PA), triethyl phosphate (TEP) and n-butyl phosphate (BP) were used to prepareBG (54.2%SiO2-35%CaO-10.8%P2O5, mol%). The obtained materials were characterized by TGA, FTIR, XRD, HEXRD, solid state 31P, 29Si NMRand by in vitro tests in SBF. It was found that the materials prepared by TEP or BP showed small amounts of crystallization, whereas the resulting material prepared by PA remained amorphous and had more P atoms as orthophosphate. In vitro assays indicated that all these materials were bioactive, while the BG prepared by PA showed the highest in vitro bioactivity, followed by TEP and, finally, BP. Based on these observations, it appears that phosphorus precursors have a significant impact on both the structure and bioactivity of the sol-gel derived BG. Results suggest that PA should be used in preference to TEP or n-butyl phosphate for the synthesis of sol gels. PA may improve the homogeneity of the sol gel glasses, reduce crystallization and lower stabilization temperatures

In vitro evaluation of a novel pH neutral calcium phosphosilicate bioactive glass that does not require preconditioning prior to use

It is well known that bioactive glasses can cause a significant increase in pH due to the rapid release of calcium and/or sodium ions. Consequently, preconditioning of the glass is usually required prior to surgery to negate the effect of this sudden release of ions. However, preconditioning for several days is far from ideal and also preconditioning is not practical for novel organic/inorganic sol-gel hybrids currently being developed since the organic phase will start to hydrolyze and dissolve. This study describes a bioactive glass that dissolves without causing a significant change in pH from physiologically optimal values and requires no preconditioning prior to use. The bioactivity of the pH neutral glass, hydroxyapatite formation, and cellular responses, are measured and compared directly with results from archetypal 45S5 and S70C30 bioactive glasses. A hydroxyapatite layer was found to rapidly form (within 1 day) on the surface of the pH neutral glass upon reacting with simulated body fluid. In addition, improved cell compatibility was observed compared with 45S5 and S70C30 glasses. Therefore, this pH neutral glass has significant potential for bone repair applications

Bioactive organic/inorganic hybrids with improved mechanical performance

New sol-gel functionalized poly-ethylene glycol (PEGM)/SiO2-CaO hybrids were prepared with interpenetrating networks of silica and PEGM through the formation of Si-O-Si bonds. Bioactive and mechanical properties were investigated for a series of hybrids containing varying organic/inorganic ratios and PEG molecular weights. In contrast to the unmodified PEG/SiO2-CaO hybrids, which rapidly dissolved and crumbled, the epoxy modified hybrids exhibited good mechanical properties and bioactivity. The compressive strength and Young's modulus were greater for higher molecular weight PEGM hybrids (PEGM600 compared to PEGM300). Compressive strengths of 138 MPa and 81 MPa were found for the 50: 50 and 60: 40 organic/inorganic hybrid samples respectively, which are comparable with cortical bone. Young's modulus values of ∼800 MPa were obtained for the 50 : 50 and 60 : 40 organic/inorganic hybrids. Bioactivity tests were conducted by immersing the hybrids into simulated body fluid and observing the formation of apatite. Apatite formation was observed within 24 hours of immersion. PEGM600 hybrids showed enhanced apatite formation compared to PEGM300 hybrids. Increased apatite formation was observed with increasing organic/inorganic ratio. 70 : 30 and 60 : 40 hybrids exhibited the greatest apatite formation. All PEGM hybrids samples had good cell viability and proliferation. The 60 : 40 PEGM600 hybrids displayed the optimal combination of bioactivity and mechanical strength. The bioactivity of these hybrids, combined with the enhanced mechanical properties, demonstrate that these materials have significant potential for bone regeneration applications

Machine learning reveals neutrophil-to-lymphocyte ratio as a crucial prognostic indicator in severe Japanese encephalitis patients

Japanese encephalitis (JE) is a severe infectious disease affecting the central nervous system (CNS). However, limited risk factors have been identified for predicting poor prognosis (PP) in adults with severe JE. In this study, we analyzed clinical data from thirty-eight severe adult JE patients and compared them to thirty-three patients without organic CNS disease. Machine learning techniques employing branch-and-bound algorithms were used to identify clinical risk factors. Based on clinical outcomes, patients were categorized into two groups: the PP group (mRs ≥ 3) and the good prognosis (GP) group (mRs ≤ 2) at three months post-discharge. We found that the neutrophil-to-lymphocyte ratio (NLR) and the percentage of neutrophilic count (N%) were significantly higher in the PP group compared to the GP group. Conversely, the percentage of lymphocyte count (L%) was significantly lower in the PP group. Additionally, elevated levels of aspartate aminotransferase (AST) and blood glucose were observed in the PP group compared to the GP group. The clinical parameters most strongly correlated with prognosis, as indicated by Pearson correlation coefficient (PCC), were NLR (PCC 0.45) and blood glucose (PCC 0.45). In summary, our findings indicate that increased serum NLR, N%, decreased L%, abnormal glucose metabolism, and liver function impairment are risk factors associated with poor prognosis in severe adult JE patients

A novel trifunctional IgG-like bispecific antibody to inhibit HIV-1 infection and enhance lysis of HIV by targeting activation of complement

BACKGROUND: The complement system is not only a key component of innate immunity but also provides a first line of defense against invading pathogens, especially for viral pathogens. Human immunodeficiency virus (HIV), however, possesses several mechanisms to evade complement-mediated lysis (CoML) and exploit the complement system to enhance viral infectivity. Responsible for this intrinsic resistance against complement-mediated virolysis are complement regulatory membrane proteins derived from the host cell that inherently downregulates complement activation at several stages of the cascade. In addition, HIV is protected from complement-mediated lysis by binding soluble factor H (fH) through the viral envelope proteins, gp120 and gp41. Whereas inhibition of complement activity is the desired outcome in the vast majority of therapeutic approaches, there is a broader potential for complement-mediated inhibition of HIV by complement local stimulation. PRESENTATION OF THE HYPOTHESIS: Our previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that another new activator of complement, consisting of two dsFv (against gp120 and against C3d respectively) linked to a complement-activating human IgG1 Fc domain ((anti-gp120 × anti-C3d)-Fc), can not only target and amplify complement activation on HIV virions for enhancing the efficiency of HIV lysis, but also reduce the infectivity of HIV through blocking the gp120 and C3d on the surface of HIV. TESTING THE HYPOTHESIS: Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified (anti-gp120 × anti-C3d)-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of (anti-gp120 × anti-C3d)-Fc lysis of HIV compared to untreated virus. IMPLICATIONS OF THE HYPOTHESIS: The targeted complement activator, (anti-gp120 × anti-C3d)-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells

Incidence and influencing factors of fertility concerns in breast cancer in young women: a systematic review and meta-analysis

ObjectiveThis systematic review and meta-analysis aimed to evaluate the prevalence and influencing factors of fertility concerns in breast cancer in young women.MethodsA literature search on PubMed, Embase, Web of Science, and Cochrane Library databases was conducted up to February 2023 and was analyzed (Revman 5.4 software) in this study. The papers were chosen based on inclusion standards, and two researchers independently extracted the data. The included studies’ quality was evaluated using criteria set out by the Agency for Healthcare Research and Quality. To identify significant variations among the risk factors, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were utilized.ResultsA total of 7 studies that included 1579 breast cancer in young women were enrolled in the study. The results showed that for breast cancer in young women, the incidence of fertility concerns 53%(95%CI [0.45,0.58]). The results showed that education (2.65, 95% CI 1.65–5.63), full-time work (0.12, 95% CI 1.03–1.93), fertility intentions (7.84, 95% CI 1.50–37.4), depression level (1.25, 95% CI 1.03–1.5), and endocrine therapy (1.32, 95% CI 1.08–1.62) were risk factors for fertility concerns in young women with BC. Having a partner (0.41, 95% CI 0.33–0.5), ≥1 child (0.3, 95% CI 0.22–0.4) were identified as protective factors against fertility concerns in young women with BC.ConclusionsThe incidence of fertility concerns in breast cancer in young women is at a moderately high level. We should pay more attention to the risk factors of fertility concerns to help breast cancer in young women cope with their fertility concerns and promote their psychological well-being

Integrated Metagenomic and Transcriptomic Analyses Reveal the Dietary Dependent Recovery of Host Metabolism From Antibiotic Exposure

The balance of gut microbiome is essential for maintaining host metabolism homeostasis. Despite widespread antibiotic use, the potential long-term detrimental consequences of antibiotics for host health are getting more and more attention. However, it remains unclear whether diet affects the post-antibiotic recovery of gut microbiome and host metabolism. In this study, through metagenomic sequencing and hepatic transcriptome analysis, we investigated the divergent impacts of short-term vancomycin (Vac), or combination of ciprofloxacin and metronidazole (CM) treatment on gut microbiome and host metabolism, as well as their recovery extent from antibiotic exposure on chow diet (CD) and high-fat diet (HFD). Our results showed that short-term Vac intervention affected insulin signaling, while CM induced more functional changes in the microbiome. However, Vac-induced long-term (45 days) changes of species were more apparent when recovered on CD than HFD. The effects of antibiotic intervention on host metabolism were long-lasting, antibiotic-specific, and diet-dependent. The number of differentially expressed gene was doubled by Vac than CM, but was comparable after recovery on CD as revealed by the hepatic transcriptomic analysis. In contrast, HFD intake during recovery could worsen the extent of post-antibiotic recovery by altering infection, immunity, and cancer-related pathways in short-term Vac-exposed rats and by shifting endocrine system-associated pathways in CM-exposed rats. Together, the presented data demonstrated the long-term recovery extent after different antibiotic exposure was diet-related, highlighting the importance of dietary management during post-antibiotic recovery