D-alanine suppressed osteoclastogenesis derived from bone marrow macrophages and downregulated ERK/p38 signalling pathways.

OBJECTIVES: D-alanine is a residue of the backbone structure of Type Ⅰ Lipoteichoic acid (LTA), which is a virulence factor in inflammation caused by gram-positive bacteria. However, the role of D-alanine in infectious bone destruction has not been investigated. We aimed to explore the role of D-alanine in the proliferation, apoptosis, and differentiation of osteoclasts. DESIGN: Mouse bone marrow-derived macrophages (BMMs) were isolated as osteoclast precursors and stimulated with D-alanine. Cell proliferation and apoptosis were detected using CCK-8 and flow cytometry, respectively. The formation of osteoclasts morphologically observed by tartrate-resistant acid phosphatase staining (TRAP) and immunofluorescence staining. The expressions of osteoclastogenic genes were measured by real-time RT-PCR. The protein expressions of osteoclastogenic markers, p38, and ERK1/2 MAPK signalling were measured by western blot. The expression level of soluble Sema4D was detected via enzyme-linked immunosorbent assay (ELISA). RESULTS: The cell proliferation of BMMs was significantly inhibited by D-alanine in a dose-dependent manner. Apoptosis of BMMs was markedly activated with the stimulation of D-alanine. The differentiation of BMMs into osteoclasts was significantly inhibited by D-alanine, and the gene and protein expressions of NFATc1, c-Fos, and Blimp decreased. Western blot showed that D-alanine inhibited the phosphorylated p38 and ERK1/2 signalling pathways of BMMs. Moreover, the expression level of soluble Sema4D significantly decreased in the supernatant of BMMs due to the D-alanine intervention. CONCLUSION: D-alanine plays a pivotal role in the inhibition of RANKL-induced osteoclastogenesis and might become a potential therapeutic drug for bone-resorptive diseases.

Quantification of alkalinity of deep eutectic solvents based on (H-) and NMR.

Alkaline deep eutectic solvents (DESs) have been widely employed across diverse fields. A comprehensive understanding of the alkalinity data is imperative for the comprehension of their performance. However, the current range of techniques for quantifying alkalinity is constrained. In this investigation, we formulated a series of alkaline DESs and assessed their basicity properties through a comprehensive methodology of Hammett functions alongside 1H NMR analysis. A correlation was established between the composition, structure and alkalinity of solvents. Furthermore, a strong linear correlation was observed between the Hammett basicity (H-) of solvents and initial CO2 adsorption rate. Machine learning techniques were employed to predict the significant impact of alkaline functional components on alkalinity levels and CO2 capture capacity. This study offers valuable insights into the design, synthesis and structure-function relationship of alkaline DESs.

Downregulation of CPSF6 leads to global mRNA 3' UTR shortening and enhanced antiviral immune responses.

Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that generates mRNA isoforms with alternative 3' untranslated regions (3' UTRs). Our previous study has revealed the global 3' UTR shortening of host mRNAs through APA upon viral infection. However, how the dynamic changes in the APA landscape occur upon viral infection remains largely unknown. Here we further found that, the reduced protein abundance of CPSF6, one of the core 3' processing factors, promotes the usage of proximal poly(A) sites (pPASs) of many immune related genes in macrophages and fibroblasts upon viral infection. Shortening of the 3' UTR of these transcripts may improve their mRNA stability and translation efficiency, leading to the promotion of type I IFN (IFN-I) signalling-based antiviral immune responses. In addition, dysregulated expression of CPSF6 is also observed in many immune related physiological and pathological conditions, especially in various infections and cancers. Thus, the global APA dynamics of immune genes regulated by CPSF6, can fine-tune the antiviral response as well as the responses to other cellular stresses to maintain the tissue homeostasis, which may represent a novel regulatory mechanism for antiviral immunity.

Analysis of the oxygen evolution activity of layered double hydroxides (LDHs) using machine learning guidance.

Layered double hydroxides (LDHs) are excellent catalysts for the oxygen evolution reaction (OER) because of their tunable properties, including chemical composition and structural morphology. An interplay between these adjustable properties and other (including external) factors might not always benefit the OER catalytic activity of LDHs. Therefore, we applied machine learning algorithms to simulate the double-layer capacitance to understand how to design/tune LDHs with targeted catalytic properties. The key factors of solving this task were identified using the Shapley Additive explanation and cerium was identified as an effective element to modify the double-layer capacitance. We also compared different modelling methods to identify the most promising one and the results revealed that binary representation is better than directly applying atom numbers as inputs for chemical compositions. Overpotentials of LDH-based materials as predicted targets were also carefully examined and evaluated, and it turns out that overpotentials can be predicted when measurement conditions about overpotentials are added as features. Finally, to confirm our findings, we reviewed additional experimental literature data and used them to test our machine algorithms to predict LDH properties. This analysis confirmed the very credible and robust generalization ability of our final model capable of achieving accurate results even with a relatively small dataset.

Effect of Enterococcus faecalis on osteoclastogenesis under cobalt-mimicked hypoxia in vitro.

OBJECTIVE: The bone destruction in persistent apical periodontitis associated with infection and a periapical hypoxic microenvironment is not well known. Thus, we aimed to investigate the effects of Enterococcus faecalis on osteoclastogenesis under cobalt-mimicked hypoxia. MATERIALS AND METHODS: Mouse bone marrow-derived macrophages (BMMs) were isolated as osteoclast precursors and stimulated by heat-killed E. faecalis in an environment of cobalt-mimicked hypoxia environment. The cell proliferation and apoptosis were detected using CCK-8 and flow cytometry, respectively. Osteoclast differentiation was determined via tartrate-resistant acid phosphatase staining (TRAP) and immunofluorescence staining. The osteoclastogenic protein and gene expressions were measured by western blotting and real-time PCR. RESULTS: Under cobalt-mimicked hypoxia, E. faecalis markedly inhibited the proliferation of the BMMs and significantly promoted the apoptosis of the BMMs. The differentiation of the BMMs into osteoclasts was enhanced in the presence of the E. faecalis under hypoxia, and the expression of Blimp, c-Fos, and NFATc1 was up-regulated, while the expression of RBP-J was inhibited. CONCLUSIONS: E. faecalis markedly promotes osteoclast differentiation under cobalt-mimicked hypoxia in vitro.

Deep insights into the viscosity of deep eutectic solvents by an XGBoost-based model plus SHapley Additive exPlanation.

Deep eutectic solvents (DESs) are emerging as novel green solvents for the processes of mass transport and heat transfer, in which the viscosity of DESs is important for their industrial applications. However, for DESs, the measurement of viscosity is time-consuming, and there are many factors influencing the viscosity, which impedes their wider application. This study aims to develop a data-driven model which could accurately and rapidly predict the viscosity of diverse DESs at different temperatures, and furthermore boost the design and screening of novel DESs. In this work, we collected 107 DESs with 994 experimental values of viscosity from published works. Given the significant effect of water on viscosity, the water content of each collected DES was labeled. The Morgan fingerprint was first employed as a feature to describe the chemical environment of DESs. And four machine learning algorithms were used to train models: support vector regression (SVR), random forest (RF), neural network (NN), and extreme gradient boosting (XGBoost), and XGBoost showed the best predictive performance. In combination with the powerful interpretation method SHapley Additive exPlanation (SHAP), we further revealed the positive or negative effect of features on viscosity. Overall, this work provides a machine learning model which could predict viscosity precisely and facilitate the design and application of DESs.

Ultrasound Technique Based on Liposome Nanovesicles in the Evaluation of Abnormal Pregnancy Outcomes in Diabetic Women.

Gestational diabetes mellitus (GDM) refers to the first occurrence or detection of glucose tolerance abnormalities during pregnancy, including cases that may have existed before pregnancy but have not been detected. It is one of the common complications during pregnancy. In recent years, the incidence of GDM is on the rise. The most common complication of GDM is macrosomia, which often causes dystocia, neonatal asphyxia, birth injury and postpartum bleached blood. Early diagnosis, appropriate treatment and maintenance of reasonable and stable blood glucose concentration can significantly reduce the incidence of complications. The purpose of this study was to investigate the application of ultrasound technique based on liposome nano-vesicles in the assessment of abnormal pregnancy outcomes in diabetic pregnant women. Objective: To investigate the value of ultrasound in the examination of fetal growth in pregnant women with gestational diabetes mellitus. Methods a total of 100 pregnant women with gestational diabetes admitted to the hospital were selected as the research objects, and the clinical data of ultrasound examination were retrospectively analyzed. According to the newborn weight, they were divided into control group (normal fetus group) and observation group (giant fetus group). The growth of fetuses in the two groups was compared, and the predictive value of each measurement index to the weight of giant fetus was analyzed.Multiple regression analysis showed that LL, AC and FL played a decisive role in fetal weight, with statistically significant differences (P<0.05). Conclusion Ultrasonography is of great value in predicting fetal growth in pregnant women with gestational diabetes mellitus and can be widely used.

Magnetic deep eutectic solvents: formation and properties.

Deep eutectic solvents (DESs) are well-known as novel solvents due to their unique properties, which are indispensable for the development of green chemistry in the future. CoCl2·6H2O and NiCl2·6H2O-based DESs, which could be called magnetic DESs (MDESs) for short in view of their responsive behavior to an external magnetic field, have been widely used in many industrial applications, such as biomass treatment, electrolytes, and material preparation. For better application and full-scale development of these MDESs in various fields, eleven MDESs were prepared in this work by using CoCl2·6H2O and NiCl2·6H2O as hydrogen bond acceptors (HBAs) with alcohols, carboxylic acids and amides as hydrogen bond donors (HBDs), respectively. The intermolecular interactions between the components of MDESs were characterized via FTIR, 1H NMR and DSC analysis. In addition, physicochemical properties including density, viscosity, conductivity, ionicity, pH values, surface tension, thermostability and solvatochromic parameters were investigated. All MDESs exhibit acid characteristics and have good conductivity comparable with ionic liquids (ILs) and other DESs used for electrolytes. The results show that stronger H-bonding networks in Ni-based MDESs make them have higher density, viscosity, polarity and surface tension values than Co-based MDESs. Moreover, all prepared MDESs possess a good conductivity behavior which could be comparable to that of common organic solvents and ILs. According to this work, we could better comprehend the behavior of Co/Ni-based MDESs and choose the appropriate one for particular applications.

Acidity scales of deep eutectic solvents based on IR and NMR.

Acidic deep eutectic solvents (ADESs) have been utilized in various applications. Clearly, it is crucial to obtain acidity information that could reveal the relationship with performance. However, appropriate methods for measuring acidity are limited. Herein, we developed two promising approaches (without additional solvents) to identify and characterize both Lewis and Brønsted acidities by applying acetonitrile as an infrared probe and trimethylphosphine oxide (TMPO) as a nuclear magnetic resonance (NMR) probe. The acetonitrile IR approach is suitable for measuring the acidity of Lewis ADESs by monitoring the peak of ν(CN) around 2300 cm-1, and the 31P-TMPO NMR approach could identify and scale both Lewis and Brønsted acidities precisely. Moreover, a perfect linear relationship between the IR shift of ν(CN) and the effective charge density of metal cations was established, which provides a better understanding of Lewis acidity. In short, this study not only offers two efficient acidity measurement methods but also provides a molecular basis for optimizing the performance of ADESs in applications.

An emerging deep eutectic solvent based on halogen-bonds.

A new deep eutectic solvent (DES) driven by halogen bonding (XB) was exploited. A family of eutectic mixtures in the liquid state was obtained by the combination of quaternary ammonium salts and dihalogens. The formation mechanism was discussed based on experiments and DFT calculations. It not only broadens the potential DES systems but unlocks the possibility of XB complexes as solvents.

Semaphorin 3A attenuates the hypoxia suppression of osteogenesis in periodontal ligament stem cells.

OBJECTIVE AND BACKGROUND: The occurrence and development of periodontitis are closely related to hypoxia of the periodontal microenvironment. Periodontal ligament stem cells (PDLSCs) are considered to have potential to regenerate periodontal tissues. Semaphorin 3A (Sema3A) plays an essential role in promoting osteogenesis. However, the effect of Sema3A on osteogenesis of PDLSCs under hypoxia remains unclear. The aim of this study was to investigate the effect of Sema3A on osteogenesis of PDLSCs under hypoxia. METHODS: Isolated PDLSCs were identified using flow cytometry. Adipogenic differentiation potential was identified by oil red O staining. Osteogenesis was measured using Alizarin Red S staining and ALP staining. Intracellular hypoxia was induced using cobalt chloride (CoCl2 ). The expression level of hypoxia-inducible factor-1α (HIF-1α) was detected via ELISA. Expression of osteogenic markers and Sema3A was analyzed using western blot and real-time PCR. RESULTS: The proliferation and osteogenesis of PDLSCs were markedly inhibited with increased concentrations of CoCl2 . Under the treatment with a low concentration of CoCl2 , expression of related osteogenic markers and Sema3A decreased in a time-dependent manner. ARS and ALP staining results also showed that osteogenic calcification decreased under hypoxia. Apigenin, an inhibitor of HIF-1α, effectively up-regulated expression of Sema3A and osteogenic markers with CoCl2 treatment. Moreover, exogenous Sema3A significantly increased the expression of osteogenesis-related markers and mineralization of PDLSCs according to ALP and ARS staining with CoCl2 treatment. CONCLUSIONS: Hypoxia markedly inhibited osteogenesis of PDLSCs. Sema3A explicitly attenuated the hypoxia suppression of osteogenesis in PDLSCs.

Solvothermal Syntheses and Characterizations of Four Quaternary Copper Sulfides BaCu3MS4 (M = In, Ga) and BaCu2MS4 (M = Sn, Ge).

Hydro(solvo)thermal syntheses of quaternary copper sulfides containing alkaline earth metal ions remain a great challenge because of the low solubility of Cu-S compounds. Herein, a new facile solvothermal method was developed, and four quaternary copper sulfides, i.e., BaCu3InS4 (1), BaCu3GaS4 (2), BaCu2SnS4 (3), and BaCu2GeS4 (4), were prepared using excess sulfur as a mineralizer. Compound 1 possesses a novel three-dimensional (3D) anionic [Cu3InS4]2- framework constructed by an 8-membered ring of [Cu4S4] and [Cu2In2S4] alternatively. Compound 2 features a unique 3D anionic [Cu3GaS4]2- framework composed of [Cu3GaS10]n14n- anionic chains and 8-membered rings, in which [Cu4S4] and [Cu2Ga2S4] reside alternatively. Compounds 3 and 4 feature 3D anionic [Cu2MS4]2- (M = Sn, Ge) frameworks composed of CuS4 and MS4 tetrahedra with Ba2+ located in the channels. It is worth noting that different 3D Cu-S frameworks exist in the title crystal structures, in which main group ions are incorporated. This paper provides a new synthetic strategy for new quaternary sulfides.

Computational insights into the mechanism of formaldehyde detection by luminescent covalent organic framework.

Luminescent covalent organic frameworks (COFs) as fluorescent sensor materials provide a distinct advantage over other materials. In this work, we investigated the hydrogen bonding between the luminescent COF Ph-An-COF and formaldehyde in its excited electronic state by using density functional theory and time-dependent density functional theory to determine whether this type of COF can be used for formaldehyde detection. Hydrogen bonding significantly changed the nature of the frontier orbital and the luminescent properties. Our study reveals that the hydrogen bonding was strengthened in the excited state and the fluorescence rate coefficient was significantly reduced, which is not favorable for the luminescence of this type of COF and would lead to a luminescence decrease or quenching phenomenon. Therefore, this type of luminescent COF can be used as a potential chemical sensor to detect formaldehyde. This work provides an insight into the design of luminescence covalent organic frameworks.

Transition metal-free α-Csp3-H oxidative sulfuration of benzyl thiosulfates with anilines to form N-aryl thioamides.

A metal-free approach to N-aryl thioamides from Bunte salts and anilines in DMSO has been developed. This method tolerated a wide range of functional groups on the aromatic ring, providing an ideal way to N-aryl thioamides in good to excellent yields from cheap and easily available starting materials. A plausible mechanism was also proposed based on the X-ray single crystal diffraction, NMR and MS analyses of DMSO-concerning intermediates.

Preparation of La-modified magnetic composite for enhanced adsorptive removal of tetracycline.

Composite adsorbents usually outperform single component adsorbents as they could combine the properties and advantages of each component. In this research, rare earth element Lanthanum was introduced into magnetic substrate by a method of chemical co-precipitation to enhance its adsorption capability. It was found that the La-modified magnetic composite with a presumed La and Fe3O4 molar ratio at 1:50 had a better adsorption performance for tetracycline than the magnetic adsorbents at other molar ratios. The La-modified magnetic composite was characterized by scanning electron microscope, X-ray diffractometer, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The results showed that the magnetic adsorbent was nano-sized, and the introduction of La did not change the crystal structure of magnetic substrate. The adsorptive removal of tetracycline was favorable at neutral pH conditions. Kinetic experiments indicated that most of the uptake occurred within the initial 120 min. Chemisorption occurred in the process while rate-determining step might be diffusive in nature. An empirical model (Langmuir model) was applied in this paper, and fitting result indicates that the q max value of the magnetic composite reached as much as 145.9 mg/g for the uptake of tetracycline at 298 K. The above indicates that method of La doping could significantly enhance the adsorption capability of an intentionally designed composite adsorbent.