3D Printing of a Porous Zn-1Mg-0.1Sr Alloy Scaffold: A Study on Mechanical Properties, Degradability, and Biosafety.

In recent years, the use of zinc (Zn) alloys as degradable metal materials has attracted considerable attention in the field of biomedical bone implant materials. This study investigates the fabrication of porous scaffolds using a Zn-1Mg-0.1Sr alloy through a three-dimensional (3D) printing technique, selective laser melting (SLM). The results showed that the porous Zn-1Mg-0.1Sr alloy scaffold featured a microporous structure and exhibited a compressive strength (CS) of 33.71 ± 2.51 MPa, a yield strength (YS) of 27.88 ± 1.58 MPa, and an elastic modulus (E) of 2.3 ± 0.8 GPa. During the immersion experiments, the immersion solution showed a concentration of 2.14 ± 0.82 mg/L for Zn2+ and 0.34 ± 0.14 mg/L for Sr2+, with an average pH of 7.61 ± 0.09. The porous Zn-1Mg-0.1Sr alloy demonstrated a weight loss of 12.82 ± 0.55% and a corrosion degradation rate of 0.36 ± 0.01 mm/year in 14 days. The Cell Counting Kit-8 (CCK-8) assay was used to check the viability of the cells. The results showed that the 10% and 20% extracts significantly increased the activity of osteoblast precursor cells (MC3T3-E1), with a cytotoxicity grade of 0, which indicates safety and non-toxicity. In summary, the porous Zn-1Mg-0.1Sr alloy scaffold exhibits outstanding mechanical properties, an appropriate degradation rate, and favorable biosafety, making it an ideal candidate for degradable metal bone implants.

Organocatalytic enantioselective decarboxylative protonation of α-alkyl-α-aryl malonate monoesters.

In contrast to the well-established enzymatic enantioselective decarboxylative protonation (EDP), the corresponding chemocatalytic reactions of acyclic malonic acid derivatives remain challenging. Herein, we developed a biomimetic EDP of α-alkyl-α-aryl malonate monoesters using a chiral 1,2-trans-diaminocyclohexane-based N-sulfonamide as an organocatalyst. The method demonstrates excellent chemical yields, good enantioselectivity, mild reaction conditions, and the generation of only CO2 as waste.

Observation of Sub-10 nm Transition Metal Dichalcogenide Nanocrystals in Rapidly Heated van der Waals Heterostructures.

Two-dimensional materials, such as transition metal dichalcogenides (TMDCs), have the potential to revolutionize the field of electronics and photonics due to their unique physical and structural properties. This research presents a novel method for synthesizing crystalline TMDCs crystals with <10 nm size using ultrafast migration of vacancies at elevated temperatures. Through in situ and ex situ processing and using atomic-level characterization techniques, we analyzed the shape, size, crystallinity, composition, and strain distribution of these nanocrystals. These nanocrystals exhibit electronic structure signatures that differ from the 2D bulk: i.e., uniform mono- and multilayers. Further, our in situ, vacuum-based synthesis technique allows observation and comparison of defect and phase evolution in these crystals formed under van der Waals heterostructure confinement versus unconfined conditions. Overall, this research demonstrates a solid-state route to synthesizing uniform nanocrystals of TMDCs and lays the foundation for materials science in confined 2D spaces under extreme conditions.

Bulk Photovoltaic Current Mechanisms in All-Inorganic Perovskite Multiferroic Materials.

After the discovery of bulk photovoltaic effect more than half a century ago, ferro-electrical and magneto-optical experiments have provided insights into various related topics, revealing above bandgap open voltages and non-central symmetrical current mechanisms. However, the nature of the photon-generated carriers responses and their microscopic mechanisms remain unclear. Here, all-inorganic perovskite Bi0.85Gd0.15Fe1-xMnxO3 thin films were prepared by a sol-gel process and the effects of Gd and Mn co-doped bismuth ferrites on their microtopography, grain boundries, multiferroic, and optical properties were studied. We discovered a simple "proof of principle" type new method that by one-step measuring the leakage current, one can demonstrate the value of photo generated current being the sum of ballistic current and shift current, which are combined to form the so-called bulk photovoltaic current, and can be related to the prototype intrinsic properties such as magneto-optical coupling and ferroelectric polarization. This result has significant potential influence on design principles for engineering multiferroic optoelectronic devices and future photovoltaic industry development.

Network Pharmacology Deciphers the Action of Bioactive Polypeptide in Attenuating Inflammatory Osteolysis via the Suppression of Oxidative Stress and Restoration of Bone Remodeling Balance.

Oxidative stress involves enormously in the development of chronic inflammatory bone disease, wherein the overproduction of reactive oxygen species (ROS) negatively impacts the bone remodeling via promoting osteoclastogenesis and inhibiting osteogenesis. Lacking effective therapies highlights the importance of finding novel treatments. Our previous study screened a novel bioactive peptide D7 and demonstrated it could enhance the cell behaviors and protect bone marrow mesenchymal stem cells (BMSCs). Since BMSCs are progenitor cells of osteoblast (OB), we therefore ask whether D7 could also protect against the progress of inflammatory osteolysis. To validate our hypothesis and elucidate the underlying mechanisms, we first performed network pharmacology-based analysis according to the molecule structure of D7, and then followed by pharmacological evaluation on D7 by in vitro lipopolysaccharide(LPS)-induced models. The result from network pharmacology identified 20 candidate targets of D7 for inflammatory osteolysis intervention. The further analysis of Gene Ontology (GO)/KEGG pathway enrichment suggested the therapeutic effect of D7 may primarily affect osteoclast (OC) differentiation and function during the inflammatory osteolysis. Through validating the real effects of D7 on OC and OB as postulated, results demonstrated suppressive effects of D7 on LPS-stimulated OC differentiation and resorption, via the inhibition on OC marker genes. Contrarily, by improving the expression of OB marker genes, D7 displayed promotive effects on OB differentiation and alleviated LPS-induced osteogenic damage. Further mechanism study revealed that D7 could reduce LPS-induced ROS formation and strengthen antioxidants expressions in both OC and OB precursors, ameliorating LPS-triggered redox imbalance in bone remodeling. Taken together, our findings unveiled therapeutic effects of D7 against LPS-induced inflammatory osteolysis through the suppression of oxidative stress and the restoration of the bone remodeling process, providing a new therapeutic candidate for chronic inflammatory bone diseases.

Cyclic Polypeptide D7 Protects Bone Marrow Mesenchymal Cells and Promotes Chondrogenesis during Osteonecrosis of the Femoral Head via Growth Differentiation Factor 15-Mediated Redox Signaling.

Osteonecrosis of the femoral head (ONFH) is a debilitating disease that is closely associated with the clinical application of high-dose glucocorticoids. Elevated oxidative stress contributes to the pathophysiological changes observed in ONFH. The lack of effective treatments besides surgical intervention highlights the importance of finding novel therapeutics. Our previous studies demonstrated that D7, a cyclic polypeptide, enhances the adhesion, expansion, and proliferation of bone marrow mesenchymal stem cells (BMSCs). Therefore, in this study, we investigated the therapeutic effects of D7 against ONFH in BMSCs and evaluated the underlying mechanisms. First, we screened for ONFH risk factors. Then, we applied D7 treatment to steroid-induced ONFH (SONFH) in an in vitro model produced by dexamethasone (DEX) to further elucidate the underlying mechanisms. We found negative correlations among oxidative stress marker expression, growth differentiation factor 15 (GDF15) levels, and ONFH. Furthermore, we demonstrated that DEX inhibited the proliferation and induced apoptosis of BMSCs by suppressing GDF15/AKT/mammalian target of rapamycin (mTOR) signaling. D7 alleviated DEX-induced BMSCs injury and restored the chondrogenic function of BMSCs by activating GDF15/AKT/mTOR signaling. In addition, DEX-induced excessive reactive oxygen species (ROS) generation was an upstream trigger of GDF15-mediated signaling, and D7 ameliorated this DEX-induced redox imbalance by restoring the expression of antioxidants, including superoxide dismutase (SOD) 1, SOD2, and catalase, via regulation of GDF15 expression. In conclusion, our findings revealed the potential therapeutic effects of D7 in SONFH and showed that this protective function may be mediated via inhibition of DEX-induced ROS and activation of GDF15/AKT/mTOR signaling, thereby providing insights into the potential applications of D7 in SONFH treatment.

Metabolomic analysis of Scenedesmus obliquus reveals new insights into the phytotoxicity of imidazolium nitrate ionic liquids.

Due to the persistence of ionic liquids (ILs) in aquatic environments, it is necessary to reveal their ecological risk to aquatic organisms. Herein, the biotoxicity of two alkyl-methylimidazolium nitrate ILs ([C10mim]NO3 and [C12mim]NO3) against Scenedesmus obliquus were studied. Results showed that the growth inhibition of S. obliquus increased with increasing concentrations of ILs, maximum values of 94.61% at 4 mg/L of [C10mim]NO3 and 97.34% at 0.8 mg/L of [C12min]NO3 were observed. The fluorescence parameters of photosystem II, such as light quantum yield and electron transfer rate, showed a negative relationship with the exposure dose. [C12mim]NO3 had a more significant effect than [C10mim]NO3. Moreover, the redox homeostasis of algae was disrupted; the accumulation of reactive oxygen species, leading to obvious inhibition of superoxide dismutase and catalase activities was observed. A metabolomic analysis indicated that the contents of most metabolites were reduced significantly, and fructose and galactose decreased significantly by 42.3% and 88.6%, respectively, in the [C10mim]NO3 treatment compared to those in the control. The inhibition of amino acid biosynthesis and glyoxylate and dicarboxylate metabolism explained the more serious biotoxicity of [C12mim]NO3 than that of [C10mim]NO3. This study facilitates a better understanding of the environmental safety and ecological risks of ILs.

An in situ masking strategy enables radical monodecarboxylative C-C bond coupling of malonic acid derivatives.

The utilization of malonic acids in radical decarboxylative functionalization is still underexploited, and the few existing examples are primarily limited to bisdecarboxylative functionalization. While radical monodecarboxylative functionalization is highly desirable, it is challenging because of the difficulty in suppressing the second radical decarboxylation step. Herein, we report the successful radical monodecarboxylative C-C bond coupling of malonic acids with ethynylbenziodoxolone (EBX) reagents enabled by an in situ masking strategy, affording synthetically useful 2(3H)-furanones in satisfactory yields. The keys to the success of this transformation include (1) the dual role of a silver catalyst as a single-electron transfer catalyst to drive the radical decarboxylative alkynylation and as a Lewis acid catalyst to promote the 5-endo-dig cyclization and (2) the dual function of the alkynyl reagent as a radical trapper and as an in situ masking group. Notably, the latent carboxylate group in the furanones could be readily released, which could serve as a versatile synthetic handle for further elaborations. Thus, both carboxylic acid groups in malonic acid derivatives have been well utilized for the rapid construction of molecular complexity.

Osthole Attenuates Bleomycin-Induced Pulmonary Fibrosis by Modulating NADPH Oxidase 4-Derived Oxidative Stress in Mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the extensive accumulation of myofibroblasts and collagens. However, the exact mechanism that underlies this condition is unclear. Growing evidence suggests that NADPH oxidases (NOXs), especially NOX4-derived oxidative stress, play an important role in the development of lung fibrosis. Bleomycin (BLM) is a tumor chemotherapeutic agent, which has been widely employed to establish IPF animal models. Osthole (OST) is an active constituent of the fruit of Cnidium ninidium. Here, we used an in vivo mouse model and found that OST suppressed BLM-induced body weight loss, lung injury, pulmonary index increase, fibroblast differentiation, and pulmonary fibrosis. OST also significantly downregulated BLM-induced NOX4 expression and oxidative stress in the lungs. In vitro, OST could inhibit TGF-ß1-induced Smad3 phosphorylation, differentiation, proliferation, collagen synthesis, NOX4 expression, and ROS generation in human lung fibroblasts in a concentration-dependent manner. Moreover, NOX4 overexpression could prevent the above effects of OST. We came to the conclusion that OST could significantly attenuate BLM-induced pulmonary fibrosis in mice, via the mechanism that involved downregulating TGF-ß1/NOX4-mediated oxidative stress in lung fibroblasts.

Scoparone alleviates Ang II-induced pathological myocardial hypertrophy in mice by inhibiting oxidative stress.

Long-term poorly controlled myocardial hypertrophy often leads to heart failure and sudden death. Activation of ras-related C3 botulinum toxin substrate 1 (RAC1) by angiotensin II (Ang II) plays a pivotal role in myocardial hypertrophy. Previous studies have demonstrated that scoparone (SCO) has beneficial effects on hypertension and extracellular matrix remodelling. However, the function of SCO on Ang II-mediated myocardial hypertrophy remains unknown. In our study, a mouse model of myocardial hypertrophy was established by Ang II infusion (2 mg/kg/day) for 4 weeks, and SCO (60 mg/kg bodyweight) was administered by gavage daily. In vitro experiments were also performed. Our results showed that SCO could alleviate Ang II infusion-induced cardiac hypertrophy and fibrosis in mice. In vitro, SCO treatment blocks Ang II-induced cardiomyocyte hypertrophy, cardiac fibroblast collagen synthesis and differentiation to myofibroblasts. Meanwhile, we found that SCO treatment blocked Ang II-induced oxidative stress in cardiomyocytes and cardiac fibroblasts by inhibiting RAC1-GTP and total RAC1 in vivo and in vitro. Furthermore, reactive oxygen species (ROS) burst by overexpression of RAC1 completely abolished SCO-mediated protection in cardiomyocytes and cardiac fibroblasts in vitro. In conclusion, SCO, an antioxidant, may attenuate Ang II-induced myocardial hypertrophy by suppressing of RAC1 mediated oxidative stress.

BMSC affinity peptide-functionalized ß-tricalcium phosphate scaffolds promoting repair of osteonecrosis of the femoral head.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a disabling disease. Early treatment is crucial to the prognosis of the disease. Core decompression (CD) is one of the most commonly used methods for the treatment of early ONFH. But it could not prevent the collapse of the necrotic femoral head. How to improve the therapeutic effect of early ONFH on the basis of CD has become an area of focused research. METHODS: Functional ß-tricalcium phosphate (ß-TCP) scaffolds modified by DPIYALSWSGMA (DPI) peptide, a bone marrow-derived mesenchymal stem cell (BMSC) affinity peptide, were constructed using an adsorption/freeze-drying strategy. The affinity of DPI peptide towards rabbit BMSCs was investigated using flow cytometry and fluorescence cytochemistry. In vitro cell adhesion assay was performed to study the adherent ability of rabbit BMSCs on functional ß-TCP scaffolds. After the rabbit model of early ONFH was established, DPI peptide-modified and pure ß-TCP scaffolds were transplanted into the remaining cavity after CD. Meanwhile, rabbits treated with pure CD were used as blank control. Twelve weeks after surgery, histological analysis was performed to show the therapeutic effect of three methods on early ONFH. RESULTS: The result of ImageXpress Micro Confocal indicated that fabricated DPI peptide-modified functional ß-TCP scaffolds exhibited green fluorescence. In flow cytometry, the average fluorescence intensity for rabbit BMSCs incubated with FITC-DPI was significantly higher than that of FITC-LSP (P = 2.733 × 10-8). In fluorescence cytochemistry, strong fluorescent signals were observed in rabbit BMSCs incubated with FITC-DPI and FITC-RGD, whereas no fluorescent signals in cells incubated with FITC-LSP. In cell adhesion assay, the number of adherent cells to ß-TCP-DPI scaffolds was more than that of pure ß-TCP scaffolds (P = 0.033). The CD + ß-TCP-DPI group expressed the lowest vacant bone lacunae percentage compared to CD group (P = 2.350 × 10-4) and CD + ß-TCP group (P = 0.020). The expression content of COL1 in CD + ß-TCP-DPI group was much higher than CD group (P = 1.262 × 10-7) and CD + ß-TCP group (P = 1.666 × 10-7) according to the integrated optical density (IOD) analyses. CONCLUSION: Functional ß-TCP scaffolds modified by DPI peptide were successfully synthesized using an adsorption/freeze-drying strategy. DPI peptide has good affinity towards rabbit BMSCs. The adhesion of rabbit BMSCs on DPI peptide-modified ß-TCP scaffolds was apparently enhanced. CD followed by implantation of DPI peptide-modified ß-TCP scaffolds can apparently improve the treatment of early ONFH compared with pure CD and CD followed by implantation of unmodified ß-TCP scaffolds. Our current study provides an improved method for the treatment of early ONFH.

Effect of ionic liquids with different cations and anions on photosystem and cell structure of Scenedesmus obliquus.

The rapid increase in the production and practical application of ionic liquids (ILs) could pose potential threats to aquatic systems. In this study, we investigated the effects of four ILs with different cations and anions, including 1-hexyl-3-methylimidazolium nitrate ([HMIM]NO3), 1-hexyl-3-methylimidazolium chloride ([HMIM]Cl), N-hexyl-3-metylpyridinium chloride ([HMPy]Cl), and N-hexyl-3-metylpyridinium bromide ([HMPy]Br), on photosystem and cellular structure of Scenedesmus obliquus. The results indicated that ILs are phytotoxic to S. obliquus. The contents of chlorophyll a, chlorophyll b and total chlorophyll decreased with increasing ILs concentrations. The chlorophyll fluorescence parameters of photosynthetic system II (PSII), including minimal fluorescence yield (F0), potential efficiency of PSII (Fv/Fo), maximum quantum efficiency of PSII photochemistry (Fv/Fm), yield of photochemical quantum [Y(II)], and non-photochemical quenching coefficient without measuring F0' (NPQ), were all affected. This indicates that ILs could damage PSII, inhibit the primary reaction of photosynthesis, interdict the process of electron-transfer and lead to loss of heat-dissipating ability. ILs also increased cell membrane permeability of S. obliquus, influenced the cellular ultrastructure, changed the morphology of algae cells and destroyed the cell wall, cell membrane and organelles. The results indicated that imidazolium ILs had greater effect than pyridinium ILs, NO3--IL and Br--IL had greater effect than Cl--IL. To minimize threats to the environment, the structure of ILs should be taken into consideration.

The toxicity of ionic liquid 1-decylpyridinium bromide to the algae Scenedesmus obliquus: Growth inhibition, phototoxicity, and oxidative stress.

Although ionic liquids (ILs) are unlikely to act as air contaminants, their high solubility and slow degradation make them a potential threat to the aquatic environment. The IL 1-decylpyridinium bromide ([DPy]Br) is a common type of pyridine IL, which has varied applications such as in extraction, separation, and catalytic synthesis. Herein, the toxicity of [DPy]Br to S. obliquus is determined. Growth was inhibited by high-concentration [DPy]Br, whereas it had a hormetic effect at low concentrations. The IC50-96h was approximately 0.06mg/L. The cell membrane permeability of S. obliquus increased with [DPy]Br concentration, indicating that [DPy]Br can cause damage to the algae cell structure. Chlorophyll content decreased at high [DPy]Br concentration; chlorophyll fluorescence parameters, such as the maximum effective quantum yield of PSII (Fv/Fm), potential activity of PSII (Fv/F0), yield of the photochemical quantum [Y(II)], and the non-photochemical quenching coefficient (NPQ) were affected, suggesting that [DPy]Br can damage PSII. The ROS fluorescent images revealed that the morphology of cells changed gradually from fusiform to round. High ROS levels were observed with high concentrations of [DPy]Br, indicating that [DPy]Br induced oxidative stress on S. obliquus. The SOD and CAT activities increased when the concentration was lower than IC50, whereas they decreased when the concentration was higher than IC50. The relative ROS content was significantly correlated with growth inhibition rate, cell membrane permeability, chlorophyll content, and SOD and CAT activities. The increase of ROS content in algal cells is an important toxicological mechanism of [DPy]Br to S. obliquus.

Detection of human novel influenza A (H1N1) viruses using multi-fluorescent real-time RT-PCR.

The novel influenza A (H1N1) virus is now rapidly spreading across the world. Early detection is one of the most effective measures to prevent further transmission of the virus. 4 sets of proprietary primers and probes designed for detection of influenza A viruses (InfA), human and swine H1N1 viruses (SH1), the novel H1N1 viruses (NH1) and RNaseP gene (RP) respectively were pooled together in a single tube for a multi-fluorescent real-time RT-PCR assay. The detection limit was found to be one order more sensitive than that employing the WHO recommended protocol. The NH1 probe was negative for all control samples including human seasonal H1N1 virus, other subtypes of human influenza A viruses (H3, H5, H9), human influenza B virus and nasopharyngeal swabs from patients with noninfluenza respiratory diseases, indicating its high specificity, capable of discriminating the novel influenza A virus from the previously identified H1N1 viruses. For confirmation, the PCR amplified fragment of the hemagglutinin gene was sequenced which could provide enough information to identify the novel H1N1 virus as a distinct cluster among all viruses of subtype H1 through average distance clustering analysis. Although these assays should be useful in the current outbreak for rapid detection and discrimination of the novel H1N1 from swine H1N1 and other human seasonal H1N1 viruses, further design improvement is suggested to match possible sequence variations in the detected region along with the course of the epidemic.