Investigation on the Osteogenic and Antibacterial Properties of Silicon Nitride-Coated Titanium Dental Implants.

The silicon nitride (Si3N4) coating exhibits promising potential in oral applications due to its excellent osteogenic and antibacterial properties. However, a comprehensive investigation of Si3N4 coatings in the context of dental implants is still lacking, especially regarding their corrosion resistance and in vivo performance. In this study, Si3N4 coatings were prepared on a titanium surface using the nonequilibrium magnetron sputtering method. A systematic comparison among the titanium group (Ti), Si3N4 coating group (Si3N4-Ti), and sandblasted and acid-etched-treated titanium group (SLA-Ti) has been conducted in vitro and in vivo. The results showed that the Si3N4-Ti group had the best corrosion resistance and antibacterial properties, which were mainly attributed to the dense structure and chemical activity of Si-O and Si-N bonds on the surface. Furthermore, the Si3N4-Ti group exhibited superior cellular responses in vitro and new bone regeneration and osseointegration in vivo, respectively. In this sense, silicon nitride coating shows promising prospects in the field of dental implantology.

ß-carboline derivative Z86 attenuates colorectal cancer cell proliferation and migration by directly targeting PI3K.

Phosphoinositide 3-kinase (PI3Ks) are lipid kinases widely involved in cell proliferation, metastasis and differentiation. Constitutive activation of the PI3K/Akt/mTOR signaling are well confirmed in colorectal cancers (CRCs). In this study, we identified isopropyl 9-ethyl-1-(naphthalen-1-yl)-9 H-pyrido[3,4-b] indole-3-carboxylate (Z86), as a novel PI3Kα inhibitor with the IC50 value of 4.28 µM. The binding of Z86 to PI3Kα was further confirmed with DARTS and CETSA assay. Immunofluorescence analysis and western blotting data demonstrated that Z86 effectively attenuated PI3K/AKT pathway. Z86 caused dramatic proliferation inhibition of CRCs through G0/G1 cycle arrest rather than apoptosis induction. Besides, the migration of CRCs was also relieved by Z86. The present study not only identified Z86 as a novel PI3Kα inhibitor with potent inhibitory efficiency on PI3K-mediated CRCs growth and migration, but also elucidated a reasonable molecular mechanism of Z86 in the Wnt signaling pathway inhibition.

Single-Atom Manganese-Catalyzed Oxygen Evolution Drives the Electrochemical Oxidation of Silane to Silanol.

The oxygen evolution reaction (OER), characterized by a four-electron transfer kinetic process, represents a significant bottleneck in improving the efficiency of hydrogen production from water electrolysis. Consequently, extensive research efforts have been directed towards identifying single-atom electrocatalysts with exceptional OER performance. Despite the comprehensive understanding of the OER mechanism, its application to other valuable synthetic reactions has been limited. Herein, we leverage the MOOH intermediate, a key species in the Mn-N-C single-atom catalyst (Mn-SA@NC), which can be cyclically delivered in the OER. We exploit this intermediate' s capability to facilitate electrophilic transfer with silane, enabling efficient silane oxidation under electrochemical conditions. The SAC electrocatalytic system exhibits remarkable performance with catalyst loadings as low as 600 ppm and an exceptional turnover number of 9132. Furthermore, the catalytic method demonstrates stability under a 10 mmol flow chemistry setup. By serving as an OER electrocatalyst, the Mn-SA@NC drives the entire reaction, establishing a practical Mn SAC-catalyzed organic electrosynthesis system. This synthesis approach not only presents a promising avenue for the utilization of electrocatalytic OER but also highlights the potential of SACs as an attractive platform for organic electrosynthesis investigations.

Phytic acid improves osteogenesis and inhibits the senescence of human bone marrow mesenchymal stem cells under high-glucose conditions via the ERK pathway.

Hyperglycaemia causes impairment of osteogenic differentiation and accelerates stem cell senescence, resulting in weakened osteogenesis and disordered bone metabolism. Phytic acid (PA) is an antioxidant that is reportedly beneficial to bone homeostasis. The present study aims to clarify how PA affects the osteogenic capacity and cellular senescence of bone marrow mesenchymal stem cells (BMSCs) exposed to high-glucose environments, as well as the potential molecular mechanisms. Our results indicate that osteogenic differentiation in BMSCs cultivated in high-glucose conditions is enhanced by PA, as evidenced by increased alkaline phosphatase activity and staining, Alizarin Red S staining, osteogenic marker in in vitro studies, and increased osteogenesis in animal experiments. PA also prevented high-glucose-induced senescence of BMSCs, as evidenced by the repression of reactive oxygen species production, senescence-associated ß-galactosidase staining, and P21 and P53 expression. Furthermore, it was found that PA rescued the high-glucose-inhibited expression of phosphorylated extracellular regulated protein kinases (p-ERK). The inhibition of ERK pathway by the specific inhibitor PD98059 blocked the PA-enhanced osteogenesis of BMSCs and promoted cell senescence. Our results revealed that PA enhances osteogenic differentiation and inhibits BMSC senescence in a high-glucose environment. In addition, the activation of the ERK pathway seems to mediate the beneficial effects of PA. The findings provide novel insights that could facilitate bone regeneration in patients with diabetes.

Accelerating the Hydrogen Production via Modifying the Fermi Surface.

The design of catalysts has attracted a great deal of attention in the field of electrocatalysis. The accurate design of the catalysts can avoid an unnecessary process that occurs during the blind trial. Based on the interaction between different metal species, a metallic compound supported by the carbon nanotube was designed. Among these compounds, RhFeP2CX (R-RhFeP2CX-CNT) was found to be in a rich-electron environment at the Fermi level (denoted as a flat Fermi surface), beneficial to the hydrogen evolution reaction (HER). R-RhFeP2CX-CNT exhibits a small overpotential of 15 mV at the current density of 10 mA·cm-2 in acidic media. Moreover, the mass activity of R-RhFeP2CX-CNT is 21597 A·g-1, which also demonstrates the advance of the active sites on R-RhFeP2CX-CNT. Therefore, R-RhFeP2CX-CNT can be an alternative catalyst applied in practical production, and the strategies of a flat Fermi surface will be a reliable strategy for catalyst designing.

Exploration of Baicalein-Core Derivatives as Potent Antifungal Agents: SAR and Mechanism Insights.

Baicalein (BE), the major component of Scutellaria Baicalensis, exhibited potently antifungal activity against drug-resistant Candida albicans, and strong inhibition on biofilm formation. Therefore, a series of baicalein-core derivatives were designed and synthesized to find more potent compounds and investigate structure-activity relationship (SAR) and mode of action (MoA). Results demonstrate that A4 and B5 exert a more potent antifungal effect (MIC80 = 0.125 µg/mL) than BE (MIC80 = 4 µg/mL) when used in combination with fluconazole (FLC), while the MIC80 of FLC dropped from 128 µg/mL to 1 µg/mL. SAR analysis indicates that the presence of 5-OH is crucial for synergistic antifungal activities, while o-dihydroxyls and vic-trihydroxyls are an essential pharmacophore, whether they are located on the A ring or the B ring of flavonoids. The MoA demonstrated that these compounds exhibited potent antifungal effects by inhibiting hypha formation of C. albicans. However, sterol composition assay and enzymatic assay conducted in vitro indicated minimal impact of these compounds on sterol biosynthesis and Eno1. These findings were further confirmed by the results of the in-silico assay, which assessed the stability of the complexes. Moreover, the inhibition of hypha of this kind of compound could be attributed to their effect on the catalytic subunit of 1,3-ß-d-glucan synthase, 1,3-ß-d-glucan-UDP glucosyltransferase and glycosyl-phosphatidylinositol protein, rather than inhibiting ergosterol biosynthesis and Eno1 activity by Induced-Fit Docking and Molecular Dynamics Simulations. This study presents potential antifungal agents with synergistic effects that can effectively inhibit hypha formation. It also provides new insights into the MoA.

Sandblasted/Acid-Etched Titanium Surface Modified with Calcium Phytate Enhances Bone Regeneration in a High-Glucose Microenvironment by Regulating Reactive Oxygen Species and Cell Senescence.

Hyperglycemia in patients with diabetes affect osteoblast function, leading to abnormal bone metabolism and implant failure. Adequate bone volume surrounding an implant is essential for osseointegration, which can be improved by implant surface modifications. In this study, titanium surfaces were hydrothermally treated with a mixture of phytic acid (PA) and calcium hydroxide to produce a calcium-decorated surface. The control group comprised pure titanium with a sandblasted/acid-etched (SLA) surface. The elemental composition, hydrophilicity, surface roughness, and morphology of the titanium surfaces were examined. Evaluation of in vitro osteogenic differentiation ability in a high-glucose environment using alkaline phosphatase (ALP) staining, ALP activity assays, Alizarin Red S staining, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and immunofluorescence staining revealed that Ca-PA-modified SLA titanium surfaces can promote osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). Evaluation of oxidative stress and aging using reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and ß-galactosidase staining revealed that Ca-PA-modified SLA titanium surfaces can reduce ROS production and ameliorate oxidative stress damage in hBMSCs. In vivo assessment of osteogenesis in a diabetic rat model revealed that Ca-PA coating promotes peri-implant osseointegration. Ca-PA-modified SLA titanium surface is a candidate for improving implant osseointegration in patients with diabetes.

Three-Component Electrochemical Aminoselenation of 1,3-Dienes.

Azoles and organoselenium compounds are pharmacologically important scaffolds in medicinal chemistry and natural products. We developed an efficient regioselective electrochemical aminoselenation reaction of 1,3-dienes, azoles, and diselenide derivatives to access selenium-containing allylazoles skeletons. This protocol is more economical and environmentally friendly and features a broad substrate scope; pyrazole, triazole, and tetrazolium were all tolerated under the standard conditions, which could be applied to the expedient synthesis of bioactive molecules and in the pharmaceutical industry.

Calcium phytate reverses high glucose-inhibited osteogenesis of BMSCs via the MAPK/JNK pathway.

OBJECTIVES: Diabetes mellitus (DM) induces oxidative tissue impairment and suppresses bone formation. Some studies have shown that phytic acid has antioxidant and anti-diabetic properties. This study aimed to investigate the potential of calcium phytate (Ca-phytate) to reverse inhibited osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) in a high glucose (HG) environment and to determine the underlying mechanism. MATERIALS AND METHODS: hBMSCs were exposed to HG and palmitic acid to simulate DM in vitro. Osteogenic differentiation was measured using alkaline phosphatase staining and activity assay, alizarin red S staining, qRT-PCR, Western blot and immunofluorescence staining. A critical-size cranial defect model of type 2 diabetes mellitus (T2DM) rats was established to evaluate bone regeneration. A specific pathway inhibitor was used to explore whether the MAPK/JNK pathway was involved. RESULTS: Treatment with 34 µM Ca-phytate had the highest effect on osteogenic differentiation in HG. Ca-phytate improved cranial bone defect healing in T2DM rats. The long-term HG environment inhibited the activation of the MAPK/JNK signalling pathway, which was restored by Ca-phytate. Blocking the JNK pathway reduced the Ca-phytate-mediated osteogenic differentiation of hBMSCs. CONCLUSION: Ca-phytate induced bone regeneration in vivo and reversed HG-inhibited osteogenesis of hBMSCs in vitro via the MAPK/JNK signalling pathway.

Methanol promotes the biodegradation of 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB 180) by the microbial consortium QY2: Metabolic pathways, toxicity evaluation and community response.

As one of the most frequently detected PCB congeners in human adipose tissue, 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB 180) has attracted much attention. However, PCB 180 is difficult to be directly utilized by microorganisms due to its hydrophobicity and obstinacy. Herein, methanol (5 mM) as a co-metabolic carbon source significantly stimulated the degradation performance of microbial consortium QY2 for PCB 180 (51.9% higher than that without methanol addition). Six metabolic products including low-chlorinated PCBs and chlorobenzoic acid were identified during co-metabolic degradation, denoting that PCB 180 was metabolized via dechlorination, hydroxylation and ring-opening pathways. The oxidative stress and apoptosis induced by PCB 180 were dose-dependent, but the addition of methanol effectively promoted the tolerance of consortium QY2 to resist unfavorable environmental stress. Additionally, the significant reduction of intracellular reactive oxygen species (ROS) and enhancement of cell viability during methanol co-metabolic degradation proved that the degradation was a detoxification process. The microbial community and network analyses suggested that the potential PCB 180 degrading bacteria in the community (e.g., Achromobacter, Cupriavidus, Methylobacterium and Sphingomonas) and functional abundance of metabolic pathways were selectively enriched by methanol, and the synergies among species whose richness increased after methanol addition might dominate the degradation process. These findings provide new insights into the biodegradation of PCB 180 by microbial consortium.

Deciphering the distinct successional patterns and potential roles of abundant and rare microbial taxa of urban riverine plastisphere.

Microbial colonization on microplastics has provoked global concern; however, many studies have not considered the successional patterns and potential roles of abundant and rare taxa of the plastisphere during colonization. Hence, we investigate the taxonomic composition, assembly, interaction and function of abundant and rare taxa in the riverine plastisphere by conducting microcosm experiments. Results showed that rare taxa occupied significantly high community diversity and niche breadth than the abundant taxa, which implies that rare taxa are essential components in maintaining the community stability of the plastisphere. However, the abundant taxa played a major role in driving the succession of plastisphere communities during colonization. Both stochastic and deterministic processes signally affected the plastisphere community assemblies; while, the deterministic patterns (heterogeneous selection) were especially pronounced for rare biospheres. Plastisphere microbial networks were shaped by the enhancement of network modularity and reinforcement of positive interactions. Rare taxa played critical roles in shaping stable plastisphere by occupying the key status in microbial networks. The strong interaction of rare and non-rare taxa suggested that multi-species collaboration might be conducive to the formation and stability of the plastisphere. Both abundant and rare taxa were enriched with plentiful functional genes related to carbon, nitrogen, phosphorus and sulfur cycling; however, their potential metabolic functions were significantly discrepant, implying that the abundant and rare microbes may play different roles in ecosystems. Overall, this study strengthens our comprehending of the mechanisms regarding the formation and maintenance of the plastisphere.

Functional bacterial consortium responses to biochar and implications for BDE-47 transformation: Performance, metabolism, community assembly and microbial interaction.

The influence of biochar on the biodegradation of persistent organic pollutants (POPs) has been extensively studied. However, the underlying mechanisms behind the response of functional microbial consortia to biochar remain poorly understood. Herein, we systematically explored the effect of biochar on 2,2',4,4'-tetrabrominated ether (BDE-47) biodegradation, and investigated the interaction and assembly mechanism of the functional bacterial consortium QY2. The results revealed that the biodegradation efficiency of QY2 for BDE-47 increased from 53.85% to 94.11% after the addition of biochar. Fluorescence excitation-emission matrix and electrochemical analysis showed that biochar-attached biofilms were rich in redox-active extracellular polymeric substances (EPS, 3.03-fold higher than free cell), whose strong interaction with biochar facilitated the electron transfer of the biofilm, thus enhancing the debromination degradation of BDE-47. Meanwhile, the assembly model and molecular ecological networks analysis indicated that bacterial community assembly in biofilms was more driven by deterministic processes (environmental selection >75.00%) upon biochar stimulation and exhibited closer interspecific cooperative interactions, leading to higher biodiversity and broader habitat niche breadth for QY2 in response to BDE-47 disturbance. Potential degraders (Methylobacterium, Sphingomonas, Microbacterium) and electrochemical bacteria (Ochrobactrum) were selectively enriched, whose role as keystone bacteria may be participated in biofilm formation and redox-active EPS secretion (r > 0.5, P < 0.05). These findings deepen the understanding of the mechanisms by which biochar promotes microbial degradation of PBDEs and provided a theoretical basis for better regulation of functional bacterial communities during environmental remediation.

Mechanisms and influencing factors for electron transfer complex in metal-biochar nanocomposites activated peroxydisulfate.

The mechanisms and influencing factors for electron transfer complex need to be further studied by comparing radical and nonradical pathways. Herein, metal-biochar (BC) nanocomposites including CuO/BC, Fe3O4/BC and ZnO/BC were prepared to activate peroxydisulfate (PDS) for bisphenol A (BPA) degradation. The existence of electron transfer complex in CuO/BC-PDS system were directly demonstrated. Whereas radical pathway was dominant in Fe3O4/BC- and ZnO/BC-PDS systems for BPA degradation. There was a relationship between PDS adsorption and catalytic reaction. The rate-limiting step for BPA degradation in nonradical pathway was PDS adsorption, but in radical pathway was BPA degradation. Interestingly, among metal-BC, CuO/BC had the most effective performance in transformation of adsorbed PDS to electron transfer complex via out-sphere complexation. After pretreatment by PDS solutions, the separated CuO/BC achieved an efficiency of 60% in ensuing BPA degradation without re-addition of PDS. In addition, the activity of electron transfer complex in BPA degradation (kobs > 0.0480 min-1) was not affected by water matrix (e.g., Cl-, HCO3-, natural organic matter (NOM) and actual water bodies), but affected by solution property (i.e., dissolved oxygen and conductivity) and oxidant species. Moreover, in BPA degradation process, nonradical pathway exhibited lower ecotoxicity instead of radical pathway.

Synthesis of baicalein derivatives and evaluation of their antiviral activity against arboviruses.

Natural plant-derived baicalein which is extracted from Chinese herb Scutellaria baicalensis Georgi belongs to the flavonoid compounds and possesses multiple pharmacological activities. In this study, we designed and synthesized new series of derivatives of baicalein (BE) through catalytic coupling reactions, and screened for their antiviral activity against arboviruses including Chikungunya virus (CHIKV), West Nile virus (WNV) or Zika virus (ZIKV). Our results revealed for the first time that BE and its derivatives had potent anti-CHIKV, anti-WNV and anti-ZIKV effects. And modification of 8 or 4' position could lead to obtain potent antiviral compounds against CHIKV, WNV and ZIKV with lower cytotoxicity. Among the baicalein derivatives, C3 and F3 showed the most potent antiviral activities against CHIKV, WNV and ZIKV, which were 5-10 times more potent than baicalein. Our findings will provide research basis for the development of baicalein derivatives as effective antiviral agents.

Synergistic antifungal effects of curcumin derivatives as fungal biofilm inhibitors with fluconazole.

Lack of novel antifungal agents and severe drug resistance has led to high incidence and associated mortality of invasive fungal infections. To tackle the challenges, novel antifungal agents with anti-resistant potency are highly desirable. Thus, derivatives of curcumin were synthesized to restore the effectiveness of fluconazole (FLC) against FLC-resistant Candida spp. and structure-activity relationships were then discussed. Some novel derivatives showed promising features as novel antifungal lead compounds. Of them, compound 4 showed good alone or synergistic antifungal activity against FLC-resistant Candida spp. Moreover, compound 4 was proven as a potent inhibitor of Candida albicans biofilm formation and yeast-to-hypha morphological transition whether used alone or in combination with FLC, which was further confirmed by the inhibitory effect on cellular surface hydrophobicity of C. albicans. Compound 4 also inhibits intracellular ATP production of C. albicans and disrupts membrane permeability of C. albicans when used in combination with FLC. The results highlighted the potential of curcumin derivatives to overcome fluconazole-related and biofilm-related drug resistance.