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Dental resin composites (DRCs) with diverse fillers added are widely-used restorative materials to repair tooth defects. The addition of fillers brings an improvement in the mechanical properties of DRCs. In the past decade, diverse fillers have emerged. However, the change of emerging fillers mainly focuses on the chemical composition, while the morphologic characteristics changes are often ignored. The fillers with new morphologies not only have the advantages of traditional fillers (particles, fibrous filler, etc.), but also endow some additional functional characteristics (stronger bonding ability to resin matrix, polymerization resistance, and wear resistance, drug release control ability, etc.). Moreover, some new morphologies are closely related to the improvement of traditional fillers, porous filler vs. glass particles, core-sheath fibrous vs. fibrous, etc. Some other new morphology fillers are combinations of traditional fillers, UHA vs. HA particles and fibrous, tetrapod-like whisker vs. whisker and fibrous filler, mesoporous silica vs. porous and silica particles. In this review, we give an overall description and a preliminary summary of the fillers, as well as our perspectives on the future direction of the development of novel fillers for next-generation DRCs.

The current lack of a straightforward and convenient modeling approach to simulate the onset of acute lung injury (ALI) has impeded fundamental research and hindered the screening of therapeutic drugs in coronavirus disease 2019 (COVID-19). The co-cultured human pulmonary alveolar epithelial cells (HPAEpics) and alveolar macrophages (AMs) were exposed to the complete medium, three concentrations of recombinant spike S1 protein (0.1, 1, and 10 μg/mL), or lipopolysaccharide (LPS) (10 μg/mL). The cells were harvested at 1, 2, and 3 days post-exposure. Lactate dehydrogenase (LDH) release, and IL-6, TNF-ɑ, and malondialdehyde (MDA) production were quantified and compared. Compared to those exposed to medium, co-cultures of HPAEpics and AMs exposed to a concentration of S1 protein at 10 μg/mL demonstrated significantly increased levels of LDH release (22.9% vs. 9.1%, and 25.7%), IL-6 (129 vs. 74, and 110 pg/mg of protein), and TNF-ɑ (75 vs. 51, and 86 pg/mg of protein) production, and similar to those exposed to LPS. However, no statistically significant differences were observed in MDA production. Compared to those harvested at 1 or 2 days post-exposure, co-cultured cells harvested at 3 days post-exposure exhibited increased levels of LDH release (23.4% vs. 14.9%, or 16.7%), IL-6 (127 vs. 81, or 97 pg/mg of protein) and MDA (5.6 vs. 3.2, or 3.8 nmol/mg of protein) production, but exhibited lower TNF-ɑ (58 vs. 79 pg/mg of protein) production than those harvested at 2 days post-exposure. After 3 days of exposure, co-cultures of HPAEpics and AMs showed significantly increased levels of LDH release (25.3% vs. 18.4%), and MDA production (5.5 vs. 4.3 nmol/mg of protein) compared to HPAEpics monocultures, and increased levels of LDH release (25.3% vs. 13.8%), IL-6 (139 vs. 98 pg/mg of protein) and MDA (5.5 vs. 4.7 nmol/mg of protein) production, and decreased TNF-ɑ (59 vs. 95 pg/mg of protein) production compared to AMs monocultures. Conclusions: The exposure to a concentration of S1 protein at 10 μg/mL in co-cultures of HPAEpics and AMs induced significant injury and inflammation three days post-exposure. This methodology for establishing a COVID-19-associated ALI model may have promising potential applications and value.

In this study, we aim to provide a deep understanding of the tumor microenvironment (TME) and its metabolic characteristics in non-small cell lung cancer (NSCLC) through single-cell RNA sequencing (scRNAseq) data obtained from public databases. Given that lung cancer is a leading cause of cancer-related deaths globally and NSCLC accounts for the majority of lung cancer cases, understanding the relationship between TME and metabolic pathways in NSCLC is crucial for developing new treatment strategies. Finally, machine learning algorithms were employed to construct a risk signature with strong predictive power across multiple independent cohorts. After quality control, 29,053 cells were retained, and PCA along with UMAP techniques were used to distinguish 13 primary cell subpopulations. Four highly activated metabolic pathways were identified within malignant cell subpopulations, which were further divided into seven distinct subgroups showing significant differences in differentiation potential and metabolic activity. WGCNA was utilized to identify gene modules and hub genes closely associated with these four metabolic pathways. Our analysis showed that DEGs between tumor and normal tissues were predominantly enriched in immune response and cell adhesion pathways. The comprehensive examination of our model revealed substantial variations in clinical and pathological characteristics, enriched pathways, cancer hallmarks, and immune infiltration scores between high-risk and low-risk groups. Wet lab experiments validated the role of KRT6B in NSCLC, demonstrating that KRT6B expression is elevated and it stimulates the proliferation of cancer cells. These observations not only enhance our understanding of metabolic reprogramming and its biological functions in NSCLC but also provide new perspectives for early detection, prognostic evaluation, and targeted therapy. However, future research should further explore the specific mechanisms of these metabolic pathways and their application potentials in clinical practice.

The Pt-chitosan-TiO2 charge transfer (CT) complex was synthesized via the sol-gel and impregnation method. The synthesized photocatalysts were thoroughly characterized, and their photocatalytic activity were evaluated toward H2 production through water reduction under visible-light irradiation. The effect of the preparation conditions of the photocatalysts (the degree of deacetylation of chitosan, addition amount of chitosan, and calcination temperature) on the photocatalytic activity was discussed. The optimal Pt-10%DD75-T200 showed a H2 generation rate of 280.4 μmol within 3 h. The remarkable visible-light photocatalytic activity of Pt-chitosan-TiO2 was due to the CT complex formation between chitosan and TiO2, which extended the visible-light absorption and induced the ligand-to-metal charge transfer (LMCT). The photocatalytic mechanism of Pt-chitosan-TiO2 was also investigated. This paper outlines a new and facile pathway for designing novel visible-light-driven photocatalysts that are based on TiO2 modified by polysaccharide biomass wastes that are widely found in nature.

Agonists selectively targeting cannabinoid receptor-like G-protein-coupled receptor (GPCR) GPR119 hold promise for treating metabolic disorders while avoiding unwanted side effects. Here we present the cryo-electron microscopy (cryo-EM) structures of the human GPR119-G s signaling complexes bound to AR231453 and MBX-2982, two representative agonists reported for GPR119. The structures reveal a one-amino acid shift of the conserved proline residue of TM5 that forms an outward bulge, opening up a hydrophobic cavity between TM4 and TM5 at the middle of the membrane for its endogenous ligands-monounsaturated lipid metabolites. In addition, we observed a salt bridge between ICL1 of GPR119 and Gβ s . Disruption of the salt bridge eliminates the cAMP production of GPR119, indicating an important role of Gβ s in GPR119-mediated signaling. Our structures, together with mutagenesis studies, illustrate the conserved binding mode of the chemically different agonists, and provide insights into the conformational changes in receptor activation and G protein coupling. Agonists selectively targeting GPR119 hold promise for treating metabolic disorders. Here, authors reveal that GPR119 adopts a non-canonical consensus structural scaffold with an extended ligand-binding pocket for chemically different agonists.

In this study, a specific and sensitive method of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed for the determination of penconazole enantiomers in rat plasma. The enantioseparation was achieved on a Chiralpak IC column by using acetonitrile/water (80:20, v/v) as the mobile phase. Penconazole enantiomers and internal standard l-lansoprazole (IS) were detected in multiple reaction monitoring (MRM) mode with positive electrospray ionization source. The method was validated over the concentration range of 2.5–250.0 ng mL−1 for penconazole enantiomers. Good linearity was obtained for both enantiomers with correlation coefficients (R) greater than 0.995. The relative error was well within the admissible range of −1.1–3.2%, and relative standard deviation was less than 6.0%. After validation, the established method was successfully applied to a stereoselective toxicokinetic study in female and male rats after oral administration of 50 mg kg−1 racemic penconazole. This is the first experiment regarding the stereospecific toxicokinetic study of penconazole and the bioanalytical approach for its quantitation in vivo.

Pulmonary vascular development is essential for alveolarization, and disruption of this process contributes to pathogenesis of bronchopulmonary dysplasia (BPD). Proper vascular development requires an orchestration of many cell types within the lung. However, the transcriptional mechanisms by which pericytes support the endothelium in the postnatal lung remain poorly understood. Herein, we identify FOXF2 as a critical transcription factor that governs pericyte maturation and function during postnatal lung development and regeneration. FOXF2 expression in pericytes increases postnatally and is selectively downregulated after neonatal hyperoxic injury. Pdgfrb-CreER mediated Foxf2 deletion in pericytes leads to pericyte hyperplasia, impaired migration, and reduced expression of angiogenic factors such as ANGPTL4. Transcriptomic and genomic studies demonstrate that FOXF2 maintains chromatin accessibility at pro-angiogenic loci and modulates paracrine signaling essential for endothelial regeneration. Loss of FOXF2 disrupts pericyte–endothelial crosstalk, leading to impaired angiogenesis and alveolarization as well as increased vascular permeability after neonatal lung injury. Altogether, FOXF2 acts as a key transcriptional regulator of the pericyte-driven vascular niche in the neonatal lung, highlighting the pathogenic role of pericyte dysfunction in BPD. Here they show that FOXF2 is required for pericyte maturation and function during postnatal alveolar morphogenesis. FOXF2 is required in pericytes to induce angiogenesis after neonatal hyperoxic injury, revealing a link between pericyte-endothelial crosstalk and bronchopulmonary dysplasia pathogenesis.

Small-angle X-ray scattering (SAXS) is an effective method to obtain microstructural information of materials. However, due to the influence of crystal surface effects, SAXS has a deviation in the characterization of the crystal microstructure. In order to solve the influence of crystal surface effect on the internal defect signal, the microstructure of Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) crystal was characterized by soaking the sample in the matching solution. We found that the absolute scattering intensity, specific surface and volume fraction of the sample in the matching solution are significantly lower than the initial sample, which solves the influence of the crystal surface effect on the test results. Comparing the scattering results of the samples in different electron density matching solutions, it was found that the best result was obtained when using GPL-107 perfluoropolyether (PFPE) matching solution and the same law was obtained by controlling the experiment with 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane (CL-20) crystal. The fitting density was calculated according to the theoretical density and void volume fraction of the sample, and the calculated results are close to the test results of Particle Density Distribution Analyzer (PDDA). Based on this paper, we provide a method to obtain the correct information of crystal microstructure.

Purpose Obsessive‐compulsive disorder (OCD) is a complex psychiatric disorder. Genetic and broad environmental factors are common risk factors for OCD. The purpose of this study is to explore the molecular mechanism of OCD and to find new molecular targets for the diagnosis and management of OCD. Methods All data were downloaded from public dataset. Key modules and candidate key mRNAs were identified based on weighted gene co‐expression network analysis (WGCNA). The “limma” R package was used for differential expression analysis of mRNAs. Subsequently, functional enrichment analysis of differentially expressed mRNAs (DEmRNAs) was also carried out. In addition, a diagnostic model was constructed. Finally, the infiltration level of immune cells in OCD and its correlation with multicentric key DEmRNAs were analyzed. Results Green and red modules were selected as the hub modules. A total of 447 mRNAs were considered candidate key mRNAs according to GS > 0.2 and MM > 0.3. A total of 26 DEmRNAs in the same direction were identified in the GSE60190 and GSE78104 datasets. A total of 26 DEmRNAs were intersected with candidate key mRNAs in WGCNA to obtain 10 intersection DEmRNAs (HSPB1, ITPK1, CBX7, PPP1R10, TAOK1, PISD, MKNK2, RWDD1, PPA1, and RELN). However, only four DEmRNAs (HSPB1, TAOK1, MKNK2, and PPA1) predicted related drugs. Subsequently, receiver operating characteristic analysis shows that the diagnostic model has high diagnostic value. Moreover, six multicentric key DEmRNAs (SNRPF, SNRNP70, PRPF8, NOP56, EPRS, and CCT2) were screened by UpSet package. Finally, six multicentric key DEmRNAs were found to be associated with immune cells. Conclusion The key molecules obtained in this study lay a foundation for further research on the molecular mechanism of OCD.

Wuling capsule is a Chinese patent medicine mainly used for the treatment of chronic liver disease in clinical practice. Our previous work has revealed that Wuling capsule could inhibit liver fibrosis by regulating macrophage polarization, and firstly demonstrated its anti-gout effects on monosodium urate (MSU)- induced acute gouty arthritis (AGA) in rats. High uric acid (UA) levels are known to be the primary cause of gout. Therefore, this study investigated the UA lowering, kidney protection effects and underlying mechanisms of Wuling capsule in vivo and in vitro, and also determined its key bioactive constituents. The efficacy of Wuling capsule for HUA symptoms in rats was evaluated. Histopathological analysis of liver and kidney tissues were detected by HE staining. The biochemical indices were measured using specific kits. The main constituents of Wuling capsule and its medicated serum were analyzed by UPLC-QTOF-MS/MS. Protective effects of saikosaponin A, tanshinone IIA, schisandrol B, and ganoderic acid A on UA-injured HK-2 cells were assessed via Hoechst 33342/PI staining and flow cytometry. Molecular docking and dynamics simulation predicted the binding energy and stability of these constituents to UA related transporters. The mRNA and protein expression levels of UA related transporters were examined using RT-qPCR and Western blotting. In HUA rats, Wuling capsule significantly reduced the serum UA level and xanthine oxidase (XOD) content in both serum and liver. Furthermore, it improved liver function markers (ALT, AST) and renal injury indicators (Cr, BUN), ameliorated renal tubule dilation and inflammatory infiltration in the kidney, and regulated the mRNA and protein expression of UA related transporters (URAT1, GLUT9, ABCG2 and OAT1). In vitro, the main constituents of Wuling capsule (saikosaponin A, tanshinone IIA, schisandrol B and ganoderic acid A) improved cell viability and inhibited cell apoptosis in UA-injured HK-2 cells. Subsequently, its four serum constituents also significantly regulated the mRNA and protein expression of URAT1, GLUT9, and ABCG2 selectively. This work demonstrated the therapeutic effect of Wuling capsule on HUA by protecting liver and kidney function and regulating UA related transporters. These findings provide novel support for the further clinical application of Wuling capsule.