Search

Abstract Background The role of periodontal ligament stem cells (PDLSCs) in repairing periodontal destruction is crucial, but their functions can be impaired by excessive oxidative stress (OS). Nocardamine (NOCA), a cyclic siderophore, has been shown to possess anti-cancer and anti-bacterial properties. This study aimed to investigate the protective mechanisms of NOCA against OS-induced cellular dysfunction in PDLSCs. Methods The cytotoxicity of NOCA on PDLSCs was assessed using a CCK-8 assay. PDLSCs were then treated with hydrogen peroxide (H2O2) to induce OS. ROS levels, cell viability, and antioxidant factor expression were analyzed using relevant kits after treatment. Small molecule inhibitors U0126 and XAV-939 were employed to block ERK signaling and Wnt pathways respectively. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) activity staining and Alizarin Red S (ARS) staining of mineralized nodules. Expression levels of osteogenic gene markers and ERK pathway were determined via real-time quantitative polymerase chain reaction (RT-qPCR) or western blot (WB) analysis. β-catenin nuclear localization was examined by western blotting and confocal microscopy. Results NOCA exhibited no significant cytotoxicity at concentrations below 20 µM and effectively inhibited H2O2-induced OS in PDLSCs. NOCA also restored ALP activity, mineralized nodule formation, and the expression of osteogenic markers in H2O2-stimulated PDLSCs. Mechanistically, NOCA increased p-ERK level and promoted β-catenin translocation into the nucleus; however, blocking ERK pathway disrupted the osteogenic protection provided by NOCA and impaired its ability to induce β-catenin nuclear translocation under OS conditions in PDLSCs. Conclusions NOCA protected PDLSCs against H2O2-induced OS and effectively restored impaired osteogenic differentiation in PDLSCs by modulating the ERK/Wnt signaling pathway.

This study explores the bioactive secondary metabolite profiles of the peels of three major cultivars of bananas (Musa acuminata and Musa balbisiana). These cultivars are primarily grown in Southeast Asia and are widely consumed due to their rich nutritional and fiber content. The research utilizes advanced analytical techniques, specifically HPLC-DAD-q-TOF-MS/MS, in conjunction with both univariate and multivariate statistical analyses, to analyze the ethanolic extracts of the banana peels. This study identifies phenolic acids, flavonoids, and proanthocyanidins as significant contributors to the differentiation of the cultivars. The secondary metabolites rutin, chlorogenic acid, and gentisic acid are pinpointed as the key discriminants. Moreover, the research demonstrates a synergistic contribution of certain phytochemicals to the antioxidant and antibacterial properties of the banana peel extracts. The fingerprint profiling tools introduced in this study offer a reliable method for identifying metabolite biomarkers for the discrimination of banana cultivars.

Allergic diseases like asthma, allergic rhinitis and dermatitis pose a significant global health burden, driving the search for novel therapies. The NLRP3 inflammasome, a key component of the innate immune system, is implicated in various inflammatory diseases. Upon exposure to allergens, NLRP3 undergoes a two-step activation process (priming and assembly) to form active inflammasomes. These inflammasomes trigger caspase-1 activation, leading to the cleavage of pro-inflammatory cytokines (IL-1β and IL-18) and GSDMD. This process induces pyroptosis and amplifies inflammation. Recent studies in humans and mice strongly suggest a link between the NLRP3 inflammasome, IL-1β, and IL-18, and the development of allergic diseases. However, further research is needed to fully understand NLRP3’s specific mechanisms in allergies. This review aims to summarize the latest advances in NLRP3 activation and regulation. We will discuss small molecule drugs and natural products targeting NLRP3 as potential therapeutic strategies for allergic diseases.

The LiFePO4 material continue to suffer from poor rate performance. Nanosized LFP can improve rate performance; however, nanofabrication typically requires expensive organic matter and high-pressure-resistant equipment. The current widely used solid-phase sintering methods employ FePO4 as the precursor, but it is difficult to suppress grain growth. Here, we propose a W–Ti codoping strategy to suppress grain growth during sintering, thereby improving rate performance of Li-ion batteries. W and Ti doping shrinks grains during the sintering process and make the Li-O bond more ionized. Li0.36WO3 accumulates at grain boundaries, hindering grain boundary diffusion and inhibiting grain growth during sintering. The resulting material exhibits refined grains and suppressed polarization growth, resulting in improved rate performance while maintaining a specific capacity of 117 mAh g−1 at a rate of 10 C. After 1000 cycles at a rate of 1 C, 91.0 % of the initial capacity was retained. In summary, this research provides a method for large-scale production of LFP with excellent rate performance.

Abstract This study evaluated the association between body pH value and preoperative deep vein thrombosis (DVT) in geriatric hip fractures. Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of the patients were collected. Multivariate binary logistic regression and generalized additive models were used to identify the linear and nonlinear associations between pH value and preoperative DVT. Analyses were performed using EmpowerStats and R software. A total of 1465 patients were included in the study. DVT occurred in 476 (32.6%) of these admitted older adults. We observed a nonlinear association between the serum pH value and preoperative DVT in geriatric patients with hip fractures. A pH value of 7.39 was the inflection point in the curve, with pH highly correlated with DVT at pH 7.39, pH was not correlated with DVT (OR 1.26; 95% CI 0.85–1.86; P = 0.2561), the odds of DVT did not vary with pH, and the highest risk of thrombosis was reached. The body pH value is nonlinearly associated with preoperative DVT in geriatric patients with hip fractures, and it could be considered a predictor of the risk of DVT. Registered information This study is registered in the website of Chinese Clinical Trial Registry (ChiCTR: ChiCTR2200057323).

Background The combination of immune-checkpoint inhibitors and antiangiogenic agents can synergistically modulate the tumor microenvironment and represents a promising treatment option. Here, we evaluated the efficacy and safety of camrelizumab plus famitinib (a receptor tyrosine kinase inhibitor) as a first-line treatment for advanced or metastatic NSCLC patients with a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥1%, in an open-label, multicenter, phase 2 basket trial.Methods Eligible patients received camrelizumab (200 mg once every 3 weeks via intravenous infusion) plus oral famitinib at an initial dose of 20 mg once daily. The primary endpoint was the objective response rate (ORR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors V.1.1. Key secondary endpoints included disease control rate (DCR), duration of respons, progression-free survival (PFS), overall survival (OS), 12-month OS rate, and safety profile.Results Of the enrolled 41 patients, 21 (51.2%) had a PD-L1 TPS of 1–49%. As of the cut-off date on June 22, 2022, the combination regimen of camrelizumab and famitinib achieved an ORR of 53.7% (95% CI 37.4% to 69.3%) and a DCR of 92.7% (95% CI 80.1% to 98.5%). The median PFS was 16.6 months (95% CI 8.3 to not reached), and OS data were not yet mature, with an estimated 12-month OS rate of 76.8% (95% CI 60.0% to 87.3%). The most common treatment-related adverse events of grade 3 or higher included hypertension (22.0%), increased alanine aminotransferase (12.2%), decreased neutrophil count (9.8%), proteinuria (7.3%), decrease platelet count (7.3%), and hypokalemia (7.3%). One (2.4%) patient died from grade 5 hemoptysis, which was considered possibly related to the study treatment by the investigator.Conclusion Camrelizumab plus famitinib demonstrated promising antitumor activity in advanced or metastatic NSCLC patients and had an acceptable safety profile. These findings suggest that this combination regimen could be an alternative therapeutic option and warrant further investigation.Trial registration number NCT04346381.

The epithelial barrier serves as a critical defense mechanism separating the human body from the external environment, fulfilling both physical and immune functions. This barrier plays a pivotal role in shielding the body from environmental risk factors such as allergens, pathogens, and pollutants. However, since the 19th century, the escalating threats posed by environmental pollution, global warming, heightened usage of industrial chemical products, and alterations in biodiversity have contributed to a noteworthy surge in allergic disease incidences. Notably, allergic diseases frequently exhibit dysfunction in the epithelial barrier. The proposed epithelial barrier hypothesis introduces a novel avenue for the prevention and treatment of allergic diseases. Despite increased attention to the role of barrier dysfunction in allergic disease development, numerous questions persist regarding the mechanisms underlying the disruption of normal barrier function. Consequently, this review aims to provide a comprehensive overview of the epithelial barrier’s role in allergic diseases, encompassing influencing factors, assessment techniques, and repair methodologies. By doing so, it seeks to present innovative strategies for the prevention and treatment of allergic diseases.

Epigallocatechin (EGC) is one of the main bioactive polyphenols in green tea. This study aims to determine the anti-tumor effect of EGC against colorectal cancer. Our results revealed that treatment of EGC led to significant suppression of cell proliferation and apoptosis in three colorectal cancer cells. Western blot confirmed that EGC activated Caspase-3 and PARP, down-regulated the phosphorylation of STAT3 and decreased Bcl-2 expression. Luciferase-reporter-activity assay further determined that EGC suppressed the promoter activity of STAT3 and downregulated the transcription of STAT3. Besides, in vivo study proved that EGC (100 mg/kg) resulted in significant suppression of tumor volume and tumor weight (decreased by 63.7 %) in mice bearing SW620 tumors. Tumor organoid assays demonstrated the inhibitory efficacy of EGC in colorectal organoids. In conclusion, our study present evidence that EGC inhibited colon cancer cell proliferation both in vitro and in vivo by down-regulation phosphorylated STAT3 and activated downstreams.

The aging phenomenon is commonly observed in quantum-dot light emitting diodes (QLEDs), involving complex chemical or physical processes. Resolving the underlying mechanism of these aging issues is crucial to deliver reliable electroluminescent devices in future display applications. Here, we report a reversible positive aging phenomenon that the device brightness and efficiency significantly improve after device operation, but recover to initial states after long-time storage or mild heat treatment, which can be termed as warming-up effects. Steady and transient equivalent circuit analysis suggest that the radiative recombination current dramatically increases but electron leakage from the quantum dots (QDs) to hole transport layer becomes more accessible during the warming-up process. Further analysis discloses that the notable enhancement of device efficiency can be ascribed to the filling of shell traps in gradient alloyed QDs. This work reveals a distinct positive aging phenomenon featured with reversibility, and further guidelines would be provided to achieve stable QLED devices in real display applications. [ABSTRACT FROM AUTHOR]

The aerobic photooxidation of sulfides into sulfoxides in eco-friendly solvents, notably water, at room temperature, represents a significant interest in the domain of synthetic chemistry. This study introduces four highly stable hexadentate Ir(III) complexes: [Ir(fpqen)](PF6) (1), [Ir(btqen)](PF6) (2), [Ir(bmpqen)](PF6) (3), and [Ir(bnqen](PF6) (4) (where bfpqen is N,N′-bis(2-(4-fluorophenyl)quinolin-8-yl)ethane-1,2-diamine, btqen is N,N′-bis(2-(4-tolyl)quinolin-8-yl)ethane-1,2-diamine, bmpqen is N,N′-bis(2-(4-methoxyphenyl)quinolin-8-yl)ethane-1,2-diamine, and bnqen is N,N′-bis(2-naphthylquinolin-8-yl)ethane-1,2-diamine). These complexes were synthesized utilizing an in situ inter-ligand C-N cross-coupling photoreaction of the precursors [Ir(L)2(en)](PF6) (L is 2-(4-fluorophenyl)quinoline, (2-(4-tolyl)quinoline, 2-(4-methoxyphenyl)quinoline or 2-naphthylquinoline, and en is 1,2-diamine) under benign conditions. This methodology furnishes a valuable and complementary approach for the in situ generation of multidentate complexes through a post-coordination inter-ligand-coupling strategy under mild conditions. Moreover, these hexadentate Ir(III) complexes exhibit pronounced catalytic activity and chemo-selectivity toward the aerobic photooxidations of sulfides into sulfoxides in aqueous media at room temperature, offering a new avenue for the sustainable synthesis of sulfoxides.

A series of reported Pt(II) carbene complexes possibly have the ability to serve as the new generation of blue emitters in luminescent devices because of their narrow emission spectra, high photoluminescence quantum yields (PLQYs), and rigid molecular skeleton. However, the combination of all carbene ligands with different multidentate structures will affect the overall planarity and horizontal dipole ratio to varying degrees, but the specific extent of this effect has not previously been analyzed in detail. In this work, density functional computation is used to study a class of platinum tetracarbene bidentate complexes with similar absorption and emission band characteristics, which is the main reason for the remarkable difference in quantum efficiency due to subtle differences in electronic states caused by different ligands. From the calculation results, the major reason, which results in significantly decrease in quantum efficiency for [Pt(cyim)2]2+, is that [Pt(cyim)2]2+ can reach the non-radiative deactivation metal-centered d-d excited state through an easier pathway compared with [Pt(meim)2]2+. The result, based on changes in the dihedral angle between ligands, can achieve the goal of improving and designing materials by adjusting the degree of the dihedral angle. (meim: bis(1,1′-dimethyl-3,3′-methylene-diimidazoline-2,2′-diylidene); cyim: bis(1,1′-dicyclohexyl-3,3′-methylene-diimidazoline-2,2′-diylidene).

Objective To investigate the expression of fatty acid binding protein 4 (FABP4) in endometrial cancer and its effects on the proliferation, migration and invasion of endometrial cancer cells line HEC-1-A. Methods The expression level of FABP4 mRNA in endometrial cancer tissues and adjacent normal tissues was detected with RT-qPCR. The correlation between FABP4 mRNA expression and pathological changes of endometrial cancer was analyzed. HEC-1-A cells were cultured in vitro and were randomly divided into control group, FABP4 negative control (si-NC) group and interference FABP4 (si-FABP4) group. RT-qPCR, MTT and Transwell assays were used respectively to detect the FABP4 mRNA expression in HEC-1-A cells, the proliferation, migration and invasion of HEC-1-A cells. Western blot was used to detect the protein expression of FABP4, matrix metalloproteinase (MMP)-2 and MMP-9 of HEC-1-A cells in each group. Results The expression level of FABP4 mRNA in endometrial cancer tissues was significantly higher than that in tissues adjacent to cancer (P＜0.05); The FABP4 mRNA expression was related to tumor TNM staging and lymph node metastasis (P＜0.05).Interference with FABP4 expression could significantly inhibit the proliferation, migration and invasion of endometrial cancer cells. Conclusions Expression of FABP4 is up-regulated in endometrial cancer and interference with FABP4 expression can inhibit the proliferation, migration and invasion of endometrial cancer cells.

Acpuncture as a branch of traditional Chinese medicine is popular in China. It can regulate the running of meridian qi to stimulate the ocular nerve activity and increase blood supply. Periocular acupuncture treatment is very frequent, but it can lead to safety hazards that cannot be ignored. For instance, ocular trauma may develop if done improperly, resulting in impaired vision and even blindness. We report a rare case of perforating ocular injury caused by acupuncture.

Abstract Background In non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs), higher blood tumor mutational burden (bTMB) was usually associated with better progression-free survival (PFS) and objective response rate (ORR). However, the association between bTMB and overall survival (OS) benefit remains undefined. It has been reported that patients harboring a high level of circulating tumor DNA (ctDNA) had poor survival. We hypothesized that ctDNA-adjusted bTMB might predict OS benefit in NSCLC patients receiving ICIs. Methods Our study was retrospectively performed in three cohorts, including OAK and POPLAR cohort (n = 853), Shanghai and Wuhan (SH&WH) cohort (n = 44), and National Cancer Center (NCC) cohort (n = 47). Durable clinical benefit (DCB) was defined as PFS lasting ≥ 6 months. The cutoff value of ctDNA-adjusted bTMB for DCB prediction was calculated based on a receiver operating characteristic curve. Interaction between treatments and ctDNA-adjusted bTMB was assessed. Results The bTMB score was significantly associated with tumor burden, while no association was observed between ctDNA-adjusted bTMB with tumor burden. In the OAK and POPLAR cohort, significantly higher ORR (P = 0.020) and DCB (P

Objective To explore the effects of miR-188 and transforming growth factor α (TGF-α) on the proliferation and migration of osteosarcoma cells. Methods The expressions of miR-188 and TGF-α in human osteosarcoma tissues and adjacent tissues were detected. TGFA was detected as the target gene of miR-188 by TargetScan and dual luciferase reporter gene assay. The migration ability of osteosarcoma cells line MG63 was examined by cell scratch assay. The xenograft model of osteosarcoma was established in nude mice and the effect of miR-188 was observed in a xenograft model of osteosarcoma of nude mice. Results The expression of miR-188 was decreased in osteosarcoma tissues (P＜0.01). miR-188 specifically bound to the 3′-UTR of TGFA and negatively regulated its expression. The transfection of miR-188 mimic could inhibit the migration ability of MG63 cells,while the inhibitor could promoted the migration ability,but the up-regulation of TGF-α and the expression of interfered TGF-α could reduce the inhibition effect. In a nude mouse model of osteosarcoma xenograft,over-expression of miR-188 reduced the inhibitory effect (P＜0.01), while down-regulating the expression of miR-188 expression had the opposite effect. TGF-α expression was significantly increased in osteosarcoma tissues (P＜0.01),while silence protiferation of osteosarcoing was decreased. Conclusions miR-188 may inhibit the proliferation and migration of MG63 cells by targeting the expression of TGF-α.