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1.
Reprod Toxicol ; 128: 108646, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38880403

ABSTRACT

OBJECTIVE: To investigate the impact of maternal smoking on chronic obstructive pulmonary disease (COPD) progression in offspring. METHODS: Using female C57BL/6 J mice, a maternal cigarette smoke exposure (CSE) model was established. Mice were exposed to cigarette smoke for 2 hours/day, 7 days/week, with a minimum 4-hour interval between exposures. Experimental groups included control (Con), pregnancy exposure (AS), pre-pregnancy exposure (SA), and pre-pregnancy + pregnancy exposure (SS). Lung function tests (Penh, PAU, TVb, EF50, Tr) were conducted on male offspring at 7 weeks. Histopathology, electron microscopy, and protein level changes were examined. RESULTS: Lung function tests revealed significant impairments in Penh, PAU, TVb, EF50, and Tr in offspring across all exposure scenarios. Specifically, AS experienced significant lung function impairment and mitochondrial dysfunction in offspring, with noticeable pulmonary lesions and increased apoptosis. SA showed similar or even more severe lung function impairment and cellular apoptosis. SS exhibited the most pronounced effects, with the highest levels of lung dysfunction, mitochondrial damage, and apoptosis. Histopathological analysis showed pulmonary lesions in offspring exposed to maternal CSE. Flow cytometry revealed increased apoptosis and reduced mitochondrial membrane potential in offspring lung cells. Electron microscopy confirmed mitochondrial dysfunction. Upregulation of apoptotic proteins and downregulation of anti-apoptotic protein Bcl-2 were found in offspring lung tissue exposed to maternal CSE. CONCLUSION: Maternal smoking induces impaired lung function, pulmonary lesions, and mitochondrial dysfunction in offspring, regardless of exposure timing and duration. Additionally, it alters expression of apoptosis-related proteins in offspring lung tissue, potentially contributing to COPD susceptibility.

2.
Discov Med ; 36(185): 1250-1259, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38926111

ABSTRACT

BACKGROUND: Cigarette smoke (CS) induces autophagy and endoplasmic reticulum (ER) stress in the lungs. Research suggests that maternal exposure to CS during pregnancy leads to decreased lung function in offspring. However, the effects of maternal CS exposure on lung autophagy and ER stress in offspring during pregnancy remain unclear. METHODS: C57BL/6J female mice were divided into the AA (air treatment during both pre-pregnancy and pregnancy), AS (air treatment during pre-pregnancy and CS treatment during pregnancy), SA (CS treatment during pre-pregnancy and air treatment during pregnancy), and SS (CS treatment during both pre-pregnancy and pregnancy) groups. The male offspring mice were selected to the study and euthanized 49 days after birth for the study. Hematoxylin and eosin (HE) staining was employed to observe pathological alterations, while transmission electron microscopy (TEM) was utilized to examine ultrastructure and autophagic vesicles. Additionally, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method was applied to identify apoptosis in lung tissues. Immunofluorescence, Real-Time PCR, and Western Blot analyses were conducted to assess the expression of ER stress and autophagy-related markers in lung tissues. RESULTS: The findings revealed that exposure to CS heightened the extent of pathological damage and the abundance of autophagosomes in the lungs of offspring mice. TUNEL results indicated an increased fluorescence intensity in the AS, SA and SS groups, with the most significant in AS and SS groups. Furthermore, CS exposure augmented the fluorescence intensity and expression of ER stress and autophagy-related proteins. The expression of C/EBP-homologous protein (CHOP) exhibited no discernible difference between the SA and SS groups but showed a significant increase in the AS group. Conversely, the expression levels of glucose-regulated protein 78 (GRP78), Caspase-12, Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3) exhibited no significant difference between the AS and SA groups, whereas they were significantly upregulated in the SS group. CONCLUSIONS: Preconceptional and gestational exposure to CS heightened ER stress and autophagy in the lungs of mouse offspring. However, in mothers who smoked, withdrawal from CS during pregnancy led to a reduction in ER stress and autophagy in the lungs of their offspring.


Subject(s)
Autophagy , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress , Lung , Maternal Exposure , Mice, Inbred C57BL , Prenatal Exposure Delayed Effects , Animals , Endoplasmic Reticulum Stress/drug effects , Female , Pregnancy , Mice , Lung/pathology , Lung/metabolism , Maternal Exposure/adverse effects , Male , Prenatal Exposure Delayed Effects/pathology , Apoptosis , Tobacco Smoke Pollution/adverse effects
3.
Cell Metab ; 36(6): 1320-1334.e9, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38838643

ABSTRACT

Circadian homeostasis in mammals is a key intrinsic mechanism for responding to the external environment. However, the interplay between circadian rhythms and the tumor microenvironment (TME) and its influence on metastasis are still unclear. Here, in patients with colorectal cancer (CRC), disturbances of circadian rhythm and the accumulation of monocytes and granulocytes were closely related to metastasis. Moreover, dysregulation of circadian rhythm promoted lung metastasis of CRC by inducing the accumulation of myeloid-derived suppressor cells (MDSCs) and dysfunctional CD8+ T cells in the lungs of mice. Also, gut microbiota and its derived metabolite taurocholic acid (TCA) contributed to lung metastasis of CRC by triggering the accumulation of MDSCs in mice. Mechanistically, TCA promoted glycolysis of MDSCs epigenetically by enhancing mono-methylation of H3K4 of target genes and inhibited CHIP-mediated ubiquitination of PDL1. Our study links the biological clock with MDSCs in the TME through gut microbiota/metabolites in controlling the metastatic spread of CRC, uncovering a systemic mechanism for cancer metastasis.


Subject(s)
Circadian Clocks , Gastrointestinal Microbiome , Myeloid-Derived Suppressor Cells , Animals , Mice , Myeloid-Derived Suppressor Cells/metabolism , Humans , Neoplasm Metastasis , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/microbiology , Mice, Inbred C57BL , Male , Tumor Microenvironment , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Lung Neoplasms/metabolism , Female , Mice, Inbred BALB C , Cell Line, Tumor
4.
Eur J Cancer ; 207: 114147, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38834016

ABSTRACT

BACKGROUND: We aim to compare the prognostic value of organ-specific dynamics with the sum of the longest diameter (SLD) dynamics in patients with metastatic colorectal cancer (mCRC). METHODS: All datasets are accessible in Project Data Sphere, an open-access platform. The tumor growth inhibition models developed based on organ-level SLD and SLD were used to estimate the organ-specific tumor growth rates (KGs) and SLD KG. The early tumor shrinkage (ETS) from baseline to the first measurement after treatment was also evaluated. The relationship between organ-specific dynamics, SLD dynamics, and survival outcomes (overall survival, OS; progression-free survival, PFS) was quantified using Kaplan-Meier analysis and Cox regression. RESULTS: This study included 3687 patients from 6 phase III mCRC trials. The liver emerged as the most frequent metastatic site (2901, 78.7 %), with variable KGs across different organs in individual patients (liver 0.0243 > lung 0.0202 > lymph node 0.0127 > other 0.0118 [week-1]). Notably, the dynamics for different organs did not equally contribute to predicting survival outcomes. In liver metastasis cases, liver KG proved to be a superior prognostic indicator for OS and surpasses the predictive performance of SLD, (C-index, liver KG 0.610 vs SLD KG 0.606). A similar result can be found for PFS. Moreover, liver ETS also outperforms SLD ETS in predicting survival. Cox regression analysis confirmed liver KG is the most significant variable in survival prediction. CONCLUSIONS: In mCRC patients with liver metastasis, liver dynamics is the primary prognostic indicator for both PFS and OS. In future drug development for mCRC, greater emphasis should be directed towards understanding the dynamics of liver metastasis development.

5.
Pest Manag Sci ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847149

ABSTRACT

BACKGROUND: Over the past two decades, bed bugs (Cimex spp.) have resurged as common urban pests around the world. The search for efficient and safe control measures has become a key interest among researchers, manufacturers, and pest control professionals. In this study, we evaluated and compared the efficacy of steam, diatomaceous earth (DE) dust, and a combination of both against tropical bed bugs (Cimex hemipterus (F.)) under laboratory and field conditions. RESULTS: In the laboratory study, the mortality of bed bugs after 2 days of exposure to DE dust was 100%. When bed bugs stayed on the surface of an object or in cracks, a brief steam treatment (1 s) caused 100% mortality. However, when bed bugs were hidden under a fabric cover, steam application for 10 s only caused 89 ± 6% mortality. Bed bugs that survived steam treatment exhibited reduced feeding activity. In a 14-week long study, there was no significant difference in the reduction rate of bed bugs between steam treatment and DE dust treatment. A 37-week long control study showed that steam and steam plus DE dust treatments eliminated 97-100% of the infestations. CONCLUSION: Applying steam and DE dust are effective strategies for eliminating natural tropical bed bug infestations. Continuous follow-up monitoring and treatment until no bed bugs are found are crucial in completely eliminating the infestation of tropical bed bugs. © 2024 Society of Chemical Industry.

6.
Front Nutr ; 11: 1356207, 2024.
Article in English | MEDLINE | ID: mdl-38863588

ABSTRACT

Background: Currently, the association between the consumption of polyunsaturated fatty acids (PUFAs) and the susceptibility to autoimmune rheumatic diseases (ARDs) remains conflict and lacks substantial evidence in various clinical studies. To address this issue, we employed Mendelian randomization (MR) to establish causal links between six types of PUFAs and their connection to the risk of ARDs. Methods: We retrieved summary-level data on six types of PUFAs, and five different types of ARDs from publicly accessible GWAS statistics. Causal relationships were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the reliability of our research findings, we used four complementary approaches and conducted multivariable MR analysis (MVMR). Additionally, we investigated reverse causality through a reverse MR analysis. Results: Our results indicate that a heightened genetic predisposition for elevated levels of EPA (ORIVW: 0.924, 95% CI: 0.666-1.283, P IVW = 0.025) was linked to a decreased susceptibility to psoriatic arthritis (PsA). Importantly, the genetically predicted higher levels of EPA remain significantly associated with an reduced risk of PsA, even after adjusting for multiple testing using the FDR method (P IVW-FDR-corrected = 0.033) and multivariable MR analysis (P MV-IVW < 0.05), indicating that EPA may be considered as the risk-protecting PUFAs for PsA. Additionally, high levels of LA showed a positive causal relationship with a higher risk of PsA (ORIVW: 1.248, 95% CI: 1.013-1.538, P IVW = 0.037). It is interesting to note, however, that the effects of these associations were weakened in our MVMR analyses, which incorporated adjustment for lipid profiles (P MV-IVW > 0.05) and multiple testing using the FDR method (P IVW-FDR-corrected = 0.062). Moreover, effects of total omega-3 PUFAs, DHA, EPA, and LA on PsA, were massively driven by SNP effects in the FADS gene region. Furthermore, no causal association was identified between the concentrations of other circulating PUFAs and the risk of other ARDs. Further analysis revealed no significant horizontal pleiotropy and heterogeneity or reverse causality. Conclusion: Our comprehensive MR analysis indicated that EPA is a key omega-3 PUFA that may protect against PsA but not other ARDs. The FADS2 gene appears to play a central role in mediating the effects of omega-3 PUFAs on PsA risk. These findings suggest that EPA supplementation may be a promising strategy for preventing PsA onset. Further well-powered epidemiological studies and clinical trials are warranted to explore the potential mechanisms underlying the protective effects of EPA in PsA.

7.
Sensors (Basel) ; 24(11)2024 May 21.
Article in English | MEDLINE | ID: mdl-38894067

ABSTRACT

This work develops a generalizable neural network, SENSORNET, for sensor feature learning across various applications. The primary challenge addressed is the poor portability of pretrained neural networks to new applications with limited sensor data. To solve this challenge, we design SensorNet, which integrates the flexibility of self-attention with multi-scale feature locality of convolution. Moreover, we invent patch-wise self-attention with stacked multi-heads to enrich the sensor feature representation. SensorNet is generalizable to pervasive applications with any number of sensor inputs, and is much smaller than the state-of-the-art self-attention and convolution hybrid baseline (0.83 M vs. 3.87 M parameters) with similar performance. The experimental results show that SensorNet is able to achieve state-of-the-art performance compared with the top five models on a competition activity recognition dataset (SHL'18). Moreover, pretrained SensorNet in a large inertial measurement unit (IMU) dataset can be fine-tuned to achieve the best accuracy on a much smaller IMU dataset (up to 5% improvement in WISDM) and to achieve the state-of-the-art performance on an EEG dataset (SLEEP-EDF-20), showing the strong generalizability of our approach.

8.
J Org Chem ; 89(12): 8601-8609, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38835151

ABSTRACT

This work reports the mild and efficient Ru-catalyzed trifluoroisopropylation of arenes using 2-bromo-1,1,1-trifluoropropane. Various bioactive molecules, such as purine and nucleoside derivatives, were well-suited for this transformation, affording the corresponding products in moderate-to-good yields. This method provides an efficient strategy for synthesizing trifluoroisopropyl molecules for drug discovery.

9.
Front Microbiol ; 15: 1356365, 2024.
Article in English | MEDLINE | ID: mdl-38835484

ABSTRACT

Objective: To examine the effects of an intervention with fructooligosaccharides (FOS), Saccharomyces boulardii, and their combination in a mouse model of colitis and to explore the mechanisms underlying these effects. Methods: The effects of FOS, S. boulardii, and their combination were evaluated in a DSS-induced mouse model of colitis. To this end, parameters such as body weight, the disease activity index (DAI), and colon length were examined in model mice. Subsequently, ELISA was employed to detect the serum levels of proinflammatory cytokines. Histopathological analysis was performed to estimate the progression of inflammation in the colon. Gas chromatography was used to determine the content of short-chain fatty acids (SCFAs) in the feces of model mice. Finally, 16S rRNA sequencing technology was used to analyze the gut microbiota composition. Results: FOS was slight effective in treating colitis and colitis-induced intestinal dysbiosis in mice. Meanwhile, S. boulardii could significantly reduced the DAI, inhibited the production of IL-1ß, and prevented colon shortening. Nevertheless, S. boulardii treatment alone failed to effectively regulate the gut microbiota. In contrast, the combined administration of FOS/S. boulardii resulted in better anti-inflammatory effects and enabled microbiota regulation. The FOS/S. boulardii combination (109 CFU/ml and 107 CFU/ml) significantly reduced the DAI, inhibited colitis, lowered IL-1ß and TNF-α production, and significantly improved the levels of butyric acid and isobutyric acid. However, FOS/S. boulardii 109 CFU/ml exerted stronger anti-inflammatory effects, inhibited IL-6 production and attenuated colon shortening. Meanwhile, FOS/S. boulardii 107 CFU/ml improved microbial regulation and alleviated the colitis-induced decrease in microbial diversity. The combination of FOS and S. boulardii significantly increased the abundance of Parabacteroides and decreased the abundance of Escherichia-Shigella. Additionally, it promoted the production of acetic acid and propionic acid. Conclusion: Compared with single administration, the combination can significantly increase the abundance of beneficial bacteria such as lactobacilli and Bifidobacteria and effectively regulate the gut microbiota composition. These results provide a scientific rationale for the prevention and treatment of colitis using a FOS/S. boulardii combination. They also offer a theoretical basis for the development of nutraceutical preparations containing FOS and S. boulardii.

10.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1749-1761, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38812187

ABSTRACT

Shenling Baizhu San(SLBZS) is a commonly used medicine for the treatment of ulcerative colitis(UC). This study aims to explore the mechanism of SLBZS in treating UC by using colonic metabolomics and network pharmacology. BALB/c mice were randomly divided into four groups: a blank group, a model group, an SLBZS group, and a sulfasalazine group. UPLC-Q-TOF-MS/MS technology was utilized to analyze the metabolic profiles of colonic tissue in mice, and differential metabolites and related metabolic pathways were screened. Based on the online database, active ingredients, action targets, and UC disease targets of SLBZS were screened. The protein-protein interaction(PPI) network of core targets of SLBZS in treating UC was constructed using STRING and Cytoscape 3.9.1. Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed using the DAVID database. A "metabolite-reaction-enzyme-gene" network was constructed to conduct a combined analysis of metabolomics and network pharmacology. SLBZS reversed the levels of 25 metabolites involved in various pathways such as D-glutamine and D-glutamate metabolism, caffeine metabolism, sphingolipid metabolism, arginine biosynthesis, lysine degradation, alanine, aspartate, and glutamate metabolism, glycerophospholipid metabolism, and pyrimidine metabolism in UC colonic tissue. 47 core targets of SLBZS in treating UC were involved in pathways including the MAPK signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, lipid and atherosclerosis, inflammatory bowel disease, and Th17 cell differentiation. Integrated analysis showed that glycerophospholipid metabolism and pyrimidine metabolism were key metabolic pathways in the treatment of UC with SLBZS. The results suggested that SLBZS improved colonic mucosal morphology by regulating colonic metabolites, down-regulated the expression of inflammation-related core target genes to reduce inflammation levels, and alleviated lipid metabolism disorders, thereby exerting a therapeutic effect on UC.


Subject(s)
Colitis, Ulcerative , Colon , Drugs, Chinese Herbal , Metabolomics , Mice, Inbred BALB C , Network Pharmacology , Animals , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/genetics , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Mice , Colon/metabolism , Colon/drug effects , Male , Humans , Protein Interaction Maps
12.
Front Neurol ; 15: 1367177, 2024.
Article in English | MEDLINE | ID: mdl-38751885

ABSTRACT

Introduction: Symptomatic intracranial hemorrhage (sICH) is a serious complication of acute ischemic stroke (AIS) after endovascular treatment (EVT). Limited data exist regarding predictors and clinical implications of sICH after EVT, underscoring the significance of identifying risk factors to enhance prevention strategies. Therefore, the main objective of this study was to evaluate the incidence of sICH and identify its predictors after EVT in patients with large infarct core-AIS in the pre-circulation stage. Methods: Using data from the EVT for the Pre-circulation Large Infarct Core-AIS Study, we enrolled patients who were treated with EVT from the Prospective Multicenter Cohort Study of Early Treatment in Acute Stroke (MAGIC) registry. Baseline demographics, medical history, vascular risk factors, blood pressure, stroke severity, radiographic features, and EVT details were collected. The patients were classified into three groups: without intracranial hemorrhage (ICH), with asymptomatic intracranial hemorrhage (aICH), and sICH, based upon the occurrence of sICH. The main outcomes were the occurrence of sICH according to the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to identify independent predictors of sICH after EVT. Results: The study recruited a total of 490 patients, of whom 13.3% (n = 65) developed sICH. Patients with sICH had less favorable outcomes than those without intracranial hemorrhage (ICH) and those with aICH (13.8% vs. 43.5% vs. 32.2%, respectively; p < 0.001). The overall mortality was 41.8% (n = 205) at 90 days post-EVT. The univariate analysis revealed significant differences among the three groups in terms of blood glucose levels at admission, probability of favorable outcomes, incidence of brain herniation, and 90-day mortality. The multifactorial logistic regression analysis revealed that the blood glucose level at admission [odds ratio (OR) 1.169, p < 0.001, confidence interval (CI) 1.076-1.269] was an independent predictor of sICH. A blood glucose level of 6.95 mmol/L at admission was the best predictor of sICH, with an area under the ROC curve (AUC) of 0.685 (95% CI: 0.616-0.754). Discussion: The study findings demonstrated that the probability of sICH after EVT was 13.3% in patients with pre-circulation large infarct core-AIS, and sICH increased the risk of an unfavorable prognosis. Higher blood glucose levels at admission were associated with sICH after EVT in patients with pre-circulation large infarct core AIS. These findings underscore the importance of early management strategies to mitigate this risk.

13.
Biomater Adv ; 161: 213899, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38772133

ABSTRACT

Large bone defects, particularly those exceeding the critical size, present a clinical challenge due to the limited regenerative capacity of bone tissue. Traditional treatments like autografts and allografts are constrained by donor availability, immune rejection, and mechanical performance. This study aimed to develop an effective solution by designing gradient gyroid scaffolds with titania (TiO2) surface modification for the repair of large segmental bone defects. The scaffolds were engineered to balance mechanical strength with the necessary internal space to promote new bone formation and nutrient exchange. A gradient design of the scaffold was optimized through Finite Element Analysis (FEA) and Computational Fluid Dynamics (CFD) simulations to enhance fluid flow and cell adhesion. In vivo studies in rabbits demonstrated that the G@TiO2 scaffold, featuring a gradient structure and TiO2 surface modification, exhibited superior healing capabilities compared to the homogeneous structure and TiO2 surface modification (H@TiO2) and gradient structure (G) scaffolds. At 12 weeks post-operation, in a bone defect representing nearly 30 % of the total length of the radius, the implantation of the G@TiO2 scaffold achieved a 27 % bone volume to tissue volume (BV/TV) ratio, demonstrating excellent osseointegration. The TiO2 surface modification provided photothermal antibacterial effects, enhancing the scaffold's biocompatibility and potential for infection prevention. These findings suggest that the gradient gyroid scaffold with TiO2 surface modification is a promising candidate for treating large segmental bone defects, offering a combination of mechanical strength, bioactivity, and infection resistance.


Subject(s)
Alloys , Surface Properties , Tissue Scaffolds , Titanium , Titanium/chemistry , Animals , Rabbits , Tissue Scaffolds/chemistry , Alloys/chemistry , Bone Regeneration/drug effects , Osseointegration/drug effects , Bone and Bones , Tissue Engineering/methods , Finite Element Analysis , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
14.
Nat Commun ; 15(1): 3859, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719821

ABSTRACT

Self-powered skin attachable and detachable electronics are under intense development to enable the internet of everything and everyone in new and useful ways. Existing on-demand separation strategies rely on complicated pretreatments and physical properties of the adherends, achieving detachable-on-demand in a facile, rapid, and universal way remains challenging. To overcome this challenge, an ingenious cellulose nanofiber-mediated manifold dynamic synergy strategy is developed to construct a supramolecular hydrogel with both reversible tough adhesion and easy photodetachment. The cellulose nanofiber-reinforced network and the coordination between Fe ions and polymer chains endow the dynamic reconfiguration of supramolecular networks and the adhesion behavior of the hydrogel. This strategy enables the simple and rapid fabrication of strong yet reversible hydrogels with tunable toughness ((Valuemax-Valuemin)/Valuemax of up to 86%), on-demand adhesion energy ((Valuemax-Valuemin)/Valuemax of up to 93%), and stable conductivity up to 12 mS cm-1. We further extend this strategy to fabricate different cellulose nanofiber/Fe3+-based hydrogels from various biomacromolecules and petroleum polymers, and shed light on exploration of fundamental dynamic supramolecular network reconfiguration. Simultaneously, we prepare an adhesive-detachable triboelectric nanogenerator as a human-machine interface for a self-powered wireless monitoring system based on this strategy, which can acquire the real-time, self-powered monitoring, and wireless whole-body movement signal, opening up possibilities for diversifying potential applications in electronic skins and intelligent devices.

15.
Int J Nanomedicine ; 19: 4181-4197, 2024.
Article in English | MEDLINE | ID: mdl-38766656

ABSTRACT

Purpose: The committed differentiation fate regulation has been a difficult problem in the fields of stem cell research, evidence showed that nanomaterials could promote the differentiation of stem cells into specific cell types. Layered double hydroxide (LDH) nanoparticles possess the regulation function of stem cell fate, while the underlying mechanism needs to be investigated. In this study, the process of embryonic stem cells (ESCs) differentiate to neural progenitor cells (NPCs) by magnesium aluminum LDH (MgAl-LDH) was investigated. Methods: MgAl-LDH with diameters of 30, 50, and 100 nm were synthesized and characterized, and their effects on the cytotoxicity and differentiation of NPCs were detected in vitro. Dot blot and MeRIP-qPCR were performed to detect the level of m6A RNA methylation in nanoparticles-treated cells. Results: Our work displayed that LDH nanoparticles of three different sizes were biocompatible with NPCs, and the addition of MgAl-LDH could significantly promote the process of ESCs differentiate to NPCs. 100 nm LDH has a stronger effect on promoting NPCs differentiation compared to 30 nm and 50 nm LDH. In addition, dot blot results indicated that the enhanced NPCs differentiation by MgAl-LDH was closely related to m6A RNA methylation process, and the major modification enzyme in LDH controlled NPCs differentiation may be the m6A RNA methyltransferase METTL3. The upregulated METTL3 by LDH increased the m6A level of Sox1 mRNA, enhancing its stability. Conclusion: This work reveals that MgAl-LDH nanoparticles can regulate the differentiation of ESCs into NPCs by increasing m6A RNA methylation modification of Sox1.


Subject(s)
Cell Differentiation , Nanoparticles , Neural Stem Cells , Cell Differentiation/drug effects , Animals , Neural Stem Cells/drug effects , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Mice , Nanoparticles/chemistry , Methylation/drug effects , Hydroxides/chemistry , Hydroxides/pharmacology , Methyltransferases/metabolism , Methyltransferases/genetics , Particle Size , Embryonic Stem Cells/drug effects , Embryonic Stem Cells/cytology , Adenosine/pharmacology , Adenosine/chemistry , Adenosine/analogs & derivatives , Aluminum Hydroxide/chemistry , Aluminum Hydroxide/pharmacology , Magnesium Hydroxide/chemistry , Magnesium Hydroxide/pharmacology
16.
Ann Med Surg (Lond) ; 86(5): 2963-2975, 2024 May.
Article in English | MEDLINE | ID: mdl-38694314

ABSTRACT

Background: Bone ring (BR) grafts have been introduced to reconstruct alveolar ridge defects with simultaneous implant placement, but their clinical effectiveness remains undetermined. The aim of the current systematic review was to critically appraise evidence from animal studies regarding the effectiveness of BR grafts in alveolar ridge reconstruction and their variations under different surgical protocols. Methods: Electronic retrieval of six databases (MEDLINE, Embase, Cochrane Library, ScienceDirect, Web of Science, and Scopus) and citation search until 11 October 2023, for animal studies on bone augmentation employing BR grafts. The outcome variables were total bone area (BA), bone volume (BV), bone-implant contact (BIC), and histology. The protocol was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered with PROSPERO (CRD42023453949). Results: Ten studies were included in the qualitative analysis according to the screening criteria. Two studies demonstrated favorable bone remodeling and osseointegration of the BR with both the implant and pristine bone. A comparative study between autogenous BRs and allogenic BRs reported a higher percentage of BA and BIC at 4 months of healing, but conflicting data were observed at 8 months. Another study indicated a significant advantage of autogenous BRs over bovine and biphasic ceramic BRs in terms of BA and BIC after 5 weeks. Three studies found that using collagen membranes did not significantly affect BA, BV, or BIC when used simultaneously with autogenous BRs during implant placement. Two studies evaluated one-stage and two-stage implant placement in conjunction with BR grafts, revealing similar levels of BA, BV, and BIC except for differences in total treatment time. Furthermore, one study found that the use of mucogingival junction incision and split-thickness flap significantly reduced the incidence of wound dehiscence compared with conventional incision and flap. Conclusions: Vertical bone augmentation surgery utilizing BR grafts with one-stage implant placement yielded histological and histomorphometric outcomes comparable to those achieved with two-stage implant placement or the additional application of collagen membrane.

17.
J Hazard Mater ; 474: 134667, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38820755

ABSTRACT

Smoldering combustion applications in energy and environmental fields have attracted increasing research attention in recent years. Smoldering has demonstrated considerable green advantages, such as having a low carbon footprint and being sustainable, for remediation of organic-contaminated soil and disposal of high-moisture, low-calorific value, slurry-type organic waste due to its self-sustaining reaction characteristic. This review aims to analyze and summarize studies on smoldering applications to refine the critical components of applied smoldering systems, key reaction characteristics, and corresponding influencing conditions that affect their effectiveness. Furthermore, the common characteristics and influencing factors of different smoldering application scenarios are compared to provide a comprehensive reference for commercial applications. Thus, this paper specifically includes an overview of the impact of inert porous media, combustible material, and oxidants in applied smoldering systems; a review of the research status of the three key reaction characteristics, including peak temperature, smoldering front propagation velocity, and self-sustainability; a summary of typical influencing factors, disposal material characteristics, and control conditions in the two mainstream application directions, which are remediation of contaminated soil and disposal of organic waste; and a comparative analysis of the common modes of applied smoldering beyond the lab scale. As a technically effective and energy-efficient emerging technology, the prospects of smoldering as a robust treatment process in environmental pollution cleanup are presented.

18.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124476, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-38776670

ABSTRACT

Malononitrile is a very important chemical material and has wide application fields in production of medicines, pesticides, and extraction of gold. However, its nonnegligible hypertoxicity inspired researchers to develop more efficient analysis techniques to sensitively and selectively detect malononitrile. Nopinone derivatives initiated by our research group have been developed as a class of organic fluorescent chemosensors for identifying multiple analytes in recent years. Different heterocyclic compounds based on nopinone were designed and synthesized to be applied in the fields of environmental analysis, food detection and bioimaging. Nevertheless, the comparison research on the optical properties of fluorescent compounds containing the nopinyl matrix with other structural analogs including alkyl, cyclohexyl and phenyl groups was deficient. Herein, four 4-(1H-imidazol-2-yl)benzaldehyde-based ratiometric fluorescent chemosensors based on o-dimethyl cyclohexyl, phenyl and nopinyl units for recognizing malononitrile were designed and developed, and their differences in the optical properties and detection performances were investigated by using spectral analysis combined with theoretical calculations. Moreover, the nopinone-based 4-(1H-imidazol-2-yl)benzaldehyde fluorescent chemosensor NMZQ was successfully applied in the dual channel fluorescence bioimaging of malononitrile in living HeLa cells and zebrafish, which attributed to its outstanding spectral property and detection performance.

19.
Plant Commun ; : 100973, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38751120

ABSTRACT

Soluble sugar and organic acids are key determinants of fruit organoleptic quality and directly affect the commodity value and economic returns of fruit crops. We performed whole-genome sequencing of the apple varieties Gala and Xiahongrou, along with their F1 hybrids, to construct a high-density bin map. Our quantitative genetic analysis pinpointed 53 quantitative trait loci (QTLs) related to 11 sugar and acid traits. We identified a candidate gene, MdNADP-ME, responsible for malate degradation, in a stable QTL on linkage group 15. Sequence analysis revealed an A/C SNP in the promoter region (MEp-799) that influences binding of the MdMYB2 transcription factor, thereby affecting MdNADP-ME expression. In our study of various apple genotypes, this SNP has been demonstrated to be linked to malate and fructose levels. We also developed a dCAPS marker associated with fruit fructose content. These results substantiate the role of MdNADP-ME in maintaining the equilibrium between sugar and acid contents in apple fruits.

20.
Mol Neurobiol ; 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38581538

ABSTRACT

Spinal cord injury (SCI) constitutes a significant clinical challenge, and there is extensive research focused on identifying molecular activities that can facilitate the repair of spinal cord injuries. Mammalian sterile 20-like kinase 2 (MST2), a core component of the Hippo signaling pathway, plays a key role in apoptosis and cell growth. However, its role in neurite outgrowth after spinal cord injury remains unknown. Through comprehensive in vitro and in vivo experiments, we demonstrated that MST2, predominantly expressed in neurons, actively participated in the natural development of the CNS. Post-SCI, MST2 expression significantly increased, indicating its activation and potential role in the early stages of neural recovery. Detailed analyses showed that MST2 knockdown impaired neurite outgrowth and motor function recovery, whereas MST2 overexpression led to the opposite effects, underscoring MST2's neuroprotective role in enhancing neural repair. Further, we elucidated the mechanism underlying MST2's action, revealing its interaction with AKT and positive regulation of AKT activity, a well-established promoter of neurite outgrowth. Notably, MST2's promotion of neurite outgrowth and motor functional recovery was diminished by AKT inhibitors, highlighting the dependency of MST2's neuroprotective effects on AKT signaling. In conclusion, our findings affirmed MST2's pivotal role in fostering neuronal neurite outgrowth and facilitating functional recovery after SCI, mediated through its positive modulation of AKT activity. In conclusion, our findings confirmed MST2's crucial role in neural protection, promoting neurite outgrowth and functional recovery after SCI through positive AKT activity modulation. These results position MST2 as a potential therapeutic target for SCI, offering new insights into strategies for enhancing neuroregeneration and functional restoration.

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