Salivary nitrate prevents osteoporosis via regulating bone marrow mesenchymal stem cells proliferation and differentiation.

Background: Nitrate, a key component of saliva, has been shown widely physiological functions in the human body. But its function on bone metabolism remains unclear. The aim of this study was to investigate the function and mechanism of saliva nitrate on osteoporosis and the function of bone marrow mesenchymal stem cells (BMSCs). Methods: Saliva nitrate removal or supplemental interventions were performed for 1 month in ovariectomized (OVX) osteopenia mice. The nitrate levels in saliva and serum were detected. The bone formation and bone microarchitecture in the OVX mouse model were investigated by quantitative Micro--computed tomography imaging, histological staining and serum bone biomarker analysis. The effects of nitrate on the functional homeostasis of BMSCs in OVX mice were explored by Ki67 immunofluorescence staining, Ki67 flow staining, alizarin red staining, qPCR and western blotting. Finally, downstream signaling pathways were screened by proteomics and verified by western blotting. Results: The results showed that nitrate deficiency exacerbated osteoporosis, while nitrate administration prevent osteoporosis in OVX mice. Nitrate increased the expression of PINP, a biomarker of bone formation, in OVX mice. Besides, nitrate enhanced the proliferative capacity and osteogenic function of BMSCs in OVX mice in vitro and in vivo. In addition, nitrate upregulated the expression levels of osteogenesis-related genes ALP, Run2 and OPN of BMSCs. EGFR and mTOR signaling were screened as the key downstream of nitrate, and phosphorylated protein levels of its subfamily members AKT, ERK and S6K were significantly upregulated by nitrate. Conclusion: The present results showed saliva nitrate preventively protects against osteoporosis through enhances the proliferation and osteogenic differentiation potential of BMSCs. The effects of nitrate on bone homeostasis are closely related to the EGFR/AKT/ERK and mTOR/S6K signaling axes. The translational potential of this article: Our study provides experimental evidence for the use of saliva nitrate as an effective candidate for the prevention of osteoporosis and maintenance of bone homeostasis.

Advances in morphology-controlled alumina and its supported Pd catalysts: synthesis and applications.

Alumina materials, as one of the cornerstones of the modern chemical industry, possess physical and chemical properties that include excellent mechanical strength and structure stability, which also make them highly suitable as catalyst supports. Alumina-supported Pd-based catalysts with the advantages of exceptional catalytic performance, flexible regulated surface metal/acid sites, and good regeneration ability have been widely used in many traditional chemical industry fields and have also shown great application prospects in emerging fields. This review aims to provide an overview of the recent advances in alumina and its supported Pd-based catalysts. Specifically, the synthesis strategies, morphology transformation mechanisms, and structural properties of alumina with various morphologies are comprehensively summarized and discussed in-depth. Then, the preparation approaches of Pd/Al2O3 catalysts (impregnation, precipitation, and other emerging methods), as well as the metal-support interactions (MSIs), are revisited. Moreover, Some promising applications have been chosen as representative reactions in fine chemicals, environmental purification, and sustainable development fields to highlight the universal functionality of the alumina-supported Pd-based catalysts. The role of the Pd species, alumina support, promoters, and metal-support interactions in the enhancement of catalytic performance are also discussed. Finally, some challenges and upcoming opportunities in the academic and industrial application of the alumina and its supported Pd-based are presented and put forward.

CD34+ synovial fibroblasts exhibit high osteogenic potential in synovial chondromatosis.

Synovial chondromatosis (SC) is a disorder of the synovium characterized by the formation of osteochondral nodules within the synovium. This study aimed to identify the abnormally differentiated progenitor cells and possible pathogenic signaling pathways. Loose bodies and synovium were obtained from patients with SC during knee arthroplasty. Single-cell RNA sequencing was used to identify cell subsets and their gene signatures in SC synovium. Cells derived from osteoarthritis (OA) synovium were used as controls. Multi-differentiation and colony-forming assays were used to identify progenitor cells. The roles of transcription factors and signaling pathways were investigated through computational analysis and experimental verification. We identified an increased proportion of CD34+ sublining fibroblasts in SC synovium. CD34+CD31- cells and CD34-CD31- cells were sorted from SC synovium. Compared with CD34- cells, CD34+ cells had larger alkaline phosphatase (ALP)-stained area and calcified area after osteogenic induction. In addition, CD34+ cells exhibited a stronger tube formation ability than CD34- cells. Our bioinformatic analysis suggested the expression of TWIST1, a negative regulator of osteogenesis, in CD34- sublining fibroblasts and was regulated by the TGF-ß signaling pathway. The experiment showed that CD34+ cells acquired the TWIST1 expression during culture and the combination of TGF-ß1 and harmine, an inhibitor of Twist1, could further stimulate the osteogenesis of CD34+ cells. Overall, CD34+ synovial fibroblasts in SC synovium have multiple differentiation potentials, especially osteogenic differentiation potential, and might be responsible for the pathogenesis of SC.

The oviposition preference and offspring performance of Aethina tumida (Coleoptera: Nitidulidae).

Given the rapid spread and potential harm caused by the small hive beetle, Aethina tumida (Coleoptera: Nitidulidae) in China, it has become imperative to comprehend the developmental biology of this invasive species. Currently, there is limited knowledge regarding the impact of A. tumida female oviposition site preference on larval growth and development. To examine this, we investigated the ovipositional preference of adult female A. tumida on bee pupae, beebread, banana, and honey through a free choice test. Furthermore, we assessed the impact of these food resources on offspring performance, which included larval development time, survival, wandering larvae weight, emerged adult body mass, reproduction, and juvenile hormone titer. Our results showed that A. tumida females exhibited a strong preference for ovipositing on bee pupae compared to other diets, while showing reluctance toward honey. Moreover, A. tumida larvae that were fed on bee pupae displayed accelerated growth compared to those fed on other diets. Furthermore, A. tumida fed on bee pupae exhibited higher weights for wandering larvae, and emerged adult, increased pupation rates, enhanced fecundity and fertility, as well as a larger number of unilateral ovarioles during the larval stage when compared to those fed on other diets. Overall, the results indicate that the oviposition preferences of A. tumida females are adaptive, as their choices can enhance the fitness of their offspring. This finding aligns broadly with the hypothesis of oviposition preference and larval performance. This study can provide a foundation for the development of attractants aimed at promoting the oviposition of the A. tumida adults.

Quality of asynchronous webchats vs in-person consultations for postpartum depression in China: a cross-sectional, mixed methods study using standardized patients.

Background: Prompt professional care for postpartum depression (PPD) is difficult to obtain in China. Though online consultations improve accessibility and reduce stigma, the quality of services compared to in-person consultations is unclear. Methods: Five trained, undisclosed "standardized patients" (SPs) made "asynchronous webchats" visits and in-person visits with psychiatrists. Visits were made to 85 psychiatrists who were based in 69 hospitals in ten provincial capital cities. The care between online and in-person consultations with the same psychiatrist was compared, including diagnosis, guideline adherence, and patient-centeredness. False discovery rate (FDR) was used to adjust p values. Third visits using asynchronous webchats were made to psychiatrists who offered discrepant diagnoses. Thematic content analysis was used for the discrepancies. Findings: The proportion of diagnostic accuracy was lower for online than in-person visits (76.5% [65/85] vs 91.8% [78/85]; pFDR = 0.0066), as were the proportions of completing questions involving clinical history (16.6% vs 42.7%; pFDR < 0.0001), and management decisions (16.2% vs 27.5%; pFDR < 0.0001) consistent with recommended guidelines. Patient-centeredness was lower online than in-person (pFDR < 0.0001). Fifteen of 16 psychiatrists completed third visits, most of them considered lack of nonverbal information online as a key barrier. Interpretation: Online consultations using asynchronous webchats were inferior to in-person consultations, with respect to diagnostic accuracy, adherence to recommended clinical guidelines, and patient-centeredness. To fully realise the potential benefits of online consultations and to prevent safety issues, there is an urgent need for major improvement in the quality and oversight of these consultations. Funding: China Medical Board, National Natural Science Foundation of China, and Swiss Agency for Development and Cooperation Global Cooperation Department.

Construction of GPC3-modified Lipopolymer SiRNA Delivery System.

BACKGROUND: Gene therapy has been widely concerned because of its unique therapeutic mechanism. However, due to the lack of safe and effective carries, it has not been widely used in clinical practice. Glypican 3 (GPC3) is a highly specific proteoglycan for hepatocellular carcinoma and is a potential diagnostic and therapeutic target for hepatocellular carcinoma. Herein, to monitor the effect of gene therapy and enhance the transfection efficiency of gene carriers, GPC3-modified lipid polyethyleneimine-modified superparamagnetic nanoparticle (GLPS), a type of visualized carrier for siRNA (small-interfering RNA) targeting the liver, was prepared. METHODS: We performed in vitro gene silencing, cytotoxicity, and agarose gel electrophoresis to identify the optimal GLPS formulation. In vitro MRI and Prussian blue staining verified the liver-targeting function of GLPS. We also analyzed the biocompatibility of GLPS by co-culturing with rabbit red blood cells. Morphological changes were evaluated using HE staining. RESULTS: The GLPS optimal formulation consisted of LPS and siRNA at a mass ratio of 25:1 and LPS and DSPE-PEG-GPC3 at a molar ratio of 2:3. GLPS exhibited evident liver-targeting function. In vitro, we did not observe morphological changes in red blood cells or hemolysis after co-culture. In vivo, routine blood analysis revealed no abnormalities after GLPS injection. Moreover, the tissue morphology of the kidney, spleen, and liver was normal without injury or inflammation. CONCLUSION: GLPS could potentially serve as an effective carrier for liver-targeted MRI monitoring and siRNA delivery.

TIM3 activates the ERK1/2 pathway to promote invasion and migration of thyroid tumors.

BACKGROUND: This study aims to study the possible action mechanism of T-cell immunoglobulin and mucin domain 3 (TIM3) on the migratory and invasive abilities of thyroid carcinoma (TC) cells. METHODS: GSE104005 and GSE138198 datasets were downloaded from the GEO database for identifying differentially expressed genes (DEGs). Functional enrichment analysis and protein-protein interaction (PPI) analysis were performed on the common DEGs in GSE104005 and GSE138198 datasets. Subsequently, in order to understand the effect of a common DEG (TIM3) on TC cells, we performed in vitro experiments using FRO cells. The migratory and invasive abilities of FRO cells were detected by wound scratch assay and Transwell assay. Proteins expression levels of the phosphorylated (p)-extracellular signal-regulated kinase (ERK)1/2, matrix metalloproteinase-2 (MMP-2) and MMP-9 were determined via Western blotting after ERK1/2 inhibition in TIM3-NC group and TIM3-mimic group. RESULTS: 316 common DEGs were identified in GSE104005 and GSE138198 datasets. These DEGs were involved in the biological process of ERK1 and ERK2 cascade. TIM3 was significantly up-regulated in TC. In vitro cell experiments showed that TIM3 could promote migration and invasion of TC cells. Moreover, TIM3 may affect the migration, invasive abilities of TC cells by activating the ERK1/2 pathway. CONCLUSION: The above results indicate that TIM3 may affect the migratory and invasive of TC cells by activating the ERK1/2 pathway.

Years of life lost due to insufficient sleep and associated economic burden in China from 2010-18.

Background: Research on the health and economic costs due to insufficient sleep remains scant in developing countries. In this study we aimed to estimate the years of life lost (YLLs) due to short sleep and quantify its economic burden in China. Methods: We estimated both individual and aggregate YLLs due to short sleep (ie, ≤6 hours) among Chinese adults aged 20 years or older by sex and five-year age groups in 2010, 2014, and 2018. YLL estimates were derived from 1) the prevalence of short sleep using three survey waves of the China Family Panel Studies, 2) relative mortality risks from meta-analyses, and 3) life tables in China. YLL was the difference between the estimated life expectancy of an individual in the short sleep category vs in the recommended sleep category. We estimated the economic cost using the human capital approach. Results: The sample sizes of the three survey waves were 31 393, 31 207, and 28 618. Younger age groups and men had more YLLs due to short sleep compared to their counterparts. For individuals aged 20-24, men had an average YLL of nearly 0.95, in contrast to the approximate 0.75 in women across the observed years of 2010, 2014, and 2018. The trend in individual YLLs remained consistent over these years. In aggregate, China experienced a rise from 66.75 million YLLs in 2010 to 95.29 million YLLs in 2014, and to 115.05 million YLLs in 2018. Compared to 2010 (USD 191.83 billion), the associated economic cost in 2014 increased to USD 422.24 billion, and the cost in 2018 more than tripled (USD 628.15 billion). The percentage of cost to Chinese gross domestic product in corresponding years was 3.23, 4.09, and 4.62%. Conclusions: Insufficient sleep is associated with substantial YLLs in China, potentially impacting the population's overall life expectancy. The escalating economic toll attributed to short sleep underscores the urgent need for public health interventions to improve sleep health at the population level.

Nirmatrelvir and ritonavir combination against COVID-19 caused by omicron BA.2.2 in the elderly: A single-center large observational study.

BACKGROUND: Since coronavirus 2019 (COVID-19) swept the world, a variety of novel therapeutic and prevention strategies have been developed, among which nirmatrelvir-ritonavir is highly recommended. We intended to assess the effectiveness and safety of nirmatrelvir-ritonavir in the elderly mild-to-moderate COVID-19 population caused by the omicron BA.2.2 variant in real-world settings. METHODS: An observational study was conducted retrospectively to review the outcomes of mild-to-moderate COVID-19 patients admitted between April 26 and June 30, 2022. Patients' baseline characteristics were collected and assessed. Participants in the intervention group were administered nirmatrelvir-ritonavir in addition to standard care, whereas those in the control group only received standard care. The primary outcome was the duration between the initial positive reverse-transcription polymerase chain reaction (RT-PCR) test and the subsequent conversion to a negative result. RESULTS: The analysis included 324 patients who were administered nirmatrelvir-ritonavir and an equal number of control patients. The patient characteristics in both groups were evenly matched. The average duration from the initial positive RT-PCR to negative conversion was similar in both groups (16.2 ± 5.0 vs. 16.1 ± 6.3 days, p = .83). Control patients exhibited slower conversion in comparison to patients who received nirmatrelvir-ritonavir treatment within 10 days of symptom onset. CONCLUSIONS: These findings suggest that administering nirmatrelvir-ritonavir within 10 days of symptom onset could potentially reduce the time it takes for SARS-CoV-2-infected patients to negative RT-PCR results, thereby expanding the current usage guidelines for nirmatrelvir-ritonavir.

Convoluted micellar morphological transitions driven by tailorable mesogenic ordering effect from discotic mesogen-containing block copolymer.

Solution-state self-assemblies of block copolymers to form nanostructures are tremendously attractive for their tailorable morphologies and functionalities. While incorporating moieties with strong ordering effects may introduce highly orientational control over the molecular packing and dictate assembly behaviors, subtle and delicate driving forces can yield slower kinetics to reveal manifold metastable morphologies. Herein, we report the unusually convoluted self-assembly behaviors of a liquid crystalline block copolymer bearing triphenylene discotic mesogens. They undergo unusual multiple morphological transitions spontaneously, driven by their intrinsic subtle liquid crystalline ordering effect. Meanwhile, liquid crystalline orderedness can also be built very quickly by doping the mesogens with small-molecule dopants, and the morphological transitions are dramatically accelerated and various exotic micelles are produced. Surprisingly, with high doping levels, the self-assembly mechanism of this block copolymer is completely changed from intramolecular chain shuffling and rearrangement to nucleation-growth mode, based on which self-seeding experiments can be conducted to produce highly uniform fibrils.

Comparison of the therapeutic effects of mesenchymal stem cells derived from human dental pulp (DP), adipose tissue (AD), placental amniotic membrane (PM), and umbilical cord (UC) on postmenopausal osteoporosis.

Background: Osteoporosis is a systemic bone disease characterized by bone loss and microstructural degeneration. Recent preclinical and clinical trials have further demonstrated that the transplantation of mesenchymal stem cells (MSCs) derived from human adipose tissue (AD), dental pulp (DP), placental amniotic membrane (AM), and umbilical cord (UC) tissues can serve as an effective form of cell therapy for osteoporosis. However, MSC-mediated osteoimmunology and the ability of these cells to regulate osteoclast-osteoblast differentiation varies markedly among different types of MSCs. Methods: In this study, we investigated whether transplanted allogeneic MSCs derived from AD, DP, AM, and UC tissues were able to prevent osteoporosis in an ovariectomy (OVX)-induced mouse model of osteoporosis. The homing and immunomodulatory ability of these cells as well as their effects on osteoblastogenesis and the maintenance of bone formation were compared for four types of MSCs to determine the ideal source of MSCs for the cell therapy-based treatment of OVX-induced osteoporosis. The bone formation and bone resorption ability of these four types of MSCs were analyzed using micro-computed tomography analyses and histological staining. In addition, cytokine array-based analyses of serological markers and bioluminescence imaging assays were employed to evaluate cell survival and homing efficiency. Immune regulation was determined by flow cytometer assay to reflect the mechanisms of osteoporosis treatment. Conclusion: These analyses demonstrated that MSCs isolated from different tissues have the capacity to treat osteoporosis when transplanted in vivo. Importantly, DP-MSCs infusion was able to maintain trabecular bone mass more efficiently with corresponding improvements in trabecular bone volume, mineral density, number, and separation. Among the tested MSC types, DP-MSCs were also found to exhibit greater immunoregulatory capabilities, regulating the Th17/Treg and M1/M2 ratios. These data thus suggest that DP-MSCs may represent an effective tool for the treatment of osteoporosis.

Stability mechanism of Monascus pigment-soy protein isolate-maltodextrin complex.

BACKGROUND: Monascus pigment (MP) is a natural food coloring with vital physiological functions but prone to degradation and color fading under light conditions. RESULTS: This study investigated the effect of complex formation of soybean protein isolate (SPI), maltodextrin (MD), and MP on the photostability of MP. Light stability was assessed through retention rate and color difference. Fluorescence spectroscopy (FS), circular dichroism (CD), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) explored MP, SPI, and MD interactions, clarifying the MP-SPI-MD complex mechanism on the light stability of MP. Microstructure and differential scanning calorimetry (DSC) analyzed the morphology and thermal properties. The retention rate of MP increased to approximately 80%, and minimal color difference was observed when adding SPI and MD simultaneously. FS revealed hydrophobic interaction between MP and SPI. FTIR analysis showed intensity changes and peak shifts in amide I band and amide II band, which proved the hydrophobic interaction. CD showed a decrease in α-helix content and an increase in ß-sheet content after complex formation, indicating strengthened hydrogen bonding interactions. Scanning electron microscopy (SEM) analysis demonstrated that MP was attached to the surface and interior of complexes. XRD showed MP as crystalline, while SPI and MD were amorphous, complexes exhibited weakened or absent peaks, suggesting MP encapsulation. The results of DSC were consistent with XRD. CONCLUSION: SPI and MD enveloped MP through hydrogen bonding and hydrophobic interaction, ultimately enhancing its light stability and providing insights for pigment-protein-polysaccharide interactions and improving pigment stability in the food industry. © 2024 Society of Chemical Industry.

Trajectory of Caregiver Burden and Associated Factors in Family Caregivers of Individuals with Colorectal Cancer: A Longitudinal, Observational Multicenter Study.

Purpose: To (1) investigate the changes in 5 domains (lack of family support, impact on finance, impact on daily schedule, impact on health, and self-esteem) of family caregiver (FC) burden and overall burden for first diagnosed colorectal cancer; (2) exploring changes in FC burden for colorectal cancer patients over time and analyze the trajectory and sub-trajectories of FC burden; and (3) identify the FC-related and patient-related factors most associated with the overall FC burden and each of its sub-trajectories. Patients and methods: This study is a descriptive longitudinal study. A convenience sampling method was used to recruit patients with colorectal cancer and their primary FCs from seven hospitals. Results: A total of 185 pairs of first diagnosed colorectal cancer patient and their FC were investigated for 4 times. The results reveal the overall burden and 5 domains of burden showed a trend of increasing first and then decreasing, and the burden was the heaviest at the time in the middle of chemotherapy. In the course of time, the aspect that caused the greatest amount of burden on average transitioned from the "effect on daily schedule" (range= 3.3 and 3.9) to the "effect on finances" (range= 3.1 to 3.4). Conclusion: Almost 88% of FCs have a either a moderate or a high level of burden. The quality of life of patients and the self-efficacy, social support and care ability of FCs have a great impact on the overall FC burden and each sub-trajectory.

1H NMR guided isolation of 3-arylisoquinoline alkaloids from Hypecoum erectum L. and their anti-inflammation activity.

Nine 3-arylisoquinoline alkaloids including five undescribed ones, hypectumines A-E (1-5), were isolated from the whole herb of Hypecoum erectum L. with the guidance of 1H-NMR. Their structures were established by a combination of 1D, 2D NMR, and HRESIMS spectrometry. Among them, hypectumines A and B possessed rare urea moieties while hypectumines C and D were characterized by 3-(methylamino)propanoic acid scaffolds. Biological assay demonstrated that alkaloids hypectumine B and 2,3-dimethoxy-N-formylcorydamine had anti-inflammatory effects by inhibiting NO production on LPS-induced RAW264.7 cells with IC50 values of 24.4 and 44.2 µM, respectively. Furthermore, hypectumine B could reduce the expression of pro-inflammatory cytokines TNF-α and IL-6, suggesting it might be a potential candidate for treating inflammatory disease.

Toxicodynamic of combined mycotoxins: MicroRNAs and acute-phase proteins as diagnostic biomarkers.

Mycotoxins, ubiquitous contaminants in food, present a global threat to human health and well-being. Mitigation efforts, such as the implementation of sound agricultural practices, thorough food processing, and the advancement of mycotoxin control technologies, have been instrumental in reducing mycotoxin exposure and associated toxicity. To comprehensively assess mycotoxins and their toxicodynamic implications, the deployment of effective and predictive strategies is imperative. Understanding the manner of action, transformation, and cumulative toxic effects of mycotoxins, moreover, their interactions with food matrices can be gleaned through gene expression and transcriptome analyses at cellular and molecular levels. MicroRNAs (miRNAs) govern the expression of target genes and enzymes that play pivotal roles in physiological, pathological, and toxicological responses, whereas acute phase proteins (APPs) exert regulatory control over the metabolism of therapeutic agents, both endogenously and posttranscriptionally. Consequently, this review aims to consolidate current knowledge concerning the regulatory role of miRNAs in the initiation of toxicological pathways by mycotoxins and explores the potential of APPs as biomarkers following mycotoxin exposure. The findings of this research highlight the potential utility of miRNAs and APPs as indicators for the detection and management of mycotoxins in food through biological processes. These markers offer promising avenues for enhancing the safety and quality of food products.

An exosomal strategy for targeting cancer-associated fibroblasts mediated tumors desmoplastic microenvironments.

Tumors desmoplastic microenvironments are characterized by abundant stromal cells and extracellular matrix (ECM) deposition. Cancer-associated fibroblasts (CAFs), as the most abundant of all stromal cells, play significant role in mediating microenvironments, which not only remodel ECM to establish unique pathological barriers to hinder drug delivery in desmoplastic tumors, but also talk with immune cells and cancer cells to promote immunosuppression and cancer stem cells-mediated drug resistance. Thus, CAFs mediated desmoplastic microenvironments will be emerging as promising strategy to treat desmoplastic tumors. However, due to the complexity of microenvironments and the heterogeneity of CAFs in such tumors, an effective deliver system should be fully considered when designing the strategy of targeting CAFs mediated microenvironments. Engineered exosomes own powerful intercellular communication, cargoes delivery, penetration and targeted property of desired sites, which endow them with powerful theranostic potential in desmoplastic tumors. Here, we illustrate the significance of CAFs in tumors desmoplastic microenvironments and the theranostic potential of engineered exosomes targeting CAFs mediated desmoplastic microenvironments in next generation personalized nano-drugs development.

CBC-1 as a Cynanbungeigenin C derivative inhibits the growth of colorectal cancer through targeting Hedgehog pathway component GLI 1.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers that results in death in worldwide. The Hedgehog (HH) signalling pathway regulates the initiation and progression of CRC. Inhibiting the HH pathway has been presented as a potential treatment strategy in recent years. Cynanbungeigenin C (CBC) is a new type of C21 steroid that has been previously reported for the treatment of medulloblastoma. However, its further investigation was limited by its poor water solubility. In this study, six new CBC derivatives were synthesized through the structural modification of CBC, and four of them showed better water solubility than CBC. Moreover, their antiproliferative activities on CRC were evaluated. It was found that CBC-1 presented the best inhibitory effect on three types of CRC cell lines, and this effect was superior to that of CBC. Mechanistically, CBC-1 inhibited the proliferation of CRC cells through regulation of mRNA and proteins of the HH pathway according to qRT-PCR and Western blotting analysis. Furthermore, Cellular Thermal Shift Assay results indicated that CBC-1 regulated this signalling pathway by targeting glioma­associated oncogene (GLI 1).In addition, cell apoptosis was induced increasingly by transfection with GLI 1 siRNA or treatment with CBC-1 to downregulate GLI 1. Last, the in vivo results demonstrated that CBC-1 significantly reduced tumour size and downregulated GLI 1 in CRC. Therefore, this study suggests that CBC-1, a new GLI 1 inhibitor derived from natural products, may be developed as a potential antitumour candidate for CRC treatment.

Dynamics of N6-methyladenosine modification during Alzheimer's disease development.

N6-methyladenosine (m6A) modification is a common RNA modification in the central nervous system and has been linked to various neurological disorders, including Alzheimer's disease (AD). However, the dynamic of mRNA m6A modification and m6A enzymes during the development of AD are not well understood. Therefore, this study examined the expression profiles of m6A and its enzymes in the development of AD. The results showed that changes in the expression levels of m6A regulatory factors occur in the early stages of AD, indicating a potential role for m6A modification in the onset of the disease. Additionally, the analysis of mRNA m6A expression profiles using m6A-seq revealed significant differences in m6A modification between AD and control brains. The genes with differential methylation were found to be enriched in GO and KEGG terms related to processes such as inflammation response, immune system processes. And the differently expressed genes (DEGs) are negatively lryassociated with genes involved in microglia hemostasis, but positively associated with genes related to "disease-associated microglia" (DAM) associated genes. These findings suggest that dysregulation of mRNA m6A modification may contribute to the development of AD by affecting the function and gene expression of microglia.