scRank infers drug-responsive cell types from untreated scRNA-seq data using a target-perturbed gene regulatory network.

Cells respond divergently to drugs due to the heterogeneity among cell populations. Thus, it is crucial to identify drug-responsive cell populations in order to accurately elucidate the mechanism of drug action, which is still a great challenge. Here, we address this problem with scRank, which employs a target-perturbed gene regulatory network to rank drug-responsive cell populations via in silico drug perturbations using untreated single-cell transcriptomic data. We benchmark scRank on simulated and real datasets, which shows the superior performance of scRank over existing methods. When applied to medulloblastoma and major depressive disorder datasets, scRank identifies drug-responsive cell types that are consistent with the literature. Moreover, scRank accurately uncovers the macrophage subpopulation responsive to tanshinone IIA and its potential targets in myocardial infarction, with experimental validation. In conclusion, scRank enables the inference of drug-responsive cell types using untreated single-cell data, thus providing insights into the cellular-level impacts of therapeutic interventions.

Influence of a mesial cantilever on stress, strain, and axial force in fixed partial dentures with a distally tilted implant in the atrophic posterior maxilla.

PURPOSE: This study aimed to investigate whether the presence of a mesial cantilever influences the biomechanical behavior and screw loosening in fixed partial dentures (FPDs) with a distally tilted implant in the atrophic posterior maxilla and where to best place the distal implant. METHODS: Two configurations of implant-supported four-unit FPDs were modelled using finite element analysis. Five interabutment distances were considered. The stress and strain distributions in the implants, abutments, and prosthetic screws were verified under occlusal loading. The development of the axial force on the abutments and screws was also examined. Two-sample t-tests were used to identify differences (P < 0.05). RESULTS: The von Mises stress distributions of the components in the two configurations were similar, as were the maximum plastic strains of the distal prosthetic screws, distal implants, and 30° abutments. The difference in the maximum plastic strains of the straight abutments was statistically significant. The preload of the 30° abutment screws was significantly reduced after the initial loading. In the absence of a mesial cantilever, the axial force on the straight abutments increased. However, when a mesial cantilever was used, the preload of the straight abutments was maintained, and the axial force on the prosthetic screws fluctuated less. The axial force fluctuation of the abutments gradually decreased as the interabutment distance increased. CONCLUSIONS: Mesial cantilever usage had minimal effect on stress or strain distribution in FPD implants, abutments, or prostheses. However, it helped resist screw loosening. The distal screw access hole was preferably positioned close to the prosthetic end.

Cycasin derivative: a potential embryotoxic component of Atractylodes macrocephala rhizome for limb malformation.

Objective: The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), called Atractylodes macrocephala rhizome (AMR) and known by its traditional name Bai Zhu, is a prominent Chinese herbal medicine employed for preventing miscarriage. However, our previous study revealed that high dosages of AMR administered during pregnancy could cause embryotoxicity but the specific embryotoxic components and their underlying mechanisms remain unclear. This study aimed to screen and identify the potential embryotoxic components of AMR. Methods: The AMR extracts and sub-fractions were analyzed by thin layer chromatography and subsequently screened by in vitro mouse limb bud micromass and mouse whole embryo culture bioassays. The embryotoxic fractions from AMR were further evaluated in vivo using a pregnant mouse model. The structures of the potential embryotoxic components were analyzed using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Results: In vitro and in vivo bioassays revealed that AMR glycoside-enriched sub-fractions (AMR-A-IIa and AMR-A-IIb) exhibited potential embryotoxicity. These sub-fractions, when administered to pregnant animals, increased the incidence of stillbirth and congenital limb malformations. MS spectrometry analysis identified cycasin derivatives in both sub-fractions, suggesting their possible role in the observed limb malformations. However, further experiments are necessary to validate this hypothesis and to elucidate the underlying mechanisms. Conclusions: Our study provides significant scientific evidence on the pharmacotoxicity of AMR, which is important for the safe clinical application of commonly used Chinese herbal medicines during pregnancy.

Fe-based cyclically catalyzing double free radical nanogenerator for tumor-targeted chemodynamic therapy.

The prosperity of chemodynamic therapy provides a new strategy for tumor treatment. However, the lack of reactive oxygen species and the specific reductive tumor microenvironment have limited the further development of chemodynamic therapy. Herein, we reported a Fe-based cyclically catalyzing double free radical system for tumor therapy by catalyzing exogenous potassium persulfate (K2S2O8) and endogenous hydrogen peroxide (H2O2). Sufficient amounts of Fe3+ and S2O82- were delivered to tumor sites via tumor-targeted hyaluronic acid (HA) encapsulated mesoporous silica nanoparticles (MSNs) and released under the dual stimulation of acid and hyaluronidase (HAase) in the tumor microenvironment. Fe3+ was reduced to Fe2+ by the reducing agents of loaded tannic acid (TA) and intracellular glutathione (GSH), and Fe2+ was subsequently reacted with S2O82- and endogenous H2O2 to produce two types of ROS (˙OH and SO4-˙), showing an excellent anti-tumor effect. This process not only supplied Fe2+ for the catalysis of active substances, but also reduced the concentration of reduced substances in cells, which was conducive to the existence of free radicals for the efficient killing of tumor cells. Therefore, this iron-based catalysis of exogenous and exogenous active substances to realize a dual-radical oncotherapy nanosystem would provide a new perspective for chemodynamic therapy.

Dental Implant Failure in Post-Menopausal Women on Oral Bisphosphonates: A Systematic Review and Meta-Analysis.

A systematic review was designed to investigate the effect of treatment with oral bisphosphonate (BP) on osseointegration of dental implants and the incidence of BP-related osteonecrosis of the jaw (BRONJ) in post-menopausal women. Multiple electronic databases, including MEDLINE (PubMed), EMBASE, and SCOPUS, were searched to find all eligible articles published since 1990. All titles and abstracts retrieved by searching information sources were evaluated independently by two authors against the eligibility criteria. The number of cases ranged from 11 to 235, and the number of controls ranged from 14 to 343. Alendronate was used in all other studies. Risedronate was used in six studies, while ibandronate was used in four studies. The number of implants in cases ranged from 25 to 1267, while in controls, the number of implants ranged from 28 to 1450. The time between the placement of implant and the follow-up visit ranged from 4-6 months to 8 years. The results show that out of 2582 placed implants, 50 (1.94%) failed in BP-treated patients. This is while out of 4050 placed implants, 188 (4.6%) failed in the non-BP group. The results from the meta-analysis demonstrated that BP therapy is significantly associated with increased implant failure rates (RR (95% CI)=1.73 (1.03-2.83), p=0.04). Overall, the qualitative assessment of this review suggests that oral treatment with BPs in post-menopausal women does not increase the rate of dental implant failure. Thus, further studies with larger sample sizes should compare BP and non-BP groups in regard to dental implants.

Revolutionizing Gastric Cancer Prevention: Novel Insights on Gastric Mucosal Inflammation-Cancer Transformation and Chinese Medicine.

The progression from gastric mucosal inflammation to cancer signifies a pivotal event in the trajectory of gastric cancer (GC) development. Chinese medicine (CM) exhibits unique advantages and holds significant promise in inhibiting carcinogenesis of the gastric mucosa. This review intricately examines the critical pathological events during the transition from gastric mucosal inflammation-cancer transformation (GMICT), with a particular focus on pathological evolution mechanisms of spasmolytic polypeptide-expressing metaplasia (SPEM). Moreover, it investigates the pioneering applications and advancements of CM in intervening within the medical research domain of precancerous transformations leading to GC. Furthermore, the analysis extends to major shortcomings and challenges confronted by current research in gastric precancerous lesions, and innovative studies related to CM are presented. We offer a highly succinct yet optimistic outlook on future developmental trends. This paper endeavors to foster a profound understanding of forefront dynamics in GMICT research and scientific implications of modernizing CM. It also introduces a novel perspective for establishing a collaborative secondary prevention system for GC that integrates both Western and Chinese medicines.

A study of the spatial distribution characteristics of Chinese surnames.

OBJECTIVES: The spatial distribution of Chinese surnames is diverse and provides rich information about the evolution of human society. This study aims to propose several indices to quantify the spatial distribution characteristics of Chinese common surnames and to explore how these distributions are related to historical evolution. METHODS: This study uses data from China's ID information system covering 1.28 billion people across 362 cities. Based on the location quotient, several new concepts, such as "moderately concentrated cities" and "highly concentrated cities," are defined. Then indices such as range, ununiformity and spatial autocorrelation are proposed and calculated to analyze the spatial characteristics of Chinese common surnames. RESULTS: A significant correlation is observed between the commonness of a surname and its spatial characteristics: the more common the surname, the wider its spatial range, the lower the ununiformity, and the higher the autocorrelation coefficient. These patterns reflect the complex interplay of historical, geographical, and cultural factors influencing surname spatial distribution. CONCLUSIONS: The spatial distribution of Chinese surnames is intricately linked to their historical evolution. Most common surnames, often with deeper historical roots, exhibit wider distributions and lower ununiformity, whereas less common surnames show higher concentrations in specific areas. These quantitative results provide a comprehensive understanding of the evolutionary characteristics of Chinese surnames.

Difference in Buccal Gingival Thickness between the Mandible and Maxilla in the Aesthetic Zone: A Systematic Review and Meta-Analysis.

Background: Fragile gingival tissue is a risk factor for the development of gingival recessions. Despite the fact that gingival recessions are more commonly seen around anterior mandibular teeth, previous research has predominantly concentrated on the gingival dimensions in the anterior maxilla. The objective was to systematically compare buccal gingival thicknesses between the upper and lower jaws in individuals with healthy gingival conditions in the aesthetic zone. Methods: A comprehensive search of three databases was carried out until October 2023. Gingival thickness differences between the maxilla and mandible were evaluated by calculating the mean differences along with the corresponding 95% confidence interval (CI). Subgroup analysis was conducted based on the measurement area, measurement method, and tooth category. Results: A total of seventeen studies were included in this systematic review. Eleven studies were included in the quantitative analysis. Quantitative analysis comparing gingival thickness around 2100 teeth in the anterior mandible to 2056 teeth in the anterior maxilla revealed a statistically significant thinner buccal gingiva in the mandible (mean difference: 0.16 mm; 95% CI [-0.24, -0.07]; p = 0.0003). Conclusions: The present systematic review revealed a more delicate buccal gingiva in the anterior mandible. However, further scientific validation is required due to the considerable heterogeneity in study design and the potential presence of confounding variables.

Changes in the alveolar bone morphology among different patterns of incisor inclination during the alignment phase in orthodontic treatment without premolar extraction.

OBJECTIVE: The present study investigated bone remodelling in the upper and lower incisor regions depending on the inclination pattern during the alignment phase of orthodontic treatment (OT). MATERIALS AND METHODS: This prospective clinical study included 71 patients undergoing OT without premolar extraction. Cone beam computed tomography scans were taken before and after the alignment phase and the changes in the inclination, alveolar bone height (ABH) and bone thickness (BT) at levels 2, 3, 4, 6, 8 and 9 mm starting from the cementoenamel junction (CEJ) were determined. RESULTS: Teeth were divided into 'Retroinclination' (lingual crown inclination <0°), 'Proclination-low' (buccal crown inclination between 0° and 5°), or 'Proclination-high' (buccal crown inclination >5°). The alignment phase of OT resulted in ABH loss. The highest ABH loss in the maxilla was observed on the buccal side in the 'Proclination-high' and was 0.71 mm. ABH loss by 1.1 mm was observed in the mandible on the lingual side in the 'Retroinclination' group. The most significant changes in BT by up to 2 mm were observed at levels 6, 8 and 9 mm and these changes exhibited a moderate to strong correlation with the alterations in the inclination of individual incisors. At levels 2, 3 and 4 mm, the highest decrease in BT by up to 0.83 mm was observed on the palatal side of upper incisors in the 'Proclination-high' group. CONCLUSION: The direction and amount of tooth inclination partially determine changes in the bone parameters during the alignment phase.

Quercetin in the Prevention of Induced Periodontal Disease in Animal Models: A Systematic Review and Meta-Analysis.

BACKGROUND: Periodontitis is an inflammatory condition initiated by oral bacteria and is associated with several systemic diseases. Quercetin is an anti-inflammatory and anti-bacterial poly-phenol present in various foods. The aim of this meta-analysis was the evaluation of the effects of quercetin administration in animal models of experimental periodontitis. METHODS: A systematic search was performed in electronic databases using the following search terms: "periodontitis" or "periodontal disease" or "gingivitis" and "quercetin" or "cyanidanol" or "sophoretin" or "pentahydroxyflavone". In vivo preclinical animal models of experimental periodontal disease with a measurement of alveolar bone loss were included in the analysis. The risk of bias of the included studies was assessed using the SYRCLE tool. RESULTS: The systematic search yielded 335 results. Five studies were included, four of them qualified for a meta-analysis. The meta-analysis showed that quercetin administration decreased alveolar bone loss (τ2 = 0.31, 1.88 mm 95%CI: 1.09, 2.67) in experimental periodontal disease animal models. However, the risk of bias assessment indicated that four SYRCLE domains had a high risk of bias. CONCLUSIONS: Quercetin diminishes periodontal bone loss and prevents disease progression in animal models of experimental periodontal disease. Quercetin might facilitate periodontal tissue hemostasis by reducing senescent cells, decreasing oxidative stress via SIRT1-induced autophagy, limiting inflammation, and fostering an oral bacterial microenvironment of symbiotic microbiota associated with oral health. Future research will show whether and how the promising preclinical results can be translated into the clinical treatment of periodontal disease.

Clinical and MRI-Based Assessment of Patients with Temporomandibular Disorders Treated by Controlled Mandibular Repositioning.

BACKGROUND: Occlusal splints and anterior repositioning splints (ARSs) are widely accepted treatments for temporomandibular disorders (TMDs). However, there is uncertainty with regard to the most suitable amount of mandibular repositioning. The aim of this study is to evaluate the clinical and functional effects of the therapeutic position (ThP) established based on the Controlled Mandibular Repositioning (CMR) method. METHODS: In this clinical trial, 20 subjects with 37 joints with disc displacement with reduction were recruited. The initial standard functional diagnostic protocol, MRI, and digital condylography were performed, and ThP was calculated with the CMR method. After a 6-month follow-up, the standard diagnostic protocol was repeated. The change in disc position was evaluated by means of MRI after 6 months of CMR therapy. RESULTS: The MRI findings in the parasagittal plane demonstrated that out of the 37 joints presenting disc displacement, 36 discs were successfully repositioned; thus, the condyle-disc-fossa relationship was re-established. Therefore, the success rate of this pilot study was 97.3%. The mean position of the displaced discs was at 10:30 o'clock of the TMJ joint and at 12:00 o'clock after CMR therapy. CONCLUSIONS: The ThP determined using the CMR approach reduced all of the anteriorly displaced discs (except one). The CMR method allowed to define an optimum ThP of the mandible thus supporting patients' effective adaptation to treatment position.

Salvianolic acid C attenuates cerebral ischemic injury through inhibiting neuroinflammation via the TLR4-TREM1-NF-κB pathway.

BACKGROUND: Stroke is a leading cause of mortality and disability with ischemic stroke being the most common type of stroke. Salvianolic acid C (SalC), a polyphenolic compound found in Salviae Miltiorrhizae Radix et Rhizoma, has demonstrated therapeutic potential in the recovery phase of ischemic stroke. However, its pharmacological effects and underlying mechanisms during the early stages of ischemic stroke remain unclear. This study aimed to examine the potential mechanism of action of SalC during the early phase of ischemic stroke using network pharmacology strategies and RNA sequencing analysis. METHODS: SalC effects on infarct volume, neurological deficits, and histopathological changes were assessed in a mouse model of transient middle cerebral artery occlusion (tMCAO). By integrating RNA sequencing data with a cerebral vascular disease (CVD)-related gene database, a cerebral ischemic disease (CID) network containing dysregulated genes from the tMCAO model was constructed. Network analysis algorithms were applied to evaluate the key nodes within the CID network. In vivo and in vitro validation of crucial targets within the identified pathways was conducted. RESULTS: SalC treatment significantly reduced infarct volume, improved neurological deficits, and reversed pathological changes in the tMCAO mouse model. The integration of RNA sequencing data revealed an 80% gene reversion rate induced by SalC within the CID network. Among the reverted genes, 53.1% exhibited reversion rates exceeding 50%, emphasizing the comprehensive rebalancing effect of SalC within the CID network. Neuroinflammatory-related pathways regulated by SalC, including the toll-like-receptor 4 (TLR4)- triggering receptor expressed on myeloid cells 1 (TREM1)-nuclear factor kappa B (NF-κB) pathway, were identified. Further in vivo and in vitro experiments confirmed that TLR4-TREM1-NF-κB pathway was down-regulated by SalC in microglia, which was essential for its anti-inflammatory effect on ischemic stroke. CONCLUSIONS: SalC attenuated cerebral ischemic injury by inhibiting neuroinflammation mediated by microglia, primarily through the TLR4-TREM1-NF-κB pathway. These findings provide valuable insights into the potential therapeutic benefits of SalC in ischemic stroke.

Integrated analysis of miRNA-mRNA expression of newly emerging swine H3N2 influenza virus cross-species infection with tree shrews.

BACKGROUND: Cross-species transmission of zoonotic IAVs to humans is potentially widespread and lethal, posing a great threat to human health, and their cross-species transmission mechanism has attracted much attention. miRNAs have been shown to be involved in the regulation of IAVs infection and immunity, however, few studies have focused on the molecular mechanisms underlying miRNAs and mRNAs expression after IAVs cross-species infection. METHODS: We used tree shrews, a close relative of primates, as a model and used RNA-Seq and bioinformatics tools to analyze the expression profiles of DEMs and DEGs in the nasal turbinate tissue at different time points after the newly emerged swine influenza A virus SW2783 cross-species infection with tree shrews, and miRNA-mRNA interaction maps were constructed and verified by RT-qPCR, miRNA transfection and luciferase reporter assay. RESULTS: 14 DEMs were screened based on functional analysis and interaction map, miR-760-3p, miR-449b-2, miR-30e-3p, and miR-429 were involved in the signal transduction process of replication and proliferation after infection, miR-324-3p, miR-1301-1, miR-103-1, miR-134-5p, miR-29a, miR-31, miR-16b, miR-34a, and miR-125b participate in negative feedback regulation of genes related to the immune function of the body to activate the antiviral immune response, and miR-106b-3p may be related to the cross-species infection potential of SW2783, and the expression level of these miRNAs varies in different days after infection. CONCLUSIONS: The miRNA regulatory networks were constructed and 14 DEMs were identified, some of them can affect the replication and proliferation of viruses by regulating signal transduction, while others can play an antiviral role by regulating the immune response. It indicates that abnormal expression of miRNAs plays a crucial role in the regulation of cross-species IAVs infection, which lays a solid foundation for further exploration of the molecular regulatory mechanism of miRNAs in IAVs cross-species infection and anti-influenza virus targets.

Development of an in-line Raman analytical method for commercial-scale CHO cell culture process monitoring: Influence of measurement channels and batch number on model performance.

The mammalian cell culture process is a key step in commercial therapeutic protein production and needs to be monitored and controlled due to its complexity. Raman spectroscopy has been reported for cell culture process monitoring by analysis of many important parameters. However, studies on in-line Raman monitoring of the cell culture process were mainly conducted on small or pilot scale. Developing in-line Raman analytical methods for commercial-scale cell culture process monitoring is more challenging. In this study, an in-line Raman analytical method was developed for monitoring glucose, lactate, and viable cell density (VCD) in the Chinese hamster ovary (CHO) cell culture process during commercial production of biosimilar adalimumab (1500 L). The influence of different Raman measurement channels was considered to determine whether to merge data from different channels for model development. Raman calibration models were developed and optimized, with minimum root mean square error of prediction of 0.22 g L-1 for glucose in the range of 1.66-3.53 g L-1 , 0.08 g L-1 for lactate in the range of 0.15-1.19 g L-1 , 0.31 E6 cells mL-1 for VCD in the range of 0.96-5.68 E6 cells mL-1 on test sets. The developed analytical method can be used for cell culture process monitoring during manufacturing and meets the analytical purpose of this study. Further, the influence of the number of batches used for model calibration on model performance was also studied to determine how many batches are needed basically for method development. The proposed Raman analytical method development strategy and considerations will be useful for monitoring of similar bioprocesses.

The Future of Molecular Studies through the Lens of Large Language Models.

The rapid advancement of large language models is reshaping research across various fields, offering a novel approach to the complex realm of molecular studies. Our evaluation of GPT-4 and GPT-3.5, focusing on their performance in generating and optimizing molecular structures, highlights GPT-4's strengths in certain aspects of molecular optimization. However, it also revealed challenges in accurately creating complex molecules. Addressing these issues, we propose possible directions for future molecular science research. These suggestions aim to forge new paths for exploring the intricacies of molecular structures, potentially bringing new efficiencies and innovations in the field.

The effect of bolus properties on muscle activation patterns and TMJ loading during unilateral chewing.

Mastication is a vital human function and uses an intricate coordination of muscle activation to break down food. Collection of detailed muscle activation patterns is complex and commonly only masseter and anterior temporalis muscle activation are recorded. Chewing is the orofacial task with the highest muscle forces, potentially leading to high temporomandibular joint (TMJ) loading. Increased TMJ loading is often associated with the onset and progression of temporomandibular disorders (TMD). Hence, studying TMJ mechanical stress during mastication is a central task. Current TMD self-management guidelines suggest eating small and soft pieces of food, but patient safety concerns inhibit in vivo investigations of TMJ biomechanics and currently no in silico model of muscle recruitment and TMJ biomechanics during chewing exists. For this purpose, we have developed a state-of-the-art in silico model, combining rigid body bones, finite element TMJ discs and line actuator muscles. To solve the problems regarding muscle activation measurement, we used a forward dynamics tracking approach, optimizing muscle activations driven by mandibular motion. We include a total of 256 different combinations of food bolus size, stiffness and position in our study and report kinematics, muscle activation patterns and TMJ disc von Mises stress. Computed mandibular kinematics agree well with previous measurements. The computed muscle activation pattern stayed stable over all simulations, with changes to the magnitude relative to stiffness and size of the bolus. Our biomedical simulation results agree with the clinical guidelines regarding bolus modifications as smaller and softer food boluses lead to less TMJ loading. The computed mechanical stress results help to strengthen the confidence in TMD self-management recommendations of eating soft and small pieces of food to reduce TMJ pain.

Entecavir versus tenofovir for prevention of hepatitis B virus-associated hepatocellular carcinoma after curative resection: study protocol for a randomized, open-label trial.

BACKGROUND: Entecavir and tenofovir disoproxil fumarate (TDF) are standard first-line treatments to prevent viral reactivation and hepatocellular carcinoma (HCC) in individuals chronically infected with the hepatitis B virus (HBV), but the long-term efficacy of the two drugs remains controversial. Also unclear is whether the drugs are effective at preventing viral reactivation or HCC recurrence after hepatectomy to treat HBV-associated HCC. This trial will compare recurrence-free survival, overall survival, viral indicators and adverse events in the long term between patients with HBV-associated HCC who receive entecavir or TDF after curative resection. METHODS: This study is a randomized, open-label trial. A total of 240 participants will be randomized 1:1 into groups receiving TDF or entecavir monotherapy. The two groups will be compared in terms of recurrence-free and overall survival at 1, 3, and 5 years after surgery; adverse events; virological response; rate of alanine transaminase normalization; and seroreactivity at 24 and 48 weeks after surgery. DISCUSSION: This study will compare long-term survival between patients with HBV-associated HCC who receive TDF or entecavir monotherapy. Numerous outcomes related to prognosis will be analyzed and compared in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02650271. Registered on January 7, 2016.

Oncolytic Newcastle disease virus inhibits IL-6 induced migration and invasion of human glioblastoma U87MG cells / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨溶瘤新城疫病毒（NDV）对IL-6诱导的人胶质母细胞瘤U87MG细胞增殖、迁移和侵袭的作用及其可能的机制。方法：将U87MG细胞分为对照组、IL-6组、NDV组、NDV+IL-6组，其中IL-6组与NDV+IL-6组用75 ng/mL IL-6预处理1 h，其余组用DMEM预处理1 h，后分别用DMEM、75 ng/mL IL-6、1 HU NDV、1 HU NDV+75 ng/mL IL-6处理24 h。MTT法、细胞划痕实验和Transwell侵袭实验分别检测IL-6、NDV对U87MG细胞增殖、迁移和侵袭的影响，WB法检测各组细胞JAK2、p-JAK2、STAT3、p-STAT3和MMP2蛋白的表达水平。结果：与对照组相比，IL-6组细胞迁移率显著升高（P<0.05），侵袭细胞数目显著增多（P<0.01）；与IL-6组相比，NDV+IL-6组U87MG细胞增殖率显著降低（P<0.05），细胞迁移率和侵袭细胞数目均显著降低（均P<0.01）。WB实验结果显示，与对照组相比，IL-6组p-STAT3/STAT3比值显著升高（P<0.01），NDV组p-JAK2/JAK2、p-STAT3/STAT3比值显著降低（P<0.05，P<0.01），MMP-2蛋白表达量显著降低（P<0.01）；与IL-6组相比，NDV+IL-6组p-STAT3/STAT3比值、MMP-2蛋白表达量均显著降低（均P<0.05）。结论：NDV能抑制IL-6对人脑胶质瘤U87MG细胞迁移和侵袭的诱导作用，其机制可能与JAK2/STAT3信号通路的参与调控有关。

Maternal exposure to E 551 during pregnancy leads to genome-wide DNA methylation changes and metabolic disorders in the livers of pregnant mice and their fetuses.

The widespread use of nanoparticles in the food industry has raised concerns regarding their potential adverse effects on human health, particularly in vulnerable populations, including pregnant mothers and fetuses. However, studies evaluating the reproductive and developmental toxicity of food-grade nanomaterials are limited. This study investigated the potential risks of prenatal dietary exposure to food-grade silica nanoparticles (E 551) on maternal health and fetal growth using conventional toxicological and epigenetic methods. The results showed that prenatal exposure to a high-dose of E 551 induces fetal resorption. Moreover, E 551 significantly accumulates in maternal and fetal livers, triggering a hepatic inflammatory response. At the epigenetic level, global DNA methylation is markedly altered in the maternal and fetal livers. Genome-wide DNA methylation sequencing revealed affected mCG, mCHG, and mCHH methylation landscapes. Subsequent bioinformatic analysis of the differentially methylated genes suggests that E 551 poses a risk of inducing metabolic disorders in maternal and fetal livers. This is further evidenced by impaired glucose tolerance in pregnant mice and altered expression of key metabolism-related genes and proteins in maternal and fetal livers. Collectively, the results of this study highlighted the importance of epigenetics in characterizing the potential toxicity of maternal exposure to food-grade nanomaterials during pregnancy.

Revealing spatial multimodal heterogeneity in tissues with SpaTrio.

Capturing and depicting the multimodal tissue information of tissues at the spatial scale remains a significant challenge owing to technical limitations in single-cell multi-omics and spatial transcriptomics sequencing. Here, we developed a computational method called SpaTrio that can build spatial multi-omics data by integrating these two datasets through probabilistic alignment and enabling further analysis of gene regulation and cellular interactions. We benchmarked SpaTrio using simulation datasets and demonstrated its accuracy and robustness. Next, we evaluated SpaTrio on biological datasets and showed that it could detect topological patterns of cells and modalities. SpaTrio has also been applied to multiple sets of actual data to uncover spatially multimodal heterogeneity, understand the spatiotemporal regulation of gene expression, and resolve multimodal communication among cells. Our data demonstrated that SpaTrio could accurately map single cells and reconstruct the spatial distribution of various biomolecules, providing valuable multimodal insights into spatial biology.