Tumor-associated macrophage-derived exosomal miR21-5p promotes tumor angiogenesis by regulating YAP1/HIF-1α axis in head and neck squamous cell carcinoma.

Extracellular vesicles (EVs) have recently received increasing attention as essential mediators of communication between tumor cells and their microenvironments. Tumor-associated macrophages (TAMs) play a proangiogenic role in various tumors, especially head and neck squamous cell carcinoma (HNSCC), and angiogenesis is closely related to tumor growth and metastasis. This research focused on exploring the mechanisms by which EVs derived from TAMs modulate tumor angiogenesis in HNSCC. Our results indicated that TAMs infiltration correlated positively with microvascular density in HNSCC. Then we collected and identified EVs from TAMs. In the microfluidic chip, TAMs derived EVs significantly enhanced the angiogenic potential of pHUVECs and successfully induced the formation of perfusable blood vessels. qPCR and immunofluorescence analyses revealed that EVs from TAMs transferred miR-21-5p to endothelial cells (ECs). And targeting miR-21-5p of TAMs could effectively inhibit TAM-EVs induced angiogenesis. Western blot and tube formation assays showed that miR-21-5p from TAM-EVs downregulated LATS1 and VHL levels but upregulated YAP1 and HIF-1α levels, and the inhibitors of YAP1 and HIF-1α could both reduce the miR-21-5p enhanced angiogenesis in HUVECs. The in vivo experiments further proved that miR-21-5p carried by TAM-EVs promoted the process of tumor angiogenesis via YAP1/HIF-1α axis in HNSCC. Conclusively, TAM-derived EVs transferred miR-21-5p to ECs to target the mRNA of LATS1 and VHL, which inhibited YAP1 phosphorylation and subsequently enhanced YAP1-mediated HIF-1α transcription and reduced VHL-mediated HIF-1α ubiquitination, contributing to angiogenesis in HNSCC. These findings present a novel regulatory mechanism of tumor angiogenesis, and miR-21-5p/YAP1/HIF-1α might be a potential therapeutic target for HNSCC.

A Family of Twisted Chiral Engineered Inorganic Nanoarchitectures.

Chiral inorganic materials possess unique asymmetric properties that could significantly impact various fields. However, their practical application has been hindered by challenges in creating structurally robust chiral materials. We report the synthesis of well-defined chiral-shaped hollow cobalt oxide nanostructures, extendable to a family of chalcogenides including sulfide, selenide, and telluride through topological transformations. Taking chiral cobalt oxide nanostructures as a representative material, we demonstrate precise control over their chiral architectures, enabling fine-tuning of parameters, such as twist degrees, handedness, and compositions. These chiral nanostructures exhibit high spin selectivity effects that influence the electron transfer processes in catalytic reactions. Leveraging this spin-selective behavior, the chiral cobalt oxide nanoarchitectures demonstrate enhanced electrocatalytic performance in the oxygen evolution reaction compared to their achiral counterparts. Our findings not only expand the library of chiral inorganic materials but also advance the application of chiral effects in fields such as catalysis, spintronics, and beyond.

CXCR4 overexpression in chronic lymphocytic leukemia associates with poorer prognosis: A prospective, single-center, observational study.

Controversial data have been reported on the prognostic value of C-X-C motif chemokine receptor 4 (CXCR4) in chronic lymphocytic leukemia (CLL). This prospective, single-center, observational study aimed to evaluate the role of CXCR4 in the pathophysiology of CLL and its prognostic role. A total of 158 patients of CLL were enrolled, and CXCR4 expression on CLL cells was detected by flow cytometry (FCM) at initial diagnosis. The patients were divided into 2 groups according to the CXCR4 mean fluorescence intensity (MFI) median. Also, four patient specimens from the CXCR4low and CXCR4high groups were selected for RNASeq analysis. The progression-free survival (PFS) of CLL patients in the CXCR4high group was significantly shorter than the CXCR4low group, with a median follow-up time of 27 months (log-rank P < 0.001). Moreover, CXCR4 overexpression (MFI > 3376) was an independent marker of poor PFS in CLL patients (P < 0.001). Analysis of RNASeq results revealed that CXCR4 plays an important role in the migration of CLL. Collectively, CXCR4 expression levels on leukemia cells can be detected rapidly by FCM. CXCR4 overexpression was significantly associated with poorer prognosis in CLL patients within a shorter follow-up time.

Chirality Engineering of Colloidal Copper Oxide Nanostructures for Tailored Spin-Polarized Catalysis.

The combination of the chiral concept and inorganic nanostructures holds great potential for significantly impacting catalytic processes and products. However, the synthesis of inorganic nanomaterials with engineered chiroptical activity and identical structure and size presents a substantial challenge, impeding exploration of the relationship between chirality (optical activity) and catalytic efficiency. Here, we present a facile wet-chemical synthesis for achieving intrinsic and tunable chiroptical activity within colloidal copper oxide nanostructures. These nanostructures exhibit strong spin-polarization selectivity compared with their achiral counterparts. More importantly, the ability to engineer chiroptical activity within the same type of chiral nanostructures allows for the manipulation of spin-dependent catalysis, facilitating a study of the connection between the chiroptical magnitude (asymmetric factor) and catalytic performance in inorganic nanostructures. Specifically, using these materials as model catalysts in a proof-of-concept catalytic reaction, we reveal a linear correlation between the asymmetric factor of chiral nanomaterials and the efficiency of the catalytic reaction. This work paves the way for the development of chiral inorganic nanosystems and their application in catalysis through chiroptical engineering.

Baicalin induces ferroptosis in oral squamous cell carcinoma by suppressing the activity of FTH1.

BACKGROUND: This study investigated the role of the ferroptosis-related gene FTH1 in oral squamous cell carcinoma (OSCC) and evaluated the therapeutic potential of baicalin in OSCC cell treatment. METHODS: A prognostic model was established by bioinformatic analysis, consisting of 12 ferroptosis related genes (FRGs), and FTH1 was selected as the most significantly up-regulated FRGs. The clinical correlation of FTH1 in OSCC samples was evaluated by both immunohistochemical and bioinformatic characterizations. The effects of FTH1 on migration, invasion, epithelial-mesenchymal transition (EMT) and proliferation were determined by wound healing assays, transwell assays, western blotting and 5'-ethynl 2'-deoxyuridine proliferation assays, respectively. The effects of FTH1 on ferroptosis were tested via ferroptosis markers and Mito Tracker staining. In addition, the therapeutic effects of baicalin on OSCC cells were confirmed using EMT, migration, invasion, proliferation and ferroptosis assays. RESULTS: The 12 FRGs were predictive of the prognosis for OSCC patients, and FTH1 expression was identified as significantly up-regulated in OSCC samples, which was highly associated with survival, immune cell infiltration and drug sensitivity. Moreover, knocking down FTH1 inhibited cell proliferation, EMT and invasive phenotypes, but induced ferroptosis in OSCC cells (Cal27 and SCC25). Furthermore, baicalin directly suppressed expression of FTH1 in OSCC cells, and effectively promoted ferroptosis and inhibited the proliferation as well as EMT by directly targeting FTH1. CONCLUSIONS: This study has demonstrated that FTH1 is a therapeutic target for OSCC treatment, and has provided evidence that baicalin offers a promising alternative for OSCC treatment.

Multicolor Circularly Polarized Luminescence from Inorganic Crystalline Nanostructures Induced by Atomic Chirality.

Circularly polarized luminescence (CPL) is well-studied in molecular systems but has been rarely reported in pure inorganic nanoscale crystals. Herein, we develop a family of pure inorganic rare-earth nanowires with robust and color-tunable CPL emissions. The chiral rare earth nanowires possess intrinsic atomic chirality with controlled handedness that is guided by the enantiomers with molecular chirality in the synthesis. By varying luminescent ions incorporated in the crystal lattice, color-tunable CPL can be achieved and is thermally robust, preserving emission over 300 °C, distinct from existing CPL-active materials. Moreover, as a proof of concept, we demonstrate that the synthesized nanostructures can be easily dispersed in a polymer matrix to enable transparent and flexible CPL films. This study opens up a promising avenue to design robust and tunable CPL materials helpful to the understanding of inorganic chiral information and capable of further applications in novel optoelectronic devices.

Proanthocyanidins Ameliorate LPS-Inhibited Osteogenesis of PDLSCs by Restoring Lysine Lactylation.

Periodontitis is a bacteria-induced inflammatory disease characterized by the progressive destruction of periodontal supporting tissues. Periodontal ligament stem cells (PDLSCs) are capable of differentiating into osteoblasts, which is an important stem cell source for endogenous periodontal tissue regeneration. Lysine lactylation (Kla) is a novel post-translational modification of proteins that is recently thought to be associated with osteogenic differentiation. Here, we found that lactylation levels are reduced both in the periodontal tissue of rats with periodontitis and lipopolysaccharide (LPS)-stimulated human PDLSCs. Proanthocyanidins were able to promote the osteogenesis of inflamed PDLSCs by restoring lactylation levels. Mechanistically, proanthocyanidins increased lactate production and restored the lactylation levels of PDLSCs, which recovered osteogenesis of inflamed PDLSCs via the Wnt/ß-catenin pathway. These results provide evidence on how epigenetic regulation by pharmacological agents influence the osteogenic phenotype of stem cells and the process of periodontal tissue repair. Our current study highlights the valuable potential of natural product proanthocyanidins in the regenerative engineering of periodontal tissues.

Evaluating sound attenuation of single trees using 3D information.

Urban tree belts reduce noise pollution, but limited research has focused on the mitigation potential of single trees. Identifying individual tree characteristics that influence noise propagation can assist in selecting trees to improve urban soundscapes at multiple scales. This study introduces a methodology to evaluate and predict the sound attenuation of single trees using 3D tree morphology data and sound observations. We extracted structural characteristics for 26 trees on Nanjing University's Xianlin campus from handheld terrestrial LiDAR. Second, the sound attenuation of each sample tree was quantified systematically using a sound source and a receiver. The sound level meter was placed in front of and behind each sample tree to record the received sound levels. The sound source was positioned 1.5m above ground to emit white noise, ensuring the front receiver recording sound levels of 55, 60, and 68 dBA. We established a support vector regression (SVR) with a linear (LN) kernel to predict the sound attenuation of single trees based on their 3D characteristics. Single trees yielded an insertion loss of 2-3 dBA, effectively eliminating sound above 500 Hz and increasing with the frequency. It is also interesting to note that the insertion loss increases with increasing source sound levels. Regression analysis revealed that an increase in crown leaf area index (ß = 0.332, p < 0.01) and average leaf inclination (ß = 0.168, p < 0.01) reduced sound significantly, indicating the tree canopy's predominant role in impeding sound propagation. The SVR-LN model, established using standardized parameters with statistical significance, exhibited strong predictive sound attenuation performance using tree characteristics (R2 = 0.74, RMSE = 0.38, and MSE = 0.15). This study addresses a research gap in the acoustic effects of single trees and provides a framework for accurately evaluating and predicting sound attenuation based on 3D characteristics. The findings can assist urban planners and policymakers in strategically planting trees to foster healthier and quieter living spaces for residents.

THBS1-Mediated Degradation of Collagen via the PI3K/AKT Pathway Facilitates the Metastasis and Poor Prognosis of OSCC.

Oral squamous cell carcinoma (OSCC) is a prevalent form of malignant tumor, characterized by a persistently high incidence and mortality rate. The extracellular matrix (ECM) plays a crucial role in the initiation, progression, and diverse biological behaviors of OSCC, facilitated by mechanisms such as providing structural support, promoting cell migration and invasion, regulating cell morphology, and modulating signal transduction. This study investigated the involvement of ECM-related genes, particularly THBS1, in the prognosis and cellular behavior of OSCC. The analysis of ECM-related gene data from OSCC samples identified 165 differentially expressed genes forming two clusters with distinct prognostic outcomes. Seventeen ECM-related genes showed a significant correlation with survival. Experimental methods were employed to demonstrate the impact of THBS1 on proliferation, migration, invasion, and ECM degradation in OSCC cells. A risk-prediction model utilizing four differentially prognostic genes demonstrated significant predictive value in overall survival. THBS1 exhibited enrichment of the PI3K/AKT pathway, indicating its potential role in modulating OSCC. In conclusion, this study observed and verified that ECM-related genes, particularly THBS1, have the potential to influence the prognosis, biological behavior, and immunotherapy of OSCC. These findings hold significant implications for enhancing survival outcomes and providing guidance for precise treatment of OSCC.

Polarization of macrophages in the trigeminal ganglion of rats with pulpitis.

BACKGROUND: Dental pulp tissues are rich in pain-related afferent nerve fibers, which originate from primary sensory neurons in the trigeminal ganglion (TG). The mechanisms of central nervous system (CNS) underlying ectopic pain following peripheral inflammation have been reported that the macrophages as inflammatory and immunologic mediators in the TG play an important role in the process of pulpitis and hyperalgesia. OBJECTIVE(S): To observe the polarization response and dynamic distribution of macrophages in the TG during the development of dental pulp inflammation. METHODS: A rat model of pulpitis was established using complete Freund's adjuvant (CFA). Hematoxylin-eosin (HE), immunohistochemistry (IHC), immunofluorescence (IF), toluidine blue (TB) staining, and RT-qPCR were performed to observe the expression of macrophage-related factors in the TG. RESULTS: The results of IHC staining showed that M2 macrophages labeled with CD206 were observed in the TG of both the control and CFA groups. The statistical analysis indicated that the number of CD206-positive macrophages in the TG increased significantly at 24 h after CFA-induced pulpitis, reached a peak at 2 weeks, and then returned to the normal level after 6 weeks. The ratio of M2/M1 in the CFA groups was significantly lower than that in the control group from 24 to 72 h, and this pattern was reversed at 2 weeks after CFA-induced pulpitis; then, the ratio increased significantly and was maintained at a high level for 4 weeks. RT-qPCR results showed that the expression of IL-10 in the TG increased significantly from 1 to 4 weeks after CFA-induced pulpitis. CONCLUSION: The trend of M2 macrophages was opposite to that of M1 macrophages in the TG during the process of pulpitis induced by CFA, which is consistent with the expression of macrophage-related cytokines. Macrophage polarization in the TG may participate in the neuroinflammation response induced by dental pulpitis.

Toxicity of surface water from Huangpu River to luminous bacteria (Vibrio qinghaiensis SP. Q67) and zebrafish (Danio rerio) embryos.

Degradation of water quality is an emerging problem in many developing countries. Bioassay is an effective approach to monitor quality of water in aquatic environments. Studies have used luminescent bacteria and zebrafish embryos as bioassay tools in monitoring river water quality. In this study, luminous bacteria (Vibrio qinghaiensis sp. Q67) assay and zebrafish (Danio rerio) embryo toxicity test were performed to assess the ecotoxicity of surface water from the Huangpu River, China, collected during 2012-2013. River water samples inhibited the luminescence [inhibition rates 0-34.6% (±4.82%)] of Q67 and increased the lethal rates and induced morphological abnormalities in zebrafish embryos. The toxicity to luminous bacteria and zebrafish embryos were higher in winter than in summer months. In addition, samples collected in industrial area, urban sampling sites near drainage outlets, and at the intersection of the tributary that flows into the Huangpu River showed higher toxicity.

[Effect of anxin granules combined with tirofiba on patients with acute myocardial infarction after elective percutaneous coronary intervention].

To investigate the influence of Anxin granules combined with tirofiban on acute myocardial infarction (AMI) Patients after elective percutaneous coronary intervention (PCI). One hundred and twenty AMI patients were randomly divided into treatment group and control group. The patients in the two groups were all given Tirofiban 30mins before PCI . The treatment group was added Anxin granules 30 mins before and after PCI. Tissue factor (TF) and von willebrand factor (vWF) were tested at 6 hours after operation. Syndromatology alteration of traditional Chinese medicine (TCM) and bleeding complications were observed at 4 weeks after operation. Both TF and vWF at 6 hours after operation of the treatment group was lower than the control group significantly (P < 0.01), while the condition of myocardial ischemia at 90 mins after operation of the treatment group was better than control group with significance. The syndromatology alteration of TCM especially spontaneous perspiration and hypodynamia of the treatment group were improved significantly compared to control group 4 weeks after operation. All patients in both groups had no bleeding complications and thrombopenia. The study suggests that Anxin granules combined with tirofiba can improve the clinical efficacy and the endothelial function of AMI patients after PCI with no increase in bleeding events.

An end-to-end bi-objective approach to deep graph partitioning.

Graphs are ubiquitous in real-world applications, such as computation graphs and social networks. Partitioning large graphs into smaller, balanced partitions is often essential, with the bi-objective graph partitioning problem aiming to minimize both the "cut" across partitions and the imbalance in partition sizes. However, existing heuristic methods face scalability challenges or overlook partition balance, leading to suboptimal results. Recent deep learning approaches, while promising, typically focus only on node-level features and lack a truly end-to-end framework, resulting in limited performance. In this paper, we introduce a novel method based on graph neural networks (GNNs) that leverages multilevel graph features and addresses the problem end-to-end through a bi-objective formulation. Our approach explores node-, local-, and global-level features, and introduces a well-bounded bi-objective function that minimizes the cut while ensuring partition-wise balance across all partitions. Additionally, we propose a GNN-based deep model incorporating a Hardmax operator, allowing the model to optimize partitions in a fully end-to-end manner. Experimental results on 12 datasets across various applications and scales demonstrate that our method significantly improves both partitioning quality and scalability compared to existing bi-objective and deep graph partitioning baselines.

Measurable Residual Disease Analysis by Flow Cytometry and Correlation With Molecular Measurable Residual Disease in Acute Promyelocytic Leukemia: A Real-World Prospective Study.

CONTEXT.­: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia distinguished by its rapidly progressive and fatal clinical course. Measurable/minimal residual disease (MRD) monitoring is vital for the prognosis and clinical management of acute myeloid leukemia. OBJECTIVE.­: To examine the immunophenotypes of the residual leukemic cells, evaluate the performance of multiparametric flow cytometry (FCM) measuring MRD, and compare it with molecular monitoring in patients diagnosed with APL. DESIGN.­: Two hundred seventy-seven patients with APL were enrolled. Immunophenotypes were prospectively analyzed by a 1-tube-10-color antibody panel via FCM. MRD of APL with PML::RARα was detected by real-time quantitative polymerase chain reaction (RQ-PCR). The clinical value of MRD as an indicator of survival was also examined. RESULTS.­: APL showed 5 distinct patterns of residual leukemic cells, based on CD45 and side-scatter scattergram, all with CD9 positivity and a previously unrealized loss of CD117. FCM-based MRD evaluation showed a concordance rate of 87.7% with PCR. At the end of the consolidation therapy, MRD measured by both PCR and FCM could differentiate patients with longer and shorter overall survival (OS) (P = .04 and P = .03, respectively). Patients with APL variant had a shorter OS than patients with APL who harbored PML::RARα (P < .001). CONCLUSIONS.­: CD9 is a reliable marker to differentiate residual leukemic cells from normally differentiating myeloid cells. FCM demonstrated a high comparability to PCR-MRD and an excellent performance in predicting OS, and thus could potentially be used as a routine indicator in the clinical management of patients with APL.

Association Between Circulating Inflammatory Cytokines and Dentofacial Anomalies.

INTRODUCTION AND AIMS: Previous studies have shown that some inflammatory cytokines are associated with dentofacial anomalies (DA), but the causal relationship is unclear. Therefore, the present study aimed to elucidate the relationship between circulating inflammatory cytokines, and DA risk by Mendelian randomization analysis. METHODS: A two-way two-sample Mendelian randomization analysis was used in our study. Data on 91 inflammatory cytokines were sourced from genome-wide association studies encompassing 14,824 participants across 11 distinct cohorts and protein quantitative trait loci from deCODE (35,559 participants). Summary statistics for DA were acquired from the FinnGen consortium (9254 cases and 245,664 controls). The inverse variance weighting method was used as the primary analysis, supplemented by a series of sensitivity analyses to determine the robustness and reliability of our findings. RESULTS: The analysis identified five cytokines - chemokine ligand 25, interleukin (IL)-10 receptor beta, IL-20, and stem cell factor - as inversely related to DA prevalence. Additionally, DA was associated with decreased levels of fibroblast growth factor (FGF)-19 and IL-24, and increased levels of FGF-23 and urokinase-type plasminogen activator. These findings were validated using protein quantitative trait loci data. CONCLUSION: Our study substantiates an association between inflammatory cytokines and DA, emphasizing inflammation's pivotal role in the aetiology of DA. CLINICAL SIGNIFICANCE: The findings provide a plausible genetic underpinning for the role of inflammation in DA, offering novel avenues for the development of targeted diagnostic and therapeutic strategies.

An all-in-one platform to deplete pathogenic bacteria for rapid and safe enrichment of plant-derived extracellular vesicles.

Plant-derived extracellular vesicles (PDEVs) have exhibited several advantages, such as high biocompatibility, improvement of skin conditions, and the prevention of skin aging. However, traditional methods of extraction for plant substances, such as heating under reflux or solvent extraction, are complicated, time-consuming, and low in purity. Accordingly, a simple and efficient platform is necessary for purely isolating natural substances from plants. In this study, we report a newly designed platform for removing impurities to purify PDEVs. The proposed platform comprises three parts: (i) inflow of samples, (ii) depletion of impurities, and (iii) collection of PDEVs. The platform is designed to flow from top to bottom using gravity without the need for electric components. The platform allows the delimitation of impurities, such as the pathogenic bacteria in PDEVs, by capturing magnetic beads coated with Concanavalin A (Con A). We validate the practicality of our platform using extracellular vesicles derived from liquorice (LdEVs). Notably, the LdEVs purified using the Con A-coated magnetic beads provide better cell uptake and wound recovery than the commercialized extract LdEVs. This highlights the therapeutic potential of fresh LdEVs purified using our platform, particularly in preventing skin aging. The findings of this study hold significant practical implications for the cosmeceutical and therapeutic field, providing a promising approach for the extraction and purification of natural substances from plants to harness their benefits effectively.

Research progress on the relationship between mitochondrial function and heart failure: A bibliometric study from 2002 to 2021.

Heart failure is one of the major public health problems in the world. In recent years, more and more attention has been paid to the relationship between heart failure and mitochondrial function. In the past 2 decades, a growing number of research papers in this field have been published. This study conducted a bibliometric analysis of the published literature on the relationship between MF and HF in the past 20 years by utilizing Microsoft Excel 2019, Biblio metric analysis platform, WoSCC database, VosViewer and Citespace. The results show that the papers have increased year by year and China and the United States are the leading countries in this field, as well as the countries with the most cooperation and exchanges. University of california system is the research institution with the greatest impacts on research results, and Yip H.K. is the author with more papers. The American Journal of Physiology-heart and Circulatory Physiology is probably the most popular magazine. At present, most of the published articles on mitochondria and HF are cited from internationally influential journals. The research focus includes oxidative stress, metabolic dysfunction, mitochondrial Ca2+ homeostasis imbalance, mitochondrial quality control and mitochondrial dysfunction mediated by inflammation in the pathogenesis of HF. Targeted regulating of mitochondria will be the keynote of future research on prevention and treatment of HF.

LIS1 interacts with CLIP170 to promote tumor growth and metastasis via the Cdc42 signaling pathway in salivary gland adenoid cystic carcinoma.

Salivary gland adenoid cystic carcinoma (SACC) is one of the most common malignant tumors, with high aggressive potential in the oral and maxillofacial regions. Lissencephaly 1 (LIS1) is a microtubule­organizing center­associated protein that regulates the polymerization and stability of microtubules by mediating the motor function of dynein. Recent studies have suggested that LIS1 plays a potential role in the malignant development of tumors, such as in mitosis and migration. However, the role of LIS1 in SACC development and its related molecular mechanisms remain unclear. Thus, the effects of LIS1 on the proliferation, apoptosis, invasion and metastasis of SACC were studied, in vivo and in vitro. The results of immunohistochemical staining showed that LIS1 was highly expressed in SACC tissues, and its expression level was associated with malignant progression. In vitro, the results of CCK­8, TUNEL, wound healing and Transwell assays demonstrated that LIS1 promotes proliferation, inhibits apoptosis, and enhances the migration and invasion of SACC­LM cells. In vivo, knockdown of LIS1 effectively suppressed the growth of subcutaneous tumors in a mouse xenograft and distant metastasis of tumor cells in the metastasis model. The co­immunoprecipitation, immunofluorescence and western blot results also revealed that LIS1 binds to cytoplasmic linker protein 170 (CLIP170) to form a protein complex (LIS1/CLIP170), which activates the cell division control protein 42 homolog (Cdc42) signaling pathway to modulate the proliferation and anti­apoptosis of tumor cells, and enhanced invasion and metastasis by regulating the formation of invadopodia and the expression of MMPs in SACC­LM cells. Therefore, the present study demonstrated that LIS1 is a cancer promoter in SACC, and the molecular mechanism of the LIS1/CLIP170/Cdc42 signaling pathway is involved in the malignant progression, which offers a promising strategy for targeted therapy of SACC.

CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma via the PI3K/AKT signaling pathway.

Background: CC chemokine receptor 9 (CCR9), an organ-specific chemokine receptor, interacts with its exclusive ligand CCL25 to promote tumor proliferation and metastasis. However, the effect of CCR9 on salivary adenoid cystic carcinoma (SACC) malignant behavior remains unknown. This study aimed to investigate the specific molecular mechanism by which CCR9/CCL25 modulates malignant progression in SACC. Methods: Immunohistochemistry staining and RT-qPCR analyses were performed to detect the correlation of CCR9 expression and tumor progression-associated markers in SACC. In vitro, SACC cell proliferation and apoptosis were evaluated using Cell Counting Kit-8 and colon formation, and cell migration and invasion were detected by wound healing and transwell assays. Vercirnon was used as an inhibitor of CCR9, and LY294002 was used as an inhibitor of the PI3K/AKT pathway in this study. Western blot and RT-qPCR assays were carried out to measure the downstream factors of the interaction of CCL25 and CCR9. The effect of CCL25 on the development of SACC in vivo was examined by a xenograft tumor model in nude mice following CCL25, Vercirnon and LY294002 treatment. Results: CCR9 was highly expressed in SACC compared with adjacent salivary gland tissues, and its level was associated with tumor proliferation and metastases. CCL25 enhanced cell proliferation, migration, and invasion through its interaction with CCR9 and exerted an antiapoptotic effect on SACC cells. Targeting CCR9 via Vercirnon significantly reduced the phosphorylation level of AKT induced by CCL25. CCL25/CCR9 could activate its downstream factors through the PI3K/AKT signaling pathway, such as cyclin D1, BCL2 and SLUG, thus promoting SACC cell proliferation, antiapoptosis, invasion and metastasis. The in vivo data from the xenograft mouse models further proved that CCL25 administration promoted malignant tumor progression by activating the PI3K/AKT pathway. Conclusion: The interaction of CCL25 and CCR9 promotes tumor growth and metastasis in SACC by activating the PI3K/AKT signaling pathway, offering a promising strategy for SACC treatment.

Quanduzhong capsules for the treatment of grade 1 hypertension patients with low-to-moderate risk: A multicenter, randomized, double-blind, placebo-controlled clinical trial.

Background: Duzhong [DZ (Eucommia ulmoides Oliv.)] is regarded as a traditional Chinese medicine with a history dating back more than 2000 years. This herb is considered a nourishing herb in China and is commonly used as a tonic to strengthen muscles and bones, nourish the kidneys and liver, and soothe miscarriages. Moreover, there is evidence that DZ is capable of regulating blood pressure (BP), and several compounds isolated from DZ have been shown to have a BP-lowering effect. Quanduzhong capsules contain an extract of DZ [Eucommia ulmoides Oliv. (Eucommiaceae; Eucommiae cortex)] that is effective in treating hypertension. This multicenter, randomized, double-blind, placebo-controlled clinical trial sought to evaluate the clinical efficacy of Quanduzhong capsules in the treatment of low-to-moderate risk grade 1 hypertension patients. Materials and methods: A total of 60 patients from 3 centers with documented low-to-moderate risk grade 1 hypertension were randomly assigned in a 1:1 ratio to the test group or the control group. After a 1 week lead-in period using sham Quanduzhong capsules, all patients who met the entry criteria (29 cases in the test group and 29 cases in the control group) entered the 4 week test period. The test group took Quanduzhong capsules, and the control group continued to take sham Quanduzhong capsules. The primary endpoints [24-h mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) determined via 24-h ambulatory blood pressure monitoring (ABPM); office SBP and DBP] and secondary endpoints [mean arterial pressure; mean pulse; daytime mean SBP and DBP; nocturnal mean SBP and DBP; SBP and DBP load; area under the blood pressure (BP) curve; morning peak BP; early morning SBP and DBP; smoothness index of SBP and DBP; 24 h BP mean coefficient of variation (CV); percentage of patients with circadian restoration in ABPM; home BP; quality of life evaluated by WHO Quality of Life-BREF questionnaire; grading and quantitative evaluation of hypertension symptoms; values of plasmatic renin activity, angiotensin II, aldosterone, ß-2 microglobulin and homocysteine] were assessed following the treatment. Drug-related adverse events and adverse drug reactions were also compared. Results: After a 4 week test period, a significant difference in the DBP CV between the two groups was observed (-2.49 ± 4.32 vs. 0.76 ± 4.3; p < .05). Moreover, the mean office SBP change was -7.62 ± 9.32 mmHg, and the mean DBP change was -4.66 ± 6.03 (p < .05). Among the three subjects with abnormal homocysteine levels in the test group, homocysteine levels decreased by 6.23 ± 9.15 µmol/L after treatment. No differences were observed between the two groups in any other indicators. After 4 weeks of treatment, there were no significant differences between the groups in terms of safety indicators (p > .05). No abnormal vital signs (except BP) or severe liver or renal function impairment were observed during the treatment periods; in addition, adverse events and drug reactions were mild. Conclusion: Treatment with Quanduzhong capsules reduced office SBP and DBP as well as DBP CV determined by 24-h ambulatory BP monitoring in patients with grade 1 hypertension at low-to-moderate risk. Clinical Trial Registration: https://www.chictr.org.cn/showproj.aspx?proj=32531, identifier ChiCTR1900021699.