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Background: The psychosocial impact of dental aesthetics (PIDA) has a significant effect on well-being and quality of life. This study aimed to explore the latent heterogeneous classes of the PIDA among adolescents and investigate the relationships among identified subtypes and sociodemographic variables, the status of left-behind children, and the clinical manifestations of malocclusion. Methods: A cross-sectional study on the PIDA among 1451 adolescents aged 11 to 12 years in elementary schools in a rural area in Guangxi, China, was conducted. The PIDA on adolescents was also investigated via latent profile analysis; each predictor was tested via ordinal logistic regression. Results: Three latent classes for the PIDA were identified: low-risk (48.2%), medium-risk (39.8%), and high-risk (11.9%) groups. There were significant differences among the three latent classes. The results revealed that being female, The duration of maternal employment outside the hometown, the largest anterior maxillary irregularity, the largest anterior mandibular irregularity, and the antero-posterior molar relationship (ORs of 1.737, 1.138, 1.117, 1.157, and OR = 1.242; P < 0.001, < 0.01, < 0.01, < 0.01 and < 0.05, respectively) had significant effects on the PIDA on adolescents. Conclusions: The occlusal features, being female and the duration of maternal employment outside the hometown are risk factors that influence the PIDA on adolescents. This provides an evidence for improving the PIDA status among rural adolescents. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "The ANGPTL4-HIF-1α loop: a critical regulator of renal interstitial fibrosis" published in the Journal of Translational Medicine. The correction states that Figure 2 in the original article was published incorrectly and provides the correct version of the graph. The article has been updated to reflect this correction. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. The authors of the article are Yan Li, Shuang Chen, Qian Yang, Xiao Liu, Weiming Zhou, Ting Kang, Weihua Wu, and Santao Ou. [Extracted from the article]

Background: Accumulating studies have highlighted the significant role of circulating metabolomics in the etiology of reproductive system disorders. However, the causal effects between genetically determined metabolites (GDMs) and reproductive diseases, including primary ovarian insufficiency (POI), polycystic ovary syndrome (PCOS), and abnormal spermatozoa (AS), still await thorough clarification. Methods: With the currently most comprehensive genome-wide association studies (GWAS) data of metabolomics, systematic two-sample Mendelian randomization (MR) analyses were conducted to disclose causal associations between 1,091 blood metabolites and 309 metabolite ratios with reproductive disorders. The inverse-variance weighted (IVW) method served as the primary analysis approach, and multiple effective MR methods were employed as complementary analyses including MR-Egger, weighted median, constrained maximum likelihood (cML-MA), contamination mixture method, robust adjusted profile score (MR-RAPS), and debiased inverse-variance weighted method. Heterogeneity and pleiotropy were assessed via MR-Egger intercept and Cochran's Q statistical analysis. Outliers were detected by Radial MR and MR-PRESSO methods. External replication and metabolic pathway analysis were also conducted. Results: Potential causal associations of 63 GDMs with POI were unearthed, and five metabolites with strong causal links to POI were emphasized. Two metabolic pathways related to the pathogenesis of POI were pinpointed. Suggestive causal effects of 70 GDMs on PCOS were detected, among which 7 metabolites stood out for strong causality with elevated PCOS risk. Four metabolic pathways associated with PCOS mechanisms were recognized. For AS, 64 GDMs as potential predictive biomarkers were identified, particularly highlighting two metabolites for their strong causal connections with AS. Three pathways underneath the AS mechanism were identified. Multiple assessments were conducted to further confirm the reliability and robustness of our causal inferences. Conclusion: By extensively assessing the causal implications of circulating GDMs on reproductive system disorders, our study underscores the intricate and pivotal role of metabolomics in reproductive ill-health, laying a theoretical foundation for clinical strategies from metabolic insights. [ABSTRACT FROM AUTHOR]

Background: Alström syndrome (AS) is a rare autosomal recessive disorder that leads to multiple organ fibrosis and failure. Precise diagnosis from the clinical symptoms is challenging due to its highly variabilities and its frequent confusion with other ciliopathies and genetic diseases. Currently, mutations in the ALMS1 gene have been reported as a major cause of AS, thus, it is crucial to focus on the detection and discovery of ALMS1 mutations. Case presentation: We present a case of a 13-year-old Chinese boy weighing 70 kg and standing 168 cm tall. He has two younger brothers. Their parents hail from different ancestral homes in eastern and northern China. The patient's primary clinical findings included visual impairment at the age of four and progressive hearing loss starting at the age of ten. Subsequently, at the age of twelve, the patient developed hyperlipidaemia and hyperinsulinemia. Ultrasonographic findings indicated the presence of gallstones and mild fatty liver. His Body Mass Index (BMI) significantly increased to 25 kg/m2 (ref: 18.5–23.9 kg/m2). Additionally, echocardiography revealed mild mitral and tricuspid regurgitation. Ultimately, Whole Exome Sequencing (WES) identified a new missense mutation in the ALMS1 gene (NG_011690.1 (NM_015120): c.9536G > A (p.R3179Q)). This missense mutation generated an aberrant splicer and disrupted the stability and hydrophobicity of proteins, which preliminarily determined as " likely pathogenic". Therefore, considering all the above symptoms and molecular analysis, we deduced that the patient was diagnosed with AS according to the guidelines. We recommended that he continue wearing glasses and undergo an annual physical examination. Conclusion: In this case report, we report a novel homozygous ALMS1 mutation associated with AS in the Chinese population, which expands the mutation spectrum of ALMS1. Genetic testing indeed should be incorporated into the diagnosis of syndromic deafness, as it can help avoid misdiagnoses of AS. While there is no specific treatment for AS, early diagnosis and intervention can alleviate the progression of some symptoms and improve patients' quality of life. [ABSTRACT FROM AUTHOR]

Background: Transcranial sonography (TCS) plays a crucial role in diagnosing Parkinson's disease. However, the intricate nature of TCS pathological features, the lack of consistent diagnostic criteria, and the dependence on physicians' expertise can hinder accurate diagnosis. Current TCS-based diagnostic methods, which rely on machine learning, often involve complex feature engineering and may struggle to capture deep image features. While deep learning offers advantages in image processing, it has not been tailored to address specific TCS and movement disorder considerations. Consequently, there is a scarcity of research on deep learning algorithms for TCS-based PD diagnosis. Methods: This study introduces a deep learning residual network model, augmented with attention mechanisms and multi-scale feature extraction, termed AMSNet, to assist in accurate diagnosis. Initially, a multi-scale feature extraction module is implemented to robustly handle the irregular morphological features and significant area information present in TCS images. This module effectively mitigates the effects of artifacts and noise. When combined with a convolutional attention module, it enhances the model's ability to learn features of lesion areas. Subsequently, a residual network architecture, integrated with channel attention, is utilized to capture hierarchical and detailed textures within the images, further enhancing the model's feature representation capabilities. Results: The study compiled TCS images and personal data from 1109 participants. Experiments conducted on this dataset demonstrated that AMSNet achieved remarkable classification accuracy (92.79%), precision (95.42%), and specificity (93.1%). It surpassed the performance of previously employed machine learning algorithms in this domain, as well as current general-purpose deep learning models. Conclusion: The AMSNet proposed in this study deviates from traditional machine learning approaches that necessitate intricate feature engineering. It is capable of automatically extracting and learning deep pathological features, and has the capacity to comprehend and articulate complex data. This underscores the substantial potential of deep learning methods in the application of TCS images for the diagnosis of movement disorders. [ABSTRACT FROM AUTHOR]

Background: Renal interstitial fibrosis (RIF) is a progressive, irreversible terminal kidney disease with a poor prognosis and high mortality. Angiopoietin-like 4 (ANGPTL4) is known to be associated with fibrosis in various organs, but its impact on the RIF process remains unclear. This study aimed to elucidate the role and underlying mechanisms of ANGPTL4 in the progression of RIF. Methods: In vivo, a chronic kidney disease (CKD) rat model of renal interstitial fibrosis was established via intragastric administration of adenine at different time points (4 and 6 weeks). Blood and urine samples were collected to assess renal function and 24-h urinary protein levels. Kidney tissues were subjected to HE and Masson staining for pathological observation. Immunohistochemistry and real-time quantitative PCR (qRT‒PCR) were performed to evaluate the expression of ANGPTL4 and hypoxia-inducible factor-1α (HIF-1α), followed by Pearson correlation analysis. Subsequently, kidney biopsy tissues from 11 CKD patients (6 with RIF and 5 without RIF) were subjected to immunohistochemical staining to validate the expression of ANGPTL4. In vitro, a fibrosis model of human renal tubular epithelial cells (HK2) was established through hypoxic stimulation. Subsequently, an HIF-1α inhibitor (2-MeOE2) was used, and ANGPTL4 was manipulated using siRNA or plasmid overexpression. Changes in ANGPTL4 and fibrosis markers were analyzed through Western blotting, qRT‒PCR, and immunofluorescence. Results: ANGPTL4 was significantly upregulated in the CKD rat model and was significantly positively correlated with renal injury markers, the fibrotic area, and HIF-1α. These results were confirmed by clinical samples, which showed a significant increase in the expression level of ANGPTL4 in CKD patients with RIF, which was positively correlated with HIF-1α. Further in vitro studies indicated that the expression of ANGPTL4 is regulated by HIF-1α, which in turn is subject to negative feedback regulation by ANGPTL4. Moreover, modulation of ANGPTL4 expression influences the progression of fibrosis in HK2 cells. Conclusion: Our findings indicate that ANGPTL4 is a key regulatory factor in renal fibrosis, forming a loop with HIF-1α, potentially serving as a novel therapeutic target for RIF. [ABSTRACT FROM AUTHOR]

Killer cell lectin-like receptor G1 (KLRG1) is an immune checkpoint receptor expressed predominantly in NK and T-cell subsets that downregulates the activation and proliferation of immune cells and participates in cell-mediated immune responses. Accumulating evidence has demonstrated the importance of KLRG1 as a noteworthy disease marker and therapeutic target that can influence disease onset, progression, and prognosis. Blocking KLRG1 has been shown to effectively mitigate the effects of downregulation in various mouse tumor models, including solid tumors and hematologic malignancies. However, KLRG1 inhibitors have not yet been approved for human use, and the understanding of KLRG1 expression and its mechanism of action in various diseases remains incomplete. In this review, we explore alterations in the distribution, structure, and signaling pathways of KLRG1 in immune cells and summarize its expression patterns and roles in the development and progression of autoimmune diseases, infectious diseases, and cancers. Additionally, we discuss the potential applications of KLRG1 as a tool for tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Carpal tunnel syndrome (CTS), an entrapment neuropathy caused by pressure of the median nerve, is a progressive condition that can lead to a decreased quality of life. Studies suggest an association between CTS and arthritis; however, previous studies examining osteoarthritis (OA) and CTS are limited in number, scope and study design. This study estimated the incidence and risk of CTS among patients with OA, both overall and by specific joints, in a large population-based cohort in the United States. Methods: Patients from the Optum claims database aged ≥ 45 years and diagnosed with OA between January 1, 2018, and December 31, 2022, were eligible for the OA cohort. The non-OA cohort included those without a diagnosis of OA at the index date and no history of OA for 12 months pre-index. Baseline characteristics were balanced using propensity score matching. The risk of CTS in the OA and non-OA cohort were evaluated using incidence rates and adjusted hazard ratios that were estimated using Cox regression. Results: After applying the inclusion/exclusion criteria, 3,610,240 of the 6,023,384 adults with a diagnosis of OA remained in the OA cohort. After propensity-score matching, each cohort included 1,033,439 individuals. The incidence rates for CTS per 1000 person-years were 7.35 (95% confidence interval [CI] 7.21–7.49) in the OA cohort and 1.44 (95% CI 1.38–1.50) in the non-OA cohort. The risk of developing CTS in patients with OA was ~ 4 times that of patients without (hazard ratio = 3.80; 95% CI 3.54–4.07). This increased risk was found across all OA joint types, with OA of the hand/wrist having the highest risk for CTS. Additionally, multiple OA joints presented a higher risk compared with a single affected joint. Conclusions: OA increases the risk of CTS, but this is not limited to patients with hand/wrist OA, suggesting a systemic impact of OA on CTS. While the risk appears highest for patients with hand/wrist OA, patients with more distant affected joints like knee or hip also have an increased risk of CTS. [ABSTRACT FROM AUTHOR]

Background: Acute type A aortic dissection (ATAAD) complicated by mesenteric malperfusion is a critical and complicated condition. The optimal treatment strategy remains controversial, debate exists as to whether aortic dissection or mesenteric malperfusion should be addressed first, and the exact time window for mesenteric ischemia intervention is still unclear. To solve this problem, we developed a new concept based on the pathophysiological mechanism of mesenteric ischemia, using a 6-hour time window to divide newly admitted patients by the time from onset to admission, applying different treatment protocols to improve the clinical outcomes of patients with ATAAD complicated by mesenteric malperfusion. Methods: This was a retrospective study that covered a five-year period. From July 2018 to December 2020(phase I), all patients underwent emergency open surgery. From January 2021 to June 2023(phase II), patients with an onset within 6 h all underwent open surgical repair, followed by immediately postoperative examination if the malperfusion is suspected, while the restoration of mesenteric perfusion and visceral organ function was performed first, followed by open repair, in patients with an onset beyond 6 h. Results: There were no significant differences in baseline and surgical data. In phase I, eleven patients with mesenteric malperfusion underwent open surgery, while in phase II, our novel strategy was applied, with sixteen patients with an onset greater than 6 h and eleven patients with an onset less than 6 h. During the waiting period, none died of aortic rupture, but four patients died of organ failure, twelve patients had organ function improvement and underwent surgery successfully survived. The overall mortality rate decreased with the use of this novel strategy (54.55% vs. 18.52%, p = 0.047). Furthermore, the surgical mortality rate between the two periods showed even stronger statistical significance (54.55% vs. 4.35%, p = 0.022). Moreover, the proportions of patients with sepsis and multiorgan failure also showed differences. Conclusions: Our novel strategy for patients with ATAAD complicated by mesenteric malperfusion not only improves the surgical success rate but also reduces the overall mortality rate. [ABSTRACT FROM AUTHOR]

Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia–reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown. In the present study, we investigated the roles of microglia-derived MPO/HOCl in mediating HMGB1 translocation and secretion, and aggravating the brain damage and blood-brain barrier (BBB) disruption in cerebral I/R injury. In vitro, under the co-culture conditions with microglia BV cells but not the single culture conditions, oxygen–glucose deprivation/reoxygenation (OGD/R) significantly increased MPO/HOCl expression in PC12 cells. After the cells were exposed to OGD/R, MPO-containing exosomes derived from BV2 cells were released and transferred to PC12 cells, increasing MPO/HOCl in the PC12 cells. The HOCl promoted disulfide HMGB1 translocation and secretion and aggravated OGD/R-induced apoptosis. In vivo, SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus different periods of reperfusion. Increased MPO/HOCl production was observed at the reperfusion stage, accomplished with enlarged infarct volume, aggravated BBB disruption and neurological dysfunctions. Treatment of MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) and HOCl scavenger taurine reversed those changes. HOCl was colocalized with cytoplasm transferred HMGB1, which was blocked by taurine in rat I/R-injured brain. We finally performed a clinical investigation and found that plasma HOCl concentration was positively correlated with infarct volume and neurological deficit scores in ischemic stroke patients. Taken together, we conclude that ischemia/hypoxia could activate microglia to release MPO-containing exosomes that transfer MPO to adjacent cells for HOCl production; Subsequently, the production of HOCl could mediate the translocation and secretion of disulfide HMGB1 that aggravates cerebral I/R injury. Furthermore, plasma HOCl level could be a novel biomarker for indexing brain damage in ischemic stroke patients. [ABSTRACT FROM AUTHOR]

Background: Neural Tube Defects (NTDs) are congenital malformations of the central nervous system resulting from the incomplete closure of the neural tube during early embryonic development. Neuroinflammation refers to the inflammatory response in the nervous system, typically resulting from damage to neural tissue. Immune-related processes have been identified in NTDs, however, the detailed relationship and underlying mechanisms between neuroinflammation and NTDs remain largely unclear. In this study, we utilized integrated multi-omics analysis to explore the role of neuroinflammation in NTDs and identify potential prenatal diagnostic markers using a murine model. Methods: Nine public datasets from Gene Expression Omnibus (GEO) and ArrayExpress were mined using integrated multi-omics analysis to characterize the molecular landscape associated with neuroinflammation in NTDs. Special attention was given to the involvement of macrophages in neuroinflammation within amniotic fluid, as well as the dynamics of macrophage polarization and their interactions with neural cells at single-cell resolution. We also used qPCR assay to validate the key TFs and candidate prenatal diagnostic genes identified through the integrated analysis in a retinoic acid-induced NTDs mouse model. Results: Our analysis indicated that neuroinflammation is a critical pathological feature of NTDs, regulated both transcriptionally and epigenetically within central nervous system tissues. Key alterations in gene expression and pathways highlighted the crucial role of STATs molecules in the JAK-STAT signaling pathway in regulating NTDs-associated neuroinflammation. Furthermore, single-cell resolution analysis revealed significant polarization of macrophages and their interaction with neural cells in amniotic fluid, underscoring their central role in mediating neuroinflammation associated with NTDs. Finally, we identified a set of six potential prenatal diagnostic genes, including FABP7, CRMP1, SCG3, SLC16A10, RNASE6 and RNASE1, which were subsequently validated in a murine NTDs model, indicating their promise as prospective markers for prenatal diagnosis of NTDs. Conclusions: Our study emphasizes the pivotal role of neuroinflammation in the progression of NTDs and underlines the potential of specific inflammatory and neural markers as novel prenatal diagnostic tools. These findings provide important clues for further understanding the underlying mechanisms between neuroinflammation and NTDs, and offer valuable insights for the future development of prenatal diagnostics. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy brings new hope to patients with advanced gastric cancer. However, liver metastases can reduce the efficacy of immunotherapy in patients. Tumor-associated macrophages (TAMs) may be the cause of this reduction in efficacy. SPP1 + TAMs are considered to have immunosuppressive properties. We aimed to investigate the involvement of SPP1 + TAMs in the metastasis of gastric cancer. Methods: The single-cell transcriptome was combined with batched BULK datasets for analysis. Animal models were used to verify the analysis results. Results: We reveal the interaction of SPP1 + TAMs with CD8 + exhausted T cells in metastatic cancer. Among these interactions, GDF15-TGFBR2 may play a key immunosuppressive role. We constructed an LR score to quantify interactions based on ligands and receptors. The LR score is highly correlated with various immune features and clinical molecular subtypes. The LR score may also guide the prediction of the efficacy of immunotherapy and prognosis. Conclusions: The crosstalk between SPP1 + TAMs and CD8 + exhausted T cells plays a key immunosuppressive role in the gastric metastatic cancer microenvironment. [ABSTRACT FROM AUTHOR]

The application of nano fertilizers is one of the hotspots in current agricultural production. In this study, nano silicon materials were mixed with compound fertilizers to make nano silicon fertilizer. The effects of different amounts of nano silicon application on the breaking-resistance strength, lodging-resistance index, lignin accumulation, lignin synthesis related enzymes, and the relative expression of lignin synthesis related genes in the second stem node of wheat were mainly studied. Four treatments were set up: CK (750 kg·ha−1 compound fertilizer), T1 (750 kg·ha−1 compound fertilizer + 0.9 kg·ha−1 nano silicon), T2 (750 kg·ha−1 compound fertilizer + 1.8 kg·ha−1 nano silicon), T3 (750 kg·ha−1 compound fertilizer + 2.7 kg·ha−1 nano silicon). The results of the two-year experiment showed that the breaking-resistance strength, lodging-resistance index, lignin accumulation in the second stem node of wheat treated with nano silicon fertilizer were higher than CK. In the first year of the experiment, the lignin accumulation of T2 was 130.73%, 5.14% and 7.25% higher than that of CK, T1 and T3 respectively at the maturity stage. In the second year of the experiment, the lignin accumulation of T2 was 20.33%, 11.19% and 9.89% higher than that of CK, T1 and T3 respectively at the maturity stage. And the activities of PAL, 4CL, CAD, and related gene expression levels were also higher than CK. And among them, T2 performed the best, indicating that the application of nano silicon fertilizer is beneficial for improving the lodging resistance of wheat stems and is of great significance for improving the quality of wheat. [ABSTRACT FROM AUTHOR]

Background: Uveitis and posterior scleritis are sight-threatening diseases with undefined pathogenesis and accurate diagnosis remains challenging. Methods: Two plasma-derived extracellular vesicle (EV) subpopulations, small and large EVs, obtained from patients with ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis were subjected to proteomics analysis alongside plasma using SWATH-MS. A comprehensive bioinformatics analysis was performed on the proteomic profiles of sEVs, lEVs, and plasma. Candidate biomarkers were validated in a new cohort using ELISA. Pearson correlation analysis was performed to analyze the relationship between clinical parameters and proteomic data. Connectivity map database was used to predict therapeutic agents. Results: In total, 3,668 proteins were identified and over 3000 proteins were quantified from 278 samples. When comparing diseased group to healthy control, the proteomic profiles of the two EV subgroups were more correlated with disease than plasma. Comprehensive bioinformatics analysis highlighted potential pathogenic mechanisms for these diseases. Potential biomarker panels for four diseases were identified and validated. We found a negative correlation between plasma endothelin-converting enzyme 1 level and mean retinal thickness. Potential therapeutic drugs were proposed, and their targets were identified. Conclusions: This study provides a proteomic landscape of plasma and EVs involved in ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis, offers insights into disease pathogenesis, identifies valuable biomarker candidates, and proposes promising therapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Langerhans cell histiocytosis (LCH) is a rare disorder. The treatment options vary depending on how many organs are involved and how extensive the disease is. In this report, a case of LCH with isolated 6th cervical vertebra (C6) collapse was presented. This case was treated with anterior corpectomy and instrumented fusion, followed by local radiotherapy (RT), with a good clinical outcome up to postoperative six months. Case presentation: This was a 47-year-old female patient with a complaint of neck pain and bilateral shoulder pain for two months before consultation. She was initially treated with analgesics, but the pain was persistent. Further radiological evaluations revealed an osteolytic lesion within the C6 vertebral body with a pathological fracture. Magnetic resonance imaging (MRI) with contrast of the cervical spine revealed diffused hypointense signal changes on the T1-weighted images and hyperintense signal changes on the T2-weighted images in the C6 vertebral body, with significant contrast-enhanced infiltration signals. Furthermore, in positron emission tomography-computed tomography (PET-CT), focal hypermetabolism and abnormal uptake signals were seen only in the C6 vertebral body. The patient underwent an anterior cervical corpectomy with instrumented fusion. The histopathological results confirmed the diagnosis of LCH. The patient reported significant pain relief on postoperative day one. Moreover, she was treated by local RT at postoperative one month. Good clinical outcomes were achieved in the form of no pain and recovery in neck mobility up to postoperative six months. No evidence of recurrence was observed at the final follow-up. Conclusions: This case report describes a treatment option for a solitary C6 collapse with LCH managed by anterior corpectomy and instrumented fusion, followed by local RT, with a good clinical outcome at postoperative six months. More studies are needed to elucidate whether such a treatment strategy is superior to surgery or RT alone. [ABSTRACT FROM AUTHOR]

Background: Radiation-induced lung injury (RILI) is considered one of the most common complications of thoracic radiation. Recent studies have focused on stem cell properties to obtain ideal therapeutic effects, and Sox9 has been reported to be involved in stem cell induction and differentiation. However, whether Sox9-expressing cells play a role in radiation repair and regeneration remains unknown. Methods: We successfully obtained Sox9CreER, RosatdTomato and RosaDTA mice and identified Sox9-expressing cells through lineage tracing. Then, we evaluated the effects of the ablation of Sox9-expressing cells in vivo. Furthermore, we investigated the underlying mechanism of Sox9-expressing cells during lung regeneration via an online single-cell RNA-seq dataset. Results: In our study, we demonstrated that Sox9-expressing cells promote the regeneration of lung tissues and that ablation of Sox9-expressing cells leads to severe phenotypes after radiation damage. In addition, analysis of an online scRNA-Seq dataset revealed that the PI3K/AKT pathway is enriched in Sox9-expressing cells during lung epithelium regeneration. Finally, the AKT inhibitor perifosine suppressed the regenerative effects of Sox9-expressing cells and the AKT pathway agonist promotes proliferation and differentiation. Conclusions: Taken together, the findings of our study suggest that Sox9-expressing cells may serve as a therapeutic target in lung tissue after RILI. [ABSTRACT FROM AUTHOR]

Background: G protein-coupled receptors (GPR) are involved in a wide range of physiological processes, some of which, however, can be hijacked by tumor cells. Over-expression of G protein-coupled receptors 137 (GPR137) are associated with the growth of tumor cells, but under-expression of GPR137 has shown to inhibit cell proliferation in several different types of cancers. Currently, the role of GPR137 in leukemia is still unclear. In this study, the effect of under-expression of GPR137 on inhibiting the proliferation of leukemia cells is explored, to identify a novel target for leukemia treatment. Materials and methods: In this study, lentivirus-mediated RNA interference (RNAi) was employed to investigate the role of GPR137 in two leukemia cell lines K562 and HL60. The gene expression of GPR137 was analyzed by RT-PCR and its protein expression was determined by Western blot. Flow cytometry and Annexin V/7-AAD Apoptosis Detection Kit was used respectively in cell cycle and apoptosis analysis. The protein expression of CyclinD1, CDK4, BCL-2 and caspase-3 were also determined. Results: There was high level of constitutive expression of GPR137 in leukemia cancer cell lines K562 and HL60. Lentivirus-mediated RNAi could significantly down-regulate gene and protein expression of GPR137 in both cell lines. Down regulation of GPR137 was associated with the reduction in proliferation rate and colony forming capacity. In addition, down regulation of GPR137 arrested cells in the G0/G1 phase of cell cycle and induced apoptosis in both leukemia cell lines K562 and HL60. Conclusions: The expression of GPR137 is associated with the proliferation of leukemia cell lines. Down regulation of GPR137 could inhibit proliferation and promote apoptosis in leukemia cells, which makes it a promising bio-marker and therapeutic target to treat patients with leukemia. [ABSTRACT FROM AUTHOR]

Background: Elevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood.Methods: The cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B. The activation state of microglia was assessed via immunoreaction using the microglial markers Iba1 and OX-42. Then, the inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) were examined by Western blot analysis and fluorescence immunohistochemistry.Results: Elevated Hcy level augmented brain damage and neural cell toxicity in the brain cortex and the dentate gyrus region of the hippocampus after cerebral ischemia/reperfusion. Meanwhile, Hcy activated microglia and induced the expression of the inflammatory factors such as TNF-α and IL-6. Moreover, Hcy caused an increase in pSTAT3 expression which occurs in microglial cells. AG490, a JAK2-STAT3 inhibitor, effectively inhibited the phosphorylation of STAT3, microglial cell activation and the secretion of IL-6, TNF-α raised by Hcy treatment.Conclusions: STAT3 signaling pathway located in microglia plays a critical role in mediating Hcy-induced activation of microglia and neuroinflammation in rat MCAO model. This suggests the feasibility of targeting the JAK2/STAT3 pathway as an effective therapeutic strategy to alleviate the progression of Hcy-associated ischemia stroke. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the impact of hypertension with or without diabetes on left ventricular (LV) remodeling in rural Chinese population.Methods: A total of 10,270 participants were classified into control group, hypertension without diabetes (HT) group, and hypertension with diabetes (HT + DM) group. We compared clinical characteristics and echocardiographic parameters, and used multivariable logistic regression analysis to assess the associations of interest.Results: HT + DM group had higher interventricular septal thickness (IVSd), posterior wall thickness (PWTd), left ventricular mass (LVM), LVM index (LVMI), relative wall thickness (RWT), left atrial diameter (LAD), A wave and lower E wave than HT group (all P < 0.05). The prevalence rates of left ventricular hypertrophy (LVH) and abnormal geometry were statistically different among three groups (P < 0.001) and eccentric hypertrophy was the highest proportion of geometry abnormality. Logistic regression analysis suggested that subjects in HT and HT + DM groups had odds ratio (OR) values of 2.81, 4.41, 2.24 and 3.94, 7.20, 2.38 for LVH, concentric hypertrophy and eccentric hypertrophy in the total population, respectively, compared to control group. When compared with HT group, those in HT + DM group had approximately 1.40-, 1.61- and 1.38-, 1.71-fold increased risk for LVH and concentric hypertrophy in the total and female population separately, but no association of HT + DM with LVH and abnormal geometrical patterns was found in men.Conclusions: This study demonstrated that, to varying degrees, hypertension was associated with LV remodeling in rural Chinese population, and this risk association was obviously increased for LVH and concentric hypertrophy when accompanied by diabetes, especially for women. [ABSTRACT FROM AUTHOR]

Background: Studies regarding the association between prehypertension and the structual changes of left heart are scanty. However, which type of the geometrical change of left heart is predominated one in prehypertension and hypertension is controversial. It is therefore important to investigate geometrical and functional changes of left heart in adults with prehypertension and hypertension because of their prognostic significance.Methods: The study was based on a cross-sectional design, a total of 10547 participants were classified into normotension group, prehypertension group and hypertension group. We analyzed clinical characteristics, echocardiographic parameters and distribution of left ventricular (LV) geometrical patterns in different groups.Results: Participants with prehypertension had higher values of most of echocardiographic parameters than those with normotension. The prevalence of left ventricular hypertrophy(LVH) was statistically different among three groups (P <0.001), and the rates of LVH in the three groups were 5.9, 8.6, 28.4 % by indexation to height(2.7) and 4.9, 5.3, 19.3 % by indexation to BSA, respectively. The prevalence rates of eccentric hypertrophy, concentric remodeling and concentric hypertrophy were 7.3 %, 5.3 % and 1.4 % in prehypertension group, and 17.8 %, 8.8 % and 10.6 % in hypertension group. Logistic regression analysis showed that systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean artery pressure (MAP) were all independent risk factors for left cardiac structural changes, and pulse pressure (PP) was independent risk factor for concentric and eccentric hypertrophy. Among four indices, DBP levels with OR values of 1.192, 1.759 and 1.278 were the strongest indicator for concentric remodeling, concentric hypertrophy and eccentric hypertrophy, respectively (P <0.001).Conclusions: There exists LV geometrical change in adults with prehypertension and hypertension in rural Chinese population, and the eccentric hypertrophy was the highest proportion of geometric alterations. SBP, DBP, MAP and PP were all positively associated with left cardiac structural changes, and the association of DBP was the strongest. [ABSTRACT FROM AUTHOR]

Background: Anti-angiogenic therapies demonstrate anti-tumor effects by decreasing blood supply to tumors and inhibiting tumor growth. However, anti-angiogenic therapy may leads to changes in tumor microenvironment and increased invasiveness of tumor cells, which in turn promotes distant metastasis and increased drug resistance. Methods: The CO-IP assays, N-STORM and cytoskeleton analysis were used to confirm the mechanism that p-VEGFR2/VE-cadherin/β-catenin/actin complex regulates vascular remodeling and improves the tumor microenvironment. 6-gingerol (6G), the major bioactive component in ginger, stabilized this complex by enhancing the binding of VEGFa to VEGFR2 with non-pathway dependent. Biacore, pull down and molecular docking were employed to confirm the interaction between 6G and VEGFR2 and enhancement of VEGFa binding to VEGFR2. Results: Here, we report that microvascular structural entropy (MSE) may be a prognostic factor in several tumor types and have potential as a biomarker in the clinic. 6G regulates the structural organization of the microvascular bed to decrease MSE via the p-VEGFR2/VE-cadherin/β-catenin/actin complex and inhibit tumor progression. 6G promotes the normalization of tumor vessels, improves the tumor microenvironment and decreases MSE, facilitating the delivery of chemotherapeutic agents into the tumor core and thereby reducing tumor growth and metastasis. Conclusions: This study demonstrated the importance of vascular normalization in tumor therapy and elucidated the mechanism of action of ginger, a medicinal compound that has been used in China since ancient times. [ABSTRACT FROM AUTHOR]

Background: Elevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood., Methods: The cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B. The activation state of microglia was assessed via immunoreaction using the microglial markers Iba1 and OX-42. Then, the inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) were examined by Western blot analysis and fluorescence immunohistochemistry., Results: Elevated Hcy level augmented brain damage and neural cell toxicity in the brain cortex and the dentate gyrus region of the hippocampus after cerebral ischemia/reperfusion. Meanwhile, Hcy activated microglia and induced the expression of the inflammatory factors such as TNF-α and IL-6. Moreover, Hcy caused an increase in pSTAT3 expression which occurs in microglial cells. AG490, a JAK2-STAT3 inhibitor, effectively inhibited the phosphorylation of STAT3, microglial cell activation and the secretion of IL-6, TNF-α raised by Hcy treatment., Conclusions: STAT3 signaling pathway located in microglia plays a critical role in mediating Hcy-induced activation of microglia and neuroinflammation in rat MCAO model. This suggests the feasibility of targeting the JAK2/STAT3 pathway as an effective therapeutic strategy to alleviate the progression of Hcy-associated ischemia stroke.