Prognostic insights, immune infiltration, and therapeutic response: Cytoplasmic poly(A) tail regulators in hepatocellular carcinoma.

The presence of a poly(A) tail is indispensable for the post-transcriptional regulation of gene expression in cancer. This dynamic and modifiable feature of transcripts is under the control of various nuclear and cytoplasmic proteins. This study aimed to develop a novel cytoplasmic poly(A)-related signature for predicting prognosis, clinical attributes, tumor immune microenvironment (TIME), and treatment response in hepatocellular carcinoma (HCC). Utilizing RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), non-negative matrix factorization (NMF), and principal-component analysis (PCA) were employed to categorize HCC patients into three clusters, thus demonstrating the pivotal prognostic role of cytoplasmic poly(A) tail regulators. Furthermore, machine learning algorithms such as least absolute shrinkage and selection operator (LASSO), survival analysis, and Cox proportional hazards modeling were able to distinguish distinct cytoplasmic poly(A) subtypes. As a result, a 5-gene signature derived from TCGA was developed and validated using International Cancer Genome Consortium (ICGC) HCC datasets. This novel classification based on cytoplasmic poly(A) regulators has the potential to improve prognostic predictions and provide guidance for chemotherapy, immunotherapy, and transarterial chemoembolization (TACE) in HCC.

Effect of hydroxy-α-sanshool on lipid metabolism in liver and hepatocytes based on AMPK signaling pathway.

BACKGROUND: With the increasing awareness of the safety of traditional Chinese medicine and food, as well as in-depth studies on the pharmacological activity and toxicity of Zanthoxylum armatum DC. (ZADC), it has been found that ZADC is hepatotoxic. However, the toxic substance basis and mechanism of action have not been fully elucidated. Hydroxy-α-sanshool (HAS) belongs to an amide compound in the fruits of ZADC, which may be hepatotoxic. However, the specific effects of HAS, including liver toxicity, are unclear. PURPOSE: The objectives of this research was to determine how HAS affects hepatic lipid metabolism, identify the mechanism underlying the accumulation of liver lipids by HAS, and offer assurances on the safe administration of HAS. METHODS: An in vivo experiment was performed by gavaging C57 BL/6 J mice with various dosages of HAS (5, 10, and 20 mg/kg). Biochemical indexes were measured, and histological analysis was performed to evaluate HAS hepatotoxicity. Hepatic lipid levels were determined using lipid indices and oil red O (ORO) staining. Intracellular lipid content were determined by biochemical analyses and ORO staining after treating HepG2 cells with different concentrations of HAS in vitro. Mitochondrial membrane potential, respiratory chain complex enzymes, and ATP levels were assessed by fluorescence labeling of mitochondria. The levels of proteins involved in lipogenesis and catabolism were determined using Western blotting. RESULTS: Mice in the HAS group had elevated alanine and aspartate aminotransferase blood levels as well as increased liver index compared with the controls. The pathological findings showed hepatocellular necrosis. Serum and liver levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were increased, whereas high-density lipoprotein cholesterol levels decreased. The ORO staining findings demonstrated elevated liver lipid levels. In vitro experiments demonstrated a notable elevation in triglyceride and total cholesterol levels in the HAS group. ATP, respiratory chain complex enzyme gene expression, mitochondrial membrane potential, and mitochondrial number were reduced in the HAS group. The levels of lipid synthesis-associated proteins (ACC, FASN, and SREBP-1c) were increased, and lipid catabolism-associated protein levels (PPARα and CPT1) and the p-AMPK/AMPK ratio were decreased in vivo and in vitro. CONCLUSION: HAS has hepatotoxic effects, which can induce fatty acid synthesis and mitochondrial function damage by inhibiting the AMPK signaling pathway, resulting in aberrant lipid increases.

Asymmetric three-component Tsuji-Trost allylation reaction enabled by chiral aldehyde/palladium combined catalysis.

Despite the long-standing exploration of the catalytic asymmetric Tsuji-Trost allylation reaction since the mid-20th century, most reported instances have adhered to a two-component approach. Here, we present a remarkably efficient three-component asymmetric allylation reaction enabled by the collaborative action of chiral aldehyde and palladium. A diverse array of NH2-unprotected amino acid esters, aryl or alkenyl iodides, and allyl alcohol esters exhibit robust participation in this reaction, resulting in the synthesis of structurally diverse non-proteinogenic α-amino acid esters with favorable experimental outcomes. Mechanistic investigations reveal the dominance of the allylation/Heck coupling cascade in reactions involving electron-rich aryl iodides, while the Heck coupling/allylation cascade emerges as the dominant pathway in reactions involving electron-deficient aryl iodides. This chiral aldehyde/palladium combining catalytic system precisely governs the chemoselectivity of C-allylation and N-allylation, the regioselectivity of linear and branched allylation, and the enantioselectivity of C-allylation products.

The first specific probe for pyrrolidine with multifunction by the interaction mechanism of atomic economic reaction.

Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10-6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

Statin use and fall risk in adults: a cross-sectional survey and mendelian randomization analysis.

Background and Objective: The issue of falls poses a significant threat to the health of the elderly population. Although statins can cause myopathy, which implies that they may cause balance problems and increase the risk of falling, this has not been tested. Our objective was to assess whether the use of statins is linked to a higher risk of falls. Methods: A cross-sectional survey study and Mendelian randomization (MR) study were conducted to examine whether the use of statins was associated with an increased risk of falling and balance problems. The cross-sectional study included 2,656 participants from the US population (NHANES) who reported information on balance and falling problems in the past year and their use of statins. Univariate and multivariate logistic regression models were used to investigate the association between statin use and the likelihood of falling or experiencing balance problems. The MR study identified five Single Nucleotide Polymorphisms (SNPs) that predict statin use across five ancestry groups: Admixed African or African, East Asian, European, Hispanic, and South Asian. Additionally, SNPs predicting the risk of falls were acquired from the UK Biobank population. A two-sample MR analysis was performed to examine whether genetically predicted statin use increased the risk of falls. Results: The use of statins was found to be associated with an increased likelihood of balance and falling problems (balance problem, OR 1.25, 95%CI 1.02 to 1.55; falling problem, OR 1.27, 95%CI 1.03-1.27). Subgroup analysis revealed that patients under the age of 65 were more susceptible to these issues when taking statins (balance problem, OR 3.42, 95%CI 1.40 to 9.30; falling problem, OR 5.58, 95%CI 2.04-15.40). The MR analysis indicated that the use of statins, as genetically proxied, resulted in an increased risk of falling problems (OR 1.21, 95% CI 1.1-1.33). Conclusion: Our study found an association between the use of statins and an increased risk of balance problems and falls in adults over 40 years old, and the MR study result suggested statin use increased risk of falls. The risk was higher in participants under 65 years old compared to those over 65 years old.

Effect of time-restricted eating regimen on weight loss is mediated by gut microbiome.

Time-restricted eating (TRE) is a promising obesity management strategy, but weight-loss efficacy varies among participants, and the underlying mechanism is unclear. The study aimed to investigate the role of gut microbiota in weight-loss response during long-term TRE intervention. We analyzed data from 51 obese adults in a 12-month TRE program, categorizing them into distinct weight loss groups (DG) and moderate weight loss groups (MG) based on their TRE responses. Shotgun metagenomic sequencing analysis revealed a significant increase in species closely associated with weight loss effectiveness and metabolic parameter changes in the DG group. Pathways related to fatty acid biosynthesis, glycogen biosynthesis, and nucleotide metabolism were reduced in the DG group and enhanced in the MG group. Next, we identified nine specific species at baseline that contributed better responses to TRE intervention and significant weight loss. Collectively, gut microbiota contributes to responsiveness heterogeneity in TRE and can predict weight-loss effectiveness.

The Role of Short Chain Fatty Acids in Inflammation and Body Health.

Short chain fatty acids (SCFAs), mainly including acetate, propionate and butyrate, are produced by intestinal bacteria during the fermentation of partially digested and indigestible polysaccharides. SCFAs play an important role in regulating intestinal energy metabolism and maintaining the homeostasis of the intestinal environment and also play an important regulatory role in organs and tissues outside the gut. In recent years, many studies have shown that SCFAs can regulate inflammation and affect host health, and two main signaling mechanisms have also been identified: the activation of G-protein coupled receptors (GPCRs) and inhibition of histone deacetylase (HDAC). In addition, a growing body of evidence highlights the importance of every SCFA in influencing health maintenance and disease development. In this review, we summarized the recent advances concerning the biological properties of SCFAs and their signaling pathways in inflammation and body health. Hopefully, it can provide a systematic theoretical basis for the nutritional prevention and treatment of human diseases.

Carbon defects-enriched NBC-C3N5@CoMn with ultrafast modulation of redox couples for efficient degradation of contaminant.

The inefficiency of catalysts in sulfate radical-based advanced oxidation processes (SR-AOPs) is primarily attributed to the sluggish circulation of redox couples. Herein, a carbon defects-enriched NBC-C3N5@CoMn (NCC) was synthesized through a self-assembly approach. The carbon defects within the NCC induce the electron trap effect, thereby facilitating the efficient cycling of redox couples in photo-Fenton-like processes during contaminant degradation. This effect enables the self-regeneration of the NCC catalyst. The reductive redox couples (Co (II) and Mn (II)) are continuously regenerated following the degradation process. Within the NCC, CoMn layered double hydroxides (LDHs) act as primary active sites, promoting the generation of hydroxyl radicals (•OH), sulfate radicals (SO4•-) and singlet oxygen (1O2) through continuous electron gain and loss. Additionally, the internal electric field established within the NCC further accelerates electron transfer. Density Functional Theory (DFT) calculations confirm that the carbon defects-enriched NCC exhibits lower adsorption energies and higher electron transfer efficiencies than carbon defect-deficient NCC. This study introduces a novel photocatalyst with self-regenerating capabilities, presenting an innovative approach to regulate redox couples in SR-AOPs for sustainable degradation.

Role of angiotensin converting enzyme in pathogenesis associated with immunity in cardiovascular diseases.

Angiotensin converting enzyme (ACE) is not only a critical component in the renin-angiotensin system (RAS), but also suggested as an important mediator for immune response and activity, such as immune cell mobilization, metabolism, biogenesis of immunoregulatory molecules, etc. The chronic duration of cardiovascular diseases (CVD) has been increasingly considered to be triggered by uncontrolled pathologic immune reactions from myeloid cells and lymphocytes. Considering the potential anti-inflammatory effect of the traditional antihypertensive ACE inhibitor (ACEi), we attempt to elucidate whether ACE and its catalytically relevant substances as well as signaling pathways play a role in the immunity-related pathogenesis of common CVD, such as arterial hypertension, atherosclerosis and arrythmias. ACEi was also reported to benefit the prognoses of COVID-19-positive patients with CVD, and COVID-19 disease with preexisting CVD or subsequent cardiovascular damage is featured by a significant influx of immune cells and proinflammatory molecules, suggesting that ACE may also participate in COVID-19 induced cardiovascular injury, because COVID-19 disease basically triggers an overactive pathologic immune response. Hopefully, the ACE inhibition and manipulation of those associated bioactive signals could supplement the current medicinal management of various CVD and bring greater benefit to patients' cardiovascular health.

[Exploring the mechanism of IgA vasculitis pathogenesis through the interaction of thrombin and inflammatory factors using urinary proteomics]. / è¿ç”¨å°¿è›‹ç™½ç»„å­¦æŠ€æœ¯æŽ¢ç´¢å‡è¡€é ¶ä¸Žç‚Žç—‡å› å­ç›¸äº’ä½œç”¨å‚ä¸ŽIgAè¡€ç®¡ç‚Žå‘ç— çš„æœºåˆ¶.

OBJECTIVES: To explore the evidence, urinary biomarkers, and partial mechanisms of hypercoagulability in the pathogenesis of IgA vasculitis (IgAV). METHODS: Differential expression of proteins in the urine of 10 healthy children and 10 children with IgAV was screened using high-performance liquid chromatography-tandem mass spectrometry, followed by Reactome pathway analysis. Protein-protein interaction (PPI) network analysis was conducted using STRING and Cytoscape software. In the validation cohort, 15 healthy children and 25 children with IgAV were included, and the expression levels of differential urinary proteins were verified using enzyme-linked immunosorbent assay. RESULTS: A total of 772 differential proteins were identified between the IgAV group and the control group, with 768 upregulated and 4 downregulated. Reactome pathway enrichment results showed that neutrophil degranulation, platelet activation, and hemostasis pathways were involved in the pathogenesis of IgAV. Among the differential proteins, macrophage migration inhibitory factor (MIF) played a significant role in neutrophil degranulation and hemostasis, while thrombin was a key protein in platelet activation and hemostasis pathways. PPI analysis indicated that thrombin directly interacted with several proteins involved in inflammatory responses, and these interactions involved MIF. Validation results showed that compared to healthy children, children with IgAV had significantly higher urine thrombin/creatinine and urine MIF/creatinine levels (P<0.05). CONCLUSIONS: Thrombin contributes to the pathogenesis of IgAV through interactions with inflammatory factors. Urinary thrombin and MIF can serve as biomarkers reflecting the hypercoagulable and inflammatory states in children with IgAV.

Neoadjuvant anthracycline followed by toripalimab combined with nab-paclitaxel in patients with early triple-negative breast cancer (NeoTENNIS): a single-arm, phase II study.

Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II-III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3-67.6) and 41 of 70 (58.6%, 95% CI 46.2-70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1-2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

Safety and efficacy of a modified endoscopic full-thickness resection technique for gastric submucosal tumors: a case series.

Objectives: Endoscopic full-thickness resection (EFTR) has proven effective and economical for patients with gastric submucosal tumors (SMTs). However, the poor operative field of view, the risk of massive hemorrhage, and the difficulties in defect closure have limited its widespread application. Herein, we described a modified EFTR technique developed to simplify the dissection and defect closure procedures using common and economical endoscopic accessories. Methods: Forty-two patients who underwent the modified EFTR for gastric SMTs in the Shenzhen Guangming District People's Hospital were enrolled in the case series. Following a cross incision to expose the intraluminal surface the tumors were captured by suction through a transparent cap and the roots were ligated using a loop. The tumors and part of the suction tissue were removed along the ligated root. A tension-relieving closure was performed by clipping the raised plica in four quadrants outside the ligated root. Patient demographics, tumor characteristics, and therapeutic outcomes were evaluated retrospectively. Results: All tumors had an R0 resection. The median procedure time was 51.8 min (IQR 34.25 min). No severe perioperative adverse events occurred. No residual lesion or recurrence was reported during the follow-up period of 9.84 months (IQR 5.0 months). Conclusion: The safety and practicability of Modified-EFTR could allow for wide clinical application in patients with micro-gastric SMTs.

Unpaired Image-text Matching via Multimodal Aligned Conceptual Knowledge.

Recently, the accuracy of image-text matching has been greatly improved by multimodal pretrained models, all of which use millions or billions of paired images and texts for supervised model learning. Different from them, human brains can well match images with texts using their stored multimodal knowledge. Inspired by that, this paper studies a new scenario as unpaired image-text matching, in which paired images and texts are assumed to be unavailable during model learning. To deal with it, we accordingly propose a simple yet effective method namely Multimodal Aligned Conceptual Knowledge (MACK). First, we collect a set of words and their related image regions from publicly available datasets, and compute prototypical region representations to obtain pretrained general knowledge. To make the obtained knowledge better suit for certain datasets, we refine it using unpaired images and texts in a self-supervised learning manner to obtain fine-tuned domain knowledge. Then, to match given images with texts based on the knowledge, we represent parsed words in the texts by prototypical region representations, and compute region-word similarity scores. At last, the scores are aggregated based on bidirectional similarity pooling into an image-text similarity score, which can be directly used for unpaired image-text matching. The proposed MACK is complementary with existing models, which can be easily extended as a re-ranking method to substantially improve their performance of zero-shot and cross-dataset image-text matching.

Micro-Computed Tomography Analysis of Resin and Calcium Silicate Based Sealers Removal in Mandibular Molars Curved Canals.

Objective: The removal of the root canal sealer is an important factor in nonsurgical retreatment. The aim of this study was to compare the removal of AH Plus, Well Root ST, and AH Plus Bioceramic Sealer using Protaper Universal retreatment files. Methods: The curved mesio-buccal canals of extracted mandibular molars were prepared with the Protaper Gold file system (up to F2). Specimens were randomly divided into 3 groups and filled with the single cone technique using AH Plus, Well-Root ST, and AH Plus Bioceramic Sealer, respectively. After two weeks, the root canal filling of all specimens was removed using Protaper Universal retreatment files. All specimens were scanned using micro-CT. The remaining volume of the root canal filling was recorded in total and the coronal, middle, and apical third of each specimen. Results: Well-Root ST and AH Plus Bioceramic Sealer groups had a higher percentage of total remaining filling material than the AH Plus group (P<0.05). Conclusion: This study has shown that the volume of remaining root canal filling was significantly higher in the samples filled with calcium silicate-based sealers.

Deficits of the "Good" Eye in Amblyopia: Processing Geometric Properties.

Purpose: Although fellow eyes of amblyopia are typically considered normal, recent studies have revealed impairments in certain aspects of vision. However, it remains unclear at which level of object processing these impairments occur. This study aims to investigate the functional level of visual perception impairment in the fellow eye of children and adults with amblyopia using the geometric functional hierarchy discrimination task based on Klein Mathematics methodology. Methods: Seventy-six patients with amblyopia (40 children and 36 adults) and 77 age-matched healthy controls (40 children and 37 adults) were recruited for this study. The participants completed four sets of geometric hierarchies (in ascending order of stability: Euclidean, affine, projective, and topology) and one set of color discrimination tasks. They were instructed to rapidly and accurately select a distinct shape from the four quadrants. Results: The participants' performance was evaluated using the inverse efficiency (IE) score (IE = response time (RT)/accuracy). The results of IEs show that the fellow eye of children with amblyopia exhibits normal topological processing, yet displays higher IEs in other geometric properties and color processing, suggesting impairments in these specific discrimination abilities. However, adults with amblyopia did not show deficits on any discrimination types compared with adult controls. Conclusions: The lack of compromised topological processing suggests that amblyopia may not have inflicted any damage to the subcortical visual pathways. Furthermore, these deficits observed in the fellow eye tend to diminish significantly during adulthood, implying that amblyopia may potentially hinder the maturation process of the fellow eye.

TGF-ß1 mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neural functional recovery in Parkinson's disease models and patients.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. METHODS: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. RESULTS: A functional assay identified that transforming growth factor-ß1 (TGF-ß1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-ß1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. CONCLUSIONS: These findings provide compelling evidence for the involvement of TGF-ß1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-ß1 may be used alone or combined with hOM-MSCs therapy for treating PD.

RBM3 Inhibits the Cell Cycle of Cutaneous Squamous Cell Carcinoma through the PI3K/AKT Signaling Pathway.

BACKGROUND: RBM3 is a key RNA-binding protein that has been implicated in various cellular processes, including cell proliferation and cell cycle regulation. However, its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. AIMS: We aimed to investigate the expression levels of RNA-binding motif protein 3 (RBM3) in patients with cSCC and evaluate its effect on cell ability in cSCC and its underlying regulatory mechanisms. METHODS: The expression of RBM3 in cSCC tissues and A431 cells was determined via immunohistochemistry and western blotting. Plenti-CMV-RBM3- Puro was used to overexpress RBM3. The effect of RBM3 on the proliferation ability of cSCC cells was evaluated using MTT and colony formation assay. Cell apoptosis and cell cycle were determined using flow cytometry, while the protein expressions of BAX, NF-κB, BCL2, CASPASE 3, CYCLIN B, CYCLIN E, CDK1, phosphorylated (P)-CDK1, CDK2, P-CDK2, ERK, P-ERK, P-AMPK, AKT, P-AKT, MDM2, and P53 were assessed using western blotting. RESULTS: RBM3 expression was significantly downregulated in cSCC tissues and A431 cells. RBM3 overexpression significantly inhibited the cell proliferation and colony formation ability of A431. Notably, RNA-seq results showed that the differentially expressed genes associated with RBM3 were primarily involved in the regulation of the cell cycle, oocyte meiosis, and P53 signaling pathway, as well as the modulation of the MAPK, AMPK, Hippo, mTOR, PI3K/AKT, Wnt, FoxO, and NF-κB signaling pathways. Additionally, our findings demonstrated that overexpression of RBM3 inhibited cell proliferation and induced cell cycle arrest of cSCC through modulation of the PI3K/AKT signaling pathway. CONCLUSION: This study provides novel insights into the suppressive roles of RBM3 in cell proliferation and the cell cycle in cSCC and highlights its therapeutic potential for cSCC.

Does Serum Uric Acid Mediate Relation between Healthy Lifestyle and Components of Metabolic Syndrome?

A healthy lifestyle is related to metabolic syndrome (MetS), but the mechanism is not fully understood. This study aimed to examine the association of components of MetS with lifestyle in a Chinese population and potential mediation role of serum uric acid (SUA) in the association between lifestyle behaviors and risk of components of MetS. Data were derived from a baseline survey of the Shaanxi urban cohort in the Regional Ethnic Cohort Study in northwest China. The relationship between components of MetS, healthy lifestyle score (HLS), and SUA was investigated by logistic or linear regression. A counterfactual-based mediation analysis was performed to ascertain whether and to what extent SUA mediated the total effect of HLS on components of MetS. Compared to those with 1 or less low-risk lifestyle factors, participants with 4-5 factors had 43.6% lower risk of impaired glucose tolerance (OR = 0.564; 95%CI: 0.408~0.778), 60.8% reduction in risk of high blood pressure (OR = 0.392; 95%CI: 0.321~0.478), 69.4% reduction in risk of hypertriglyceridemia (OR = 0.306; 95%CI: 0.252~0.372), and 47.3% lower risk of low levels of HDL cholesterol (OR = 0.527; 95%CI: 0.434~0.641). SUA mediated 2.95% (95%CI: 1.81~6.16%) of the total effect of HLS on impaired glucose tolerance, 14.68% (95%CI: 12.04~18.85%) on high blood pressure, 17.29% (95%CI: 15.01~20.5%) on hypertriglyceridemia, and 12.83% (95%CI: 10.22~17.48%) on low levels of HDL cholesterol. Increased HLS tends to reduce risk of components of MetS partly by decreasing the SUA level, which could be an important mechanism by which lifestyle influences MetS.

Novel associations between MTDH gene polymorphisms and invasive ductal breast cancer: a case-control study.

OBJECTIVE: To reveal the contributing effects of MTDH gene SNPs in the risk of invasive ductal breast cancer (IDC). PATIENTS AND METHODS: A case-control study was conducted, recruiting a total of 300 cases of IDC and 565 cancer-free controls from East China. Genotyping of three single-nucleotide polymorphisms (SNPs) in the MTDH gene was performed. Genomic DNA was extracted from peripheral blood samples of patients. The three SNPs (rs1311 T > C, rs16896059 G > A, rs2449512 A > G) in the MTDH gene were selected for detection using a TaqMan real-time polymerase chain reaction assay. The association between MTDH and the risk of IDC was analyzed employing an epidemiology case-control study and a multinomial logistic regression model. RESULTS: Among the three evaluated SNPs, rs1311 T > C, rs16896059 G > A, and rs2449512 A > G demonstrated a significant association with an increased risk of IDC. Furthermore, stratified analysis revealed that individuals carrying the rs1311 CC genotype, rs16896059 GA/AA genotypes, and rs2449512 GG genotype were more susceptible to developing IDC in subgroups of patients younger than 53 years, without family history of IDC, pre-menopause status, clinical stage 2, high grade, with no distant metastasis or invasion, Her2-positive type, ER positive, PR positive, and Ki67 cells less than 10%. However, carriers of the rs16896059 GA/AA genotypes and rs2449512 GG genotype had an elevate the risk of IDC in patients with tumor size larger than 2 cm, post-menopause status, clinical stage 3, with invasion, lymph node infiltration, ER negative, PR negative, Her2 negative, and Ki67 cells exceeding 10%. Compared to the reference haplotype TGA, haplotypes TAA, TAG, and TGG were significantly associated with an increased IDC risk. CONCLUSION: In this study, we demonstrated a significant association between MTDH gene polymorphisms and an increased risk of IDC. Moreover, our findings suggested that MTDH gene polymorphisms could serve as a potential biomarker for IDC subtyping and therapeutic selection.