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Heavy metal pollution is becoming a serious issue in developing countries such as China, and the public is increasingly aware of its adverse health impacts in recent years. We assessed the potential health risks in a lead-zinc mining area and attempted to identify the key exposure pathways. We evaluated the spatial distributions of personal exposure using indigenous exposure factors and field monitoring results of water, soil, food, and indoor and outdoor air samples. The risks posed by 10 metals and the contribution of inhalation, ingestion and dermal contact pathways to these risks were estimated. Human hair samples were also analyzed to indicate the exposure level in the human body. Our results show that heavy metal pollution may pose high potential health risks to local residents, especially in the village closest to the mine (V1), mainly due to Pb, Cd and Hg. Correspondingly, the residents in V1 had higher Pb (8.14 mg/kg) levels in hair than those in the other two villages. Most of the estimated risks came from soil, the intake of self-produced vegetables and indoor air inhalation. This study highlights the importance of site-specific multipathway health risk assessments in studying heavy-metal exposures in China.

p53, circRNAs and miRNAs are important components of the regulatory network that activates the EMT program in cancer metastasis. In prostate cancer (PCa), however, it has not been investigated whether and how p53 regulates EMT by circRNAs and miRNAs. Here we show that a Amotl1-derived circRNA, termed circAMOTL1L, is downregulated in human PCa, and that decreased circAMOTL1L facilitates PCa cell migration and invasion through downregulating E-cadherin and upregulating vimentin, thus leading to EMT and PCa progression. Mechanistically, we demonstrate that circAMOTL1L serves as a sponge for binding miR-193a-5p in PCa cells, relieving miR-193a-5p repression of Pcdha gene cluster (a subset of the cadherin superfamily members). Accordingly, dysregulation of the circAMOTL1L-miR-193a-5p-Pcdha8 regulatory pathway mediated by circAMOTL1L downregulation contributes to PCa growth in vivo. Further, we show that RBM25 binds directly to circAMOTL1L and induces its biogenesis, whereas p53 regulates EMT via direct activation of RBM25 gene. These findings have linked p53/RBM25-mediated circAMOTL1L-miR-193a-5p-Pcdha regulatory axis to EMT in metastatic progression of PCa. Targeting this newly identified regulatory axis provides a potential therapeutic strategy for aggressive PCa.

The N(6)-methyladenosine (m6A) modification is the most pervasive modification of human RNAs. In recent years, an increasing number of studies have suggested that m6A likely plays important roles in cancers. Many studies have demonstrated that m6A is involved in the biological functions of cancer cells, such as proliferation, invasion, metastasis, and drug resistance. In addition, m6A is closely related to the prognosis of cancer patients. In this review, we highlight recent advances in understanding the function of m6A in various cancers. We emphasize the importance of m6A to cancer progression and look forward to describe future research directions.

Cardiovascular disease ranks among the leading causes of death globally, posing a severe threat to human health. Consequently, rapid and accurate identification of cardiovascular disease has become a critical research endeavor. Electrocardiograms (ECGs), as a non-invasive detection tool, are widely used in cardiovascular disease detection due to their convenience and effectiveness. However, existing methods are often limited to single-modality analysis, neglecting the interaction between clinical data (such as age, gender, weight, etc.) and ECG features in classification tasks, resulting in limited recognition accuracy. Integrating multimodal data is key to improving CVD diagnostic accuracy. To address this, we propose MAF-Net (Multimodal Cross-Attention-based Fusion Network), a multi-class classification model that fuses clinical data features with ECG signal features for cardiovascular disease classification. The model comprises three components: (1) X Branch (Clinical Data Processing): Generates high-order interaction features via a second-order polynomial feature cross-layer and employs channel attention-weighted selection to identify key clinical factors;(2) Y Branch (Multi-scale ECG Feature Extraction): Parallel multi-scale convolutional modules (64@7, 128@3, 256@3) capture local morphological features, while Bi-LSTM models long-range temporal dependencies, supplemented by multi-head attention to focus on pathological segments;(3) Bidirectional Modality Fusion Module: Employing a bidirectional cross-attention mechanism, it uses clinical features as Query and ECG features as Key/Value to deeply fuse clinical and ECG data features. On the dataset, experiments targeting five super-categories of arrhythmias— NORM (Normal), MI (Myocardial Infarction), STTC (ST-T Segment Changes), CD (Conduction Disturbance), HYP (Hypertrophy). showed an accuracy rate of 90.75% ± 0.32%, precision of 84.58% ± 0.41%, and recall of 87.12% ± 0.38%, with an F1 score of 0.8069 ± 0.005 and a ROC-AUC value of 0.9407 ± 0.002. Results indicate that this model outperforms existing methods across key metrics, demonstrating its potential for application in clinical decision support.

Human interaction recognition technology is a hot topic in the field of computer vision, and its application prospects are very extensive. At present, there are many difficulties in human interaction recognition such as the spatial complexity of human interaction, the differences in action characteristics at different time periods, and the complexity of interactive action features. The existence of these problems restricts the improvement of recognition accuracy. To investigate the differences in the action characteristics at different time periods, we propose an improved fusion time-phase feature of the Gaussian model to obtain video keyframes and remove the influence of a large amount of redundant information. Regarding the complexity of interactive action features, we propose a multi-feature fusion network algorithm based on parallel Inception and ResNet. This multi-feature fusion network not only reduces the network parameter quantity, but also improves the network performance; it alleviates the network degradation caused by the increase in network depth and obtains higher classification accuracy. For the spatial complexity of human interaction, we combined the whole video features with the individual video features, making full use of the feature information of the interactive video. A human interaction recognition algorithm based on whole–individual detection is proposed, where the whole video contains the global features of both sides of action, and the individual video contains the individual detail features of a single person. Making full use of the feature information of the whole video and individual videos is the main contribution of this paper to the field of human interaction recognition and the experimental results in the UT dataset (UT–interaction dataset) showed that the accuracy of this method was 91.7%.

Cyclin-dependent kinases (CDKs) regulate cell cycle progression and the transcription of a number of genes, including lipid metabolism-related genes, and aberrant lipid metabolism is involved in prostate carcinogenesis. Previous studies have shown that CDK13 expression is upregulated and fatty acid synthesis is increased in prostate cancer (PCa). However, the molecular mechanisms linking CDK13 upregulation and aberrant lipid metabolism in PCa cells remain largely unknown. Here, we showed that upregulation of CDK13 in PCa cells increases the fatty acyl chains and lipid classes, leading to lipid deposition in the cells, which is positively correlated with the expression of acetyl-CoA carboxylase (ACC1), the first rate-limiting enzyme in fatty acid synthesis. Gain- and loss-of-function studies showed that ACC1 mediates CDK13-induced lipid accumulation and PCa progression by enhancing lipid synthesis. Mechanistically, CDK13 interacts with RNA-methyltransferase NSUN5 to promote its phosphorylation at Ser327. In turn, phosphorylated NSUN5 catalyzes the m5C modification of ACC1 mRNA, and then the m5C-modified ACC1 mRNA binds to ALYREF to enhance its stability and nuclear export, thereby contributing to an increase in ACC1 expression and lipid deposition in PCa cells. Overall, our results disclose a novel function of CDK13 in regulating the ACC1 expression and identify a previously unrecognized CDK13/NSUN5/ACC1 pathway that mediates fatty acid synthesis and lipid accumulation in PCa cells, and targeting this newly identified pathway may be a novel therapeutic option for the treatment of PCa.

Approximately 78.3% of patients with t(8;21) acute myeloid leukemia (AML) express CD19, making it a potential target for chimeric antigen receptor (CAR)-T cell therapy focused on CD19. This prospective phase II trial (NCT03896854) evaluated the safety and efficacy of CD19 CAR-T cell treatment in 10 relapsed CD19-positive t(8;21) AML patients. This study enrolled eight patients with hematologic and two with molecular relapsed AML. The median bone marrow blast percentage was 12.4% (0.1–50.2%), and the blasts exhibited a median CD19 positivity of 55.7% (22.6–97.1%). Genetic profiling revealed TP53 alterations ( n  = 1), KIT ( n  = 3) and FLT3 -ITD ( n  = 1) mutations. After lymphodepletion with fludarabine and cyclophosphamide (FC), 5–20 × 10 6 cells per kilogram of CAR-T cells were administered. All patients experienced grade 3 or higher hematologic toxicities following tumor-reduction chemotherapy and the FC regimen, which were managed for a median of two weeks after CAR-T treatment. Non-hematological toxicities were mild and reversible. Eight patients presented with mild (grade 1–2) cytokine release syndrome (CRS), and one experienced grade 3 CRS. The immune effector cell-associated neurotoxicity syndrome was not observed. All patients achieved complete remission (CR) after CAR-T, with 60% achieving a molecularly MRD-negative CR. RUNX1::RUNX1T1 fusion transcript levels demonstrated a median 2.5-log reduction (range: 0.7–4.5 log; P  = 0.002). At a median follow-up of 64.6 months (range: 11.2–88.8 months), the median overall survival and leukemia-free survival were 11.6 and 3.8 months, respectively. The 12-month cumulative incidence of relapse was 53.3%. These findings indicated that CD19 CAR-T was a safe and effective option for relapsed CD19-positive t(8;21) AML.

Background Both E2F transcription factor and cyclin-dependent kinases (CDKs), which increase or decrease E2F activity by phosphorylating E2F or its partner, are involved in the control of cell proliferation, and some circRNAs and miRNAs regulate the expression of E2F and CDKs. However, little is known about whether dysregulation among E2Fs, CDKs, circRNAs and miRNAs occurs in human PCa. Methods The expression levels of CDK13 in PCa tissues and different cell lines were determined by quantitative real-time PCR and Western blot analysis. In vitro and in vivo assays were preformed to explore the biological effects of CDK13 in PCa cells. Co-immunoprecipitation anlysis coupled with mass spectrometry was used to identify E2F5 interaction with CDK13. A CRISPR-Cas9 complex was used to activate endogenous CDK13 and circCDK13 expression. Furthermore, the mechanism of circCDK13 was investigated by using loss-of-function and gain-of-function assays in vitro and in vivo. Results Here we show that CDK13 is significantly upregulated in human PCa tissues. CDK13 depletion and overexpression in PCa cells decrease and increase, respectively, cell proliferation, and the pro-proliferation effect of CDK13 is strengthened by its interaction with E2F5. Mechanistically, transcriptional activation of endogenous CDK13, but not the forced expression of CDK13 by its expression vector, remarkably promotes E2F5 protein expression by facilitating circCDK13 formation. Further, the upregulation of E2F5 enhances CDK13 transcription and promotes circCDK13 biogenesis, which in turn sponges miR-212-5p/449a and thus relieves their repression of the E2F5 expression, subsequently leading to the upregulation of E2F5 expression and PCa cell proliferation. Conclusions These findings suggest that CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 is responsible for PCa development. Targeting this newly identified regulatory axis may provide therapeutic benefit against PCa progression and drug resistance.

β-Arrestins (βarrs) interact with G protein-coupled receptors (GPCRs) to desensitize G protein signaling, to initiate signaling on their own, and to mediate receptor endocytosis. Prior structural studies have revealed two unique conformations of GPCR–βarr complexes: the “tail” conformation, with βarr primarily coupled to the phosphorylated GPCR C-terminal tail, and the “core” conformation, where, in addition to the phosphorylated C-terminal tail, βarr is further engaged with the receptor transmembrane core. However, the relationship of these distinct conformations to the various functions of βarrs is unknown. Here, we created a mutant form of βarr lacking the “finger-loop” region, which is unable to form the core conformation but retains the ability to form the tail conformation. We find that the tail conformation preserves the ability to mediate receptor internalization and βarr signaling but not desensitization of G protein signaling. Thus, the two GPCR–βarr conformations can carry out distinct functions.

Background Scar-related complications remain a significant concern following melanocytic nevus excision in children. However, validated risk prediction tools for this specific population are lacking. This study aimed to develop and validate a prediction model for unfavorable scar formation after pediatric melanocytic nevus excision. Methods A retrospective cohort study was conducted at Plastic Surgery Hospital, Chinese Academy of Medical Sciences from March 2024 to August 2024. Pediatric patients who underwent melanocytic nevus excision were included. Patients were classified into favorable and unfavorable scar groups based on morphological characteristics, POSAS scores, and persistent symptoms. Multivariable logistic regression identified independent risk factors, and a nomogram was constructed. Model performance was evaluated using discrimination, calibration, and decision curve analysis, with internal validation via bootstrap resampling. Results Among 300 patients, 73 (24.3%) developed unfavorable scars. Six independent predictors were identified: older age was protective (OR = 0.871), while congenital nevus type (OR = 2.280), larger diameter (OR = 1.818), trunk location (OR = 4.536), extremity location (OR = 3.314), high wound tension (OR = 8.365), moderate wound tension (OR = 2.971), and junctional depth (OR = 2.050) increased the risk. The model demonstrated good discrimination (AUC = 0.839; bootstrap-corrected AUC = 0.821) and calibration (Brier score = 0.132, calibration slope = 0.968). At the optimal threshold, sensitivity was 0.753 and specificity was 0.834. Decision curve analysis confirmed clinical utility across threshold probabilities of 0.10–0.80. Conclusion This prediction model incorporating six clinical factors may facilitate perioperative risk stratification and informed consent discussions for pediatric patients undergoing melanocytic nevus excision. External validation is warranted before clinical implementation.