Nanoscale octopus guiding telomere entanglement: An innovative strategy for inducing apoptosis in cancer cells.

Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment. In this study, we introduce a nanoscale octopus-like structure designed to induce physical entangling of telomere, thereby efficiently triggering telomere dysfunction. The nanoscale octopus, composed of eight-armed PEG (8-arm-PEG), are functionalized with cell penetrating peptide (TAT) to facilitate nuclear entry and are covalently bound to N-Methyl Mesoporphyrin IX (NMM) to target G-quadruplexes (G4s) present in telomeres. The multi-armed configuration of the nanoscale octopus enables targeted binding to multiple G4s, physically disrupting and entangling numerous telomeres, thereby triggering telomere dysfunction. Both in vitro and in vivo experiments indicate that the nanoscale octopus significantly inhibits cancer cell proliferation, induces apoptosis through telomere entanglement, and ultimately suppresses tumor growth. This research offers a novel perspective for the development of innovative anti-cancer interventions and provides potential therapeutic options for targeting telomeres.

KDM4A promotes malignant progression of breast cancer by down-regulating BMP9 inducing consequent enhancement of glutamine metabolism.

BACKGROUND: Recent studies have found that histone-modified genes play an increasingly important role in tumor progression. Lysine(K) specific demethylase 4A (KDM4A) is a histone lysine-specific demethylase highly expressed in a variety of malignant tumors, data showed that KDM4A was negatively correlated with the Bone Morphogenetic Protein 9 (BMP9) in breast cancer. And previous experiments have demonstrated that exogenous BMP9 significantly inhibits breast cancer development. MATERIALS AND METHODS: We detected the expression of KDM4A in breast cancer and the relationship between KDM4A and BMP9 using real-time quantitative PCR (RT-qPCR) and Western blot, and verified the interaction between KDM4A and BMP9 by ChIP experiments. At the same time, we also detected whether KDM4A had effects on the RNA and protein stability of BMP9 using actinomycin D and cycloheximide. Measurement of alpha-ketoglutarate (α-KG) level by ELISA to observe the effect of BMP9 on glutamine metabolism in breast cancer cells. Nucleoplasmic distribution of KDM4A after exogenous BMP9 treatment in breast cancer cells were observed by immunofluorescence staining and Western blot. A subcutaneous xenograft tumor model in nude mice was used to study the therapeutic effects of exogenous BMP9 and KDM4A inhibitor (JIB-04) in breast cancer. CCK-8, conoly formation, Transwell, wound healing, and immunohistochemistry were used to monitor the growth of tumor and cell function. RESULTS: We found that KDM4A was abnormally highly expressed in breast cancer, and silenced BMP9 expression by removing histone methyl groups from the BMP9 gene region. Meanwhile, KDM4A could also reduce the stability of BMP9 protein. BMP9 inhibit glutamine metabolism in breast cancer, resulting in a decrease in its product α-KG, is confirmed by ELISA. Altered nucleoplasmic distribution of KDM4A due to decreased α-KG was confirmed by immunofluorescence staining and Western blot. Animal experiments confirm that the combination of exogenous BMP9 and JIB-04 shows significantly better results in breast cancer. CONCLUSIONS: KDM4A silences BMP9 expression by removing histone methyl groups from the BMP9 gene region, leading to further enhancement of glutamine metabolism, which contributes to malignant tumor progression. In addition, using JIB-04 in combination with exogenous BMP9 could inhibit the malignant progression of breast cancer cells and the growth of tumors more significantly.

Data-mining-based biomarker evaluation and experimental validation of SHTN1 for bladder cancer.

BACKGROUND: Gene therapy in bladder cancer (BLCA) remains an area ripe for exploration. Recent studies have highlighted the crucial role of SHTN1 in the initiation and progression of various cancers and SHTN1 may have interacted with the FGFR gene. However, its specific function in BLCA remains unclear. MATERIALS AND METHODS: We investigated the association between SHTN1 expression and prognosis, immune infiltration, and the tumor microenvironment (TME) across multiple malignancies using 433 BLCA samples from The Cancer Genome Atlas (TCGA). Differential gene expression analysis, functional annotation via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed for SHTN1-related genes by using R packages. Immune response and TME scores, along with drug sensitivity profiles of SHTN1, were analyzed using R packages. Immunohistochemistry (IHC) and western blotting were conducted to assess SHTN1 expression in surgical specimens from BLCA patients.CCK8 assay and cells wound healing assay were performed.The bioinformatics was analyzed by R software. Significant differences were evaluated using unpaired t test. RESULTS: SHTN1 expression levels were significantly elevated in BLCA associated with poor prognosis (p < 0.01). Receiver operating characteristic (ROC) curves and nomograms demonstrated the diagnostic and prognostic efficacy of SHTN1 in BLCA. Notably, SHTN1 expression was higher in high-grade BLCA compared to lower-grade (p = 5.6e-10), a finding corroborated by IHC and western blotting. Pathway enrichment analysis revealed significant involvement of the Neuroactive ligand-receptor interaction and Chemical carcinogenesis - DNA adducts signaling pathways among SHTN1 differentially expressed genes. In terms of immune infiltration, T cells CD8, T cells follicular helper, and dendritic cells were predominant in the SHTN1 low-expression group, whereas macrophages M0 and M2, and mast cells were predominant in the high-expression group. Multivariate Cox regression analysis identified SHTN1 as an independent prognostic factor for overall survival (HR = 2.93; 95 % CI = 1.40-6.13; p = 0.004).CCK8 and wound healing experiments showed that SHTN1 knockdown reduced the cell proliferation and migration. Western blot showed that the EMT pathway was clearly associated with SHTN1. CONCLUSIONS: Our findings suggest that SHTN1 holds promise as a prognostic and diagnostic biomarker for BLCA. Moreover, it is closely associated with elevated immune infiltration and distinct characteristics of the tumor microenvironment in BLCA.

Chemoexcited Formation and Radiationless Decay Dynamics of Firefly Chromophore.

Multistate nonadiabatic dynamics combined with Mixed-Reference Spin-Flip Time-Dependent Density Functional Theory (MRSF-TDDFT) were performed to investigate the chemoexcitation dynamics of firefly dioxetanone (FDO- in S0) to oxyluciferin (OxyLH- in S1) and its subsequent decay dynamics. The formation of oxyluciferin occurs within approximately 100 fs and is primarily controlled by oscillatory CO2 decarboxylation. Unexpected radiationless decay from oxyluciferin was also observed, facilitated by intramolecular rotation. Simulations under three thermal conditions reveal that higher initial thermal energy not only enhances the formation of oxyluciferin but also increases radiationless decay by surpassing barriers to the ground state. Conversely, lower thermal energy conditions reduce oxyluciferin formation but suppress radiationless decay. These findings suggest that optimal conditions for higher chemiluminescence quantum yield involve initial high thermal energy to accelerate CO2 decarboxylation and gradual thermal dissipation to prevent intramolecular rotation of oxyluciferin. This approach could enhance the chemiluminescence quantum yield beyond the current limit of 40%, offering significant potential for applications in biological imaging and analytical chemistry.

Anatomic variation of the vertebral artery: a case involving a persistent first intersegmental artery at C1-C2.

BACKGROUND: We observed a rare anatomical variation of a persistent first intersegmental vertebral artery in the C1-C2 region in an elderly Chinese male cadaver at Changzhi Medical College. In this case, the vertebral artery, rather than passing through the transverse foramen of the atlas, exits the transverse foramen of C2 and enters the spinal canal at the lower portion of the C1 posterior arch. The original transverse foramen of C1 was filled with connective tissue. This report details the anatomical characteristics of this abnormal vertebral artery and discusses its anatomical, surgical, and developmental implications. PURPOSE: We describe the detailed morphological features of a rare VA variant and discuss the anatomical, clinical, and developmental aspects of this case. METHODS: A case of head dissection. The anatomical characteristics of the VA were studied and documented, and anatomical measurements were collected. RESULTS: In this case, the vertebral artery, rather than passing through the transverse foramen of the atlas, exits the transverse foramen of C2 and enters the spinal canal at the lower portion of the C1 posterior arch. The original transverse foramen of C1 was filled with connective tissue. CONCLUSION: The anomalous development of segmental arteries in our case is linked to failures in the embryonic sclerotome reconstruction during development and failure.

Automated data collection tool for real-world cohort studies of chronic hepatitis B: Leveraging OCR and NLP technologies for improved efficiency.

Background: Collecting and standardizing clinical research data is a very tedious task. This study is to develop an intelligent data collection tool, named CHB-EDC, for real-world cohort studies of chronic hepatitis B (CHB), which can assist in standardized and efficient data collection. Methods: CHB_EDC is capable of automatically processing various formats of data, including raw data in image format, using internationally recognized data standards, OCR, and NLP models. It can automatically populate the data into eCRFs designed in the REDCap system, supporting the integration of patient data from electronic medical record systems through commonly used web application interfaces. This tool enables intelligent extraction and aggregation of data, as well as secure and anonymous data sharing. Results: For non-electronic data collection, the average accuracy of manual collection was 98.65 %, with an average time of 63.64 min to collect information for one patient. The average accuracy CHB-EDC was 98.66 %, with an average time of 3.57 min to collect information for one patient. In the same data collection task, CHB-EDC achieved a comparable average accuracy to manual collection. However, in terms of time, CHB-EDC significantly outperformed manual collection (p < 0.05). Our research has significantly reduced the required collection time and lowered the cost of data collection while ensuring accuracy. Conclusion: The tool has significantly improved the efficiency of data collection while ensuring accuracy, enabling standardized collection of real-world data.

Construction of a cuproptosis­related lncRNA signature to predict biochemical recurrence of prostate cancer.

Biochemical recurrence (BCR) is common in prostate cancer (PCa), and patients with BCR usually have a poor prognosis. Cuproptosis is a unique type of cell death, and copper homeostasis is crucial to the occurrence and development of malignancies. The present study aimed to explore the prognostic value of cuproptosis-related long non-coding RNAs (lncRNAs; CRLs) in PCa and to develop a predictive signature for forecasting BCR in patients with PCa. Using The Cancer Genome Atlas database, transcriptomic, mutation and clinical data were collected from patients with PCa. A total of 121 CRLs were identified using Pearson's correlation coefficient. Subsequently, a 6-CRL signature consisting of AC087276.2, CNNM3-DT, AC090198.1, AC138207.5, METTL14-DT and LINC01515 was created to predict the BCR of patients with PCa through Cox and least absolute shrinkage and selection operator regression analyses. Kaplan-Meier curve analysis demonstrated that high-risk patients had a low BCR-free survival rate. In addition, there was a substantial difference between the high- and low-risk groups in the immune microenvironment, immune therapy, drug sensitivity and tumor mutational burden. A nomogram integrating the Gleason score, 6-CRL signature and clinical T-stage was established and evaluated. Finally, the expression of signature lncRNAs in PCa cells was verified through reverse transcription-quantitative PCR. In conclusion, the 6-CRL signature may be a potential tool for making predictions regarding BCR in patients with PCa, and the prognostic nomogram may be considered a practical tool for clinical decision-making.

International Alliance of Urolithiasis (IAU) guidelines on the management of pediatric urolithiasis.

The aim of this study was to construct the sixth in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis (IAU) that by providing a clinical framework for the management of pediatric patients with urolithiasis based on the best available published literature. All recommendations were summarized following a systematic review and assessment of literature in the PubMed database from January 1952 to December 2023. Each generated recommendation was graded using a modified GRADE methodology. Recommendations are agreed upon by Panel Members following review and discussion of the evidence. Guideline recommendations were developed that addressed the following topics: etiology, risk factors, clinical presentation and symptoms, diagnosis, conservative management, surgical interventions, prevention, and follow-up. Similarities in the treatment of primary stone episodes between children and adults, incorporating conservative management and advancements in technology for less invasive stone removal, are evident. Additionally, preventive strategies aiming to reduce recurrence rates, such as ensuring sufficient fluid intake, establishing well-planned dietary adjustments, and selective use pharmacologic therapies will also result in highly successful outcomes in pediatric stone patients. Depending on the severity of metabolic disorders and also anatomical abnormalities, a careful and close follow-up program should inevitably be planned in each pediatric patient to limit the risk of future recurrence rates.

ICAT-Mediated Crosstalk Between Cervical Cancer Cells and Macrophages Promotes M2-Like Macrophage Polarization to Reinforce Tumor Malignant Behaviors.

Inhibitor of ß-catenin and T-cell factor (ICAT) is a classical inhibitor of the Wnt signaling pathway. Nonetheless, our previous work found that ICAT is overexpressed in cervical cancer (CC), resulting in the augmentation of migration and invasion capabilities of CC cells. It remains unclear what molecular mechanism underlies this phenomenon. The interaction between cancer cells and the tumor microenvironment (TME) promotes the outgrowth and metastasis of tumors. Tumor-associated macrophages (TAMs) are a major constituent of the TME and have a significant impact on the advancement of CC. Consequently, our inquiry pertains to the potential of ICAT to facilitate tumor development through its modulation of the cervical TME. In this study, we first verified that ICAT regulated the secretion of cytokines interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) in CC cells, leading to M2-like macrophage polarization and enhancement of the migration and invasion of CC cells. Furthermore, the system of co-culturing human umbilical vein endothelial cells (HUVECs) with macrophages revealed that depending on the CC cells' overexpression or inhibition of ICAT, the vascular tube formation by HUVECs can be either increased or decreased. Overall, our study indicates that ICAT stimulates M2-like polarization of TAMs via upregulating IL-10 and TGF-ß, which results in increased neovascularization, tumor metastasis, and immunosuppression in CC. In upcoming times, inhibiting crosstalk between CC cells and TAMs may be a possible strategy for CC therapy.

Visualization of Biomolecular Radiation Damage at the Single-Particle Level Using Lanthanide-Sensitized DNA Origami.

Precise monitoring of biomolecular radiation damage is crucial for understanding X-ray-induced cell injury and improving the accuracy of clinical radiotherapy. We present the design and performance of lanthanide-DNA-origami nanodosimeters for directly visualizing radiation damage at the single-particle level. Lanthanide ions (Tb3+ or Eu3+) coordinated with DNA origami nanosensors enhance the sensitivity of X-ray irradiation. Atomic force microscopy (AFM) revealed morphological changes in Eu3+-sensitized DNA origami upon X-ray irradiation, indicating damage caused by ionization-generated electrons and free radicals. We further demonstrated the practical applicability of Eu3+-DNA-origami integrated chips in precisely monitoring radiation-mediated cancer radiotherapy. Quantitative results showed consistent trends with flow cytometry and histological examination under comparable X-ray irradiation doses, providing an affordable and user-friendly visualization tool for preclinical applications. These findings provide new insights into the impact of heavy metals on radiation-induced biomolecular damage and pave the way for future research in developing nanoscale radiation sensors for precise clinical radiography.

TFAP2A Activates S100A2 to Mediate Glutamine Metabolism and Promote Lung Adenocarcinoma Metastasis.

BACKGROUND: Lung adenocarcinoma (LUAD) is a fatal disease with metabolic abnormalities. The dysregulation of S100 calcium-binding protein A2 (S100A2), a member of the S100 protein family, is connected to the development of various cancers. The impact of S100A2 on the LUAD occurrence and metastasis, however, has not yet been reported. The functional mechanism of S100A2 on LUAD cell metastasis was examined in this article. METHODS: The expression of TFAP2A and S100A2 in LUAD tissues and cells was analyzed by bioinformatics and qRT-PCR, respectively. The enrichment pathway analysis was performed on S100A2. Bioinformatics analysis determined the binding relationship between TFAP2A and S100A2, and their interaction was validated through dual-luciferase and chromatin immunoprecipitation experiments. Cell viability was determined using cell counting kit-8 (CCK-8). A transwell assay was performed to analyze the invasion and migration of cells. Immunofluorescence was conducted to obtain vimentin and E-cadherin expression, and a western blot was used to detect the expression of MMP-2, MMP-9, GLS, and GLUD1. The kits measured the NADPH/NADP ratio, glutathione (GSH)/glutathione disulfide (GSSG) levels, and the contents of glutamine, α-KG, and glutamate. RESULTS: S100A2 was upregulated in LUAD tissues and cells, and S100A2 mediated glutamine metabolism to induce LUAD metastasis. Additionally, the transcriptional regulator TFAP2A was discovered upstream of S100A2, and TFAP2A expression was upregulated in LUAD, which indicated that TFAP2A promoted the S100A2 expression. The rescue experiment found that upregulation of S100A2 could reverse the inhibitory effects of silencing TFAP2A on glutamine metabolism and cell metastasis. CONCLUSION: In conclusion, by regulating glutamine metabolism, the TFAP2A/S100A2 axis facilitated LUAD metastasis. This suggested that targeting S100A2 could be beneficial for LUAD treatment.

CAB39 modulates epithelial-mesenchymal transition through NF-κB signaling activation, enhancing invasion, and metastasis in bladder cancer.

Bladder cancer (BC), the predominant urological malignancy in men, exhibits complex molecular underpinnings contributing to its progression. This investigation aims to elucidate the expression dynamics of calcium-binding protein 39 (CAB39) in both healthy and cancerous tissues and to explore its functional role in the epithelial-mesenchymal transition (EMT) within human bladder cancer contexts. Utilizing immunohistochemistry and quantitative reverse transcription analyses, we assessed CAB39 expression across BC specimens and cell lines. Further, we implemented wound healing, cell invasion, and CCK-8 proliferation assays in CAB39-knockdown cell lines, alongside a nude mouse xenograft model, to gauge the impact of diminished CAB39 expression on the invasive, migratory, and proliferative capacities of BC cells. Our gene set enrichment analysis probed into the repertoire of genes augmented by increased CAB39 expression in BC cells, with subsequent validation via western blotting. Our findings reveal a pronounced overexpression of CAB39 in both BC tissues and cellular models, inversely correlated with disease prognosis. Remarkably, the oncogenic trajectory of bladder cancer was mitigated upon the establishment of shRNA-mediated CAB39 knockdown in vitro and in vivo, effectively reversing the cancer's invasive and metastatic behaviors and curbing tumorigenesis in xenograft models. Hence, CAB39 emerges as a critical biomarker for bladder cancer progression, significantly implicated in facilitating EMT via the upregulation of neural cadherin (N-cadherin) and the suppression of epithelial cadherin through NF-κB signaling pathways. CU-T12-9 effectively overturned the downregulation of p65-NF-kB and N-cadherin, key elements involved in EMT and cell motility, induced by CAB39 knockdown. This study underscores CAB39's pivotal role in bladder cancer pathophysiology and its potential as a therapeutic target.

Biosensor-based active ingredient recognition system for screening potential small molecular Severe acute respiratory syndrome coronavirus 2 entry blockers targeting the spike protein from Rugosa rose.

The traditional formulation Hanchuan zupa granules (HCZPs) have been widely used for controlling coronavirus disease 2019 (COVID-19). However, its active components remain unknown. Here, HCZP components targeting the spike receptor-binding domain (S-RBD) of SARS-CoV-2 were investigated using a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). Recombinant S-RBD proteins were immobilized on the SPR chip by amine coupling for the prescreening of nine HCZP medicinal herbs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) identified gallic acid (GA) and methyl gallate (MG) from Rosa rugosa as S-RBD ligands, with KD values of 2.69 and 0.95 µM, respectively, as shown by SPR. Molecular dynamics indicated that GA formed hydrogen bonds with G496, N501, and Y505 of S-RBD, and MG with G496 and Y505, inhibiting S-RBD binding to angiotensin-converting enzyme 2 (ACE2). SPR-based competition analysis verified that both compounds blocked S-RBD and ACE2 binding, and SPR demonstrated that GA and MG bound to ACE2 (KD = 5.10 and 4.05 µM, respectively), suggesting that they blocked the receptor and neutralized SARS-CoV-2. Infection with SARS-CoV-2 pseudovirus showed that GA and MG suppressed viral entry into 293T-ACE2 cells. These S-RBD inhibitors have potential for drug design, while the findings provide a reference on HCZP composition and its use for treating COVID-19.

Integrating multi-omics data of childhood asthma using a deep association model.

Childhood asthma is one of the most common respiratory diseases with rising mortality and morbidity. The multi-omics data is providing a new chance to explore collaborative biomarkers and corresponding diagnostic models of childhood asthma. To capture the nonlinear association of multi-omics data and improve interpretability of diagnostic model, we proposed a novel deep association model (DAM) and corresponding efficient analysis framework. First, the Deep Subspace Reconstruction was used to fuse the omics data and diagnostic information, thereby correcting the distribution of the original omics data and reducing the influence of unnecessary data noises. Second, the Joint Deep Semi-Negative Matrix Factorization was applied to identify different latent sample patterns and extract biomarkers from different omics data levels. Third, our newly proposed Deep Orthogonal Canonical Correlation Analysis can rank features in the collaborative module, which are able to construct the diagnostic model considering nonlinear correlation between different omics data levels. Using DAM, we deeply analyzed the transcriptome and methylation data of childhood asthma. The effectiveness of DAM is verified from the perspectives of algorithm performance and biological significance on the independent test dataset, by ablation experiment and comparison with many baseline methods from clinical and biological studies. The DAM-induced diagnostic model can achieve a prediction AUC of 0.912, which is higher than that of many other alternative methods. Meanwhile, relevant pathways and biomarkers of childhood asthma are also recognized to be collectively altered on the gene expression and methylation levels. As an interpretable machine learning approach, DAM simultaneously considers the non-linear associations among samples and those among biological features, which should help explore interpretative biomarker candidates and efficient diagnostic models from multi-omics data analysis for human complex diseases.

Intraoperative radiotherapy: An alternative to whole-breast external beam radiotherapy in the management of highly selective breast cancer: A SEER database analysis.

OBJECTIVE: This study aimed to verify if intraoperative radiotherapy (IORT) can achieve the same survival outcome as whole-breast external beam radiotherapy (EBRT) in early breast cancer after breast-conserving surgery (BCS), and to explore the suitable candidates that can safely receive IORT after BCS. METHODS: Eligible post-BCS patients who received IORT or EBRT were included in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2018. Risk factors that affected 5-year overall survival (OS) or breast cancer specific survival (BCSS) were identified by Cox proportional hazards regression analysis. Clinical characteristics, OS, and BCSS were comparatively analyzed between the two treatment modalities. RESULTS: The survival analysis after propensity score matching confirmed that patients who received IORT (n = 2200) had a better 5-year OS than those who received EBRT (n = 2200) (p = 0.015). However, the two groups did not differ significantly in 5-year BCSS (p = 0.381). This feature persisted even after multivariate analyses that took into account numerous clinical characteristics. Although there was no significant difference in BCSS between different subgroups of patients treated with IORT or EBRT, patients over 55 years of age, with T1, N0, non-triple negative breast cancers, hormone receptor-positive, and histologic grade II showed a better OS after receiving IORT. CONCLUSION: In low-risk, early-stage breast cancer, IORT was not inferior to EBRT considering 5-year BCSS and OS. Considering the equivalent clinical outcome but less radiotoxicity, IORT might be a reasonable alternative to EBRT in highly selective patients undergoing BCS.

Investigating the causal relationship between major depressive disorder and benign prostatic hyperplasia: a bidirectional Mendelian randomisation study.

BACKGROUND: Evidence from various cohort studies indicate a potential association between depressive disorder and benign prostatic hyperplasia (BPH), yet findings are inconsistent. This study employs bidirectional two-sample Mendelian randomisation (MR) analysis to explore the causal relationship between BPH and major depressive disorder (MDD). METHODS: Genetic variants strongly associated with MDD were extracted as instrumental variables conducted by the Psychiatric Genomics Consortium (PGC). Two sets of genetic variants associated with BPH were extracted from the recent FinnGen and Medical Research Council-Integrative Epidemiology Unit Consortium of BPH as the discovery and replication stages, respectively. Bidirectional MR analysis employed methods such as inverse variance weighted, MR-Egger, weighted median, maximum likelihood, and weighted mode. The inverse variance weighted method was primarily used to evaluate the causal relationship. RESULTS: MR analysis in both the discovery and replication stages showed a significant causal relationship between MDD and the risk of BPH (discovery stages, odds ratio (OR) = 1.1146, 95% CI 1.0058-1.2353, P = 0.03852; replication stage, OR: 1.0042, 95% CI 1.0019-1.0065, P = 0.0004). No causal relationship was found between BPH and MDD risk in the reverse MR analysis. CONCLUSIONS: Our findings highlight a significant association between MDD and an increased risk of BPH development. Further investigation is needed to elucidate the underlying mechanisms linking depression and BPH.

Duck gut metagenome reveals the microbiome signatures linked to intestinal regional, temporal development, and rearing condition.

The duck gastrointestinal tract (GIT) harbors an abundance of microorganisms that play an important role in duck health and production. Here, we constructed the first relatively comprehensive duck gut microbial gene catalog (24 million genes) and 4437 metagenome-assembled genomes using 375 GIT metagenomic samples from four different duck breeds across five intestinal segments under two distinct rearing conditions. We further characterized the intestinal region-specific microbial taxonomy and their assigned functions, as well as the temporal development and maturation of the duck gut microbiome. Our metagenomic analysis revealed the similarity within the microbiota of the foregut and hindgut compartments, but distinctive taxonomic and functional differences between distinct intestinal segments. In addition, we found a significant shift in the microbiota composition of newly hatched ducks (3 days), followed by increased diversity and enhanced stability across growth stages (14, 42, and 70 days), indicating that the intestinal microbiota develops into a relatively mature and stable community as the host duck matures. Comparing the impact of different rearing conditions (with and without water) on duck cecal microbiota communities and functions, we found that the bacterial capacity for lipopolysaccharide biosynthesis was significantly increased in ducks that had free access to water, leading to the accumulation of pathogenic bacteria and antibiotic-resistance genes. Taken together, our findings expand the understanding of the microbiome signatures linked to intestinal regional, temporal development, and rearing conditions in ducks, which highlight the significant impact of microbiota on poultry health and production.

A Retrospective Observation of Gasserian Ganglion Pulsed Radiofrequency Therapy Combined with Low-Dose Morphine Injection in the Treatment of Ophthalmic Herpetic Neuralgia.

Purpose: This retrospective study was to investigate the efficacy of Gasserian ganglion pulsed radiofrequency therapy (PRF) combined with low-dose morphine injection in the treatment of refractory ophthalmic herpetic neuralgia. Patients and methods: A total of 40 intractable ophthalmic herpetic neuralgia patients who received Gasserian ganglion PRF therapy in Pain Department of Nanjing Drum Tower Hospital were retrospectively analysed, with an average age of 70.2 ± 8.5 years and an average disease course of 30 (30, 60) days. According to different interventions, they were divided into two groups: Group A, 19 patients who received Gasserian ganglion PRF therapy combined with 0.2 mg morphine injection via puncture needle; Group B, 21 patients who received only Gasserian ganglion PRF therapy. Data related to the length of hospital stay and associated costs, numerical rating scale scores (NRS), intravenous morphine and oral oxycodone doses during hospitalization, Short form McGill pain questionnaire and Pittsburgh sleep quality index (PSI), and conditions of opioid use and postherpetic neuralgia after discharge were collected in the two groups. SPSS 25.0 was used to perform statistical analysis on data. Results: The hospital stay, hospitalization costs, and oxycodone dosages for Group A were lower than those for Group B (p = 0.02, p = 0.015 and p = 0.023, respectively). The proportion of patients in group A still taking oral opioids 1 month after discharge and experiencing postherpetic neuralgia 6 months after the onset was lower than that in group B (p = 0.004 and p = 0.049). The NRS upon discharge, as well as the McGill and PSQI scores at the time of discharge and at 1, 3, 6 and 12 months post-discharge, were all significantly reduced compared to those measured upon admission in two groups (p = 0.000). Conclusion: Gasserian ganglion PRF therapy combined with low-dose morphine injection offers an alternative option for managing intractable herpetic neuralgia and prevention of postherpetic neuralgia in ocular branches. Clinical Trial Registration: ChiCTR2300073281.

Deep Learning of radiology-genomics integration for computational oncology: A mini review.

In the field of computational oncology, patient status is often assessed using radiology-genomics, which includes two key technologies and data, such as radiology and genomics. Recent advances in deep learning have facilitated the integration of radiology-genomics data, and even new omics data, significantly improving the robustness and accuracy of clinical predictions. These factors are driving artificial intelligence (AI) closer to practical clinical applications. In particular, deep learning models are crucial in identifying new radiology-genomics biomarkers and therapeutic targets, supported by explainable AI (xAI) methods. This review focuses on recent developments in deep learning for radiology-genomics integration, highlights current challenges, and outlines some research directions for multimodal integration and biomarker discovery of radiology-genomics or radiology-omics that are urgently needed in computational oncology.

Developing BioNavi for Hybrid Retrosynthesis Planning.

Illuminating synthetic pathways is essential for producing valuable chemicals, such as bioactive molecules. Chemical and biological syntheses are crucial, and their integration often leads to more efficient and sustainable pathways. Despite the rapid development of retrosynthesis models, few of them consider both chemical and biological syntheses, hindering the pathway design for high-value chemicals. Here, we propose BioNavi by innovating multitask learning and reaction templates into the deep learning-driven model to design hybrid synthesis pathways in a more interpretable manner. BioNavi outperforms existing approaches on different data sets, achieving a 75% hit rate in replicating reported biosynthetic pathways and displaying superior ability in designing hybrid synthesis pathways. Additional case studies further illustrate the potential application of BioNavi in a de novo pathway design. The enhanced web server (http://biopathnavi.qmclab.com/bionavi/) simplifies input operations and implements step-by-step exploration according to user experience. We show that BioNavi is a handy navigator for designing synthetic pathways for various chemicals.