Identification of endocrine-disrupting chemicals targeting key OP-associated genes via bioinformatics and machine learning.

Osteoporosis (OP), a metabolic disorder predominantly impacting postmenopausal women, has seen considerable progress in diagnosis and treatment over the past few decades. However, the intricate interplay between genetic factors and endocrine disruptors (EDCs) in the pathogenesis of OP remains inadequately elucidated. The objective of this research is to examine the environmental pollutants and their regulatory mechanisms that could potentially influence the pathogenesis of OP, in order to establish a theoretical foundation for the targeted prevention and medical management of individuals with OP. Utilizing CTD and GEO datasets, network toxicology and bioinformatics analyses were conducted to identify target genes from a pool of 98 co-associated genes. Subsequently, a novel prediction model was developed employing a multiple machine learning algorithm. The efficacy of the model was validated based on the area under the receiver operating characteristic curve. Finally, real-time quantitative polymerase chain reaction (qRT-PCR) was used to confirm the expression levels of key genes in clinical samples. We have identified significant genes (FOXO3 and LUM) associated with OP and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, immune infiltration analysis, and molecular docking analysis. Through the analysis of these key genes, we have identified 13 EDCs that have the potential to impact OP. Several endocrine disruptors, such as Dexamethasone, Perfluorononanoic acid, genistein, cadmium, and bisphenol A, have been identified as notable environmental pollutants that impact the OP. Molecular docking analysis revealed significant binding affinity of major EDCs to the post-translational protein structures of key genes. This study demonstrates that EDCs, including dexamethasone, perfluorononanoic acid, genistein, cadmium, and bisphenol A, can be identified as important environmental pollutants affecting OP, and that FOXO3 and LUM have the potential to be diagnostic markers for OP. These results elucidate a novel association between EDCs regulated by key genes and the onset of OP.

Molecular Subtypes Defined by Cuproptosis-Associated Genes, Prognostic Model Development, and Tumor Immune Microenvironment Characterization in Adrenocortical Carcinoma.

Introduction: This study aims to explore the role of cuproptosis-related genes in ACC, utilizing data from TCGA and GEO repositories, and to develop a predictive model for patient stratification. Methods: A cohort of 123 ACC patients with survival data was analyzed. RNA-seq data of 17 CRGs were examined, and univariate Cox regression identified prognostic CRGs. A cuproptosis-related network was constructed to show interactions between CRGs. Consensus clustering classified ACC into three subtypes, with transcriptional and survival differences assessed by PCA and survival analysis. Gene set variation analysis (GSVA) and ssGSEA evaluated functional and immune infiltration characteristics across subtypes. Differentially expressed genes (DEGs) were identified, and gene clusters were established. A risk score (CRG_score) was generated using LASSO and multivariate Cox regression, validated across datasets. Tumor microenvironment, stem cell index, mutation status, drug sensitivity, and hormone synthesis were examined in relation to the CRG_score. Protein expression of key genes was validated, and functional studies on ASF1B and NDRG4 were performed. Results: Three ACC subtypes were identified with distinct survival outcomes. Subtype B showed the worst prognosis, while subtype C had the best. We identified 214 DEGs linked to cell proliferation and classified patients into three gene clusters, confirming their prognostic value. The CRG_score predicted patient outcomes, with high-risk patients demonstrating worse survival and possible resistance to immunotherapy. Drug sensitivity analysis suggested higher responsiveness to doxorubicin and etoposide in high-risk patients. Conclusion: This study suggests the potential prognostic value of CRGs in ACC. The CRG_score model provides a robust tool for risk stratification, with implications for treatment strategies.

Exploration of Genes Related to Intramuscular Fat Deposition in Xinjiang Brown Cattle.

The aim of this study was to investigate the differentially expressed genes associated with intramuscular fat deposition in the longissimus dorsi muscle of Xinjiang Brown Bulls. The longissimus dorsi muscles of 10 Xinjiang Brown Bulls were selected under the same feeding conditions. The intramuscular fat content of muscle samples was determined by the Soxhlet extraction method, for which 5 samples with high intramuscular fat content (HIMF group) and 5 samples with low intramuscular fat content (LIMF group) were selected. It was found that the intramuscular fat content of the HIMF group was 46.054% higher than that of the LIMF group. Muscle samples produced by paraffin sectioning were selected for morphological observation. It was found that the fat richness of the HIMF group was better than that of the LIMF group. Transcriptome sequencing technology was used to analyze the gene expression differences of longissimus dorsi muscle. Through in-depth analysis of the longissimus dorsi muscle by transcriptome sequencing technology, we screened a total of 165 differentially expressed genes. The results of Gene Ontology (GO) enrichment analysis showed that the differentially expressed genes in the two groups were mainly clustered in biological pathways related to carbohydrate metabolic processes, redox processes and oxidoreductase activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the differentially expressed genes were significantly clustered in 15 metabolic pathways, which mainly covered fatty acid metabolism (related to lipid metabolism and glucose metabolism), the pentose phosphate pathway, the Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathway and other important metabolic processes. The three genes that were predominantly enriched in the glycolipid metabolic pathway by analysis were SCD5, CPT1C and FBP2, all of which directly or indirectly affect intramuscular fat deposition. In summary, the present study investigated the differences in gene expression between high and low intramuscular fat content in the longissimus dorsi muscle of Xinjiang Brown Bulls by transcriptome sequencing technology and revealed the related signaling pathways. Therefore, we hypothesized that SCD5, CPT1C and FBP2 were the key genes responsible for the significant differences in intramuscular fat content of the longissimus dorsi muscles in a population of Xinjiang Brown Bulls. We expect that these findings will provide fundamental support for subsequent studies exploring key genes affecting fat deposition characteristics in Xinjiang Brown Bulls.

Prediction of lymphovascular invasion of gastric cancer based on contrast-enhanced computed tomography radiomics.

Background: Lymphovascular invasion (LVI) is a significant risk factor for lymph node metastasis in gastric cancer (GC) and is closely related to the prognosis and recurrence of GC. This study aimed to establish clinical models, radiomics models and combination models for the diagnosis of GC vascular invasion. Methods: This study enrolled 146 patients with GC proved by pathology and who underwent radical resection of GC. The patients were assigned to the training and validation cohorts. A total of 1,702 radiomic features were extracted from contrast-enhanced computed tomography images of GC. Logistic regression analyses were performed to establish a clinical model, a radiomics model and a combined model. The performance of the predictive models was measured by the receiver operating characteristic (ROC) curve. Results: In the training cohort, the age of LVI negative (-) patients and LVI positive (+) patients were 62.41 ± 8.41 and 63.76 ± 10.08 years, respectively, and there were more male (n = 63) than female (n = 19) patients in the LVI (+) group. Diameter and differentiation were the independent risk factors for determining LVI (-) and (+). A combined model was found to be relatively highly discriminative based on the area under the ROC curve for both the training (0.853, 95% CI: 0.784-0.920, sensitivity: 0.650 and specificity: 0.907) and the validation cohorts (0.742, 95% CI: 0.559-0.925, sensitivity: 0.736 and specificity: 0.700). Conclusions: The combined model had the highest diagnostic effectiveness, and the nomogram established by this model had good performance. It can provide a reliable prediction method for individual treatment of LVI in GC before surgery.

Comparison of Laparoendoscopic Single-Site Adrenalectomy with the Aid of Intracavitary Retractors and Multiport Laparoendoscopic Adrenalectomy.

Objective: To evaluate the operative outcome of the use of intracavitary retractors in transumbilical laparoendoscopic single-site (LESS) adrenalectomy in comparison with the conventional multiport laparoendoscopic procedure. Methods: Between July 2021 and December 2023, 34 patients underwent transumbilical LESS adrenalectomy with intracavitary retractors, while 47 patients underwent conventional multiport laparoscopic adrenalectomy. Comprehensive data were compared, including demographics, intraoperative outcomes, perioperative complications, postoperative visual analog pain scale score, analgesic requirement, and short-term measures of convalescence. Results: Baseline characteristics were similar between the groups. All procedures were successfully completed without additional access or open conversion. The mean operative time and estimated blood loss for LESS adrenalectomy were comparable with multiport adrenalectomy. The LESS group had significantly shorter incision length (3.07 cm versus 5.16 cm, P < .01), lower postoperative pain scores (3.29 versus 4.91, P < .01), less analgesic drug use (29% versus 53%, P = .03), and better cosmetic scores (9.29 versus 7.28, P < .01). No significant differences were observed in time to resume oral intake, time to ambulation, or postoperative hospital stay. Complication rates were similar between the groups. Conclusion: The utilization of intracavitary retractors in transumbilical LESS adrenalectomy has demonstrated feasibility, effectiveness, and the potential to reduce technical complexities with satisfactory cosmetic effects. This technique enhances visualization of the surgical field without the need for extra ports.

Liquid-liquid phase separation-related genes associated with prognosis, tumor microenvironment characteristics, and tumor cell features in bladder cancer.

OBJECTIVE: This study aimed to explore the Liquid-liquid phase separation (LLPS)-related genes associated with the prognosis of bladder cancer (BCa) and assess the potential application of LLPS-related prognostic signature for predicting prognosis in BCa patients. METHODS: Clinical information and transcriptome data of BCa patients were extracted from the Cancer Genome Atlas-BLCA (TCGA-BLCA) database and the GSE13507 database. Furthermore, 108 BCa patients who received treatment at our institution were subjected to a retrospective analysis. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an LLPS-related prognostic signature for BCa. The CCK8, wound healing and Transwell assays were performed. RESULTS: Based on 62 differentially expressed LLPS-related genes (DELRGs), three DELRGs were screened by LASSO analysis including kallikrein-related peptidase 5 (KLK5), monoacylglycerol O-acyltransferase 2 (MOGAT2) and S100 calcium-binding protein A7 (S100A7). Based on three DELRGs, a novel LLPS-related prognostic signature was constructed for individualized prognosis assessment. Kaplan-Meier curve analyses showed that LLPS-related prognostic signature was significantly correlated with overall survival (OS) of BCa. ROC analyses demonstrated the LLPS-related prognostic signature performed well in predicting the prognosis of BCa patients in the training group (the area under the curve (AUC) = 0.733), which was externally verified in the validation cohort 1 (AUC = 0.794) and validation cohort 2 (AUC = 0.766). Further experiments demonstrated that inhibiting KLK5 could affect the proliferation, migration, and invasion of BCa cells. CONCLUSIONS: In this study, a novel LLPS-related prognostic signature was successfully developed and validated, demonstrating strong performance in predicting the prognosis of BCa patients.

Yak DEFB123 alleviates lung injury caused by Klebsiella pneumoniae through MAPKs signaling pathway.

Beta-defensins, such as ß-defensin 123 (DEFB123), are vital components of the immune system's defense against infections due to their strong antimicrobial properties and capacity for modulating the body's immunological responses. In this study, we successfully cloned and analyzed the yak DEFB123 gene sequence. Subsequently, we obtained recombinant protein DEFB123 (rDEFB123) through prokaryotic expression. Our results demonstrate that rDEFB123 effectively inhibits the growth of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. Furthermore, rDEFB123 enhances the phagocytic activity of macrophages by regulating specific factors. In a mouse model infected with Klebsiella pneumoniae, the administration of rDEFB123 showed significantly lower levels of serum ALT and AST compared to the control group. Moreover, IFN-γ and IgG were significantly increased in the rDEFB123-treated groups, indicating an enhanced immune response. In the MAPKs signaling pathway of the infected mouse lungs, the expressions of JNK, TRAF2, TRAF6, MIF, and IL-1ß genes were downregulated in the rDEFB123-treated groups. Moreover, the levels of p-JNK protein were significantly decreased in these groups as well. Klebsiella pneumoniae caused systemic infection with organ damage in mice. However, the administration of rDEFB123 suppressed the expressions of inflammatory factors, thereby mitigating organ injury and regulating the activity of apoptosis-related factors to enhance immunity. These findings provide valuable theoretical data for future exploration of the functionality and potential applications of DEFB123 in yak.

A chemical screen identifies PRMT5 as a therapeutic vulnerability for paclitaxel-resistant triple-negative breast cancer.

Paclitaxel-resistant triple negative breast cancer (TNBC) remains one of the most challenging breast cancers to treat. Here, using an epigenetic chemical probe screen, we uncover an acquired vulnerability of paclitaxel-resistant TNBC cells to protein arginine methyltransferases (PRMTs) inhibition. Analysis of cell lines and in-house clinical samples demonstrates that resistant cells evade paclitaxel killing through stabilizing mitotic chromatin assembly. Genetic or pharmacologic inhibition of PRMT5 alters RNA splicing, particularly intron retention of aurora kinases B (AURKB), leading to a decrease in protein expression, and finally results in selective mitosis catastrophe in paclitaxel-resistant cells. In addition, type I PRMT inhibition synergies with PRMT5 inhibition in suppressing tumor growth of drug-resistant cells through augmenting perturbation of AURKB-mediated mitotic signaling pathway. These findings are fully recapitulated in a patient-derived xenograft (PDX) model generated from a paclitaxel-resistant TNBC patient, providing the rationale for targeting PRMTs in paclitaxel-resistant TNBC.

Assessment of perianal fistulizing Crohn's disease activity with endoanal ultrasound: A retrospective cohort study.

BACKGROUND: Perianal fistulas pose dual challenges to Crohn's disease (CD) patients. Low patient compliance due to the complexity of existing examination methods plagues the treatment and follow-up management of perianal CD. AIM: To determine the accuracy of endoanal ultrasound (EUS) and shear wave elastography (SWE) for evaluating perianal fistulizing CD (PFCD) activity. METHODS: This was a retrospective cohort study. A total of 67 patients from August 2022 to December 2023 diagnosed with CD were divided into three groups: Non-anal fistula group (n = 23), low-activity perianal fistulas [n = 19, perianal disease activity index (PDAI) ≤ 4], high-activity perianal fistulas (n = 25, PDAI > 4) based on the PDAI. All patients underwent assessments including EUS + SWE, pelvic magnetic resonance [pelvic magnetic resonance imaging (MRI)], C-reactive protein, fecal calprotectin, CD activity index, PDAI. RESULTS: The percentage of fistulas indicated by pelvic MRI and EUS was consistent at 82%, and there was good consistency in the classification of perianal fistulas (Kappa = 0.752, P < 0.001). Significant differences were observed in the blood flow Limberg score (χ 2 = 8.903, P < 0.05) and shear wave velocity (t = 2.467, P < 0.05) between group 2 and 3. Shear wave velocity showed a strong negative correlation with magnetic resonance novel index for fistula imaging in CD (Magnifi-CD) score (r = -0.676, P < 0.001), a weak negative correlation with the PDAI score (r = -0.386, P < 0.05), and a weak correlation between the Limberg score and the PDAI score (r = 0.368, P < 0.05). CONCLUSION: EUS combined with SWE offers a superior method for detecting and quantitating the activity of perianal fistulas in CD patients. It may be the ideal tool to assess PFCD activity objectively for management strategies.

Genome-wide sRNA and mRNA transcriptomic profiling insights into carbapenem-resistant Acinetobacter baumannii.

Introduction: Acinetobacter baumannii (AB) is rising as a human pathogen of critical priority worldwide as it is the leading cause of opportunistic infections in healthcare settings and carbapenem-resistant AB is listed as a "super bacterium" or "priority pathogen for drug resistance" by the World Health Organization. Methods: Clinical isolates of A. baumannii were collected and tested for antimicrobial susceptibility. Among them, carbapenem-resistant and carbapenem-sensitive A. baumannii were subjected to prokaryotic transcriptome sequencing. The change of sRNA and mRNA expression was analyzed by bioinformatics and validated by quantitative reverse transcription-PCR. Results: A total of 687 clinical isolates were collected, of which 336 strains of A. baumannii were resistant to carbapenem. Five hundred and six differentially expressed genes and nineteen differentially expressed sRNA candidates were discovered through transcriptomic profile analysis between carbapenem-resistant isolates and carbapenem-sensitive isolates. Possible binding sites were predicted through software for sRNA21 and adeK, sRNA27 and pgaC, sRNA29 and adeB, sRNA36 and katG, indicating a possible targeting relationship. A negative correlation was shown between sRNA21 and adeK (r = -0.581, P = 0.007), sRNA27 and pgaC (r = -0.612, P = 0.004), sRNA29 and adeB (r = -0.516, P = 0.020). Discussion: This study preliminarily screened differentially expressed mRNA and sRNA in carbapenem-resistant A. baumannii, and explored possible targeting relationships, which will help further reveal the resistance mechanism and provide a theoretical basis for the development of drugs targeting sRNA for the prevention and treatment of carbapenem-resistant A. baumannii infection.

A comparative cross-platform analysis of cuproptosis-related genes in human nonobstructive azoospermia: An observational study.

This study aimed to identify novel biomarkers associated with cuproptosis in human nonobstructive azoospermia (NOA). We obtained 4 NOA microarray datasets (GSE145467, GSE9210, GSE108886, and GSE45885) from the NCBI Gene Expression Omnibus database and merged them into training set. Another NOA dataset (GSE45887) was used as validation set. Differentially expressed cuproptosis-related genes were identified from training set. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted. Least absolute shrinkage and selection operator regression and support vector machine-recursive feature elimination were used to identify hub cuproptosis-related genes. We calculated the expression of the hub cuproptosis-related genes in both validation set and patients with NOA. Gene set variation analysis was used to explore their potential biological functions. The risk prediction model was built by logistic regression analysis and was evaluated in the validation set. Finally, we constructed a competing endogenous RNA network. The training set included 29 patents in the control group and 92 in the NOA group, and 10 cuproptosis-related differentially expressed genes were identified. Subsequently, we screened 6 hub cuproptosis-related genes (DBT, GCSH, NFE2L2, NLRP3, PDHA1, and SLC31A1) by least absolute shrinkage and selection operator regression and support vector machine-recursive feature elimination. GCSH, NFE2L2, NLRP3, and SLC31A1 expressed higher in NOA group than in control group (P < .05) in the validation set (4 patients in control and 16 in NOA groups), while the expression levels of GCSH, NFE2L2, NLRP3, PDHA1, and SLC31A1 were higher in NOA group than in control group (P < .05) in our patients (3 patients in control and 4 in NOA groups). The model based on the 6-gene signature showed superior performance with an AUC value of 0.970 in training set, while 1.0 in validation set. Gene set variation analysis revealed a higher enrichment score of "homologous recombination" in the high expression groups of the 6 hub genes. Finally, we constructed a competing endogenous RNA network and found hsa-miR-335-3p and hsa-miR-1-3p were the most frequently related to the 6 hub genes. DBT, GCSH, NFE2L2, NLRP3, PDHA1, and SLC31A1 may serve as predictors of cuproptosis and play important roles in the NOA pathogenesis.

Nanozyme-catalyzed and zwitterion-modified swabs based for the detection of Listeria monocytogenes in complex matrices.

In recent years, nanozymes have been widely used in the field of biosensing and food safety testing due to their advantages of low cost, high stability, easy modification and adjustable catalytic activity. However, how to reduce the signal interference generated by reducing substances, macromolecules and colored substances in the food matrix in nanozymes-based colorimetric sensing is still a major challenge. In this paper, using Listeria monocytogenes as a model analyte, sodium sulfonyl methacrylate (SBMA) polymers were modified onto cotton swabs by photothermal polymerization and combined with Listeria monocytogenes-specific aptamer (Apt1) to prepare swabs that can specifically capture and isolate Listeria monocytogenes from complex matrices (SBMA/Apt1 cotton swab). In addition, in combination with the inhibitory effect of the aptamer (Apt2) on the oxidase activity of Mn3O4 NPs, a colorimetric biosensor based on nanozymes that can quantitatively, sensitively, and specifically identify Listeria monocytogenes in food products was constructed. The results showed that the colorimetric signal of the method was linear with the concentration of Listeria monocytogenes in the range of 2.83-2.83 × 105 CFU/mL, and the limit of detection was 2.64 CFU/mL, which can be used for the detection of Listeria monocytogenes in complex environments and food samples.

High sensitivity fiber SPR sensor based on a spiral coarse cone structure.

A fiber SPR sensor can achieve rapid and portable detection of trivalent arsenic ions (As3+) in drinking water or food, but their sensitivity and detection limit need to be further improved and developed toward specific detection. This article proposed the implementation of the SPR sensor using a biased core fiber spiral coarse cone structure. The fine core of the biased core fiber was used to reduce the mode of transmitted light. By controlling the pitch of the spiral core to control the SPR incidence angle, a significant increase in the sensitivity of the fiber SPR sensor was achieved. Meanwhile, the harmless glutathione (GSH) was modified on the surface of the sensing gold film to achieve the specific detection of As3+. The experimental results indicate that the spiral coarse cone fiber SPR sensor proposed in this article has a detection sensitivity of 32.48 nm/ppb for As3+, with a detection limit as low as 0.011 ppb, meeting the detection requirements of the World Health Organization for As3+ in water, which provides a new feasible solution for fast, portable, and highly sensitive detection of metal ions in water and food.

Structural and Mutational Analyses of Trehalose Synthase from Deinococcus radiodurans Reveal the Interconversion of Maltose-Trehalose Mechanism.

Trehalose synthase (TreS) catalyzes the reversible interconversion of maltose to trehalose, playing a vital role in trehalose production. Understanding the catalytic mechanism of TreS is crucial for optimizing the enzyme activity and enhancing its suitability for industrial applications. Here, we report the crystal structures of both the wild type and the E324D mutant of Deinococcus radiodurans trehalose synthase in complex with the trehalose analogue, validoxylamine A. By employing structure-guided mutagenesis, we identified N253, E320, and E324 as crucial residues within the +1 subsite for isomerase activity. Based on these complex structures, we propose the catalytic mechanism underlying the reversible interconversion of maltose to trehalose. These findings significantly advance our comprehension of the reaction mechanism of TreS.

High-Sensitivity Refractive Index Sensor with Dual-Channel Based on Surface Plasmon Resonance Photonic Crystal Fiber.

In order to achieve a high-precision synchronous detection of two different refractive index (RI) analytes, a D-type surface plasmon resonance (SPR) photonic crystal fiber (PCF) RI sensor based on two channels is designed in this paper. The sensor uses a D-shaped planar region of the PCF and a large circular air hole below the core as the sensing channels. Surface plasmon resonance is induced by applying a coating of gold film on the surface. The full-vector finite-element method (FEM) is used to optimize the structural parameters of the optical fiber, and the sensing characteristics are studied, including wavelength sensitivity, RI resolution, full width at half maximum (FWHM), figure of merit (FOM), and signal-to-noise ratio (SNR). The results show that the channel 1 (Ch 1) can achieve RI detection of 1.36-1.39 in the wavelength range of 1500-2600 nm, and the channel 2 (Ch 2) can achieve RI detection of 1.46-1.57 in the wavelength range of 2100-3000 nm. The two sensing channels can detect independently or simultaneously measure two analytes with different RIs. The maximum wavelength sensitivity of the sensor can reach 30,000 nm/RIU in Channel 1 and 9900 nm/RIU in Channel 2. The RI resolutions of the two channels are 3.54 × 10-6 RIU and 10.88 × 10-6 RIU, respectively. Therefore, the sensor realizes dual-channel high- and low-RI synchronous detection in the ultra-long wavelength band from near-infrared to mid-infrared and achieves an ultra-wide RI detection range and ultra-high wavelength sensitivity. The sensor has a wide application prospect in the fields of chemical detection, biomedical sensing, and water environment monitoring.

Microscopic Study on Superexchange Dynamics of Composite Spin-1 Bosons.

We report on an experimental simulation of the spin-1 Heisenberg model with composite bosons in a one-dimensional chain based on the two-component Bose-Hubbard model. Exploiting our site- and spin-resolved quantum gas microscope, we observed faster superexchange dynamics of the spin-1 system compared to its spin-1/2 counterpart, which is attributed to the enhancement effect of multi-bosons. We further probed the nonequilibrium spin dynamics driven by the superexchange and single-ion anisotropy terms, unveiling the linear expansion of the spin-spin correlations, which is limited by the Lieb-Robinson bound. Based on the superexchange process, we prepared and verified the entangled qutrits pairs with these composite spin-1 bosons, potentially being applied in qutrit-based quantum information processing.

Blocker-SELEX: a structure-guided strategy for developing inhibitory aptamers disrupting undruggable transcription factor interactions.

Despite the well-established significance of transcription factors (TFs) in pathogenesis, their utilization as pharmacological targets has been limited by the inherent challenges in modulating their protein interactions. The lack of defined small-molecule binding pockets and the nuclear localization of TFs do not favor the use of traditional tools. Aptamers possess large molecular weights, expansive blocking surfaces and efficient cellular internalization, making them compelling tools for modulating TF interactions. Here, we report a structure-guided design strategy called Blocker-SELEX to develop inhibitory aptamers (iAptamers) that selectively block TF interactions. Our approach leads to the discovery of iAptamers that cooperatively disrupt SCAF4/SCAF8-RNAP2 interactions, dysregulating RNAP2-dependent gene expression, which impairs cell proliferation. This approach is further applied to develop iAptamers blocking WDR5-MYC interactions. Overall, our study highlights the potential of iAptamers in disrupting pathogenic TF interactions, implicating their potential utility in studying the biological functions of TF interactions and in nucleic acids drug discovery.

Robot-assisted Single-port Radical Prostatectomy with the SHURUI SP and da Vinci SP Platforms: Comparison of the Technology, Intraoperative Performance, and Outcomes.

Background and objective: The purpose-built SHURUI single-port (SP) robotic platform has recently been introduced for several procedures in urology, general surgery, and gynecology. However, comparative evidence on its performance in relation to earlier models such as the da Vinci SP is lacking. Our aim was to compare the step-by-step techniques and 1-yr outcomes for radical prostatectomy (RP) between the SHURUI SP and da Vinci SP robots. Methods: Data were retrieved from two prospectively maintained databases. The SHURUI SP robot was used to perform RP in 34 patients in China (September 2021 to August 2022); the da Vinci SP robot was used to perform 100 consecutive RP cases in the USA (June 2019 to October 2020). A comparative analysis was conducted before and after 1:1 propensity score matching for age, body mass index, American Urological Association symptom score, prostate size, prostate-specific antigen (PSA) levels, biopsy grade group, and D'Amico risk group. Intraoperative performance and short-term oncological and continence outcomes were compared between the groups. Biochemical recurrence was defined as two consecutive postoperative PSA levels >0.2 ng/ml. Continence was defined as full recovery of urinary control without the use of pads. The Kaplan-Meier method was used to estimate continence recovery curves, and a log-rank test for trend was used to detect ordered differences in continence recovery between the SHURUI SP and da Vinci SP groups after surgery. Key findings and limitations: For the matched SHURUI and da Vinci groups, median age (69 vs 69 yr), median PSA (8.4 vs 7.1 ng/ml), and the proportion of patients with low-risk (33.3% vs 29.6%), intermediate-risk (66.7% vs 63%), and high-risk disease (0% vs 7.4%) were comparable (all p > 0.05). All surgeries were successfully accomplished without conversion. A higher percentage of cases in the SHURUI group involved extraperitoneal access (81.5% vs 0%; p < 0.001) and a pure SP approach (25.9% vs 0%; p = 0.01), while a higher percentage of cases in the da Vinci group had nerve-sparing surgery. The median total operative (215 vs 110 min; p < 0.001) and median console time (162 vs 75 min; p < 0.001) were significantly longer in the SHURUI group. No intraoperative or major postoperative complications were observed in either group. Rates of positive surgical margins (18.5% vs 14.8%; p = 1.0) and extraprostatic extension (14.8% vs 29.6%; p = 0.19) were similar. At median follow-up of 13.5 versus 15.9 mo, none of the patients had experienced biochemical recurrence. At 1 yr after surgery, the continence rate was 96.3% in both groups. Conclusions: Despite differences in driving mechanisms between the two SP robotic systems, RP can be performed safely and effectively with the SHURUI RP robot during the initial learning phase, with similar short-term oncological and continence outcomes to those with the da Vinci SP robot. Patient summary: We compared two surgical robots (SHURUI SP and da Vinci SP) used to perform robotic surgery to remove the prostate through a single keyhole incision instead of multiple incisions. Our results show comparable technology and similar surgical and short-term cancer control outcomes for the two robots.