Molecular-Scale Visualization of Steric Effects of Ligand Binding to Reconstructed Au(111) Surfaces.

Direct imaging of single molecules at nanostructured interfaces is a grand challenge with potential to enable new, precise material architectures and technologies. Of particular interest are the structural morphology and spectroscopic signatures of the adsorbed molecule, where modern probes are only now being developed with the necessary spatial and energetic resolution to provide detailed information at the molecule-surface interface. Here, we directly characterize the adsorption of individual m-terphenyl isocyanide ligands on a reconstructed Au(111) surface through scanning tunneling microscopy and inelastic electron tunneling spectroscopy. The site-dependent steric pressure of the various surface features alters the vibrational fingerprints of the m-terphenyl isocyanides, which are characterized with single-molecule precision through joint experimental and theoretical approaches. This study provides molecular-level insights into the steric-pressure-enabled surface binding selectivity as well as its effect on the chemical properties of individual surface-binding ligands.

Iron deficiency affects oxygen transport and activates HIF1 signaling pathway to regulate phenotypic transformation of VSMC in aortic dissection.

BACKGROUND: Aortic dissection (AD) is a macrovascular disease which is pathologically characterized by aortic media degeneration.This experiment aims to explore how iron deficiency (ID) affects the function of vascular smooth muscle cell (VSMC) and participates in the occurrence and development of AD by regulating gene expression. METHODS: The relationship between iron and AD was proved by Western-blot (WB) and immunostaining experiments in human and animals. Transcriptomic sequencing explored the transcription factors that were altered downstream. WB, flow cytometry and immunofluorescence were used to demonstrate whether ID affected HIF1 expression through oxygen transport. HIF1 signaling pathway and phenotypic transformation indexes were detected in cell experiments. The use of the specific HIF1 inhibitor PX478 further demonstrated that ID worked by regulating HIF1. RESULTS: The survival period of ID mice was significantly shortened and the pathological staining results were the worst. Transcriptomic sequencing indicated that HIF1 was closely related to ID and the experimental results indicated that ID might regulate HIF1 expression by affecting oxygen balance. HIF1 activation regulates the phenotypic transformation of VSMC and participates in the occurrence and development of AD in vivo and in vitro.PX478, the inhibition of HIF1, can improve ID-induced AD exacerbation.

Amplification-Free Analysis of Bladder Cancer MicroRNAs on Wrinkled Silica Nanoparticles with DNA-Functionalized Quantum Dots.

Bladder cancer (BC) occurrence and progression are accompanied by alterations in microRNAs (miRNAs) expression levels. Simultaneous detection of multiple miRNAs contributes to the accuracy and reliability of the BC diagnosis. In this work, wrinkled silica nanoparticles (WSNs) were applied as the microreactor for multiplex miRNAs analysis without enzymes or nucleic acid amplification. Conjugated on the surface of WSNs, the S9.6 antibody was adopted as the universal module for binding DNA/miRNA duplexes, regardless of their sequence. Furthermore, single-stranded DNA (ssDNA) was labeled with quantum dots (QDs) for identifying a given miRNA to form QDs-ssDNA/miRNA, which enabled the specific capture of the corresponding QDs on the wrinkled surface of WSNs. Based on the detection of fluorescence signals that were ultimately focused on WSNs, target miRNAs could be sensitively identified to a femtomolar level (5 fM) with a wide dynamic range of up to 6 orders of magnitude. The proposed strategy achieved high specificity to obviously distinguish single-base mutation sequences and possessed multiplex assay capability. Moreover, the assay exhibited excellent practicability in the multiplex detection of miRNAs in clinical serum specimens.

Robot-assisted single-port retroperitoneal partial nephrectomy with a novel purpose-built single-port robotic system with deformable surgical instruments.

OBJECTIVE: To investigate the safety and feasibility of using a novel purpose-built single-port robotic system (the SHURUI Robotic Surgical System) with deformable surgical instruments to perform retroperitoneal single-port partial nephrectomy. MATERIALS AND METHODS: A prospective study was conducted to recruit patients with a single renal tumor no more than 4 cm. Robot-assisted single-port partial nephrectomy was performed by using the novel purpose-built single-port robotic system with deformable surgical instruments. Patients' demographics, tumor characteristics, and perioperative parameters were recorded and analyzed. RESULTS: Sixteen patients were recruited to the study. The median tumor size was 2.0 cm (IQR: 1.2-2.4 cm). The median R.E.N.A.L score was 6 (IQR: 4-4.5). In 3 cases, pure single-port surgery was carried out, and all the assistance was through the robotic port. Median docking time was 15.5 min (IQR: 14.25-22.25 min). Median operating time was 148.5 min (IQR: 178-238.5 min). Median console time was 107 min (IQR: 92.75-149.75 min). Median warm ischemic time was 26.5 min (IQR: 24.5-30 min). Median blood loss was 17.5 ml (IQR: 10-50 ml). CONCLUSIONS: Retroperitoneal partial nephrectomy can be safely performed with this novel purpose-built single-port robotic system (SHURUI) with deformable surgical instruments. Further studies are needed to fully evaluate the role of this new platform.

Second-trimester triglyceride-glucose index to predict adverse outcomes in women with gestational diabetes mellitus: A retrospective multicenter cohort study.

AIMS/INTRODUCTION: Women with gestational diabetes mellitus are at high risk for adverse maternal and neonatal outcomes. The study aimed to evaluate the performance of the triglyceride-glucose index in predicting the risk of developing adverse outcomes in women with gestational diabetes mellitus. MATERIALS AND METHODS: This retrospective multicenter cohort study included 8,808 pregnant women with gestational diabetes mellitus in two grade-A tertiary hospitals in China during 2018-2022. The triglyceride-glucose index was defined as ln [triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. Significant adverse gestational diabetes mellitus outcomes were chosen by generalized linear models as the main outcomes. Multivariable logistic regression models evaluated their association with the triglyceride-glucose index. Areas under the receiver operating characteristic curves predicted adverse pregnancy outcomes. The prediction efficiency was validated in the sensitivity analysis dataset and validation cohort. RESULTS: The triglyceride-glucose index was associated with preeclampsia, severe preeclampsia, preterm birth, placenta accreta spectrum, and macrosomia before and after adjusting for confounding factors (P < 0.05). The predictive performance of the triglyceride-glucose index was relatively moderate. Incorporating the triglyceride-glucose index into the baseline clinical risk model improved the area under curves for the diagnosis of preeclampsia (0.749 [0.714-0.784] vs 0.766 [0.734-0.798], P = 0.033) and macrosomia (0.664 [0.644-0.685] vs 0.676 [0.656-0.697], P = 0.002). These predictive models exhibited good calibration and robustness. CONCLUSIONS: The triglyceride-glucose index is positively associated with preeclampsia, severe preeclampsia, preterm birth, placenta accreta spectrum, and macrosomia and is useful for the early prediction and prevention of adverse outcomes in women with gestational diabetes mellitus.

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.

CircZNF609 inhibited bladder cancer immunotherapy sensitivity via enhancing fatty acid uptake through IGF2BP2/CD36 pathway.

Circular RNAs (circRNAs) are gaining attention for their involvement in immune escape and immunotherapy sensitivity regulation. CircZNF609 is a well-known oncogene in various solid tumours. Our previous research revealed its role in reducing the chemosensitivity of bladder cancer (BCa) to cisplatin. However, the underlying role of circZNF609 in BCa immune escape and immunotherapy sensitivity remains unknown. We conducted BCa cells-CD8 + T cells co-culture assays, cell line-derived xenograft and patient-derived xenograft mouse models with human immune reconstitution to further confirm the role of circZNF609 in BCa immune escape and immunotherapy sensitivity. Overexpression of circZNF609 promoted BCa immune escape in vitro and in vivo. Mechanistically, circZNF609 was bound to IGF2BP2, enhancing its interaction with the 3'-untranslated region of CD36. This increased the stability of the CD36 mRNA, leading to enhanced fatty acid uptake by BCa cells and fatty acid depletion within the tumour microenvironment. Additionally, the nuclear export of circZNF609 was regulated by DDX39B. CircZNF609 promoted immune escape and suppressed BCa immunotherapy sensitivity by regulating the newly identified circZNF609/IGF2BP2/CD36 cascade. Therefore, circZNF609 holds potential as both a biomarker and therapeutic target in BCa immunotherapy.

Network pharmacology and experimental evaluation strategies to decipher the underlying pharmacological mechanism of Traditional Chinese Medicine CFF-1 against prostate cancer.

Prostate cancer (PCa) is a common malignancy in elderly men. We have applied Traditional Chinese Medicine CFF-1 in clinical treatments for PCa for several years. Here, we aimed to identify the underlying mechanism of CFF-1 on PCa using network pharmacology and experimental validation. Active ingredients, potential targets of CFF-1 were acquired from the public databases. Subsequently, protein-protein interaction (PPI) and the herbs-active ingredients-target network was constructed. A prognostic model for PCa was also constructed based on key targets. In vitro experiments using PCa cell lines CWR22Rv1 and PC-3 were carried out to validate the potential mechanism of CFF-1 on PCa. A total of 112 bioactive compounds and 359 key targets were screened from public databases. PPI and herbs-active ingredients-target network analysis determined 12 genes as the main targets of CFF-1 on PCa. Molecular docking studies indicated that the primary active ingredients of CFF-1 possess strong binding affinity to the top five hub targets. DNMT3B, RXRB and HPRT1 were found to be involved in immune regulation of PCa. In vitro, CFF-1 was found to inhibit PCa cell proliferation, migration, invasion and induce apoptosis via PI3K-Akt, HIF-1, TNF, EGFR-TKI resistance and PD-1 checkpoint signaling pathways. This study comprehensively elucidates the underlying molecular mechanism of CFF-1 against PCa, offering a strong rationale for clinical application of CFF-1 in PCa treatment.

Ultrastable Electrolytic Zn-I2 Batteries Based on Nanocarbon Wrapped by Highly Efficient Single-Atom Fe-NC Iodine Catalysts.

Aqueous Zn-iodine (Zn-I2) conversion batteries with iodine redox chemistry suffers the severe polyiodide shuttling and sluggish redox kinetics, which impede the battery lifespan and rate capability. Herein, an ultrastable Zn-I2 battery is introduced based on single-atom Fe-N-C encapsulated high-surface-area carbon (HC@FeNC) as the core-shell cathode materials, which accelerate the I-/I3 -/I° conversion significantly. The robust chemical-physical interaction between polyiodides and Fe-N4 sites tightly binds the polyiodide ions and suppresses the polyiodide shuttling, thereby significantly enhancing the coulombic efficiency. As a result, the core-shell HC@FeNC cathode endows the electrolytic Zn-I2 battery with an excellent capacity, remarkable rate capability, and an ultralong lifespan over 60 000 cycles. More importantly, a practical 253 Wh kg-1 pouch cell shows good capacity retention of 84% after 100 cycles, underscoring its considerable potential for commercial Zn-I2 batteries.

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.