Robot-Assisted Radical Nephroureterectomy Using the KangDuo Surgical Robot-01 System: A Prospective, Single-Center, Single-Arm Clinical Study.

PURPOSE: To investigate the feasibility, safety, and efficacy of the KangDuo Surgical Robot-01 (KD-SR-01) system for robot-assisted radical nephroureterectomy (UTUC). MATERIALS AND METHODS: This prospective, single-center, single-arm clinical study of patients with UTUC was conducted from August 2022 to July 2023 using the KD-SR-01 system. The perioperative and follow-up data were prospectively recorded. The National Aeronautics and Space Administration Task Load Index was calculated to present ergonomics. The technique was described in detail. RESULTS: A total of 13 patients underwent RARNU. None of the cases conversed to laparoscopic surgery or open surgery. The median docking time and console time were 524 (range, 139-963) seconds and 102.2 (range, 55.3-249.3) minutes, respectively. The median estimated blood loss was 40 (range, 10-100) ml. None of the patients required intraoperative blood transfusion. The median postoperative hospital stay was 4 (range, 2-7) days. Intraoperative or postoperative complications (Clavien-Dindo grade I) occurred in 9 patients. The surgeon Task Load Index global score achieved 1.05±1.86. Three patients received the single-docking technique, demonstrating similar perioperative results compared to patients with re-docking. CONCLUSIONS: The KD-SR-01 system was feasible, safe, and effective for robot-assisted radical nephroureterectomy.

Improved Catalytic Activity of Spherical Nucleic Acid Enzymes by Hybridization Chain Reaction and Its Application for Sensitive Analysis of Aflatoxin B1.

Conventional spherical nucleic acid enzymes (SNAzymes), made with gold nanoparticle (AuNPs) cores and DNA shells, are widely applied in bioanalysis owing to their excellent physicochemical properties. Albeit important, the crowded catalytic units (such as G-quadruplex, G4) on the limited AuNPs surface inevitably influence their catalytic activities. Herin, a hybridization chain reaction (HCR) is employed as a means to expand the quantity and spaces of G4 enzymes for their catalytic ability enhancement. Through systematic investigations, we found that when an incomplete G4 sequence was linked at the sticky ends of the hairpins with split modes (3:1 and 2:2), this would significantly decrease the HCR hybridization capability due to increased steric hindrance. In contrast, the HCR hybridization capability was remarkably enhanced after the complete G4 sequence was directly modified at the non-sticky end of the hairpins, ascribed to the steric hindrance avoided. Accordingly, the improved SNAzymes using HCR were applied for the determination of AFB1 in food samples as a proof-of-concept, which exhibited outstanding performance (detection limit, 0.08 ng/mL). Importantly, our strategy provided a new insight for the catalytic activity improvement in SNAzymes using G4 as a signaling molecule.

Accurate and robust segmentation of cerebral vasculature on four-dimensional arterial spin labeling magnetic resonance angiography using machine-learning approach.

Segmentation of cerebral vasculature on MR vascular images is of great significance for clinical application and research. However, the existing cerebrovascular segmentation approaches are limited due to insufficient image contrast and complicated algorithms. This study aims to explore the potential of the emerging four-dimensional arterial spin labeling magnetic resonance angiography (4D ASL-MRA) technique for fast and accurate cerebrovascular segmentation with a simple machine-learning approach. Nine temporal features were extracted from the intensity-time signal of each voxel, and eight spatial features from the neighboring voxels. Then, the unsupervised outlier detection algorithm, i.e. Isolation Forest, is used for segmentation of the vascular voxels based on the extracted features. The total length of the centerlines of the intracranial arterial vasculature, the dice similarity coefficient (DSC), and the average Hausdorff Distance (AVGHD) on the cross-sections of small- to large-sized vessels were calculated to evaluate the performance of the segmentation approach on 4D ASL-MRA of 18 subjects. Experiments show that the temporal information on 4D ASL-MRA can largely improve the segmentation performance. In addition, the proposed segmentation approach outperforms the traditional methods that were performed on the 3D image (i.e. the temporal average intensity projection of 4D ASL-MRA) and the previously proposed frame-wise approach. In conclusion, this study demonstrates that accurate and robust segmentation of cerebral vasculature is achievable on 4D ASL-MRA by using a simple machine-learning approach with appropriate features.

Comprehensive Analysis of N6-Methylandenosine-Related lncRNAs in Clear Cell Renal Cell Carcinoma: A Correlation With Prognosis, Tumor Progression, and Therapeutic Response.

This study aims to develop a prognostic signature based on m6A-related lncRNAs for clear cell renal cell carcinoma (ccRCC). Differential expression analysis and Pearson correlation analysis were used to identify m6A-related lncRNAs associated with patient outcomes in The Cancer Genome Atlas (TCGA) database. Our approach led to the development of an m6A-related lncRNA risk score (MRLrisk), formulated using six identified lncRNAs: NFE4, AL008729.2, AL139123.1, LINC02154, AC124854.1 and ARHGAP31-AS1. Higher MRLrisk was identified as a risk factor for patients' prognosis in ccRCC. Furthermore, an MRLrisk-based nomogram was developed and demonstrated as a reliable tool for prognosis prediction in ccRCC. Enrichment analysis and tumor mutation signature studies were conducted to investigate MRLrisk-related biological phenotypes. The tumor immune dysfunction and exclusion (TIDE) score was employed to infer patients' response to immunotherapy, indicating a negative correlation between high MRLrisk and immunotherapy response. Our focus then shifted to LINC02154 for deeper exploration. We assessed LINC02154 expression in 28 ccRCC/normal tissue pairs and 3 ccRCC cell lines through quantitative real-time polymerase chain reaction (qRT-PCR). Functional experiments, including EdU incorporation, flow cytometry and transwell assays, were performed to assess the role of LINC02154 in ccRCC cell functions, discovering that its downregulation hinders cancer cell proliferation and migration. Furthermore, the influence of LINC02154 on ccRCC cells' sensitivity to Sunitinib was explored using CCK-8 assays, demonstrating that decreased LINC02154 expression increases Sunitinib sensitivity. In summary, this study successfully developed an MRLrisk model with significant prognostic value for ccRCC and established LINC02154 as a critical biomarker and prospective therapeutic target in ccRCC management.

Ileal ureter replacement and ileocystoplasty for the treatment of bilateral ureteral strictures and bladder contracture: technique and outcomes.

BACKGROUND: The aim of this study was to explore the feasibility of ileal ureter replacement and ileocystoplasty for the treatment of bilateral long-segment ureteral strictures combined with bladder contracture. METHODS: A retrospective review of clinical data from seven patients who underwent bilateral Ileal Ureter Replacement and ileocystoplasty from April 2019 to February 2023 was conducted. The surgeries were performed using open, laparoscopic, and robot-assisted laparoscopic approaches. Baseline characteristics, perioperative, and mid-term results of the patients were collected. Follow-up period of 3-28 months. A detailed description of the technique was reported. RESULTS: The mean age of the patients was 52.86±6.06 years. The average duration of surgery was 365±28.54 minutes, and the estimated intraoperative blood loss was 357.14±184.06 mL. The mean length of harvested ileum was 37.86±8.40 cm. The preoperative serum creatinine level was 88.02±18.05 µmol/L, postoperative day 1 creatinine level was 90.7±12.93µmol/L, postoperative 3-month creatinine level was 93.77±33.34 µmol/L, and the mean creatinine level at the last follow-up was 94.89±27.89µmol/L. The postoperative bladder capacity was 249.43±32.50 mL on average. The average length of hospital stay was 26.57±15.46 days. No complications of Clavien-Dindo grade 3 or higher were observed. During the follow-up period, no patients experienced deterioration of renal function after surgery. CONCLUSIONS: Bilateral ileal ureter replacement and ileocystoplasty are effective surgical technique for the treatment of bilateral long-segment ureteral strictures combined with bladder contracture caused by radiation therapy.

The interplay between autophagy and ferroptosis presents a novel conceptual therapeutic framework for neuroendocrine prostate cancer.

In American men, the incidence of prostate cancer (PC) is the highest among all types of cancer, making it the second leading cause of mortality associated with cancer. For advanced or metastatic PC, antiandrogen therapies are standard treatment options. The administration of these treatments unfortunately carries the potential risk of inducing neuroendocrine prostate cancer (NEPC). Neuroendocrine differentiation (NED) serves as a crucial indicator of prostate cancer development, encompassing various factors such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Yes-associated protein 1 (YAP1), AMP-activated protein kinase (AMPK), miRNA. The processes of autophagy and ferroptosis (an iron-dependent form of programmed cell death) play pivotal roles in the regulation of various types of cancers. Clinical trials and preclinical investigations have been conducted on many signaling pathways during the development of NEPC, with the deepening of research, autophagy and ferroptosis appear to be the potential target for regulating NEPC. Due to the dual nature of autophagy and ferroptosis in cancer, gaining a deeper understanding of the developmental programs associated with achieving autophagy and ferroptosis may enhance risk stratification and treatment efficacy for patients with NEPC.

Integrating Tertiary Lymphoid Structure-Associated Genes into Computational Models to Evaluate Prognostication and Immune Infiltration in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor response to all therapeutic modalities and dismal prognosis. The presence of tertiary lymphoid structures (TLSs) in various solid cancers is of crucial prognostic significance, highlighting the intricate interplay between the tumor microenvironment and immune cells aggregation. However, the extent to which TLS and immune status affect PDAC prognosis remains incompletely understood. Here, we sought to unveil the unique properties of TLS in PDAC by leveraging both single-cell and bulk transcriptomics, and culminating in a risk model that predicts clinical outcomes. We used TLS score based on 12 genes (CCL2, CCL3, CCL4, CCL5, CCL8, CCL18, CCL19, CCL21, CXCL9, CXCL10, CXCL11 and CXCL13) and 9 genes (PTGDS, RBP5, EIF1AY, CETP, SKAP1, LAT, CCR6, CD1D and CD79B) signature, respectively, and examined their distribution in cell clusters of single-cell data from PDAC samples. The markers involved in these clusters were selected to develop a prognostic model using The Cancer Genome Atlas Program (TCGA) database as the training cohort and Gene Expression Omnibus (GEO) database as the validation cohort. Further we compared the immune infiltration, drug sensitivity, enriched and differentially expressed genes between the high-risk and low-risk groups in our model. Therefore, we established a risk model that has significant implications for the prognostic assessment of PADC patients with remarkable differences in immune infiltration and chemo-sensitivity between the low-risk and high-risk groups. And this paradigm established by TLS-related cell marker genes provides a prognostic prediction and a panel of novel therapeutic targets for exploring potential immunotherapy.

Laparoscopic continent cutaneous urinary diversion using a modified Yang-Monti technique in an adult: A case report including 5-year follow-up.

Continuous cutaneous urinary diversion is challenging when the appendix is physically unavailable. The Yang-Monti channel is an alternative to the tunneled appendix for urinary diversion. We present a case involving a 49-year-old man who underwent total urethrectomy and cystostomy 10 months previously. No tumor recurrence was observed; however, the patient experienced severe catheter-related bladder irritation after the procedure. The patient was readmitted to the authors' hospital and underwent laparoscopic continent cutaneous urinary diversion using extracorporeal construction of a modified Yang-Monti channel. The operation lasted 232 minutes, with an estimated blood loss of 10 mL. The patient was discharged from hospital 6 days after surgery and removal of the cystostomy tube. After this, clean intermittent catheterization was performed every 3 hours for 4 weeks. Five years after the procedure, the modified Yang-Monti channel was still used for clean intermittent catheterization without any stomal stenosis being observed. The patient was satisfied with his postoperative quality of life.

Modified Ileal Conduit for Pelvic Lipomatosis: Technique Description and Outcome.

INTRODUCTION: To present the surgical technique and clinical outcomes of modified ileal conduit for pelvic lipomatosis (PL). METHODS: From 2020 to 2022, we prospectively enrolled 9 patients with PL undergoing modified ileal conduit. The patient characteristics, perioperative variables, and follow-up outcomes as well as the description of surgical technique were reported. RESULTS: All 9 patients successfully completed the operation. Two patients had perioperative complications of Clavien-Dindo grade I. The mean operation time and bleeding volumes were 253±51.4 min and 238.9±196.9 ml, with a mean postoperative follow-up time of 13.0±5.6 months. The postoperative 3-month and 1-year creatinine values were significantly decreased versus the preoperative (P=0.006 and P=0.024). The postoperative 3-month and 1-year eGFR values were significantly increased comapred with those before operation (P=0.0002 and P=0.018). The separation value of left renal pelvis collection system after operation were significantly reduced compared with preoperative evaluation (P=0.023 at 3 month and P=0.042 at 1 year) and so was the right side (P=0.019 and P=0.023). CONCLUSION: Modified ileal conduit is safe and feasible for PL. A large sample cohort with long-term follow-up is needed to evaluate the clinical outcomes of PL.

Metal-Assisted Carbohydrate Assembly.

The sequence-controlled assembly of nucleic acids and amino acids into well-defined superstructures constitutes one of the most revolutionary technologies in modern science. The elaboration of such superstructures from carbohydrates, however, remains elusive and largely unexplored on account of their intrinsic constitutional and configurational complexity, not to mention their inherent conformational flexibility. Here, we report the bottom-up assembly of two classes of hierarchical superstructures that are formed from a highly flexible cyclo-oligosaccharide─namely, cyclofructan-6 (CF-6). The formation of coordinative bonds between the oxygen atoms of CF-6 and alkali metal cations (i) locks a myriad of flexible conformations of CF-6 into a few rigid conformations, (ii) bridges adjacent CF-6 ligands, and (iii) gives rise to the multiple-level assembly of three extended frameworks. The hierarchical superstructures present in these frameworks have been shown to modulate their nanomechanical properties. This research highlights the unique opportunities of constructing convoluted superstructures from carbohydrates and should encourage future endeavors in this underinvestigated field of science.

TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype-phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions: We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Cell division machinery drives cell-specific gene activation during differentiation in Bacillus subtilis.

When faced with starvation, the bacterium Bacillus subtilis transforms itself into a dormant cell type called a "spore". Sporulation initiates with an asymmetric division event, which requires the relocation of the core divisome components FtsA and FtsZ, after which the sigma factor σF is exclusively activated in the smaller daughter cell. Compartment-specific activation of σF requires the SpoIIE phosphatase, which displays a biased localization on one side of the asymmetric division septum and associates with the structural protein DivIVA, but the mechanism by which this preferential localization is achieved is unclear. Here, we isolated a variant of DivIVA that indiscriminately activates σF in both daughter cells due to promiscuous localization of SpoIIE, which was corrected by overproduction of FtsA and FtsZ. We propose that the core components of the redeployed cell division machinery drive the asymmetric localization of DivIVA and SpoIIE to trigger the initiation of the sporulation program.

Resting cell formation in the marine diatom Thalassiosira pseudonana.

Resting cells represent a survival strategy employed by diatoms to endure prolonged periods of unfavourable conditions. In the oceans, many diatoms sink at the end of their blooming season and therefore need to endure cold and dark conditions in the deeper layers of the water column. How they survive these conditions is largely unknown. We conducted an integrative analysis encompassing methods from histology, physiology, biochemistry, and genetics to reveal the biological mechanism of resting-cell formation in the model diatom Thalassiosira pseudonana. Resting-cell formation was triggered by a decrease in light and temperature with subsequent catabolism of storage compounds. Resting cells were characterised by an acidic and viscous cytoplasm and altered morphology of the chloroplast ultrastructure. The formation of resting cells in T. pseudonana is an energy demanding process required for a biophysical alteration of the cytosol and chloroplasts to endure the unfavourable conditions of the deeper ocean as photosynthetic organisms. However, most resting cells (> 90%) germinate upon return to favorable growth conditions.

Pivotal Role of GSTO2 in Ferroptotic Neuronal Injury After Intracerebral Hemorrhage.

Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke.

Mild and Efficient Preparation of N-Heterocyclic Organic Molecules by Catalyst-free and Solvent-free Methods.

AIMS: The small organic molecular compounds with biological activity containing C-C and C-N or C-O bonding were efficiently prepared without catalyst and solvent in the hydrothermal synthesis reactor. OBJECTIVES: Our goal was to explore new applications for the more environmentally friendly and efficient synthesis of bis(indolyl)methyl, xanthene, quinazolinone, and N-heterocyclic derivatives in hydrothermal synthesis reactors under solvent-free and catalyst-free conditions. METHODS: A greener and more efficient method was successfully developed for the synthesis of bis(indolyl)methyl, heteroanthracene, quinazolinone, and N-heterocyclic derivatives using a hydrothermal synthesis reactor in a solvent- and catalyst-free manner. RESULTS: In a hydrothermal synthesis reactor, bis(indoyl)methyl, xanthene, quinazolinone, and N-heterocyclic derivatives were synthesized without catalysts and solvents. CONCLUSION: Overall, it is proved once again that the catalyst-free and solvent-free synthesis method has universal value and is a more ideal and environmentally friendly new method, especially the hydrothermal reactor for synthesis.

Adaptive Knowledge Distillation for High-Quality Unsupervised MRI Reconstruction with Model-Driven Priors.

Magnetic Resonance Imaging (MRI) reconstruction has made significant progress with the introduction of Deep Learning (DL) technology combined with Compressed Sensing (CS). However, most existing methods require large fully sampled training datasets to supervise the training process, which may be unavailable in many applications. Current unsupervised models also show limitations in performance or speed and may face unaligned distributions during testing. This paper proposes an unsupervised method to train competitive reconstruction models that can generate high-quality samples in an end-to-end style. Firstly teacher models are trained by filling the re-undersampled images and compared with the undersampled images in a self-supervised manner. The teacher models are then distilled to train another cascade model that can leverage the entire undersampled k-space during its training and testing. Additionally, we propose an adaptive distillation method to re-weight the samples based on the variance of teachers, which represents the confidence of the reconstruction results, to improve the quality of distillation. Experimental results on multiple datasets demonstrate that our method significantly accelerates the inference process while preserving or even improving the performance compared to the teacher model. In our tests, the distilled models show 5%-10% improvements in PSNR and SSIM compared with no distillation and are 10 times faster than the teacher. Source code of our work could be acquired at https://github.com/BITwzl/unsupervised_mri_reconstruction.