Resilience and vulnerabilities of tumor cells under purine shortage stress.

Purpose: Purine metabolism is a promising therapeutic target in cancer; however, how cancer cells respond to purine shortage, particularly their adaptation and vulnerabilities, remains unclear.

Experimental Design: Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated the responses in prostate, lung, and glioma cancer models.

Results: We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multi-protein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency.

The Impact of Animal Models and Strain Standardization on the Evaluation of Tuberculosis Vaccine Efficacy.

Tuberculosis (TB) remains one of the most significant challenges to global public health. Vaccine development is a critical strategy for the prevention and control of TB. However, evaluating the protective efficacy of TB vaccines faces numerous challenges, particularly in the selection of animal models and bacterial strains.

Oxidative stress activates YAP/TEAD1/NCOA4 axis to promote ferroptosis of endplate chondrocytes and aggravate intervertebral disc degeneration.

Background: Intervertebral disc degeneration (IDD) is a major cause of low back pain, with cartilaginous endplate (CEP) degeneration playing a critical role. While Yes-associated protein (YAP) and its involvement in CEP degeneration and ferroptosis remain unclear. This study aimed to investigate the regulatory role of YAP in CEP ferroptosis and its underlying mechanisms.

Spatial multi-vector and multi-rigid-body obstacle avoidance planning for multi-robot coordinated suspension system.

Multi-robot coordinated suspension systems (MCSS) face challenges such as difficulties in decoupling due to strong coupling in multi-body dynamics, computational complexity explosion caused by high-dimensional state spaces, and a scarcity of obstacle avoidance planning methods for multi-rigid-body systems. To address these issues, the telescopic pyramidal configuration (TPC) and the multi-strategy geyser-inspired algorithm (MGEA) are proposed. These methods enable multi-vector and multi-rigid-body obstacle avoidance planning via a hierarchical-search and step-optimization (HSSO) framework.

Association between thyroid function and type 2 diabetes mellitus based on the NHANES and Mendelian randomization study.

Objectives: Many observational studies have reported an association between thyroid function and type 2 diabetes mellitus (T2DM), but the causal relationship remains unclear. This study aims to examine the association between thyroid function and T2DM by using the National Health and Nutrition Examination Survey (NHANES) database 2007-2012 and Mendelian randomization (MR) analysis.

Methods: A cross-sectional analysis was performed utilizing data from the NHANES, and logistic regression was employed to investigate the relationship between thyroid function and T2DM.

A pilot study of [F]F-fluciclovine positron emission tomography/computed tomography for staging muscle invasive bladder cancer preceding radical cystectomy.

Aim: To assess the ability of [F]F-fluciclovine-PET/CT to stage muscle invasive bladder cancer (MIBC) before radical cystectomy.

Methods: This single-site prospective pilot study enrolled patients with MIBC and T2-T4, N0 disease on CT/MRI slated to undergo radical cystectomy (RC). Dynamic and static [F]F-fluciclovine-PET/CT images were acquired.

Effects of fourteen essential minerals and vitamins on acute and chronic tubulointerstitial nephritis: a multivariate Mendelian randomization study.

Objective: To investigate the causal relationship between minerals and vitamins and acute and chronic tubulointerstitial nephritis by Mendelian randomization.

Methods: We selected fourteen minerals and vitamins from the GWAS database and acute tubulointerstitial nephritis and chronic tubulointerstitial nephritis from the Finnish database. Minerals and vitamins were first analyzed by two-sample Mendelian randomization for acute and chronic tubulointerstitial nephritis.

Resilience and vulnerabilities of tumor cells under purine shortage stress.

Purine metabolism is a promising therapeutic target in cancer; however how cancer cells respond to purine shortage,particularly their adaptation and vulnerabilities, remains unclear. Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated these responses in prostate, lung and glioma cancer models. We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multi-protein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency.

Single-cell assay for transposase-accessible chromatin sequencing of human clear cell renal cell carcinoma.

Regulating the occurrence and progression of tumor cells at the epigenetic level is a new insight of clear cell renal cell carcinoma (ccRCC). Chromatin accessibility is an important pathway of epigenetic regulation, which may explain the mystery of tumor occurrence. Assay for transposase-accessible chromatin sequencing (ATAC-seq) provides insight into the epigenetic regulatory features of ccRCC, especially at the single-cell level.

Ferristatin II protects nucleus pulposus against degeneration through inhibiting ferroptosis and activating HIF-1α pathway mediated mitophagy.

Background: Nucleus pulposus (NP) degeneration represents a significant contributing factor in the pathogenesis of intervertebral disc (IVD) degeneration (IVDD), and is a key underlying mechanism in several lumbar spine pathologies. Nevertheless, the precise mechanisms that govern NP degeneration remain unclear. A significant contributing factor to IVDD has been identified as ferroptosis.

Global, regional, and national epidemiology of childhood neuroblastoma (1990-2021): a statistical analysis of incidence, mortality, and DALYs.

Background: Neuroblastoma is the most prevalent extracranial solid tumor in pediatric populations worldwide, representing 8-10% of childhood malignancies and contributing to approximately 15% of pediatric cancer-related fatalities. This study aims to report global trends in the incidence, mortality, and disability-adjusted life years (DALYs) of childhood neuroblastoma from 1990 to 2021.

Methods: The study utilized data from the Global Burden of Disease (GBD) database to analyze neuroblastoma incidence, mortality, and DALYs in children aged 0-14 years.

Three new taxa of the lichen genus (Megasporaceae, Ascomycota) from China.

Two new species; Lun Wang & Y. Y. Zhang, Lun Wang & Y.

Decoding 11-oxygenated androgen synthesis: insights from enzyme gene expression and LC-MS/MS quantification.

Background: Adrenal-origin and peripheral tissue-transformed 11-oxygenated androgens are recognized as significant androgens. However, our current understanding of the synthesis of 11-oxygenated androgens, including the organs and cell types involved, remains limited.

Methods: We performed comprehensive analyses on an extensive dataset of normal human tissues, which included bulk RNA data from 30 tissues, single-cell RNA sequencing (scRNA) data from 16 tissues and proteomics data from 29 tissues, to characterize the expression profiles of enzyme-encoding genes.

Galactokinase 1 is the source of elevated galactose-1-phosphate and cerebrosides are modestly reduced in a mouse model of classic galactosemia.

Classic galactosemia (CG) arises from loss-of-function mutations in the gene, which codes for the enzyme galactose-1-phosphate uridylyltransferase (GALT), a central component in galactose metabolism. The neonatal fatality associated with CG can be prevented by galactose dietary restriction, but for decades it has been known that limiting galactose intake is not a cure and patients often have lasting complications. Even on a low-galactose diet, GALT's substrate galactose-1-phosphate (Gal1P) is elevated and one hypothesis is that elevated Gal1P is a driver of pathology.

Unfolding the mysteries of heterogeneity from a high-resolution perspective: integration analysis of single-cell multi-omics and spatial omics revealed functionally heterogeneous cancer cells in ccRCC.

The genomic landscape of clear cell renal cell carcinoma (ccRCC) has a considerable intra-tumor heterogeneity, which is a significant obstacle in the field of precision oncology and plays a pivotal role in metastasis, recurrence, and therapeutic resistance of cancer. The mechanisms of intra-tumor heterogeneity in ccRCC have yet to be fully established. We integrated single-cell RNA sequencing (scRNA-seq) and transposase-accessible chromatin sequencing (scATAC-seq) data from a single-cell multi-omics perspective.

HIF-2α/TFR1 mediated iron homeostasis disruption aggravates cartilage endplate degeneration through ferroptotic damage and mtDNA release: A new mechanism of intervertebral disc degeneration.

Backgroud: Iron overload is a prevalent condition in the elderly, often associated with various degenerative diseases, including intervertebral disc degeneration (IDD). Nevertheless, the mechanisms responsible for iron ion accumulation in tissues and the mechanism that regulate iron homeostasis remain unclear. Transferrin receptor-1 (TFR1) serves as the primary cellular iron gate, playing a pivotal role in controlling intracellular iron levels, however its involvement in IDD pathogenesis and the underlying mechanism remains obscure.

Association Between ACE2 and Lung Diseases.

Angiotensin-converting enzyme 2 (ACE2) is an important regulator of the Renin-Angiotensin System (RAS). Additionally, it has been identified as a functional receptor for the Coronavirus. Research indicates that ACE2 plays a role in the regulation of cardiovascular systems by modulating blood pressure and electrolyte balance.

Strengthening Mechanism and Damping Properties of SiC/Al-Mg Composites Prepared by Combining Colloidal Dispersion with a Squeeze Melt Infiltration Process.

SiC-fiber-reinforced Al-Mg matrix composites with different mass fractions of Mg were fabricated by combining colloidal dispersion with a squeeze melt infiltration process. The microstructure, mechanical and damping properties, and the corresponding mechanisms were investigated. Microstructure analyses found that SiC/Al-Mg composites presented a homogeneous distribution of SiC fibers, and the relative density was higher than 97% when the mass fraction of Mg was less than 20%; the fiber-matrix interface bonded well, and no obvious reaction occurred at the interface.

Feasibility and Effectiveness of Repeat Laparoscopic Pyeloplasty for Recurrent Ureteropelvic Junction Obstruction in Pediatric Patients.

To assess the outcomes of redo laparoscopic pyeloplasty (RLP) in pediatric patients with recurrent ureteropelvic junction obstruction (UPJO) in contrast to redo open pyeloplasty (ROP). In addition, evaluate the feasibility and efficacy of RLP as a treatment modality for recurrent UPJO in children. The data of 44 patients from March 2012 to March 2022, who underwent redo pyeloplasty, were retrospectively reviewed.

Vector integration and fate in the hemophilia dog liver multiple years after AAV-FVIII gene transfer.

Gene therapy using adeno-associated virus (AAV) vectors is a promising approach for the treatment of monogenic disorders. Long-term multiyear transgene expression has been demonstrated in animal models and clinical studies. Nevertheless, uncertainties remain concerning the nature of AAV vector persistence and whether there is a potential for genotoxicity.

Multidimensional Transcriptomics Unveils RNF34 as a Prognostic Biomarker and Potential Indicator of Chemotherapy Sensitivity in Wilms' Tumour.

Nephroblastoma, colloquially known as Wilms' tumour (WT), is the predominant malignant renal neoplasm arising in the paediatric population. Modern therapeutic approaches for WT incorporate a synergistic combination of surgical intervention, radiotherapy, and chemotherapy, which substantially ameliorate the overall patient survival rate. Despite this, the optimal sequence of chemotherapy and surgical intervention remains a matter of contention, with each strategy presenting its own strengths and weaknesses that could influence clinical decision-making.

Prophylactic Prednisolone Promotes AAV5 Hepatocyte Transduction Through the Novel Mechanism of AAV5 Coreceptor Platelet-Derived Growth Factor Receptor Alpha Upregulation and Innate Immune Suppression.

Adeno-associated virus (AAV) vectors are used to deliver therapeutic transgenes, but host immune responses may interfere with transduction and transgene expression. We evaluated prophylactic corticosteroid treatment on AAV5-mediated expression in liver tissue. Wild-type C57BL/6 mice received 6 × 10 vg/kg AAV5-HLP-hA1AT, an AAV5 vector carrying a human α1-antitrypsin (hA1AT) gene with a hepatocyte-specific promoter.

Unveiling the hidden AP-1: revealing the crucial role of AP-1 in ccRCC at single-cell resolution.

Clear cell renal cell carcinoma (ccRCC), as the most common histological subtype of kidney cancer, has been reported to originate primarily from proximal tubule (PT) cells in the kidney. However, the current research on its associated molecular mechanisms remains relatively limited. In our study, we analyzed multiple single-cell multi-omics datasets obtained from various research teams, revealing the significant role of the activator protein 1 (AP-1) in ccRCC tumorigenesis.