Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression.

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.

Free-electron lasing at 27 nanometres based on a laser wakefield accelerator.

X-ray free-electron lasers can generate intense and coherent radiation at wavelengths down to the sub-ångström region1-5, and have become indispensable tools for applications in structural biology and chemistry, among other disciplines6. Several X-ray free-electron laser facilities are in operation2-5; however, their requirement for large, high-cost, state-of-the-art radio-frequency accelerators has led to great interest in the development of compact and economical accelerators. Laser wakefield accelerators can sustain accelerating gradients more than three orders of magnitude higher than those of radio-frequency accelerators7-10, and are regarded as an attractive option for driving compact X-ray free-electron lasers11. However, the realization of such devices remains a challenge owing to the relatively poor quality of electron beams that are based on a laser wakefield accelerator. Here we present an experimental demonstration of undulator radiation amplification in the exponential-gain regime by using electron beams based on a laser wakefield accelerator. The amplified undulator radiation, which is typically centred at 27 nanometres and has a maximum photon number of around 1010 per shot, yields a maximum radiation energy of about 150 nanojoules. In the third of three undulators in the device, the maximum gain of the radiation power is approximately 100-fold, confirming a successful operation in the exponential-gain regime. Our results constitute a proof-of-principle demonstration of free-electron lasing using a laser wakefield accelerator, and pave the way towards the development of compact X-ray free-electron lasers based on this technology with broad applications.

PD-L1 (B7-H1) Competes with the RNA Exosome to Regulate the DNA Damage Response and Can Be Targeted to Sensitize to Radiation or Chemotherapy.

Programmed death ligand 1 (PD-L1, also called B7-H1) is an immune checkpoint protein that inhibits immune function through its binding of the programmed cell death protein 1 (PD-1) receptor. Clinically approved antibodies block extracellular PD-1 and PD-L1 binding, yet the role of intracellular PD-L1 in cancer remains poorly understood. Here, we discovered that intracellular PD-L1 acts as an RNA binding protein that regulates the mRNA stability of NBS1, BRCA1, and other DNA damage-related genes. Through competition with the RNA exosome, intracellular PD-L1 protects targeted RNAs from degradation, thereby increasing cellular resistance to DNA damage. RNA immunoprecipitation and RNA-seq experiments demonstrated that PD-L1 regulates RNA stability genome-wide. Furthermore, we developed a PD-L1 antibody, H1A, which abrogates the interaction of PD-L1 with CMTM6, thereby promoting PD-L1 degradation. Intracellular PD-L1 may be a potential therapeutic target to enhance the efficacy of radiotherapy and chemotherapy in cancer through the inhibition of DNA damage response and repair.

An RNA-informed dosage sensitivity map reflects the intrinsic functional nature of genes.

Understanding dosage sensitivity or why Mendelian diseases have dominant vs. recessive modes of inheritance is crucial for uncovering the etiology of human disease. Previous knowledge of dosage sensitivity is mainly based on observations of rare loss-of-function mutations or copy number changes, which are underpowered due to ultra rareness of such variants. Thus, the functional underpinnings of dosage constraint remain elusive. In this study, we aim to systematically quantify dosage perturbations from cis-regulatory variants in the general population to yield a tissue-specific dosage constraint map of genes and further explore their underlying functional logic. We reveal an inherent divergence of dosage constraints in genes by functional categories with signaling genes (transcription factors, protein kinases, ion channels, and cellular machinery) being dosage sensitive, while effector genes (transporters, metabolic enzymes, cytokines, and receptors) are generally dosage resilient. Instead of being a metric of functional dispensability, we show that dosage constraint reflects underlying homeostatic constraints arising from negative feedback. Finally, we employ machine learning to integrate DNA and RNA metrics to generate a comprehensive, tissue-specific map of dosage sensitivity (MoDs) for autosomal genes.

Vimentin regulates nuclear segmentation in neutrophils.

Granulocytes are indispensable for various immune responses. Unlike other cell types in the body, the nuclei of granulocytes, particularly neutrophils, are heavily segmented into multiple lobes. Although this distinct morphological feature has long been observed, the underlying mechanism remains incompletely characterized. In this study, we utilize cryo-electron tomography to examine the nuclei of mouse neutrophils, revealing the cytoplasmic enrichment of intermediate filaments on the concave regions of the nuclear envelope. Aided by expression profiling and immuno-electron microscopy, we then elucidate that the intermediate-filament protein vimentin is responsible for such perinuclear structures. Of importance, exogenously expressed vimentin in nonimmune cells is sufficient to form cytoplasmic filaments wrapping on the concave nuclear surface. Moreover, genetic deletion of the protein causes a significant reduction of the number of nuclear lobes in neutrophils and eosinophils, mimicking the hematological condition of the Pelger-Huët anomaly. These results have uncovered a new component establishing the nuclear segmentation of granulocytes.

IAnimal: a cross-species omics knowledgebase for animals.

With the exponential growth of multi-omics data, its integration and utilization have brought unprecedented opportunities for the interpretation of gene regulation mechanisms and the comprehensive analyses of biological systems. IAnimal (https://ianimal.pro/), a cross-species, multi-omics knowledgebase, was developed to improve the utilization of massive public data and simplify the integration of multi-omics information to mine the genetic mechanisms of objective traits. Currently, IAnimal provides 61 191 individual omics data of genome (WGS), transcriptome (RNA-Seq), epigenome (ChIP-Seq, ATAC-Seq) and genome annotation information for 21 species, such as mice, pigs, cattle, chickens, and macaques. The scale of its total clean data has reached 846.46 TB. To better understand the biological significance of omics information, a deep learning model for IAnimal was built based on BioBERT and AutoNER to mine 'gene' and 'trait' entities from 2 794 237 abstracts, which has practical significance for comprehending how each omics layer regulates genes to affect traits. By means of user-friendly web interfaces, flexible data application programming interfaces, and abundant functional modules, IAnimal enables users to easily query, mine, and visualize characteristics in various omics, and to infer how genes play biological roles under the influence of various omics layers.

Integrating a Biomineralized Nanocluster for H2S-Sensitized ROS Bomb against Breast Cancer.

Nanomaterial-assisted chemodynamic therapy (CDT) has received considerable attention in recent years. It outperforms other modalities by its distinctive reactive oxygen species (ROS) generation through a nonexogenous stimulant. However, CDT is limited by the insufficient content of endogenous hydrogen peroxide (H2O2). Herein, a biodegradable MnS@HA-DOX nanocluster (MnS@HA-DOX NC) was constructed by in situ biomineralization from hyaluronic acid, to enlarge the ROS cascade and boost Mn2+-based CDT. The acid-responsive NCs could quickly degrade after internalization into endo/lysosomes, releasing Mn2+, H2S gas, and anticancer drug doxorubicin (DOX). The Fenton-like reaction catalyzed by Mn2+ was amplified by both H2S and DOX, producing a mass of cytotoxic ·OH radicals. Through the combined action of gas therapy (GT), CDT, and chemotherapy, oxidative stress would be synergistically enhanced, inducing irreversible DNA damage and cell cycle arrest, eventually resulting in cancer cell apoptosis.

Thermally and Mechanically Stable Perovskite Artificial Synapse as Tuned by Phase Engineering for Efferent Neuromuscular Control.

The doping of perovskites with mixed cations and mixed halides is an effective strategy to optimize phase stability. In this study, we introduce a cubic black phase perovskite CsyFA(1-y)Pb(BrxI(1-x))3 artificial synapse, using phase engineering by adjusting the cesium-bromide content. Low-bromine mixed perovskites are suitable to improve the electric pulse excitation sensitivity and stability of the device. Specifically, the low-bromine and low-cesium mixed perovskite (x = 0.15, y = 0.22) annealed at 373 K allows the device to maintain logic response even after 1000 mechanical flex/flat cycles. The device also shows good thermal stability up to temperatures of 333 K. We have demonstrated reflex-arc behavior with MCMHP synaptic units, capable of making sensory warnings at high frequency. This compositionally engineered, dual-mixed perovskite synaptic device provides significant potential for perceptual soft neurorobotic systems and prostheses.

Gate-Tunable Quantum Acoustoelectric Transport in Graphene.

Transport probes the motion of quasi-particles in response to external excitations. Apart from the well-known electric and thermoelectric transport, acoustoelectric transport induced by traveling acoustic waves has rarely been explored. Here, by adopting hybrid nanodevices integrated with piezoelectric substrates, we establish a simple design of acoustoelectric transport with gate tunability. We fabricate dual-gated acoustoelectric devices based on hBN-encapsulated graphene on LiNbO3. Longitudinal and transverse acoustoelectric voltages are generated by launching a pulsed surface acoustic wave. The gate dependence of zero-field longitudinal acoustoelectric signal presents strikingly similar profiles to that of Hall resistivity, providing a valid approach for extracting carrier density without magnetic field. In magnetic fields, acoustoelectric quantum oscillations appear due to Landau quantization, which are more robust and pronounced than Shubnikov-de Haas oscillations. Our work demonstrates a feasible acoustoelectric setup with gate tunability, which can be extended to the broad scope of various van der Waals materials.

Lipidomics Study of Type 1 Diabetic Rats Using Online Phase Transition Trapping-Supercritical Fluid Extraction-Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry.

Chromatography-mass spectrometry-based lipidomics represents an essential tool for elucidating lipid dysfunction mechanisms and is extensively employed in investigating disease mechanisms and identifying biomarkers. However, the detection of low-abundance lipids in biological matrices, along with cumbersome operational procedures, complicates comprehensive lipidomic analyses, necessitating the development of highly sensitive, environmentally friendly, and automated methods. In this study, an online phase transition trapping-supercritical fluid extraction-chromatography-mass spectrometry (PTT-SFEC-MS/MS) method was developed and successfully applied to plasma lipidomics analysis in Type 1 diabetes (T1D) rats. The PTT strategy captured entire extracts at the column head by converting CO2 from a supercritical state to a gaseous state, thereby preventing peak spreading, enhancing peak shape for precise quantification, and boosting sensitivity without any sample loss. This method utilized only 5 µL of plasma and accomplished sample extraction, separation, and detection within 27 min. Ultimately, 77 differential lipids were identified, including glycerophospholipids, sphingolipids, and glycerolipids, in T1D rat plasma. The results indicated that the progression of the disease might be linked to alterations in glycerophospholipid and sphingolipid metabolism. Our findings demonstrated a green, highly efficient, and automated method for the lipidomics analysis of biological samples, providing a scientific foundation for understanding the pathogenesis and diagnosis of T1D.

An Octacarboxylate-Linked Sodium Metal-Organic Framework with High Porosity.

Alkali metal-based metal-organic frameworks (MOFs) with permanent porosity are scarce because of their high tendency to coordinate with solvents such as water. However, these MOFs are lightweight and bear gravimetric benefits for gas adsorption related applications. In this study, we present the successful construction of a microporous MOF, designated as HIAM-111, built solely on sodium ions by using an octacarboxylate linker. The structure of HIAM-111 is based on 8-connected Na4 clusters and exhibits a novel topology with an underlying 32,42,8-c net. Remarkably, HAM-111 possesses a robust and highly porous framework with a BET surface area of 1561 m2/g, significantly surpassing that of the previously reported Na-MOFs. Further investigations demonstrate that HIAM-111 is capable of separating C2H2/CO2 and purifying C2H4 directly from C2H4/C2H2/C2H6 with high adsorption capacities. The current work may shed light on the rational design of robust and porous MOFs based on alkali metals.

A new emu genome illuminates the evolution of genome configuration and nuclear architecture of avian chromosomes.

Emu and other ratites are more informative than any other birds in reconstructing the evolution of the ancestral avian or vertebrate karyotype because of their much slower rate of genome evolution. Here, we generated a new chromosome-level genome assembly of a female emu, and estimated the tempo of chromosome evolution across major avian phylogenetic branches, by comparing it to chromosome-level genome assemblies of 11 other bird and one turtle species. We found ratites exhibited the lowest numbers of intra- and inter-chromosomal changes among birds since their divergence with turtles. The small-sized and gene-rich emu microchromosomes have frequent inter-chromosomal contacts that are associated with housekeeping genes, which appears to be driven by clustering their centromeres in the nuclear interior, away from the macrochromosomes in the nuclear periphery. Unlike nonratite birds, only less than one-third of the emu W Chromosome regions have lost homologous recombination and diverged between the sexes. The emu W is demarcated into a highly heterochromatic region (WS0) and another recently evolved region (WS1) with only moderate sequence divergence with the Z Chromosome. WS1 has expanded its inactive chromatin compartment, increased chromatin contacts within the region, and decreased contacts with the nearby regions, possibly influenced by the spreading of heterochromatin from WS0. These patterns suggest that alteration of chromatin conformation comprises an important early step of sex chromosome evolution. Overall, our results provide novel insights into the evolution of avian genome structure and sex chromosomes in three-dimensional space.

Band Structure Tuning via Pt Single Atom Induced Rapid Hydroxyl Radical Generation toward Efficient Photocatalytic Reforming of Lignocellulose into H2.

Photocatalytic lignocellulose reforming for H2 production presents a compelling solution to solve environmental and energy issues. However, achieving scalable conversion under benign conditions faces consistent challenges including insufficient active sites for H2 evolution reaction (HER) and inefficient lignocellulose oxidation directly by photogenerated holes. Herein, it is found that Pt single atom-loaded CdS nanosheet (PtSA -CdS) would be an active photocatalyst for lignocellulose-to-H2 conversion. Theoretical and experimental analyses confirm that the valence band of CdS shifts downward after depositing isolated Pt atoms, and the slope of valence band potential on pH for PtSA -CdS is more positive than Nernstian equation. These characteristics allow PtSA -CdS to generate large amounts of •OH radicals even at pH 14, while the capacity is lacking with CdS alone. The employment of •OH/OH- redox shuttle succeeds in relaying photoexcited holes from the surface of photocatalyst, and the •OH radicals can diffuse away to decompose lignocellulose efficiently. Simultaneously, surface Pt atoms, featured with a thermoneutral Δ G H ∗ $\Delta G_{\mathrm{H}}^{\mathrm{*}}$ , would collect electrons to expedite HER. Consequently, PtSA -CdS performs a H2 evolution rate of 10.14 µmol h-1 in 1 m KOH aqueous solution, showcasing a remarkable 37.1-fold enhancement compared to CdS. This work provides a feasible approach to transform waste biomass into valuable sources.

Multiple Treatment of Triple-Negative Breast Cancer Through Gambogic Acid-Loaded Mesoporous Polydopamine.

Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, characterized by aggressiveness and high recurrence rate. As monotherapy provides limited benefit to TNBC patients, combination therapy emerges as a promising treatment approach. Gambogic acid (GA) is an exceedingly promising anticancer agent. Nonetheless, its application potential is hampered by low drug loading efficiency and associated toxic side effects. To overcome these limitations, using mesoporous polydopamine (MPDA) endowed with photothermal conversion capabilities is considered as a delivery vehicle for GA. Meanwhile, GA can inhibit the activity of heat shock protein 90 (HSP90) to enhance the photothermal effect. Herein, GA-loaded MPDA nanoparticles (GA@MPDA NPs) are developed with a high drug loading rate of 75.96% and remarkable photothermal conversion performance. GA@MPDA NPs combined with photothermal treatment (PTT) significantly inhibit the tumor growth, and effectively trigger the immunogenic cell death (ICD), which thereby increase the number of activated effector T cells (CD8+ T cells and CD4+ T cells) in the tumor, and hoist the level of immune-inflammatory cytokines (IFN-γ, IL-6, and TNF-α). The above results suggest that the combination of GA@MPDA NPs with PTT expected to activate the antitumor immune response, thus potentially enhancing the clinical therapeutic effect on TNBC.

The oncogenic role and regulatory mechanism of ACAA2 in human ovarian cancer.

Acetyl-CoAacyltransferase2 (ACAA2) is a key enzyme in the fatty acid oxidation pathway that catalyzes the final step of mitochondrial ß oxidation, which plays an important role in fatty acid metabolism. The expression of ACAA2 is closely related to the occurrence and malignant progression of tumors. However, the function of ACAA2 in ovarian cancer is unclear. The expression level and prognostic value of ACAA2 were analyzed by databases. Gain and loss of function were carried out to explore the function of ACAA2 in ovarian cancer. RNA-seq and bioinformatics methods were applied to illustrate the regulatory mechanism of ACAA2. ACAA2 overexpression promoted the growth, proliferation, migration, and invasion of ovarian cancer, and ACAA2 knockdown inhibited the malignant progression of ovarian cancer as well as the ability of subcutaneous tumor formation in nude mice. At the same time, we found that OGT can induce glycosylation modification of ACAA2 and regulate the karyoplasmic distribution of ACAA2. OGT plays a vital role in ovarian cancer as a function of oncogenes. In addition, through RNA-seq sequencing, we found that ACAA2 regulates the expression of DIXDC1. ACAA2 regulated the malignant progression of ovarian cancer through the WNT/ß-Catenin signaling pathway probably. ACAA2 is an oncogene in ovarian cancer and has the potential to be a target for ovarian cancer therapy.

GREAP: a comprehensive enrichment analysis software for human genomic regions.

The rapid development of genomic high-throughput sequencing has identified a large number of DNA regulatory elements with abundant epigenetics markers, which promotes the rapid accumulation of functional genomic region data. The comprehensively understanding and research of human functional genomic regions is still a relatively urgent work at present. However, the existing analysis tools lack extensive annotation and enrichment analytical abilities for these regions. Here, we designed a novel software, Genomic Region sets Enrichment Analysis Platform (GREAP), which provides comprehensive region annotation and enrichment analysis capabilities. Currently, GREAP supports 85 370 genomic region reference sets, which cover 634 681 107 regions across 11 different data types, including super enhancers, transcription factors, accessible chromatins, etc. GREAP provides widespread annotation and enrichment analysis of genomic regions. To reflect the significance of enrichment analysis, we used the hypergeometric test and also provided a Locus Overlap Analysis. In summary, GREAP is a powerful platform that provides many types of genomic region sets for users and supports genomic region annotations and enrichment analyses. In addition, we developed a customizable genome browser containing >400 000 000 customizable tracks for visualization. The platform is freely available at http://www.liclab.net/Greap/view/index.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Emergence of multidrug-resistant Bacillus spp. derived from animal feed, food and human diarrhea in South-Eastern Bangladesh.

BACKGROUND: Antimicrobial resistance poses a huge risk to human health worldwide, while Bangladesh is confronting the most severe challenge between the food supply and the huge consumption of antibiotics annually. More importantly, probiotics containing Bacillus spp. are claimed to be an alternative to antimicrobial stewardship programs. However, their antibiotic resistance remains elusive. Thus, we employed the antimicrobial susceptibility test and PCR to assess the prevalence of resistance, including multidrug resistance (MDR) and resito-genotyping of isolated Bacillus spp. RESULTS: The phenotypic profile showed that Bacillus spp. were 100% sensitive to gentamicin (2 µg/mL), whereas lowered sensitivity to levofloxacin (67.8%, 0.5-1 µg/mL), ciprofloxacin (62.3%, 0.5-1 µg/mL), clindamycin (52.2%, 0.25-0.5 µg/mL), amoxicillin-clavulanic acid (37.6%, 0.06 µg/mL), azithromycin (33.4%, 1-2 µg/mL), tetracycline (25.6%, 2-4 µg/mL), nitrofurantoin (21.1%, 16-32 µg/mL), co-trimoxazole (19.2%, 2 µg/mL), and erythromycin (18.8%, 0.25-0.5 µg/mL). The strains were completely resistant to penicillin, amoxicillin-clavulanic acid, cefixime, ceftriaxone, vancomycin, and co-trimoxazole, and a species-specific trend was seen in both phenotypic and genotypic resistance patterns. Genotypic resistance indicated prevalence of the bla1 (71.5%), tetA (33%), erm1 (27%), blaTEM (13.1%), blaCTX-M-1/blaCTX-M-2 /sul1 (10.1%), blaSHV (9.6%), and qnrS (4.1%) genes. The ß-lactamase resistance gene bla1 was found in all penicillin-resistant (MIC ≥ 32 µg/mL) Bacillus spp. One hundred ninety-one isolates (89.6%) were MDR, with 100% from diarrhea, 90.3% from food, and 88.7% from animal feed. CONCLUSION: Based on the MIC value and profile analysis of antibiotic resistance genes, this is the first study that Bacillus spp. antimicrobial susceptibilities have been identified in Bangladesh, and our study will shed light on the adverse effects of feed-borne Bacillus spp. emerging from animal feed to the food chain. A comprehensive investigation is urgently needed by policymakers on tolerance limits and harmful effects in the animal industry.

2 × 4†kW near-single-mode laser output assisted by an optimized bidirectional oscillating-amplifying integrated fiber laser configuration.

Bidirectional output oscillating-amplifying integrated fiber laser (B-OAIFL) can achieve the two-ports laser amplification based on a single cavity, showcasing a promising prospect. In order to improve both the laser power and beam quality, we first simulate and optimize the stimulated Raman scattering (SRS) effect in the B-OAIFL. The simulation results show the SRS effect can be suppressed by optimizing the diameter as well as the length of the active fiber at different locations. With the guidance of theoretical and experimental analysis for the combined suppression of SRS and transverse mode instability (TMI), a near-single-mode B-OAIFL with 2 × 4 kW was demonstrated. Based on this foundation, we further devoted ourselves to the pursuit of the optimization of the structure and performance. The necessity of the configuration of side pump, which was initially introduced for its exceptional performance in stabilizing temporal chaos, was reevaluated in detail. With its negative impacts on efficiency improvement and SRS suppression were analyzed and verified, we removed this configuration and finally demonstrated a more simplified design with superior performance. A total bidirectional output of 8105 W was achieved, with an O-O efficiency of 79.6% and a near-single-mode beam quality of M A 2∼1.36,M B 2∼1.63. No signs of TMI were observed, and the signal-to-SRS suppression ratio was over 38 dB. The results still demonstrate a promising potential for power scaling based on this configuration and parameters.

Urine and serum metabolomic analysis of endometrial cancer diagnosis and classification based on ultra-performance liquid chromatography mass spectrometry.

OBJECTIVE: This study aimed to reveal the urinary and serum metabolic pattern of endometrial cancer (EC) and establish diagnostic models to identify EC from controls, high-risk from low-risk EC, and type II from type I EC. METHOD: This study included 146 EC patients (comprising 79 low-risk and 67 high-risk patients, including 124 type I and 22 type II) and 59 controls. The serum and urine samples were analyzed using ultraperformance liquid chromatography mass spectrometry. Analysis was used to elucidate the distinct metabolites and altered metabolic pathways. Receiver operating characteristic (ROC) analyses were employed to discover and validate the potential biomarker models. RESULTS: Serum and urine metabolomes displayed significant differences between EC and controls, with metabolites related to amino acid and nicotinamide metabolisms. The serum and urine panels distinguished these two groups with Area Under the Curve (AUC) of 0.821 and 0.902, respectively. The panel consisting of serum and urine metabolites demonstrated the best predictive ability (AUC = 0.953 and 0.976 in discovering and validation group). In comparing high-risk and low risk EC, differential metabolites were enriched in purine and glutamine metabolism. The AUC values for serum and urine panels were 0.818, and 0.843, respectively. The combined panel exhibited better predictive accuracy (0.881 in discovering group and 0.936 in external validation). In the comparison between type I and type II group, altered folic acid metabolism was identified. The serum, urine and combined panels discriminated these two groups with the AUC of 0.829, 0.913 and 0.922, respectively. CONCLUSION: The combined urine and serum metabolome effectively revealed the metabolic patterns in EC patients, offering valuable diagnostic models for EC diagnosis and classification.