Vacancy-Driven High-Performance Metabolic Assay for Diagnosis and Therapeutic Evaluation of Depression.

Depression is one of the most common mental illnesses and is a well-known risk factor for suicide, characterized by low overall efficacy (<50%) and high relapse rate (40%). A rapid and objective approach for screening and prognosis of depression is highly desirable but still awaits further development. Herein, a high-performance metabolite-based assay to aid the diagnosis and therapeutic evaluation of depression by developing a vacancy-engineered cobalt oxide (Vo-Co3O4) assisted laser desorption/ionization mass spectrometer platform is presented. The easy-prepared nanoparticles with optimal vacancy achieve a considerable signal enhancement, characterized by favorable charge transfer and increased photothermal conversion. The optimized Vo-Co3O4 allows for a direct and robust record of plasma metabolic fingerprints (PMFs). Through machine learning of PMFs, high-performance depression diagnosis is achieved, with the areas under the curve (AUC) of 0.941-0.980 and an accuracy of over 92%. Furthermore, a simplified diagnostic panel for depression is established, with a desirable AUC value of 0.933. Finally, proline levels are quantified in a follow-up cohort of depressive patients, highlighting the potential of metabolite quantification in the therapeutic evaluation of depression. This work promotes the progression of advanced matrixes and brings insights into the management of depression.

Hollow multishelled heterostructures with enhanced performance for laser desorption/ionization mass spectrometry based metabolic diagnosis.

High-performance metabolic diagnosis-based laser desorption/ionization mass spectrometry (LDI-MS) improves the precision diagnosis of diseases and subsequent treatment. Inorganic matrices are promising for the detection of metabolites by LDI-MS, while the structure and component impacts of the matrices on the LDI process are still under investigation. Here, we designed a multiple-shelled ZnMn2O4/(Co, Mn)(Co, Mn)2O4 (ZMO/CMO) as the matrix from calcined MOF-on-MOF for detecting metabolites in LDI-MS and clarified the synergistic impacts of multiple-shells and the heterostructure on LDI efficiency. The ZMO/CMO heterostructure allowed 3-5 fold signal enhancement compared with ZMO and CMO with the same morphology. Furthermore, the ZMO/CMO heterostructure with a triple-shelled hollow structure displayed a 3-fold signal enhancement compared to its nanoparticle counterpart. Taken together, the triple-shelled hollow ZMO/CMO exhibits 102-fold signal enhancement compared to the commercial matrix products (e.g., DHB and DHAP), allowing for sensitive metabolic profiling in bio-detection. We directly extracted metabolic patterns by the optimized triple-shelled hollow ZMO/CMO particle-assisted LDI-MS within 1 s using 100 nL of serum and used machine learning as the readout to distinguish hepatocellular carcinoma from healthy controls with the area under the curve value of 0.984. Our approach guides us in matrix design for LDI-MS metabolic analysis and drives the development of a nanomaterial-based LDI-MS platform toward precision diagnosis.

Construction of a ternary component chip with enhanced desorption efficiency for laser desorption/ionization mass spectrometry based metabolic fingerprinting.

Introduction: In vitro metabolic fingerprinting encodes diverse diseases for clinical practice, while tedious sample pretreatment in bio-samples has largely hindered its universal application. Designed materials are highly demanded to construct diagnostic tools for high-throughput metabolic information extraction. Results: Herein, a ternary component chip composed of mesoporous silica substrate, plasmonic matrix, and perfluoroalkyl initiator is constructed for direct metabolic fingerprinting of biofluids by laser desorption/ionization mass spectrometry. Method: The performance of the designed chip is optimized in terms of silica pore size, gold sputtering time, and initiator loading parameter. The optimized chip can be coupled with microarrays to realize fast, high-throughput (∼second/sample), and microscaled (∼1 µL) sample analysis in human urine without any enrichment or purification. On-chip urine fingerprints further allow for differentiation between kidney stone patients and healthy controls. Discussion: Given the fast, high throughput, and easy operation, our approach brings a new dimension to designing nano-material-based chips for high-performance metabolic analysis and large-scale diagnostic use.

Designed Concave Octahedron Heterostructures Decode Distinct Metabolic Patterns of Epithelial Ovarian Tumors.

Epithelial ovarian cancer (EOC) is a polyfactorial process associated with alterations in metabolic pathways. A high-performance screening tool for EOC is in high demand to improve prognostic outcome but is still missing. Here, a concave octahedron Mn2 O3 /(Co,Mn)(Co,Mn)2 O4 (MO/CMO) composite with a heterojunction, rough surface, hollow interior, and sharp corners is developed to record metabolic patterns of ovarian tumors by laser desorption/ionization mass spectrometry (LDI-MS). The MO/CMO composites with multiple physical effects induce enhanced light absorption, preferred charge transfer, increased photothermal conversion, and selective trapping of small molecules. The MO/CMO shows ≈2-5-fold signal enhancement compared to mono- or dual-enhancement counterparts, and ≈10-48-fold compared to the commercialized products. Subsequently, serum metabolic fingerprints of ovarian tumors are revealed by MO/CMO-assisted LDI-MS, achieving high reproducibility of direct serum detection without treatment. Furthermore, machine learning of the metabolic fingerprints distinguishes malignant ovarian tumors from benign controls with the area under the curve value of 0.987. Finally, seven metabolites associated with the progression of ovarian tumors are screened as potential biomarkers. The approach guides the future depiction of the state-of-the-art matrix for intensive MS detection and accelerates the growth of nanomaterials-based platforms toward precision diagnosis scenarios.

Ruthenium-Catalyzed ortho-C-H Hydroxyfluoroalkylation of Arenes with Fluorinated Alcohols.

A facile and mild Ru(II)-catalyzed ortho-C-H hydroxyfluoroalkylation of arenes with cheap and easily accessible fluorinated alcohols has been developed in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO). The readily available fluorinated alcohols were used as hydroxyfluoroalkylation reagents to form various α-aryl-α-trifluoromethyl alcohols. The present work provides a new method for the introduction of hydroxyfluoroalkyl groups into arenes.

Copper-assisted trifluoromethylthiolation/radical cascade cyclization of alkynes to construct SCF3-containing dioxodibenzothiazepines.

A mild and efficient Cu-assisted trifluoromethylthiolation/radical cascade cyclization of alkynes with readily available and stable AgSCF3 as the trifluoromethylthiolating reagent has been disclosed. This transformation provides an opportunity to construct a series of potential medicinally valuable trifluoromethylthio-substituted dioxodibenzothiazepines with wide functional group compatibility. This protocol opens up a new avenue for the construction of useful trifluoromethylthiolated seven-membered N-heterocycles.

Dendrimer-Modified Silica Nanoparticles for Efficient Enrichment of Low-Concentration Peptides.

Peptide profiling based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is of particular interest as it can provide physiologically and pathologically related information of the bio-samples. Due to the complexity of real biological samples, MALDI-TOF MS-based peptide mapping methods rely strongly on particular enrichment methods to improve the signal intensity. This paper introduces third-generation dendrimer-modified SBA-15 with the surface functionalization of amino and carboxyl group, respectively (denoted as SBA-15/G3-NH2 and SBA-15/G3-COOH), for the efficient capture of low-abundance peptides. The enrichment ability of the nanocomposites was evaluated by standard peptides digests and real biological samples. The synthesized nanocomposites incorporated the benefit of dendrimers and mesoporous silica nanomaterial SBA-15, showing enhanced peptide enrichment ability. Therefore, this work may provide a new class of nanomaterials for peptide mapping from biological samples.

Hollow Cobalt Oxide/Carbon Hybrids Aid Metabolic Encoding for Active Systemic Lupus Erythematosus during Pregnancy.

A noninvasive, easy operation, and accurate diagnostic protocol is highly demanded to assess systemic lupus erythematosus (SLE) activity during pregnancy, promising real-time activity monitoring during the whole gestational period to reduce adverse pregnancy outcomes. Here, machine learning of serum metabolic fingerprints (SMFs) is developed to assess the SLE activity for pregnant women. The SMFs are directly extracted through a hollow-cobalt oxide/carbon (Co3 O4 /C)-composite-assisted laser desorption/ionization mass spectrometer (LDI MS) platform. The Co3 O4 /C composite owns enhanced light absorption, size-selective trapping, and better charge-hole separation, enabling improved ionization efficiency and selectivity for LDI MS detection toward small molecules. Metabolic fingerprints are collected from ≈0.1 µL serum within 1 s without enrichment and encoded by the optimized elastic net algorithm. The averaged area under the curve (AUC) value in the differentiation of active SLE from inactive SLE and healthy controls reaches 0.985 and 0.990, respectively. Further, a simplified panel based on four identified metabolites is built to distinguish SLE flares in pregnant women with the highest AUC value of 0.875 for the blind test. This work sets an accurate and practical protocol for SLE activity assessment during pregnancy, promoting precision diagnosis of disease status transitions in clinics.

Inorganic Matrices Assisted Laser Desorption/Ionization Mass Spectrometry for Metabolic Analysis in Biofluids.

Metabolic analysis in biofluids interprets the end products in the bioprocess, emerging as an irreplaceable disease diagnosis and monitoring platform. Laser desorption/ionization mass spectrometry (LDI MS)-based metabolic analysis holds great potential for clinical applications in terms of high throughput, rapid signal readout, and minimal sample preparation. There are two essential elements to construct the LDI MS-based metabolic analysis: 1) well-designed nanomaterials as matrices; 2) machine learning algorithms for data analysis. This review highlights the development of various inorganic matrices to comprehend the advantages of LDI MS in metabolite detection and the recent diagnostic applications based on target metabolite detection and untargeted metabolic fingerprints in biological fluids.

Visible-Light-Induced Radical Difluoromethylation/Cyclization of Unactivated Alkenes: Access to CF2H-Substituted Quinazolinones.

A mild and efficient visible-light-induced radical difluoromethylation/cyclization of unactivated alkenes toward the synthesis of substituted quinazolinones with easily accessible difluoromethyltriphenylphosphonium bromide has been developed. The transformation has the advantages of wide functional group compatibility, a broad substrate scope, and operational simplicity. The benign protocol offers a facile access to pharmaceutically valuable difluoromethylated polycyclic quinazolinones.

Design of Multi-Shelled Hollow Cr2 O3 Spheres for Metabolic Fingerprinting.

Schizophrenia (SZ) detection enables effective treatment to improve the clinical outcome, but objective and reliable SZ diagnostics are still limited. An ideal diagnosis of SZ suited for robust clinical screening must address detection throughput, low invasiveness, and diagnosis accuracy. Herein, we built a multi-shelled hollow Cr2 O3 spheres (MHCSs) assisted laser desorption/ionization mass spectrometry (LDI MS) platform for the direct metabolic profiling of biofluids towards SZ diagnostics. The MHCSs displayed strong light absorption for enhanced ionization and microscale surface roughness with stability for the effective LDI of metabolites. We profiled urine and serum metabolites (≈1 µL) with the enhanced LDI efficacy in seconds. We discriminated SZ patients (SZs) from healthy controls (HCs) with the highest area under the curve (AUC) value of 1.000 for the blind test. We identified four compounds with optimal diagnostic power as a simplified metabolite panel for SZ and demonstrated the metabolite quantification for clinic use. Our approach accelerates the growth of new platforms toward a precision diagnosis in the near future.

Visible-Light-Induced Direct Csp2-H Radical Trifluoroethylation of Coumarins with 1,1,1-Trifluoro-2-iodoethane (CF3CH2I).

Herein, we developed the first visible-light-induced direct Csp2-H radical 2,2,2-trifluoroethylation of coumarins with commercially available and cheap reagent CF3CH2I at room temperature. This transformation proceeded smoothly under mild conditions and showed excellent functional group compatibility. The synthetic value of the protocol was also demonstrated by the successful functionalization of several pharmaceuticals.

Nanocomposite-Based Matrices in Laser Desorption/Ionization Mass Spectrometry for Small-Molecule Analysis.

The efficient detection of small molecules is of significance for environmental monitoring, pharmacology, metabolomics, and lipidomics. The laser desorption/ionization mass spectrometry (LDI MS) platform enables high sensitivity, accuracy, resolution, and throughput in molecular analysis, but its analytical capability with respect to small molecules is limited due to inherent drawbacks arising from conventional organic matrices. The selection of an appropriate matrix is thus a precondition for small molecule detection by LDI MS. To date, various inorganic matrices have been developed, with a growing interest in composite materials displaying synergetic effects. This Minireview highlights the development of nanocomposites as LDI matrices driven by numerous innovations in material science, and their emerging use in small-molecule analysis.

Synthesis of cube-rod-tube triblock asymmetric nanostructures for enhanced heterogeneous catalysis.

A triblock asymmetric nanostructure composed of a core-shell Fe2O3@SiO2 cube as the head, SiO2 rod as the body and SiO2 tube as the tail is fabricated via a sequential growth process combining solution-liquid-solid and droplet soft templating mechanisms, which can be used as a nano stir bar with accelerated catalytic performance.

FeOOH@Metal-Organic Framework Core-Satellite Nanocomposites for the Serum Metabolic Fingerprinting of Gynecological Cancers.

High-throughput metabolic analysis is of significance in diagnostics, while tedious sample pretreatment has largely hindered its clinic application. Herein, we designed FeOOH@ZIF-8 composites with enhanced ionization efficiency and size-exclusion effect for laser desorption/ionization mass spectrometry (LDI-MS)-based metabolic diagnosis of gynecological cancers. The FeOOH@ZIF-8-assisted LDI-MS achieved rapid, sensitive, and selective metabolic fingerprints of the native serum without any enrichment or purification. Further analysis of extracted serum metabolic fingerprints successfully discriminated patients with gynecological cancers (GCs) from healthy controls and also differentiated three major subtypes of GCs. Given the low cost, high-throughput, and easy operation, our approach brings a new dimension to disease analysis and classification.