Knowledge-based in silico fragmentation and annotation of mass spectra for natural products with MassKG.

Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is a potent analytical technique utilized for identifying natural products from complex sources. However, due to the structural diversity, annotating LC-MS/MS data of natural products efficiently remains challenging, hindering the discovery process of novel active structures. Here, we introduce MassKG, an algorithm that combines a knowledge-based fragmentation strategy and a deep learning-based molecule generation model to aid in rapid dereplication and the discovery of novel NP structures. Specifically, MassKG has compiled 407,720 known NP structures and, based on this, generated 266,353 new structures using chemical language models for the discovery of potential novel compounds. Furthermore, MassKG demonstrates exceptional performance in spectra annotation compared to state-of-the-art algorithms. To enhance usability, MassKG has been implemented as a web server for annotating tandem mass spectral data (MS/MS, MS2) with a user-friendly interface, automatic reporting, and fragment tree visualization. Lastly, the interpretive capability of MassKG is comprehensively validated through composition analysis and MS annotation of Panax notoginseng, Ginkgo biloba, Codonopsis pilosula, and Astragalus membranaceus. MassKG is now accessible at https://xomics.com.cn/masskg.

Overlooked Complexation and Competition Effects of Phenolic Contaminants in a Mn(II)/Nitrilotriacetic Acid/Peroxymonosulfate System: Inhibited Generation of Primary and Secondary High-Valent Manganese Species.

Organic contaminants with lower Hammett constants are typically more prone to being attacked by reactive oxygen species (ROS) in advanced oxidation processes (AOPs). However, the interactions of an organic contaminant with catalytic centers and participating ROS are complex and lack an in-depth understanding. In this work, we observed an abnormal phenomenon in AOPs that the degradation of electron-rich phenolics, such as 4-methoxyphenol, acetaminophen, and 4-presol, was unexpectedly slower than electron-deficient phenolics in a Mn(II)/nitrilotriacetic acid/peroxymonosulfate (Mn(II)/NTA/PMS) system. The established quantitative structure-activity relationship revealed a volcano-type dependence of the degradation rates on the Hammett constants of pollutants. Leveraging substantial analytical techniques and modeling analysis, we concluded that the electron-rich phenolics would inhibit the generation of both primary (Mn(III)NTA) and secondary (Mn(V)NTA) high-valent manganese species through complexation and competition effects. Specifically, the electron-rich phenolics would form a hydrogen bond with Mn(II)/NTA/PMS through outer-sphere interactions, thereby reducing the electrophilic reactivity of PMS to accept the electron transfer from Mn(II)NTA, and slowing down the generation of reactive Mn(III)NTA. Furthermore, the generated Mn(III)NTA is more inclined to react with electron-rich phenolics than PMS due to their higher reaction rate constants (8314 ± 440, 6372 ± 146, and 6919 ± 31 M-1 s-1 for 4-methoxyphenol, acetaminophen, and 4-presol, respectively, as compared with 671 M-1 s-1 for PMS). Consequently, the two-stage inhibition impeded the generation of Mn(V)NTA. In contrast, the complexation and competition effects are insignificant for electron-deficient phenolics, leading to declined reaction rates when the Hammett constants of pollutants increase. For practical applications, such complexation and competition effects would cause the degradation of electron-rich phenolics to be more susceptible to water matrixes, whereas the degradation of electron-deficient phenolics remains largely unaffected. Overall, this study elucidated the intricate interaction mechanisms between contaminants and reactive metal species at both the electronic and kinetic levels, further illuminating their implications for practical treatment.

A free radical interlocking co-deposition strategy based on the oxidative pyrolysis mechanism of polyethylene terephthalate to achieve green energy recovery.

Accidental combustion and energy recovery of polyethylene terephthalate (PET) result in the formation of harmful organic substances and excessive emissions of CO2 and CO. This paper presents our recent efforts to unravel the formation mechanism of these harmful substances during the PET combustion process using thermal analysis and simulation calculations (DFT, CDFT, and ReaxFF). Our findings reveal that PET oxidative pyrolysis produces free radicals, harmful small molecule gases, and CO2. The interaction between aromatic free radicals and oxygen initiates unstable peroxy bonds, triggering uncontrollable chain exothermic reactions and producing oxygenated polycyclic aromatic hydrocarbon (OPAH) precursors. We propose a straightforward and eco-friendly free radical interlocking co-deposition inhibition strategy for PET by incorporating polycarbonate (PC). This strategy aims to facilitate green energy recovery by curbing OPAH formation and reducing CO2 and CO emissions during PET waste combustion. Our investigation into the oxidative pyrolysis of PET challenges conventional wisdom dominated by C-H bond fracture, paving the way for efficient, low-pollution green energy recovery.

Icariin alleviates cellular injury induced by cardiac ischemia-reperfusion injury by inhibiting IRE1/JNK-induced ferroptosis.

BACKGROUND: Ischemia-induced cellular damage and stress responses significantly impact cellular viability and function. Icariin (ICA), known for its protective effects, has been studied to understand its role in mitigating oxygen-glucose deprivation/reperfusion (OGD/R)-induced endoplasmic reticulum (ER) stress and ferroptosis in H9C2 cardiomyoblast cells. METHODS: We employed an in vitro OGD/R model using H9C2 cells. ICA's effects were analyzed across multiple concentrations. Key indicators of ER stress, autophagy, and ferroptosis-including markers like Bip, PERK, IRE1, ATF6, P62, FTH1, LC3II/LC3I, and NCOA4-were assessed using Western blotting, electron microscopy, and biochemical assays. Additionally, the role of the IRE1/JNK pathway in mitochondrial dynamics and its influence on mitochondrial dynamics protein was explored through specific inhibition and activation experiments. RESULTS: ICA significantly reduced the activation of UPR pathways, decreased autophagic vacuole formation, and maintained cell viability in response to OGD/R and Erastin-induced ferroptosis. These protective effects were associated with modulated autophagic processes, reduced lipid peroxidation, and decreased ferrous ion accumulation. Inhibition of the IRE1/JNK pathway and subsequent Drp1 activity demonstrated reduced mitochondrial recruitment and mitophagy, correlating with decreased ferroptosis markers and improved cell survival. CONCLUSION: Our findings highlight ICA's potential in modulating IRE1/JNK pathway, autophagy, providing a therapeutic avenue for mitigating ferroptosis in myocardial ischemia-reperfusion injury (MIRI).

Coupling Photocatalytic Hydrogen Production with Key Oxidation Reactions.

Hydrogen represents a clean and sustainable energy source with wide applications in fuel cells and hydrogen energy storage systems. Photocatalytic strategies emerge as a green and promising solution for hydrogen production, which still reveals several critical challenges in enhancing the efficiency and stability and improving the whole value. This review systematically elaborates on various coupling approaches for photocatalytic hydrogen production, aiming to improve both efficiency and value through different oxidation half-reactions. Firstly, the fundamental mechanism is discussed for photocatalytic hydrogen production. Then, the advances, challenges, and opportunities are expanded for the coupling of photocatalytic hydrogen production, which focuses on the integration of value-added reactions including O2 production, H2O2 production, biomass conversion, alcohol oxidation, and pollutants treatment. Finally, the challenges and outlook of photocatalytic H2 production technology are analyzed from the aspects of coupling hydrogen production value, photocatalyst design and reaction system construction. This work presents a holistic view of the field, emphasizing the synergistic benefits of coupled reactions and their practical application potential, rather than focusing on catalysts or single reaction systems. This review provides valuable references for the development and application of photocatalytic hydrogen production in energy conversion and environmental conservation through sustainable, eco-friendly and economic pathways.

Five-Axis Curved-Surface Multi-Material Printing on Conformal Surface to Construct Aqueous Zinc-Ion Battery Modules.

Compact batteries and electronic devices offer a plethora of advantages, including space optimization, portability, integration capability, responsiveness, and reliability. These attributes are crucial technical enablers for the design and implementation of various electronic devices and systems within scientific exploration. Thus, the group harnesses additive manufacturing technology, specifically utilizing five-axis curved-surface multi-material printing equipment, to fabricate aqueous zinc-ion batteries with tungsten-doped manganese dioxide cathode for enhanced adaptability and customization. The five-axis linkage motion system facilitates shorter ion transportation paths for compact batteries and ensures precise and efficient molding of non-developable curved surfaces. Afterward, the compact cell is integrated with a printed nano-silver serpentine resistor temperature sensor, and an integrated functional circuit is created using intense-pulse sintering. Incorporating an emitting Light Emitting Diode (LED) allows temperature measurement through variations in LED brightness. The energy storage module with a high degree of conformity on the carrier surface has the advantages of small size and improved space utilization. The capability to produce Zinc-ion batteries (ZIBs) on curved surfaces presents new avenues for innovation in energy storage technologies, paving the way for the realization of flexible and conformal power sources.

Dynamic Active Sites in Electrocatalysis.

In-depth understanding of the real-time behaviors of active sites during electrocatalysis is essential for the advancement of sustainable energy conversion. Recently, the concept of dynamic active sites has been recognized as a potent approach for creating self-adaptive electrocatalysts that can address a variety of electrocatalytic reactions, outperforming traditional electrocatalysts with static active sites. Nonetheless, the comprehension of the underlying principles that guide the engineering of dynamic active sites is presently insufficient. In this review, we systematically analyze the fundamentals of dynamic active sites for electrocatalysis and consider important future directions for this emerging field. We reveal that dynamic behaviors and reversibility are two crucial factors that influence electrocatalytic performance. By reviewing recent advances in dynamic active sites, we conclude that implementing dynamic electrocatalysis through variable reaction environments, correlating the model of dynamic evolution with catalytic properties, and developing localized and ultrafast in-situ/operando techniques are keys to designing high-performance dynamic electrocatalysts. This review paves the way to the development of the next-generation electrocatalyst and the universal theory for both dynamic and static active sites.

Yttrium doping stabilizes the structure of Ni3(NO3)2(OH)4 cathodes for application in advanced Ni-Zn batteries.

Ni3(NO3)2(OH)4 has a high theoretical specific capacitance, low cost, and environmental friendliness, making it a promising electrode material. Specifically, Ni3(NO3)2(OH)4 electrodes have a larger layer spacing (c = 6.898 Å) than Ni(OH)2 electrodes since NO3- has a much larger ionic radius than OH-. The larger layer spacing stores more electrolyte ions, significantly improving the electrochemical activity of the electrodes. Additionally, the interlayer NO3- can enhance the structural stability of Ni3(NO3)2(OH)4. However, since Ni3(NO3)2(OH)4 has a higher molar mass than Ni(OH)2, it has a lower theoretical specific capacity. Consequently, Ni3(NO3)2(OH)4 has not been used in zinc-based alkaline batteries. Studies showed that doping could enhance the electrochemical performance of electrode materials. Therefore, this study used a simple solvothermal reaction to synthesize yttrium-doped Ni3(NO3)2(OH)4 (Y-Ni3(NO3)2(OH)4), assembling a Y-Ni3(NO3)2(OH)4//Zn battery for electrochemical testing. Y-Ni3(NO3)2(OH)4 served as the cathode in the battery. The analysis of Y-Ni3(NO3)2(OH)4 showed that yttrium (Y) doping increased the specific surface area and pore size of Ni3(NO3)2(OH)4 significantly. The increased specific surface area improved the active material utilization, and the abundant mesopores facilitated OH- transport, substantially enhancing the battery's specific capacity and energy density. Ultimately, the specific discharge capacity of the advanced Y-Ni3(NO3)2(OH)4//Zn battery reached 177.97 mA h g-1 at a current density of 4 A g-1, nearly doubling the capacity of the earlier Ni3(NO3)2(OH)4//Zn battery (103.59 mA h g-1).

Tuning the Inter-Metal Interaction between Ni and Fe Atoms in Dual-Atom Catalysts to Boost CO2 Electroreduction.

Dual-atom catalysts (DACs) are promising for applications in electrochemical CO2 reduction due to the enhanced flexibility of the catalytic sites and the synergistic effect between dual atoms. However, precisely controlling the atomic distance and identifying the dual-atom configuration of DACs to optimize the catalytic performance remains a challenge. Here, the Ni and Fe atomic pairs were constructed on nitrogen-doped carbon support in three different configurations: NiFe-isolate, NiFe-N bridge, and NiFe-bonding. It was found that the NiFe-N bridge catalyst with NiN4 and FeN4 sharing two N atoms exhibited superior CO2 reduction activity and promising stability when compared to the NiFe-isolate and NiFe-bonding catalysts. A series of characterizations and density functional theory calculations suggested that the N-bridged NiFe sites with an appropriate distance between Ni and Fe atoms can exert a more pronounced synergy. It not only regulated the suitable adsorption strength for the *COOH intermediate but also promoted the desorption of *CO, thus accelerating the CO2 electroreduction to CO. This work provides an important implication for the enhancement of catalysis by the tailoring of the coordination structure of DACs, with the identification of distance effect between neighboring dual atoms.

Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator.

Objective: This study aims to address the substantive issue of lacking reliable prognostic biomarkers in hepatocellular carcinoma (HCC) by investigating the relationship between TP53-inducible glycolysis and apoptosis regulator (TIGAR) and HCC prognosis using The Cancer Genome Atlas database. Methods: (1) Integrated statistical analyses, including logistic regression, Wilcoxon signed-rank test, and Kruskal-Wallis test, were conducted to explore the association between TIGAR expression and clinical-pathological features of HCC. (2) The Kaplan-Meier method combined with univariate and multivariate Cox regression models underscored TIGAR as a prognostic factor in HCC. (3) Gene set enrichment analysis (GSEA) revealed key pathways associated with TIGAR, while single-sample gene set enrichment analysis (ssGSEA) determined its relevance to cancer immune infiltration. Results: (1) Elevated TIGAR expression was significantly correlated with decreased survival outcomes in HCC patients. (2) GSEA highlighted the significant link between TIGAR and humoral immunity. (3) ssGSEA revealed a positive correlation between TIGAR expression and infiltration of Th1 and Th2 cells and a negative correlation with Th17 cell infiltration. Conclusion: TIGAR, as a potential prognostic biomarker for HCC, holds significant value in immune infiltration. Understanding the role of TIGAR could contribute to improved prognostic predictions and personalized treatment strategies for HCC patients.

Coordination and Hydrogen Bond Chemistry in Tungsten Oxide@Polyaniline Composite toward High-Capacity Aqueous Ammonium Storage.

Aqueous ammonium ion batteries (AAIBs) have garnered significant attention due to their unique energy storage mechanism. However, their progress is hindered by the relatively low capacities of NH4 + host materials. Herein, the study proposes an electrodeposited tungsten oxide@polyaniline (WOx@PANI) composite electrode as a NH4 + host, which achieves an ultrahigh capacity of 280.3 mAh g-1 at 1 A g-1, surpassing the vast majority of previously reported NH4 + host materials. The synergistic interaction of coordination chemistry and hydrogen bond chemistry between the WOx and PANI enhances the charge storage capacity. Experimental results indicate that the strong interfacial coordination bonding (N: →W6+) effectively modulates the chemical environment of W atoms, enhances the protonation level of PANI, and thus consequently the conductivity and stability of the composites. Spectroscopy analysis further reveals a unique NH4 +/H+ co-insertion mechanism, in which the interfacial hydrogen bond network (N-H···O) accelerates proton involvement in the energy storage process and activates the Grotthuss hopping conduction of H+ between the hydrated tungsten oxide layers. This work opens a new avenue to achieving high-capacity NH4 + storage through interfacial chemistry interactions, overcoming the capacity limitations of NH4 + host materials for aqueous energy storage.

Hydrogen bonding chemistry in aqueous ammonium ion batteries.

Aqueous ammonium ion batteries (AIBs) pose the advantages of high safety, low cost, and high efficiency, capturing substantial research interest. The intrinsic chemical properties of NH4+ promote the formation of hydrogen bonds with other constituents in AIBs, critically influencing the processes of NH4+ transfer, storage, and diffusion. This review delves into the pivotal role of hydrogen bonding chemistry in AIBs. Firstly, the principles of hydrogen bond are elucidated as the dominant chemical interaction governing NH4+ dynamics in AIBs. Subsequently, a detailed analysis is conducted on the impacts of hydrogen bonds in both electrolytes and electrode materials. Furthermore, the practical applications of hydrogen bonding chemistry within the context of AIBs are assessed. Finally, strategic insights and future research directions are proposed to harness hydrogen bonding effects for optimizing AIB performance. This review aims to define the mechanisms and impacts of hydrogen bonds in AIBs, providing robust strategies to enhance electrochemical performance, deepen the understanding of energy storage mechanisms, and guide the future advancement of AIBs technology.

Organic-Inorganic Coupling Strategy: Clamp Effect to Capture Mg2+ for Aqueous Magnesium Ion Capacitor.

The rapid transport kinetics of divalent magnesium ions are crucial for achieving distinguished performance in aqueous magnesium-ion battery-based energy storage capacitors. However, the strong electrostatic interaction between Mg2+ with double charges and the host material significantly restricts Mg2+ diffusivity. In this study, a new composite material, EDA-Mn2O3, with double-energy storage mechanisms comprising an organic phase (ethylenediamine, EDA) and an inorganic phase (manganese sesquioxide) was successfully synthesized via an organic-inorganic coupling strategy. Inorganic-phase Mn2O3 serves as a scaffold structure, enabling the stable and reversible intercalation/deintercalation of magnesium ions. The organic phase EDA adsorbed onto the surface of Mn2O3 as an elastic matrix, works synergistically with Mn2O3, and utilizes bidentate chelating ligands to capture Mg2+. The robust coordination effect of terminal biprotonic amine in EDA enhances the structural diversity and specific capacity characteristics of the composite material, as further corroborated by density functional theory (DFT) calculations, ex-situ XRD, XPS, and Raman spectroscopy. As expected, an aqueous magnesium ion capacitor with EDA-Mn2O3 serving as the cathode can reach 110.17 Wh/kg. This study aimed to explore the practical application value of organic‒inorganic composite electrodes with double-energy storage mechanisms.

The Function and Mechanism of Long Noncoding RNAs in Adipogenic Differentiation.

Adipocytes are crucial for maintaining energy balance. Adipocyte differentiation involves distinct stages, including the orientation stage, clone amplification stage, clone amplification termination stage, and terminal differentiation stage. Understanding the regulatory mechanisms governing adipogenic differentiation is essential for comprehending the physiological processes and identifying potential biomarkers and therapeutic targets for metabolic diseases, ultimately improving glucose and fat metabolism. Adipogenic differentiation is influenced not only by key factors such as hormones, the peroxisome proliferator-activated receptor (PPAR) family, and the CCATT enhancer-binding protein (C/EBP) family but also by noncoding RNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA). Among these, lncRNA has been identified as a significant regulator in adipogenic differentiation. Research has demonstrated various ways in which lncRNAs contribute to the molecular mechanisms of adipogenic differentiation. Throughout the adipogenesis process, lncRNAs modulate adipocyte differentiation and development by influencing relevant signaling pathways and transcription factors. This review provides a brief overview of the function and mechanism of lncRNAs in adipogenic differentiation.

Mg ions intercalated with V3O7·H2O to construct ultrastable cathode materials for aqueous zinc-ion batteries.

V3O7·H2O (VO) stands out as a highly promising cathode material for aqueous zinc-ion batteries (AZIB). However, due to the instability of the VO structure and the limited ion transport rate, achieving the required specific capacity and extended cycling lifespan has been challenging. To tackle this issue, we synthesized Mg-ion intercalated VO (MgVO) using a straightforward hydrothermal method. Introducing Mg2+ as an interlayer support enhanced the flexibility of MgVO within the confined layer space, stabilized its lamellar structure, and expanded the VO layer spacing. The AZIB employing the MgVO cathode demonstrated a high specific capacity of 382.7 mA h g-1 at a current density of 0.1 A g-1 and showed excellent cycling stability. The robust structural stability of MgVO suggests promising applications for large-scale energy storage, while the Mg2+ intercalation strategy presents a novel approach for exploring other potential cathode materials.

Promoting Photon-to-Chemical Conversion through a Dielectric Antenna-Hybrid Bilayered Reactor Configuration.

The application of scattered light via an antenna-reactor configuration is promising for converting thermocatalysts into photocatalysts. However, the efficiency of dielectric antennas in photon-to-chemical conversion remains suboptimal. Herein, we present an effective approach to promote light utilization efficiency by designing dielectric antenna-hybrid bilayered reactors. Experimental studies and finite-difference time-domain simulations demonstrate that the engineered SiO2-carbon/metal dielectric antenna-hybrid bilayered reactors exhibit a synergy of absorption superposition and electric field confinement between carbon and metals, leading to the improved absorption of scattered light, upgraded charge carriers density, and ultimately promoted photoactivity in hydrogenating chlorobenzene with an average benzene formation rate of 18 258 µmol g-1 h-1, outperforming the reported results. Notably, the carbon interlayer proves to be more effective than the commonly explored dielectric TiO2 interlayer in boosting the benzene formation rate by over 3 times. This research paves the way for promoting near-field scattered photon-to-chemical conversion through a dielectric antenna-hybrid reactor configuration.

Atomic Confinement Empowered CoZn Dual-Single-Atom Nanotubes for H2O2 Production in Sequential Dual-Cathode Electro-Fenton Process.

Single-atom catalysts (SACs) are flourishing in various fields because of their 100% atomic utilization. However, their uncontrollable selectivity, poor stability and vulnerable inactivation remain critical challenges. According to theoretical predictions and experiments, a heteronuclear CoZn dual-single-atom confined in N/O-doped hollow carbon nanotube reactors (CoZnSA@CNTs) is synthesized via spatial confinement growth. CoZnSA@CNTs exhibit superior performance for H2O2 electrosynthesis over the entire pH range due to dual-confinement of atomic sites and O2 molecule. CoZnSA@CNTs is favorable for H2O2 production mainly because the synergy of adjacent atomic sites, defect-rich feature and nanotube reactor promoted O2 enrichment and enhanced H2O2 reactivity/selectivity. The H2O2 selectivity reaches ∼100% in a range of 0.2-0.65 V versus RHE and the yield achieves 7.50 M gcat -1 with CoZnSA@CNTs/carbon fiber felt, exceeding most of the reported SACs in H-type cells. The obtained H2O2 is converted directly to sodium percarbonate and sodium perborate in a safe way for H2O2 storage/transportation. The sequential dual-cathode electron-Fenton process promotes the formation of reactive oxygen species (•OH, 1O2 and •O2 -) by activating the generated H2O2, enabling accelerated degradation of various pollutants and Cr(VI) detoxification in actual wastewater. This work proposes a promising confinement strategy for catalyst design and selectivity regulation of complex reactions.

Lipoprotein (a)-Related Inflammatory Imbalance: A Novel Horizon for the Development of Atherosclerosis.

PURPOSE OF REVIEW: The primary objective of this review is to explore the pathophysiological roles and clinical implications of lipoprotein(a) [Lp(a)] in the context of atherosclerotic cardiovascular disease (ASCVD). We seek to understand how Lp(a) contributes to inflammation and arteriosclerosis, aiming to provide new insights into the mechanisms of ASCVD progression. RECENT FINDINGS: Recent research highlights Lp(a) as an independent risk factor for ASCVD. Studies show that Lp(a) not only promotes the inflammatory processes but also interacts with various cellular components, leading to endothelial dysfunction and smooth muscle cell proliferation. The dual role of Lp(a) in both instigating and, under certain conditions, mitigating inflammation is particularly noteworthy. This review finds that Lp(a) plays a complex role in the development of ASCVD through its involvement in inflammatory pathways. The interplay between Lp(a) levels and inflammatory responses highlights its potential as a target for therapeutic intervention. These insights could pave the way for novel approaches in managing and preventing ASCVD, urging further investigation into Lp(a) as a therapeutic target.

Potential of FGF21 in type 2 diabetes mellitus treatment based on untargeted metabolomics.

Fibroblast growth factor 21 (FGF21) has promise for treating diabetes and its associated comorbidities. It has been found to reduce blood glucose in mice and humans; however, its underlying mechanism is not known. Here, the metabolic function of FGF21 in diabetes was investigated. Diabetic db/db mice received intraperitoneal injections of FGF21 for 28 days, the serum of each mouse was collected, and their metabolites were analyzed by untargeted metabolomics using UHPLC-MS/MS. It was found that FGF21 reduced blood glucose and oral glucose tolerance without causing hypoglycemia. Moreover, administration of FGF21 reduced the levels of TG and LDL levels while increasing those of HDL and adiponectin. Importantly, the levels of 45 metabolites, including amino acids and lipids, were significantly altered, suggesting their potential as biomarkers. We speculated that FGF21 may treat T2DM through the regulation of fatty acid biosynthesis, the TCA cycle, and vitamin digestion and absorption. These findings provide insight into the mechanism of FGF21 in diabetes and suggest its potential for treating diabetes.