Oxygen Vacancies Boosted Hydronium Intercalation: A Paradigm Shift in Aluminum-Based Batteries.

In aqueous aluminum-ion batteries (AAIBs), the insertion/extraction chemistry of Al3+ often leads to poor kinetics, whereas the rapid diffusion kinetics of hydronium ions (H3O+) may offer the solution. However, the presence of considerable Al3+ in the electrolyte hinders the insertion reaction of H3O+. Herein, we report how oxygen-deficient α-MoO3 nanosheets unlock selective H3O+ insertion in a mild aluminum-ion electrolyte. The abundant oxygen defects impede the insertion of Al3+ due to excessively strong adsorption, while allowing H3O+ to be inserted/diffused through the Grotthuss proton conduction mechanism. This research advances our understanding of the mechanism behind selective H3O+ insertion in mild electrolytes.

[Characteristics of Microplastic Pollution in Sediment of Silty Coast in Culture Bay].

Microplastic pollution is a central issue of great concern in the current environmental field. Microplastic pollution in marine environmental media is widely reported, but the characteristics of microplastic pollution in deep sediments are rarely reported. Based on this, three sampling points were set up on the muddy coast near the Haizhou Bay, a typical aquaculture sea area, to analyze the characteristics of microplastic pollution in sediment column samples. The study showed that the abundance of microplastics in the sediments of the study area was(0.12 ± 0.07)n·g-1, which was at the medium pollution level. The total amount of microplastics in the sediment column was 3.43-6.00 times the abundance of microplastics in the surface sediment (5 cm). The abundance of microplastics in the sediment column samples showed regional differences. There was no significant difference in the abundance of microplastics in the sediment at different depths, but the index decreased with the increase in depth. The relationship between sediment moisture content, depth, and microplastics indicated that the abundance of microplastics in sediment was related to the physical properties of the sediment. Transparent and black microplastics accounted for the highest proportion in each station. Fiber was the most common form of microplastics in the sediment, and microplastics with small particle size accounted for the majority. The density of microplastics did not prevent its appearance in the sediment. The pollution characteristics of microplastics varied greatly in different depths of sediments.

An insular cortical circuit required for itch sensation and aversion.

Itch encompasses both sensory and emotional dimensions, with the two dimensions reciprocally exacerbating each other. However, whether a shared neural circuit mechanism governs both dimensions remains elusive. Here, we report that the anterior insular cortex (AIC) is activated by both histamine-dependent and -independent itch stimuli. The activation of AIC elicits aversive emotion and exacerbates pruritogen-induced itch sensation and aversion. Mechanistically, AIC excitatory neurons project to the GABAergic neurons in the dorsal bed nucleus of the stria terminalis (dBNST). Manipulating the activity of the AIC → dBNST pathway affects both itch sensation and itch-induced aversion. Our study discovers the shared neural circuit (AIC â†’ dBNST pathway) underlying the itch sensation and aversion, highlights the critical role of the AIC as a central hub for the itch processing, and provides a framework to understand the neural mechanisms underlying the sensation and emotion interaction.

Atom-by-atom optimizing the surface termination of Fe-Pt intermetallic catalysts for alkaline hydrogen evolution reaction.

Controlling the atomic arrangement of elemental atoms in intermetallic catalysts to govern their surface and subsurface properties is a crucial but challenging endeavor in electrocatalytic reactions. In hydrogen evolution reaction (HER), adjusting the d-band center of the conventional noble-metallic Pt by introducing Fe enables the optimization of catalytic performance. However, a notable gap exists in research on the effective transition from disordered Fe/Pt alloys to highly ordered intermetallic compounds (IMCs) such as FePt3 in the alkaline HER, hampering their broader application. In this study, a series of catalysts FePt3-xH (x = 5, 6, 7, 8 and 9) supported on carbon nanotubes (CNTs) were synthesized via a simple impregnation method, along with a range of heat treatment processes, including annealing in a reductive atmosphere, to regulate the order degree of the arrangement of Fe/Pt atoms within the FePt3 catalyst. By using advanced microscopy and spectroscopy techniques, we systematically explored the impact of the order degree of FePt3 in the HER. The as-prepared FePt3-8H exhibited notable HER catalytic activity with low overpotentials (η = 37 mV in 1.0 mol L-1 KOH) at j = 10 mA cm-2. The surface of the L12 FePt3-8H catalyst was demonstrated to be Pt-rich. The Pt on the surface was not easily oxidized due to the unique Fe/Pt coordination, resulting in significant enhancement of HER performance.

Multi-omics analyses reveal bacteria and catalase associated with keloid disease.

BACKGROUND: The pathology of keloid and especially the roles of bacteria on it were not well understood. METHODS: In this study, multi-omics analyses including microbiome, metaproteomics, metabolomic, single-cell transcriptome and cell-derived xenograft (CDX) mice model were used to explore the roles of bacteria on keloid disease. FINDINGS: We found that the types of bacteria are significantly different between keloid and healthy skin. The 16S rRNA sequencing and metaproteomics showed that more catalase (CAT) negative bacteria, Clostridium and Roseburia existed in keloid compared with the adjacent healthy skin. In addition, protein mass spectrometry shows that CAT is one of the differentially expressed proteins (DEPs). Overexpression of CAT inhibited the proliferation, migration and invasion of keloid fibroblasts, and these characteristics were opposite when CAT was knocked down. Furthermore, the CDX model showed that Clostridium butyricum promote the growth of patient's keloid fibroblasts in BALB/c female nude mice, while CAT positive bacteria Bacillus subtilis inhibited it. Single-cell RNA sequencing verified that oxidative stress was up-regulated and CAT was down-regulated in mesenchymal-like fibroblasts of keloid. INTERPRETATION: In conclusion, our findings suggest that bacteria and CAT contribute to keloid disease. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

The occurrence of pollutants in organisms and water of inland mariculture systems: Shrimp aquaculture is a procession of Microplastics accumulation.

Microplastics (MPs) pollution in the ocean was widely concerned, but the current study on MPs pollution in the mariculture system is relatively lacking. This study researched the MPs pollution characteristics in water and shrimp at different stages of the pond and industrial aquaculture. The study shows that in the same aquaculture stage, MPs abundance in shrimp and water in pond aquaculture mode is higher than that in industrial aquaculture mode. The MPs pollution characteristics in shrimp and water show significant consistency. The hazard index of MPs in pond water and industrial models are 122 (Level Ⅲ) and 540 (Level Ⅲ), respectively, indicating that industrial aquaculture models may suffer from more severe MPs stress. The aquaculture period and mode significantly affected the MPs abundance of water and shrimp, but there was no interaction between the aquaculture period and mode. MPs abundance in shrimp show a significant relationship with the length of crustacean and weight. This study further enhanced the understanding of MPs pollution of water and organisms in different aquaculture modes at different stages, and warned MPs is widely spread in mariculture systems.

The Lateral Parabrachial Nucleus Inputs to the Lateral Hypothalamus Trigger Nocifensive Behaviors.

The lateral parabrachial nucleus (LPBN) is known to play a key role in relaying noxious information from the spinal cord to the brain. Different LPBN efferent mediate different aspects of the nocifensive response. However, the function of the LPBN â†’ lateral hypothalamus (LH) circuit in response to noxious stimuli has remained unknown. Here, we show that LPBN â†’ LH circuit is activated by noxious stimuli. Interestingly, either activation or inhibition of this circuit induced analgesia. Optogenetic activation of LPBN afferents in the LH elicited spontaneous jumping and induced place aversion. Optogenetic inhibition inhibited jumping behavior to noxious heat. Ablation of LH glutamatergic neurons could abolish light-evoked analgesia and jumping behavior. Our study revealed a role for the LPBN â†’ LH pathway in nocifensive behaviors.

A case study on microplastics pollution characteristics in fouling organisms in typical aquaculture bay, China.

Microplastics (MPs) and fouling organisms are prevalent in oceans worldwide. The study aims to investigate the pollution characteristics of MPs in fouling organisms. The study found significant inter-specific differences in the MPs abundance, while the length of MPs is consistent. The average number of MPs in N. exigua is 0.00 ± 0.00. There is a correlation between MPs abundance and weight in sessile group, while gastropods don't. Direct observation has demonstrated that the radulae of N. radula can envelop MPs. Fiber and blue are the predominant forms and colors of MPs found in fouling organisms. It is noteworthy that all film and fragment MPs observed were of a blue hue and had a size limitation of 500 µm. The characteristics of MPs between sessile organisms are more similar than those between gastropods. This study has improved our understanding of the pollution characteristics of MPs in fouling organisms, specifically gastropods.

Distribution and characteristics of microplastics in 16 benthic organisms in Haizhou Bay, China: Influence of habitat, feeding habits and trophic level.

Microplastics (MPs) are widely found in the ocean and cause a serious risk to marine organisms. However, fewer studies have been conducted on benthic organisms. This study conducted a case study on the pollution characteristics of MPs on 16 marine benthic organisms in Haizhou Bay, and analyzed the effects of habitat, trophic level, and feeding mode on the MPs pollution characters. The results showed that MPs were detected in all 16 organisms with an average abundance of 8.84 ± 9.14 items/individual, which is in the middle-high level in the international scale. Among the detected MPs, the main material was cellophane. This study showed that benthic organisms can be used as indicator organisms for MPs pollution. MPs in organisms can be affected by their habitat, trophic level, and feeding mode. Comprehensive analysis of MPs in benthic organisms will contribute to fully understand the characterization and source resolution of MPs pollution.

Ultrafast Nucleation Reverses Dissolution of Transition Metal Ions for Robust Aqueous Batteries.

The dissolution of transition metal ions causes the notorious peeling of active substances and attenuates electrochemical capacity. Frustrated by the ceaseless task of pushing a boulder up a mountain, Sisyphus of the Greek myth yearned for a treasure to be unearthed that could bolster his efforts. Inspirationally, by using ferricyanide ions (Fe(CN)63-) in an electrolyte as a driving force and taking advantage of the fast nucleation rate of copper hexacyanoferrate (CuHCF), we successfully reversed the dissolution of Fe and Cu ions that typically occurs during cycling. The capacity retention increased from 5.7% to 99.4% at 0.5 A g-1 after 10,000 cycles, and extreme stability of 99.8% at 1 A g-1 after 40,000 cycles was achieved. Fe(CN)63- enables atom-by-atom substitution during the electrochemical process, enhancing conductivity and reducing volume change. Moreover, we demonstrate that this approach is applicable to various aqueous batteries (i.e., NH4+, Li+, Na+, K+, Mg2+, Ca2+, and Al3+).

Exosomes from circ-Astn1-modified adipose-derived mesenchymal stem cells enhance wound healing through miR-138-5p/SIRT1/FOXO1 axis regulation.

BACKGROUND: Wound healing impairment is a dysfunction induced by hyperglycemia and its effect on endothelial precursor cells (EPCs) in type 2 diabetes mellitus. There is increasing evidence showing that exosomes (Exos) derived from adipose-derived mesenchymal stem cells (ADSCs) exhibit the potential to improve endothelial cell function along with wound healing. However, the potential therapeutic mechanism by which ADSC Exos contribute to wound healing in diabetic mice remains unclear. AIM: To reveal the potential therapeutic mechanism of ADSC Exos in wound healing in diabetic mice. METHODS: Exos from ADSCs and fibroblasts were used for high-throughput RNA sequencing (RNA-Seq). ADSC-Exo-mediated healing of full-thickness skin wounds in a diabetic mouse model was investigated. We employed EPCs to investigate the therapeutic function of Exos in cell damage and dysfunction caused by high glucose (HG). We utilized a luciferase reporter (LR) assay to analyze interactions among circular RNA astrotactin 1 (circ-Astn1), sirtuin (SIRT) and miR-138-5p. A diabetic mouse model was used to verify the therapeutic effect of circ-Astn1 on Exo-mediated wound healing. RESULTS: High-throughput RNA-Seq analysis showed that circ-Astn1 expression was increased in ADSC Exos compared with Exos from fibroblasts. Exos containing high concentrations of circ-Astn1 had enhanced therapeutic effects in restoring EPC function under HG conditions by promoting SIRT1 expression. Circ-Astn1 expression enhanced SIRT1 expression through miR-138-5p adsorption, which was validated by the LR assay along with bioinformatics analyses. Exos containing high concentrations of circ-Astn1 had better therapeutic effects on wound healing in vivo compared to wild-type ADSC Exos. Immunofluorescence and immunohistochemical investigations suggested that circ-Astn1 enhanced angiopoiesis through Exo treatment of wounded skin as well as by suppressing apoptosis through promotion of SIRT1 and decreased forkhead box O1 expression. CONCLUSION: Circ-Astn1 promotes the therapeutic effect of ADSC-Exos and thus improves wound healing in diabetes via miR-138-5p absorption and SIRT1 upregulation. Based on our data, we advocate targeting the circ-Astn1/miR-138-5p/SIRT1 axis as a potential therapeutic option for the treatment of diabetic ulcers.

Secondary Rhinaria Contribute to Major Sexual Dimorphism of Antennae in the Aphid Semiaphis heraclei (Takahashi).

Sexual generation is an important generation in the life cycle of host-alternating aphids, and its population size determines the intensity of the peak in the next spring. Although male trapping techniques based on olfactory stimuli have been successfully established in the field, the biological basis of olfactory perception in males is unclear. In this study, we compared the morphology of antennae and the types, sizes, numbers, and distribution of sensilla between males and sexual females in the host-alternating aphid Semiaphis heraclei (Hemiptera: Aphididae). We found that flagellum length differentiation contributed to the majority of the sexual dimorphism of antennae. Most sensillum types or subtypes, including trichoid sensilla subtype I, campaniform sensilla, and primary rhinaria subtypes I and II, were enlarged in males. In addition, males bore more trichoid sensilla subtype I than sexual females. In particular, secondary rhinaria were present in males only and could not be detected in sexual females. These results revealed the structural basis of male olfactory perception. Our findings provide insight into the mechanism underlying chemical communication between sexual aphids and could thus be useful for pest control.

Structural and Functional Diversity in Rigid Thiosemicarbazones with Extended Aromatic Frameworks: Microwave-Assisted Synthesis and Structural Investigations.

The long-standing interest in thiosemicarbazones (TSCs) has been largely driven by their potential toward theranostic applications including cellular imaging assays and multimodality imaging. We focus herein on the results of our new investigations into: (a) the structural chemistry of a family of rigid mono(thiosemicarbazone) ligands characterized by extended and aromatic backbones and (b) the formation of their corresponding thiosemicarbazonato Zn(II) and Cu(II) metal complexes. The synthesis of new ligands and their Zn(II) complexes was performed using a rapid, efficient and straightforward microwave-assisted method which superseded their preparation by conventional heating. We describe hereby new microwave irradiation protocols that are suitable for both imine bond formation reactions in the thiosemicabazone ligand synthesis and for Zn(II) metalation reactions. The new thiosemicarbazone ligands, denoted HL, mono(4-R-3-thiosemicarbazone)quinone, and their corresponding Zn(II) complexes, denoted ZnL2, mono(4-R-3-thiosemicarbazone)quinone, where R = H, Me, Ethyl, Allyl, and Phenyl, quinone = acenapthnenequinone (AN), aceanthrenequinone (AA), phenanthrenequinone (PH), and pyrene-4,5-dione (PY) were isolated and fully characterized spectroscopically and by mass spectrometry. A plethora of single crystal X-ray diffraction structures were obtained and analyzed and the geometries were also validated by DFT calculations. The Zn(II) complexes presented either distorted octahedral geometry or tetrahedral arrangements of the O/N/S donors around the metal center. The modification of the thiosemicarbazide moiety at the exocyclic N atoms with a range of organic linkers was also explored, opening the way to bioconjugation protocols for these compounds. The radiolabeling of these thiosemicarbazones with 64Cu was achieved under mild conditions for the first time: this cyclotron-available radioisotope of copper (t1/2 = 12.7 h; ß+ 17.8%; ß- 38.4%) is well-known for its proficiency in positron emission tomography (PET) imaging and for its theranostic potential, on the basis of the preclinical and clinical cancer research of established bis(thiosemicarbazones), such as the hypoxia tracer 64Cu-labeled copper(diacetyl-bis(N4-methylthiosemicarbazone)], [64Cu]Cu(ATSM). Our labeling reactions proceeded in high radiochemical incorporation (>80% for the most sterically unencumbered ligands) showing promise of these species as building blocks for theranostics and synthetic scaffolds for multimodality imaging probes. The corresponding "cold" Cu(II) metalations were also performed under the mild conditions mimicking the radiolabeling protocols. Interestingly, room temperature or mild heating led to Cu(II) incorporation in the 1:1, as well as 1:2 metal: ligand ratios in the new complexes, as evident from extensive mass spectrometry investigations backed by EPR measurements, and the formation of Cu(L)2-type species prevails, especially for the AN-Ph thiosemicarbazone ligand (L-). The cytotoxicity levels of a selection of ligands and Zn(II) complexes in this class were further tested in commonly used human cancer cell lines (HeLa, human cervical cancer cells, and PC-3, human prostate cancer cells). Tests showed that their IC50 levels are comparable to that of the clinical drug cis-platin, evaluated under similar conditions. The cellular internalizations of the selected ZnL2-type compounds Zn(AN-Allyl)2, Zn(AA-Allyl)2, Zn(PH-Allyl)2, and Zn(PY-Allyl)2 were evaluated in living PC-3 cells using laser confocal fluorescent spectroscopy and these experiments showed exclusively cytoplasmic distributions.

Self-powered photoelectrochemical aptasensor based on hollow tubular g-C3N4/Bi/BiVO4 for tobramycin detection.

A highly sensitive photoelectrochemical aptasensor based on phosphorus-doped hollow tubular g-C3N4/Bi/BiVO4 (PT-C3N4/Bi/BiVO4) for tobramycin (TOB) detecting was developed. This aptasensor is a self-powered sensing system which could generate the electrical output under visible light irradiation with no external voltage supply. Based on the surface plasmon resonance (SPR) effect and unique hollow tubular structure of PT-C3N4/Bi/BiVO4, the PEC aptasensor exhibited an enhanced photocurrent and favorably specific response to TOB. Under the optimized conditions, the sensitive aptasensor presented a wider linearity to TOB in the range of 0.01-50 ng mL-1 with a low detection limit of 4.27 pg mL-1. This sensor also displayed a satisfying photoelectrochemical performance with optimistic selectivity and stability. In addition, the proposed aptasensor was successfully applied to the detection of TOB in river water and milk samples.

A Nomogram with the Keloid Activity Assessment Scale for Predicting the Recurrence of Chest Keloid after Surgery and Radiotherapy.

BACKGROUND: Patients with chest keloids undergoing surgery and adjuvant radiotherapy still have a high recurrence rate, which is a critical problem. The level of keloid activity has not been studied, and a nomogram model for predicting keloid recurrence has not been established in previous studies. METHODS: A total of 145 patients with chest keloids who underwent surgery and radiotherapy between January 2015 and January 2019 at Peking Union Medical College Hospital were included in our study. Demographic and clinical features and the score of KAAS were analyzed. We compared the area under the curve (AUC) and decision curve analysis (DCA) between KAAS and the Vancouver scar scale (VSS) and established a nomogram model for predicting the risk of recurrence. We used bootstrap and calibration plots to evaluate the performance of the nomogram. RESULTS: The KAAS can predict recurrence in patients with chest keloids after surgery and radiotherapy. Areas under the curve (AUCs) of KAAS and VSS were 0.858 and 0.711, respectively (p < 0.001). Decision curve analysis (DCA) demonstrated that the KAAS was better than the VSS. Complications after treatment may be risk factors for keloid recurrence. We created a nomogram by using complications and KAAS. The AUC was 0.871 (95% CI 0.812-0.930). The ROC of the model's bootstrap was 0.865 and was well calibrated. CONCLUSIONS: The KAAS can be used to predict the recurrence and we developed a nomogram for predicting the recurrence of chest keloids after surgery and adjuvant radiotherapy. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Insights into the interaction of cyclooxygenase and lipoxygenase with natural compound 3,4',5,7-Tetrahydroxyflavone based on multi-spectroscopic and metabolomics.

Hypoxia induce right ventricular dysfunction in human heart, but the molecular mechanism remains limited. As known, cyclooxygenases (COX) and lipoxygenases (LOX) play a key role in the cardiovascular system under hypoxia. 3,4',5,7-Tetrahydroxyflavone (THF), which widely exists in a variety of plants and vegetables, is famous for good ability to relieve cardiac injury, but the mechanism remains to be further understood. In this study, we firstly estimated the preventive role of THF against hypoxia-induced right ventricular dysfunction. Metabolomics analysis showed there were differential metabolites involved in above process, which helped us to screen the crucial regulated enzymes of these metabolites. Molecular docking and multi-spectroscopic revealed the molecular mechanism of interaction between THF and COX/LOX. Results suggested that THF bound to COX/LOX through static quenching and these bindings were driven by hydrogen bonds. After binding with THF, the secondary structure of COX/LOX was changed. In general, this study indicated that THF inhibited COX/LOX by spontaneously forming complexes with them.

"Turn-off" photoelectrochemical aptasensor based on g-C3N4/WC/WO3 composites for tobramycin detection.

Tobramycin (TOB), as a widely used antibiotic, poses severe unpredictable risks to ecology and health. Here, a novel photoelectrochemical (PEC) aptasensor based on a "turn-off" PEC mode was constructed for TOB detection. The working electrode could be modified by g-C3N4/WC/WO3 composites and TOB aptamer probes in turn. The TOB aptamer probes could anchor on the g-C3N4/WC/WO3 through π-π stacking interaction to avoid interference from other modifications. When TOB was captured by the aptamer probes anchored on the modified fluorine-doped tin oxide (FTO) electrode, a decreased photocurrent was obtained owing to steric hindrance and hinder electron transfer. Under optimal conditions, 0.005-5 ng mL-1 of TOB could be detected with a detection limit as low as 2 pg mL-1. Meanwhile, actual samples were investigated as well. The proposed sensor shows high specificity, satisfactory detectability, great reproducibility, and may provide a new thought for detecting other pollutants.

Optical coherence tomography angiography for the characterisation of retinal microvasculature alterations in pregnant patients with anaemia: a nested case‒control study.

AIMS: To characterise retinal microvascular alterations in the eyes of pregnant patients with anaemia (PA) and to compare the alterations with those in healthy controls (HC) using optical coherence tomography angiography (OCTA). METHODS: This nested case‒control study included singleton PA and HC from the Eye Health in Pregnancy Study. Fovea avascular zone (FAZ) metrics, perfusion density (PD) in the superficial capillary plexus, deep capillary plexus and flow deficit (FD) density in the choriocapillaris (CC) were quantified using FIJI software. Linear regressions were conducted to evaluate the differences in OCTA metrics between PA and HC. Subgroup analyses were performed based on comparisons between PA diagnosed in the early or late trimester and HC. RESULTS: In total, 99 eyes of 99 PA and 184 eyes of 184 HC were analysed. PA had a significantly reduced FAZ perimeter (ß coefficient=-0.310, p<0.001), area (ß coefficient=-0.121, p=0.001) and increased circularity (ß coefficient=0.037, p<0.001) compared with HC. Furthermore, higher PD in the central (ß coefficient=0.327, p=0.001) and outer (ß coefficient=0.349, p=0.007) regions were observed in PA. PA diagnosed in the first trimester had more extensive central FD (ß coefficient=4.199, p=0.003) in the CC, indicating impaired perfusion in the CC. CONCLUSION: It was found that anaemia during pregnancy was associated with macular microvascular abnormalities, which differed in PA as pregnancy progressed. The results suggest that quantitative OCTA metrics may be useful for risk evaluation before clinical diagnosis. TRIAL REGISTRATION NUMBERS: 2021KYPJ098 and ChiCTR2100049850.

Accumulation of microplastics in fugu (Takifugu bimaculatus): A comparative study between fishing grounds and aquafarms.

Microplastics (MPs) in fish have attracted attention recently, for their ecological and food safety risks. However, knowledge gaps still exist regarding MPs in fugu, a special poisonous but precious seafood, especially that accumulated in its tissues. Accordingly, this study investigated the characteristics of MPs in cultured Takifugu bimaculatus which raised on three aquafarms and in wild individuals from three fishing grounds. More than 98.85 % of T. bimaculatus were contaminated by MPs and the average MPs abundance in wild fugu (4.25 ± 2.63 items/individual) was lower than that of cultured fugu (7.91 ± 2.16 items/individual). The abundance of MPs in fugu's tissues under different life patterns shows significant differences. There were marked differences in size of MPs presented in various tissues. This study adds to the knowledge on MPs accumulation in the tissues of wild and cultured fugu, providing warnings about its transmission and ecological risks in the food chain.

Targeted metabolomics combined with network pharmacology to reveal the protective role of luteolin in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease that significantly endangers human health, where metabolism may drive pathogenesis: a shift from mitochondrial oxidation to glycolysis occurs in diseased pulmonary vessels and the right ventricle. An increase in pulmonary vascular resistance in patients with heart failure with a preserved ejection fraction portends a poor prognosis. Luteolin exists in numerous foods and is marketed as a dietary supplement assisting in many disease treatments. However, little is known about the protective effect of luteolin on metabolism disorders in diseased pulmonary vessels. In this study, we found that luteolin apparently reversed the pulmonary vascular remodeling of PAH rats by inhibiting the abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs). Moreover, network pharmacology and metabolomics results revealed that the arachidonic acid pathway, amino acid pathway and TCA cycle were dysregulated in PAH. A total of 14 differential metabolites were significantly changed during the PAH, including DHA, PGE2, PGD2, LTB4, 12-HETE, 15-HETE, PGF2α, and 8-iso-PGF2α metabolites in the arachidonic acid pathway, and L-asparagine, oxaloacetate, N-acetyl-L-ornithine, butane diacid, ornithine, glutamic acid metabolites in amino acid and TCA pathways. However, treatment with luteolin recovered the LTB4, PGE2, PGD2, 12-HETE, 15-HETE, PGF2α and 8-iso-PGF2α levels close to normal. Meanwhile, we showed that luteolin also downregulated the gene and protein levels of COX 1, 5-LOX, 12-LOX, and 15-LOX in the arachidonic acid pathway. Collectively, this work highlighted the metabolic mechanism of luteolin-protected PAH and showed that luteolin would hold great potential in PAH prevention.