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A comprehensive phytochemical investigation of the flower buds and leaves/twigs of Heptacodium miconioides, a cultivated ornamental plant native to China and categorized as 'vulnerable', has led to the isolation of 45 structurally diverse compounds, which comprise 18 phenylpropanoids (1-4, 7-20), 11 pentacyclic triterpenoids (5, 6, 21-29), eight secoiridoid glycosides (30-37), three quinic acid derivatives (38-40), and a few miscellaneous components (41-45). Among them, (+)-α-intermedianol (1), (+)-holophyllol A (2), and (-)-pseudolarkaemin A (3) represent previously unreported enantiomeric lignans, while (+)-7'(R)-hydroxymatairesinol (4) is an undescribed naturally occurring lignan. Heptacoacids A (5) and B (6) are undescribed 24-nor-urs-28-oic acid derivatives. Their chemical structures were determined by 2D-NMR, supplemented by evidence from specific rotations and circular dichroism spectra. Given the uncertainty surrounding the systematic position of Heptacodium, integrative taxonomy (ITA), a method utilized to define contentious species, is applied. Chemotaxonomy, a vital aspect of ITA, becomes significant. By employing hierarchical clustering analysis (HCA) and syntenic pattern analysis methods, a taxonomic examination based on the major specialized natural products from the flower buds of H. miconioides and two other Caprifoliaceae plants (i.e., Lonicera japonica and Abelia × grandiflora) could offer enhanced understanding of the systematic placement of Heptacodium. Additionally, compounds 39 and 40 displayed remarkable inhibitory activities against ATP-citrate lyase (ACL), with IC50 values of 0.11 and 1.10 µM, respectively. In summary, the discovery of medical properties and refining systematic classification can establish a sturdy groundwork for conservation efforts aimed at mitigating species diversity loss while addressing human diseases.
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Four undescribed polyketides, beshanzones A (1) and B (2) as well as beshanhexanols A (3) and B (4), along with three known ones (5-7) were isolated from the rice fermentation of two endophytic fungi associated with the critically endangered Chinese endemic conifer Abies beshanzuensis. γ-Butyrolactone derivatives 1, 2, and 5 were isolated from Phomopsis sp. BSZ-AZ-2, an interesting strain that drawn our attention this time. The cyclohexanol derivatives 3, 4, 6, and 7 were obtained during a follow-up investigation on Penicillium commune BSZ-P-4-1. The chemical structures including absolute configurations of compounds 1-4 were determined by spectroscopic methods, Mo2(OAc)4 induced electronic circular dichroism (IECD), GIAO NMR calculations and DP4+ probability analyses. In particular, compound 2 contains a novel 5/5 bicyclic ring system, which might be biogenetically derived from the known compound 5 through hydrolysis followed by an Aldol reaction. All isolates were evaluated for their antimicrobial activities against a small panel of bacterial and fungal pathogens. Compounds 6 and 7 showed moderate inhibitory activities against Candida albicans, with MIC values of 16 and 32 µg/mL, respectively.
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Abies , Espécies em Perigo de Extinção , Endófitos , Policetídeos , Endófitos/química , Policetídeos/farmacologia , Policetídeos/isolamento & purificação , Policetídeos/química , Estrutura Molecular , China , Abies/química , Phomopsis/química , Testes de Sensibilidade Microbiana , Penicillium/química , Bactérias/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , 4-Butirolactona/análogos & derivados , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , 4-Butirolactona/químicaRESUMO
An extensive phytochemical investigation on the EtOAc-soluble fraction of the 90% MeOH extract from the twigs and needles of the 'vulnerable' Chinese endemic conifer Tsuga forrestii (Forrest's hemlock) led to the isolation and characterization of 50 structurally diverse diterpenoids, including 15 unreported C-18 carboxylated ones (tsugaforrestiacids A-O, 1-15, resp.). Among them, compounds 1-7 are abieten-18-oic acids, compound 8 is an abieten-18-succinate, and compounds 10-12 are podocarpen-18-oic acids, whereas compounds 13-15 are pimarane-type, isopimarane-type, and totarane-type diterpenoid acids, respectively. Their structures and absolute configurations were determined by a combination of spectroscopic methods, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism (ECD) data, and single crystal X-ray diffraction analyses. All the isolates were evaluated for their inhibitory activities against the ATP-citrate lyase (ACL), a key enzyme in cellular metabolism. Tsugaforrestiacids E (5) and H (8) were found to have significant inhibitory effects against ACL, with IC50 values of 5.3 and 6.2 µM, respectively. The interactions of the bioactive molecules with the ACL enzyme were examined by molecular docking studies. The isolated diterpenoids also provide chemotaxonomic evidence to support the delimitation of Tsuga from its closest sister group (Nothotsuga). The above findings highlight the importance of protecting plant species with unique and diverse secondary metabolites, which may be potential sources of new therapeutic agents for the treating ACL-associated diseases.
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ATP Citrato (pro-S)-Liase , Diterpenos , Compostos Fitoquímicos , Diterpenos/química , Diterpenos/farmacologia , Diterpenos/isolamento & purificação , ATP Citrato (pro-S)-Liase/antagonistas & inibidores , ATP Citrato (pro-S)-Liase/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , China , Estrutura Molecular , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Espécies em Perigo de Extinção , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Folhas de Planta/químicaRESUMO
An extensive phytochemical investigation on the rare medicinal plant Semiliquidambar cathayensis (family: Hamamelidaceae) led to the isolation of four new (1-4, named semiliquidacids A-D, respectively) and 25 related known pentacyclic triterpenoids. The new structures with absolute configurations were elucidated by spectroscopic methods, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compound 1 represents the first naturally occurring ursane-type triterpenoid featuring an uncommon C-25 formyl group. Compound 4 and oleanolic acid (13) exhibited remarkable inhibitory effects against the ATP-citrate lyase (ACL, an emerging drug target for hyperlipidemia and related metabolic disorders) with IC50 values of 6.5 and 11.9 µM, respectively. The molecular interaction and binding mode between the bioactive triterpenoids and ACL were elaborated by conducting a molecular docking study. Meanwhile, the chemotaxonomic significance of the isolated triterpenoids has been briefly discussed.
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ATP Citrato (pro-S)-Liase , Simulação de Acoplamento Molecular , Triterpenos Pentacíclicos , Plantas Medicinais , Estrutura Molecular , Plantas Medicinais/química , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/química , ATP Citrato (pro-S)-Liase/antagonistas & inibidores , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/química , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , China , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/químicaRESUMO
Platelet-rich plasma (PRP) has the capability of assisting in the recovery of damaged tissues by releasing a variety of biologically active factors to initiate a hemostatic cascade reaction and promote the synthesis of new connective tissue and revascularization. It is now widely used for tissue engineering repair. In addition, PRP has demonstrated nerve repair and pain relief, and has been studied and applied to the facial nerve, median nerve, sciatic nerve, and central nerve. These suggest that PRP injection therapy has a positive effect on nerve repair. This indicates that PRP has high clinical value and potential application in nerve repair. It is worthwhile for scientists and medical workers to further explore and study PRP to expand its application in nerve repair, and to provide a more reliable scientific basis for the opening of a new approach to nerve repair.
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Acute liver failure caused by hepatic ischemia reperfusion injury (HIRI) poses a severe threat to life, emphasizing the urgent need for precise and timely early diagnosis. Viscosity, a key parameter reflecting active analyte levels at the cellular level, remains underexplored in relation to HIRI. To address this gap, we have developed a groundbreaking near-infrared molecule rotator, PN, exhibiting exceptional characteristics. PN demonstrates remarkable sensitivity, with a 32-fold change in response to viscosity, ranging from PBS to glycerol solution. PN's distinctive features include maximum emission wavelength 790 nm, as well as an impressive Stokes shift 190 nm. Moreover, PN exhibits the ability to sensitively and selectively differentiate nystatin-induced viscosity changes within living cells, and can be used for the detection of viscosity changes in the HIRI mouse model. This capability enhances our understanding of cellular responses, opening avenues for potential applications within disease models. The versatility of PN extends to its potential role in guiding timely monitoring and imaging of viscosity, offering valuable insights into disease progression.
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BACKGROUND: Tooth replacement patterns of early-diverging ornithischians, which are important for understanding the evolution of the highly specialized dental systems in hadrosaurid and ceratopsid dinosaurs, are poorly known. The early-diverging neornithischian Jeholosaurus, a small, bipedal herbivorous dinosaur from the Early Cretaceous Jehol Biota, is an important taxon for understanding ornithischian dental evolution, but its dental morphology was only briefly described previously and its tooth replacement is poorly known. RESULTS: CT scanning of six specimens representing different ontogenetic stages of Jeholosaurus reveals significant new information regarding the dental system of Jeholosaurus, including one or two replacement teeth in nearly all alveoli, relatively complete tooth resorption, and an increase in the numbers of alveoli and replacement teeth during ontogeny. Reconstructions of Zahnreihen indicate that the replacement pattern of the maxillary dentition is similar to that of the dentary dentition but with a cyclical difference. The maxillary tooth replacement rate in Jeholosaurus is probably 46 days, which is faster than that of most other early-diverging ornithischians. During the ontogeny of Jeholosaurus, the premaxillary tooth replacement rate slows from 25 days to 33 days with similar daily dentine formation. CONCLUSIONS: The tooth replacement rate exhibits a decreasing trend with ontogeny, as in Alligator. In a phylogenetic context, fast tooth replacement and multi-generation replacement teeth have evolved at least twice independently in Ornithopoda, and our analyses suggest that the early-diverging members of the major ornithischian clades exhibit different tooth replacement patterns as an adaption to herbivory.
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Dinossauros , Dente , Animais , Filogenia , Dinossauros/anatomia & histologia , Herbivoria , Fósseis , Dente/diagnóstico por imagem , Dente/cirurgia , Dente/anatomia & histologiaRESUMO
Field Oriented Control (FOC) effectively realizes independent control of flux linkage and torque, and is widely used in application of Permanent Magnet Synchronous Motor (PMSM). However, it is necessary to detect the phase current information of the motor to realize the current closed-loop control. The phase current detection method based on a sampling resistor will cause a measurement error due to the influence of parasitic parameters of the sampling resistor, which will lead to the decrease in PMSM control performance. This paper reveals the formation mechanism of the current sampling error caused by parasitic inductance and capacitance of the sampling resistor, and further confirms that the above error will lead to the fluctuation of the electromagnetic torque output by simulation. Moreover, we propose an approach for online observation and compensation of the current sampling error based on PI-type observer to suppresses the torque pulsation of PMSM. The phase current sampling error is estimated by the proportional and integral (PI) observer, and the deviation value of current sampling is obtained by low-pass filter (LPF). The above deviation value is further injected into the phase current close-loop for error compensation. The PI observer continues to work to keep the current sampling error close to zero. The simulation platform of Matlab/Simulink (Version: R2021b) is established to verify the effectiveness of online error observation and compensation. Further experiments also prove that the proposed method can effectively improve the torque fluctuation of the PMSM and enhance its control accuracy performance of rotation speed.
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Staphylococcus aureus can readily form biofilm which enhances the drug-resistance, resulting in life-threatening infections involving different organs. Biofilm formation occurs due to a series of developmental events including bacterial adhesion, aggregation, biofilm maturation, and dispersion, which are controlled by multiple regulatory systems. Rapidly increasing research and development outcomes on natural products targeting S. aureus biofilm formation and/or regulation led to an emergent application of active phytochemicals and combinations. This review aimed at providing an in-depth understanding of biofilm formation and regulation mechanisms for S. aureus, outlining the most important antibiofilm strategies and potential targets of natural products, and summarizing the latest progress in combating S. aureus biofilm with plant-derived natural products. These findings provided further evidence for novel antibiofilm drugs research and clinical therapies.
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With the increasing prevalence of Staphylococcus aureus infections, rapid emergence of drug resistance and the slow healing of infected wounds, developing an efficient antibiotic-free multifunctional wound dressing for inhibiting S. aureus and simultaneously facilitating wound healing have become a huge challenge. Due to their excellent biocompatibility and biodegradability, some carbopol hydrogels based on plant extracts or purified compounds have already been applied in wound healing treatment. In China, Euphorbia humifusa Willd. (EuH) has been traditionally used as a medicine and food homologous medicine for the treatment of furuncles and carbuncles mainly caused by S. aureus infection. In an earlier study, EuH-originated flavonoids quercetin (QU) and luteolin (LU) could serve as a potential source for anti-S. aureus drug discovery when used in synergy. However, the in vivo effects of QU and LU on S. aureus-infected wound healing are still unknown. In this study, we found a series of Carbopol 940-based hydrogels loading QU and LU in combination could disinfect S. aureus and also could promote wound healing. In the full-thickness skin defect mouse model infected with S. aureus, the wound contraction ratio, bacterial burden, skin hyperplasia and inflammation score, as well as collagen deposition and blood vessels were then investigated. The results indicate that the optimized QL2 [QU (32 µg mL-1)-LU (8 µg mL-1)] hydrogel with biocompatibility significantly promoted S. aureus-infected wound healing through anti-infection, anti-inflammation, collagen deposition, and angiogenesis, revealing it as a promising alternative for infected wound repair.
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BACKGROUND: Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is a devastating bacterial disease that reduces citrus yield and quality, posing a serious threat to the citrus industry. Several conventional chemicals have been used to control citrus canker. However, this approach often leads to the excessive use of chemical agents, can exacerbate environmental pollution and promotes the development of resistant Xcc. Therefore, there is significant interest in the development of efficient and environmentally friendly technologies to control citrus canker. RESULTS: In this study, water-soluble ZnO quantum dots (ZnO QDs) were synthesised as an efficient nanopesticide against Xcc. The results showed that the antibacterial activity of ZnO QDs irradiated with visible light [half-maximal effective concentration (EC50) = 33.18 µg mL-1] was ~3.5 times higher than that of the dark-treated group (EC50 = 114.80 µg mL-1). ZnO QDs induced the generation of reactive oxygen species (â¢OH, â¢O- 2 and 1O2) under light irradiation, resulting in DNA damage, cytoplasmic destruction, and decreased catalase and superoxide dismutase activities. Transcription analysis showed downregulation of Xcc genes related to 'biofilms, virulence, adhesion' and 'DNA transfer' exposure to ZnO QDs. More importantly, ZnO QDs also promoted the growth of citrus. CONCLUSION: This research provides new insights into the photocatalytic antibacterial mechanisms of ZnO QDs and supports the development of more efficient and safer ZnO QDs-based nanopesticides to control citrus canker. © 2024 Society of Chemical Industry.
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Citrus , Luz , Doenças das Plantas , Pontos Quânticos , Xanthomonas , Óxido de Zinco , Pontos Quânticos/química , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Xanthomonas/efeitos dos fármacos , Xanthomonas/efeitos da radiação , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Citrus/microbiologia , Antibacterianos/farmacologiaRESUMO
Three undescribed (1-3) and nine known (4-12) platanosides were isolated and characterized from a bioactive extract of the May leaves of Platanus × acerifolia that initially showed inhibition against Staphylococcus aureus. Targeted compound mining was guided by an LC-MS/MS-based molecular ion networking (MoIN) strategy combined with conventional isolation procedures from a unique geographic location. The novel structures were mainly determined by 2D NMR and computational (NMR/ECD calculations) methods. Compound 1 is a rare acylated kaempferol rhamnoside possessing a truxinate unit. 6 (Z,E-platanoside) and 7 (E,E-platanoside) were confirmed to have remarkable inhibitory effects against both methicillin-resistant S. aureus (MIC: ≤ 16 µg/mL) and glycopeptide-resistant Enterococcus faecium (MIC: ≤ 1 µg/mL). These platanosides were subjected to docking analyses against FabI (enoyl-ACP reductase) and PBP1/2 (penicillin binding protein), both of which are pivotal enzymes governing bacterial growth but not found in the human host. The results showed that 6 and 7 displayed superior binding affinities towards FabI and PBP2. Moreover, surface plasmon resonance studies on the interaction of 1/7 and FabI revealed that 7 has a higher affinity (KD = 1.72 µM), which further supports the above in vitro data and is thus expected to be a novel anti-antibacterial drug lead.
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Glicosídeos , Staphylococcus aureus Resistente à Meticilina , Fenóis , Sepse , Infecções Estafilocócicas , Humanos , Antibacterianos/química , Cromatografia Líquida , Enoil-(Proteína de Transporte de Acila) Redutase (NADH) , Testes de Sensibilidade Microbiana , Espectrometria de Massas em Tandem , Relação Estrutura-AtividadeRESUMO
An investigation on the secondary metabolites from a rice culture broth of the endophytic fungus Neurospora terricola HDF-Br-2 derived from the vulnerable conifer Pseudotsuga gaussenii led to the isolation and characterization of 34 structurally diverse polyketides (1-34). Seven of them are previously undescribed, including five unprecedented dihydropyran-containing (terricoxanthones A-E, 1-5, resp.) and one rare tetrahydrofuran-containing (terricoxanthone F, 6) dimeric xanthones. The structures were elucidated by spectroscopic methods and single-crystal X-ray diffraction analyses. Terricoxanthones each were obtained as a racemic mixture. Their plausible biosynthetic relationships were briefly proposed. Compounds 6, aspergillusone A (8), and alatinone (27) displayed considerable inhibition against Candida albicans with MIC values of 8-16 µg/mL. 4-Hydroxyvertixanthone (12) and 27 exhibited significant inhibitory activities against Staphylococcus aureus, with MIC values of 4-8 µg/mL. Furthermore, compounds 8 and 27 could disrupt biofilm of S. aureus and C. albicans at 128 µg/mL. The findings not only extend the skeletons of xanthone dimers and contribute to the diversity of metabolites of endophytes associated with the endangered Chinese conifer P. gaussenii, but could further reveal the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutics.
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Neurospora , Pseudotsuga , Traqueófitas , Xantonas , Staphylococcus aureus , Fungos , Xantonas/química , Estrutura Molecular , Testes de Sensibilidade MicrobianaRESUMO
Seventeen undescribed sesquiterpene-alkaloid hybrids (liriogerphines E-U, 1-17) were isolated and identified during a further phytochemical investigation on the branches and leaves of Chinese tulip tree (Liriodendron chinense), a rare medicinal and ornamental plant endemic to China. These unique heterodimers are conjugates of germacranolide-type sesquiterpenoids with structurally diverse alkaloids [i.e., aporphine- (1-15), proaporphine- (16), and benzyltetrahydroisoquinoline-type (17)] via the formation of a C-N bond. The previously undescribed structures were elucidated by comprehensive spectroscopic data analyses and electronic circular dichroism calculations. Such a class of sesquiterpene-alkaloid hybrids presumably biosynthesized via an aza-Michael addition is quite rare from terrestrial plants. In particular, the sesquiterpene-benzyltetrahydroisoquinoline hybrid skeleton has never been reported until the present study. All the isolates were evaluated for their cytotoxic effects against a small panel of leukemia cell lines (Raji, Jeko-1, Daudi, Jurkat, MV-4-11 and HL-60), and some of them exhibited considerable activities.
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Alcaloides , Antineoplásicos , Liriodendron , Sesquiterpenos , Liriodendron/química , Alcaloides/química , Folhas de Planta/química , Sesquiterpenos/química , Estrutura MolecularRESUMO
Diaphorina citri Kuwayama (Hemiptera: Liviidae), commonly known as the Asian citrus psyllid, is a prominent citrus tree pest that serves as a vector for Asian huanglongbing (HLB). The substantial costs incurred by the citrus industry as a consequence of this disease have spurred considerable interest in the combined control of D. citri using insecticides and natural enemies. However, the successful implementation of such integrated pest management strategies is dependent on ensuring the compatibility of using natural enemies in the presence of insecticides. In this regard, we evaluated the lethal and sublethal effects of flupyradifurone on Orius strigicollis (Poppius) (Heteroptera: Anthocoridae), an important predatory biological control agent, in which we assessed the risk of exposure to flupyradifurone under both in- and off-field scenario. The median lethal rate (LR50) value of flupyradifurone against O. strigicollis (9.089 g a.i. ha-1), was found to be significantly lower than the maximum field recommended rate (MFRR, 170 g a.i. ha-1). Additionally, at 0.254 g a.i. ha-1, flupyradifurone was established to significantly prolong the developmental duration of O. strigicollis from the first to third instar nymphs. Although we detected no significant difference in the survival of immature O. strigicollis subjected to 0.064 g a.i. ha-1 and control treatments, survival was significantly lower in 0.127 and 0.254 g a.i. ha-1 treatments. Moreover, whereas there were no significant differences in adult longevity between the 0.127 g a.i. ha-1 and control treatments, we recorded a significant reduction in fecundity. Furthermore, there were reductions in peak life expectancy, reproductive value, finite rate of increase, intrinsic rate of increase, and net reproduction rate in response to exposure to increasing flupyradifurone rate. Additionally, at 0.127 g a.i. ha-1, the mean generation time was significantly longer than that under control conditions. Following simulated exposure to flupyradifurone for 100 days, population of O. strigicollis in the 0.064 g a.i. ha-1 and control treatments were found to be significantly larger than those exposed to 0.127 g a.i. ha-1. On the basis on LR50 evaluations, whereas the risk of exposure risk was unacceptable for O. strigicollis under in-field scenario, it remained acceptable off-field. Nonetheless, the sublethal effect of prolonged exposure to residual flupyradifurone could pose an unacceptable off-field risk to O. strigicollis (e.g., in adjacent habitats). Consequently, the effects of different flupyradifurone exposure scenarios on O. strigicollis should be thoroughly assessed, and reducing the dosage of flupyradifurone could be advantageous for the control of D. citri when combine with augmentative release of O. strigicollis.
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Citrus , Heterópteros , Inseticidas , Animais , Agentes de Controle Biológico , Inseticidas/toxicidadeRESUMO
Empoasca onukii is a major pest that attacks tea plants. To seek effective and sustainable methods to control the pest, it is necessary to assess its host preference among different species of tea and understand the critical factors behind this behavior. In this study, the behavioral preference of E. onukii for volatile organic compounds (VOCs) of three potted tea species was evaluated. The VOCs released by the three tea species were analyzed using gas chromatography-mass spectrometry, and the major components were used to test the pest's preference. Transcriptome analysis was used to infer the key genes that affect the biosyntheses of the VOCs. The results showed that the tendency of E. onukii toward the VOCs of the three tea species was the strongest in green tea, followed by white tea, and the weakest in red tea. This behavioral preference was significantly and positively correlated with the relative levels of hexanol, linalool, and geraniol in tea volatiles. Relative hexanol was significantly and positively correlated with the expression of genes TEA009423 (LOX2.1), TEA009596 (LOX1.5), TEA008699 (HPL), TEA018669 (CYPADH), and TEA015686 (ADHIII). Relative linalool was significantly and positively correlated with the expression of genes TEA001435 (CAD) and Camellia_sinensis_newGene_22126 (TPS). Relative geraniol was significantly and positively correlated with the expression of genes TEA001435 (CAD), TEA002658 (CYP76B6), TEA025455 (CYP76T24), and Camellia_sinensis_newGene_22126 (TPS). The above findings suggested that three volatiles (hexanol, linalool, and geraniol) determined the behavioral preference of E. onukii toward tea plants, and their biosynthesis was mainly affected by nine genes (TEA009423, TEA009596, TEA008699, TEA018669, TEA015686, TEA001435, TEA002658, TEA025455, and Camellia_sinensis_newGene_22126).
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Acute liver injury leading to acute liver failure can be a life-threatening condition. Therefore, timely and accurate early diagnosis of the onset of acute liver injury in vivo is critical. Viscosity is one of the key parameters that can accurately reflect the levels of relevant active analytes at the cellular level. Herein, a novel near-infrared molecule rotator, DJM, was designed and synthesized. This probe exhibited a highly sensitive (461-fold from PBS solution to 95% glycerol solution) and selective response to viscosity with a maximum emission wavelength of 760 nm and a Stokes shift of 240 nm. Furthermore, DJM has exhibited a remarkable capacity to discern viscosity changes induced by nystatin in viable cells with sensitivity and selectivity and further applied in the zebrafish and mouse model of acute liver injury. Additionally, DJM may potentially offer direction for the timely observation and visualization of viscosity in more relevant disease models in the future.
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BACKGROUND: Heavy metals have been reported to affect liver function. However, there is currently little and inconsistent knowledge about the effects of combined and individual urinary metals on specific parameters of liver function in the general population. Therefore, this study aimed to investigate their associations. METHODS: This study involved 807 general population from the China National Human Biomonitoring of Zhejiang Province 2017-2018. Concentrations of urinary metals, including Chromium (Cr), Cobalt (Co), Nickle (Ni), Arsenic (As), Selenium (Se), Molybdenum (Mo), Cadmium (Cd), Thallium (Tl) and Lead (Pb) were measured. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), direct bilirubin (DBIL), total bilirubin (TBIL) as liver function biomarkers. Multivariable linear regression and weighted quantile sum (WQS) regression were employed to explore the associations of urinary metals with liver function biomarkers. Subgroup analysis stratified by gender and age, excluding smokers and drinkers for sensitivity analysis. RESULTS: Both statistical models indicated that urinary metals were positively associated with ALT and AST, while negatively with TP, ALB, DBIL and TBIL. In the WQS analysis, each quartile increase in the ln-transformed levels of metal mixtures was associated with 4.11 IU/L (95% CI: 1.07, 7.15) higher ALT and 3.00 IU/L (95% CI: 1.75, 4.25) higher AST, as well as, with 0.67 g/L (95% CI: 1.24, -0.11) lower TP, 0.74 g/L (95% CI: 1.09, -0.39) lower ALB, 0.38 µmol/L (95% CI: 0.67, -0.09) lower DBIL, and 1.56 µmol/L (95% CI: 2.22, -0.90) lower TBIL. The association between urinary metals and ALT was primarily driven by Cd (55.8%), Cr contributed the most to the association with AST (20.2%) and TBIL (45.2%), while the association with TP was primarily driven by Ni (38.2%), the association with ALB was primarily driven by As (32.8%), and the association with DBIL was primarily driven by Pb (30.9%). The associations between urinary metals and liver function might differ by sex and age. CONCLUSION: Urinary metals were significantly associated with liver function parameters. Further studies are required to clarify the relationship between heavy metals and liver function.