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Studies of two-dimensional electron systems in a strong magnetic field revealed the quantum Hall effect1, a topological state of matter featuring a finite Chern number C and chiral edge states2,3. Haldane4 later theorized that Chern insulators with integer quantum Hall effects could appear in lattice models with complex hopping parameters even at zero magnetic field. The ABC-trilayer graphene/hexagonal boron nitride (ABC-TLG/hBN) moiré superlattice provides an attractive platform with which to explore Chern insulators because it features nearly flat moiré minibands with a valley-dependent, electrically tunable Chern number5,6. Here we report the experimental observation of a correlated Chern insulator in an ABC-TLG/hBN moiré superlattice. We show that reversing the direction of the applied vertical electric field switches the moiré minibands of ABC-TLG/hBN between zero and finite Chern numbers, as revealed by large changes in magneto-transport behaviour. For topological hole minibands tuned to have a finite Chern number, we focus on quarter filling, corresponding to one hole per moiré unit cell. The Hall resistance is well quantized at h/2e2 (where h is Planck's constant and e is the charge on the electron), which implies C = 2, for a magnetic field exceeding 0.4 tesla. The correlated Chern insulator is ferromagnetic, exhibiting substantial magnetic hysteresis and a large anomalous Hall signal at zero magnetic field. Our discovery of a C = 2 Chern insulator at zero magnetic field should open up opportunities for discovering correlated topological states, possibly with topological excitations7, in nearly flat and topologically nontrivial moiré minibands.
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MOTIVATION: Due to the varying delivery methods of mRNA vaccines, codon optimization plays a critical role in vaccine design to improve the stability and expression of proteins in specific tissues. Considering the many-to-one relationship between synonymous codons and amino acids, the number of mRNA sequences encoding the same amino acid sequence could be enormous. Finding stable and highly expressed mRNA sequences from the vast sequence space using in silico methods can generally be viewed as a path-search problem or a machine translation problem. However, current deep learning-based methods inspired by machine translation may have some limitations, such as recurrent neural networks, which have a weak ability to capture the long-term dependencies of codon preferences. RESULTS: We develop a BERT-based architecture that uses the cross-attention mechanism for codon optimization. In CodonBERT, the codon sequence is randomly masked with each codon serving as a key and a value. In the meantime, the amino acid sequence is used as the query. CodonBERT was trained on high-expression transcripts from Human Protein Atlas mixed with different proportions of high codon adaptation index codon sequences. The result showed that CodonBERT can effectively capture the long-term dependencies between codons and amino acids, suggesting that it can be used as a customized training framework for specific optimization targets. AVAILABILITY AND IMPLEMENTATION: CodonBERT is freely available on https://github.com/FPPGroup/CodonBERT.
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Códon , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Biologia Computacional/métodos , Sequência de Aminoácidos , Redes Neurais de Computação , Algoritmos , Aprendizado ProfundoRESUMO
Sepsis is a life-threatening organ dysfunction due to dysregulated host response to infection, accompanied by a high rate of mortality worldwide. During sepsis progression, toll-like receptors (TLRs) play essential roles in the aberrant inflammatory response that contributes to sepsis-related mortality. Here, we demonstrated a critical role of TLR9 in the progression of sepsis. A septic mouse model was established by cecal ligation and puncture (CLP), then administered with lentivirus encoding si-TLR9/LY294002. TLR9 protein expression and p65 nuclear translocation level/TLR9 protein positive expression/interaction between TLR9 and myeloid differentiation primary response protein 88 (MyD88) in the cecal tissues were examined by Western blot/immunohistochemistry/co-immunoprecipitation assays. Serum levels of pro-inflammatory factors [e.g., interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α)] as well as bacterial contents in the liver/spleen/mesenteric lymph nodes (MLN) were measured by ELISA and bacterial mobility assay. TLR9 expression was augmented in the cecal tissues, TLR9 and MyD88 interaction was enhanced, nuclear p65 protein level was increased, cytoplasmic p65 protein level was decreased, and the nuclear factor kappa B (NF-κB) pathway was activated in CLP-induced septic mice, while TLR9 knockout protected against CLP-induced sepsis via the MyD88/NF-κB pathway inactivation. Briefly, TLR9 inhibition-mediated protection against CLP-induced sepsis was associated with a reduction in pro-inflammatory cytokine release and a promotion of bacterial clearance via a mechanism involving the MyD88/NF-κB pathway inactivation.
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NF-kappa B , Sepse , Receptor Toll-Like 9 , Animais , Camundongos , Citocinas/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Sepse/genética , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Understanding the mechanism of high-transition-temperature (high-Tc) superconductivity is a central problem in condensed matter physics. It is often speculated that high-Tc superconductivity arises in a doped Mott insulator1 as described by the Hubbard model2-4. An exact solution of the Hubbard model, however, is extremely challenging owing to the strong electron-electron correlation in Mott insulators. Therefore, it is highly desirable to study a tunable Hubbard system, in which systematic investigations of the unconventional superconductivity and its evolution with the Hubbard parameters can deepen our understanding of the Hubbard model. Here we report signatures of tunable superconductivity in an ABC-trilayer graphene (TLG) and hexagonal boron nitride (hBN) moiré superlattice. Unlike in 'magic angle' twisted bilayer graphene, theoretical calculations show that under a vertical displacement field, the ABC-TLG/hBN heterostructure features an isolated flat valence miniband associated with a Hubbard model on a triangular superlattice5,6 where the bandwidth can be tuned continuously with the vertical displacement field. Upon applying such a displacement field we find experimentally that the ABC-TLG/hBN superlattice displays Mott insulating states below 20 kelvin at one-quarter and one-half fillings of the states, corresponding to one and two holes per unit cell, respectively. Upon further cooling, signatures of superconductivity ('domes') emerge below 1 kelvin for the electron- and hole-doped sides of the one-quarter-filling Mott state. The electronic behaviour in the ABC-TLG/hBN superlattice is expected to depend sensitively on the interplay between the electron-electron interaction and the miniband bandwidth. By varying the vertical displacement field, we demonstrate transitions from the candidate superconductor to Mott insulator and metallic phases. Our study shows that ABC-TLG/hBN heterostructures offer attractive model systems in which to explore rich correlated behaviour emerging in the tunable triangular Hubbard model.
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Tryptophanyl-tRNA synthetase (TrpRS) links tryptophan to tRNATrp, thereby playing an indispensable role in protein translation. Unlike most class I aminoacyl-tRNA synthetases (AARSs), TrpRS functions as a homodimer. Herein, we captured an 'open-closed' asymmetric structure of Escherichia coli TrpRS (EcTrpRS) with one active site occupied by a copurified intermediate product and the other remaining empty, providing structural evidence for the long-discussed half-of-the-sites reactivity of bacterial TrpRS. In contrast to its human counterpart, bacterial TrpRS may rely on this asymmetric conformation to functionally bind with substrate tRNA. As this asymmetric conformation is probably a dominant form of TrpRS purified from bacterial cells, we performed fragment screening against asymmetric EcTrpRS to support antibacterial discovery. Nineteen fragment hits were identified, and 8 of them were successfully cocrystallized with EcTrpRS. While a fragment named niraparib bound to the L-Trp binding site of the 'open' subunit, the other 7 fragments all bound to an unprecedented pocket at the interface between two TrpRS subunits. Binding of these fragments relies on residues specific to bacterial TrpRS, avoiding undesired interactions with human TrpRS. These findings improve our understanding of the catalytic mechanism of this important enzyme and will also facilitate the discovery of bacterial TrpRS inhibitors with therapeutic potential.
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Anti-Infecciosos , Proteínas de Escherichia coli , Escherichia coli , Triptofano-tRNA Ligase , Sítios de Ligação , Domínio Catalítico , Triptofano/metabolismo , Triptofano-tRNA Ligase/genética , Escherichia coli/enzimologia , Escherichia coli/genética , Proteínas de Escherichia coli/genéticaRESUMO
Electrochemical nitrogen reduction reaction (eNRR) offers a sustainable route for ammonia synthesis; however, current electrocatalysts are limited in achieving optimal performance within narrow potential windows. Herein, inspired by the heliotropism of sunflowers, we present a biomimetic design of Ru-VOH electrocatalyst, featuring a dynamic Ru-O-V pyramid electron bridge for eNRR within a wide potential range. In situ spectroscopy and theoretical investigations unravel the fact that the electrons are donated from Ru to V at lower overpotentials and retrieved at higher overpotentials, maintaining a delicate balance between N2 activation and proton hydrogenation. Moreover, N2 adsorption and activation were found to be enhanced by the Ru-O-V moiety. The catalyst showcases an outstanding Faradaic efficiency of 51.48% at -0.2 V (vs RHE) with an NH3 yield rate exceeding 115 µg h-1 mg-1 across the range of -0.2 to -0.4 V (vs RHE), along with impressive durability of over 100 cycles. This dynamic M-O-V pyramid electron bridge is also applicable to other metals (M = Pt, Rh, and Pd).
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MOTIVATION: Quantitative determination of protein thermodynamic stability is a critical step in protein and drug design. Reliable prediction of protein stability changes caused by point variations contributes to developing-related fields. Over the past decades, dozens of structure-based and sequence-based methods have been proposed, showing good prediction performance. Despite the impressive progress, it is necessary to explore wild-type and variant protein representations to address the problem of how to represent the protein stability change in view of global sequence. With the development of structure prediction using learning-based methods, protein language models (PLMs) have shown accurate and high-quality predictions of protein structure. Because PLM captures the atomic-level structural information, it can help to understand how single-point variations cause functional changes. RESULTS: Here, we proposed THPLM, a sequence-based deep learning model for stability change prediction using Meta's ESM-2. With ESM-2 and a simple convolutional neural network, THPLM achieved comparable or even better performance than most methods, including sequence-based and structure-based methods. Furthermore, the experimental results indicate that the PLM's ability to generate representations of sequence can effectively improve the ability of protein function prediction. AVAILABILITY AND IMPLEMENTATION: The source code of THPLM and the testing data can be accessible through the following links: https://github.com/FPPGroup/THPLM.
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Aprendizado Profundo , Proteínas/química , Redes Neurais de Computação , Software , Processamento de Proteína Pós-TraducionalRESUMO
OBJECTIVES: To describe the longitudinal study and long-term prognosis of multicentre large inception cohort of patients with anti-SAE positive DM. METHODS: We retrospectively recruited patients with anti-SAE+DM in four tertiary referral centers from China between March 2005 and December 2022. Long-term survival analysis was performed in the enrolled patients. The Myositis Damage Index (MDI) and Cutaneous Disease Area and Severity Index (CDASI) were used to evaluate the degree of different organ damage and the extent of skin rashes. Longitudinal computed tomographic (CT) patterns were analyzed. Phenotypes were characterized using unsupervised cluster analysis. RESULTS: All-cause death occurred in 10.5% (4/38) of all patients, in which three patients succumbed to malignancies at 13, 18, and 36 months. Most patients had favorable long-term outcomes, 35.3% of them were in drug-free remission. Skin rashes showed significant improvement evaluated by CDASI with time. However, damage to different systems was observed in 70.6% of the surviving patients using the MDI, which mainly consisted in skin damage, accounting for 47.1%. Nine patients with anti-SAE+DM associated interstitial lung disease (ILD) underwent repeat CT showed marked radiological improvement at 6 months or being stable after 12 months. In further, different characteristics and outcomes were also showed in three clusters identified by unsupervised analysis. CONCLUSIONS: Anti-SAE+DM is characterized with lower mortality rate and the development of malignancies being the primary cause of death. Patients who survived showed notable cutaneous damage, while the ILD tends to stabilize. Clusters identified with unsupervised analysis could assist physicians in identifying higher risk of mortality.
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BACKGROUND AND AIMS: Nuclear protein testis (NUT) carcinoma (NC) is a rare and highly aggressive tumour characterised by chromosomal rearrangement of the nuclear protein testis family member 1 (NUTM1) gene, also known as the NUT gene. NC occurs mainly in the head and neck, mediastinum and lung. In general, primary NC in the oral cavity is extremely rare and reported sporadically. METHODS: A total of 111 formalin-fixed and paraffin-embedded specimens of poorly differentiated oral and oropharyngeal tumours were collected from 10 hospitals. NUT protein IHC staining was performed on these samples, and fluorescence in-situ hybridisation (FISH) and RNA sequencing detection were further carried out for NUT IHC-positive cases. RESULTS: The expression of NUT protein in tumour cells was detected in five cases (five of 111, 4.5%). The tumours in these cases were located in the oral floor, lip, base of the tongue, gingiva and hard palate. FISH detection results showed BRD4::NUT rearrangement in three patients and a non-BRD4::NUT rearrangement pattern in two patients. RNA sequencing results confirmed BRD4::NUT rearrangement in two cases. CONCLUSIONS: To our knowledge, this is the first and largest retrospective study of oral NC, and we found that NC is easily misdiagnosed as poorly differentiated oral squamous cell carcinoma (SCC) or poorly differentiated carcinoma. The morphology and immunophenotype of four NC cases were similar to SCC, and abrupt keratinisation was observed in three cases. Therefore, it is necessary to detect NUT protein for NC screening in oral malignant tumours with these morphologies, especially for young patients who are more likely to be misdiagnosed with other types of cancer.
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We use MOFs material as precursor to synthesize carbon based two-dimensional (2D) materials loaded with In2 S3 -In2 O3 (In-S-O) nanoparticles. The In-S-O nanoparticles have exhibited Janus architecture composed of two compounds with different crystal structures that are combined in-plane on 2D carbon material surface. The excellent properties of this in-plane Janus material include 2D nanoarchitecture and its Janus properties formed by combining two different crystal structures. It has exhibited excellent electrochemical performances due to its abundant electrochemical active sites and large specific surface area. According to experiments, the electron transfer number of the material for two-electron oxygen reduction is about 2.4, and the hydrogen peroxide yield is 32â mg/h cm2 . In the further test of liquid flow electrolytic cell, the yield can reach up to 172â mg/h cm2 .
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AIMS: Androgen receptor inhibitors (ARIs) have become an effective treatment for advanced prostate cancer (PC). However, it is unknown which ARI is the most helpful and safe for men with advanced PC. Our aim is to help physicians make clinical decisions and provide medication guidelines for patients with advanced PC to avoid potential risks when using ARIs for treatment. METHODS: We systematically searched the following databases: PubMed, Embase and Cochrane Library, with a literature publication deadline of February 2023. The primary efficacy outcomes were 18-month overall survival (OS), treatment-emergent adverse events (TEAEs), hypertension and fatigue. The network meta-analysis (NMA) was performed by Stata 15.1, and Revman 5.3 was used to assess the included studies' risk of bias. RESULTS: The analysis included 26 trials with 26 263 people. The surface under the cumulative ranking curve (SUCRA) concluded that enzalutamide (86.8%) showed the best effect in prolonging the OS of patients. Flutamide led to the highest risk of TEAEs (29.9%) and AEs leading to discontinuation (12.8%). Apalutamide (13.4%) led to the highest risk of grade ≥3 TEAEs. Enzalutamide had the highest risk of hypertension (0.2%), grade ≥3 hypertension (4.5%) and fatigue (5.2%). CONCLUSIONS: This NMA indicates there is no one ARI to reach both the most effective and safe therapy aims for treating advanced PC and that there is a compromise between the efficacy and safety of ARIs in the treatment of advanced PC. Physicians should weigh the risks to safety against the anticipated benefits when prescribing these drugs to patients with PC.
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The aims of this study were to determine the distribution and prevalence of gastroenteritis caused by human adenovirus (HAdV) in children in Yunnan province, China, in 2015-2021 and to identify preventive measures that can be taken to reduce morbidity and mortality in children.HAdV is a significant agent of diarrhea in children, but limited data are available regarding the epidemiology and genetic diversity of HAdV in children with diarrhea in Yunnan province, China. A total of 1754 fecal samples were subjected to real-time RT-PCR to detect and quantify HAdV. Positive samples were further analyzed using next-generation sequencing (NGS), and epidemiological data were analyzed as well.1754 patients with diarrhea were enrolled, of which 1041 were male and 713 were female (M:F ratio: 1.46). Seventy-two stool samples out of 1754 (4.10%) were positive for HAdV. The detection rates of all age groups varied from 2.50-4.78%. The highest incidence of HAdV was observed in children under 2 years of age, especially in children 12-24 months-old. From 2015-2021, the annual detection rate ranged from 1.62-12.26%. HAdV was detected throughout the year, but with marked seasonality. Children were most likely to be positive for HAdV in June and November. We detected HAdV in 15.53% (16/103) of samples collected in June and in 8.19% (14/171) of those collected in November. The entire viral genome was successfully sequenced for 13 of the 72 HAdV-positive samples, and 76.92% (10/13) of these were classified as genotype F41 and 23.08% (3/13) were classified as genotype C2.ConclusionsIn Yunnan province, children of all ages are susceptible to HAdV infection, but there has been marked variation in the yearly prevalence. The highest rate of HAdV detection was in June, followed by November. Priority should be given to disease prevention over the development of targeted antiviral therapies, and effective vaccines for preventing HAdV diarrhea are needed. It is also important to establish a surveillance system to collect relevant clinical and epidemiological data quickly in order to assess the potential risk of HAdV infection in children and to identify epidemic strains for the development of effective vaccines.
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Adenovírus Humanos , Vacinas , Criança , Humanos , Feminino , Masculino , Lactente , Pré-Escolar , China , Diarreia , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
BACKGROUND: Olfaction plays an important role in host-seeking by parasitoids, as they can sense chemical signals using sensitive chemosensory systems. Psyttalia incisi (Silvestri) (Hymenoptera: Braconidae) is the dominant parasitoid of Bactrocera dorsalis (Hendel) in fruit-producing regions of southern China. The olfactory behavior of P. incisi has been extensively studied; however, the chemosensory mechanisms of this species are not fully understood. RESULTS: Bioinformatics analysis of 64,515 unigenes from the antennal transcriptome of both male and female adults P. incisi identified 87 candidate chemosensory genes. These included 13 odorant-binding proteins (OBPs), seven gustatory receptors (GRs), 55 odorant receptors (ORs), 10 ionotropic receptors (IRs), and two sensory neuron membrane proteins (SNMPs). Phylogenetic trees were constructed to predict evolutionary relationships between these chemosensory genes in hymenopterans. Moreover, the tissue expression profiles of 13 OBPs were analyzed by quantitative real-time PCR, revealing high expression of seven OBPs (1, 3, 6, 7, 8, 12, and 13) in the antennae. CONCLUSION: This study represents the first identification of chemosensory genes and the determination of their expression patterns in different tissues of P. incisi. These results contribute to a better understanding of the function of the chemosensory system of this parasitoid species.
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Himenópteros , Receptores Odorantes , Tephritidae , Animais , Himenópteros/genética , Filogenia , Perfilação da Expressão Gênica , Transcriptoma/genética , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismoRESUMO
BACKGROUND: This study intends to explore the role and molecular mechanism of hsa_circ_0005519 in acute kidney injury (AKI). METHODS: We conducted reverse transcription-qPCR for human serum to determine levels of hsa_circ_0005519 in AKI patients and healthy controls. Hsa_circ_0005519 was inhibited for expression in HK-2 cells using specific siRNAs. A number of techniques, MTT and ELISA assays, were used to analyze the potential role of hsa_circ_0005519 in cell viability, oxidative stress, and inflammation of LPS-induced HK-2 cells. RESULTS: The serum of patients with AKI exhibited a significant increase in hsa_circ_0005519 expression, compared with healthy controls. Hsa_circ_0005519 was knockdown by siRNA, and its knockdown led to cell viability increase in LPS-induced HK-2 cells. Inhibition of hsa_circ_0005519 can reverse the TNF-α, IL-6 and IL-1ß increase in LPS-induced HK-2 cells. Inhibiting hsa_circ_0005519 led to downregulation of MPO and MDA levels. MiR-98-5p was a downstream miRNA for hsa_circ_0005519. MiR-98-5p can offset the effects of hsa_circ_0005519 on LPS-induced HK-2 cells. IFG1R was a target gene for miR-98-5p. CONCLUSIONS: These findings indicate that the highly expressed hsa_circ_0005519 plays a promoting role in AKI.
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Injúria Renal Aguda , MicroRNAs , Humanos , RNA Circular/genética , Lipopolissacarídeos , MicroRNAs/genética , Injúria Renal Aguda/genética , Sobrevivência Celular , RNA Interferente Pequeno , Apoptose , Proliferação de CélulasRESUMO
Objective: Due to the escalating global prevalence of allergic rhinitis (AR) and its status as an independent risk factor for asthma, timely and effective control of AR is crucial. Achieving this often involves the accurate assessment of AR. Currently, the Control of Allergic Rhinitis and Asthma Test (CARAT) is widely used as an assessment tool, but its measurement effectiveness in Chinese AR patients remains unclear. Therefore, this study aims to evaluate the reliability and validity of the Chinese version of the CARAT10 scale (CARAT10-C) and analyze its application value in the assessment of allergic rhinitis and asthma control trials. Methods: The study enrolled 130 patients with AR from the Ear, Nose, and Throat (ENT) outpatient department of a comprehensive teaching hospital from March to May 2022 as participants. The reliability and validity of the CARAT10-C scale were assessed using Cronbach's alpha coefficient (CAC), Kaiser-Meyer-Olkin (KMO), and Bartlett's sphericity test. Additionally, the study analyzed the effectiveness of the CARAT10-C scale in its application within the Control of Allergic Rhinitis and Asthma Test (CARAT). Results: The Cronbach's alpha coefficient ranges between 0 and 1, with higher values indicating better reliability. Significant differences in exploratory factor analysis suggest good validity. The Cronbach's alpha coefficient of the CARAT10-C scale was 0.806. Exploratory factor analysis revealed that the eigenvalues of Component 1 (3.851) and Component 2 (2.193) were both greater than 1, with a cumulative variance contribution rate (CVCR) of 60.436%. Items 6-10 were primarily loaded on Component 1 (Asthma), while items 1-4 were mainly influenced by Component 2 (AR), with loading ranges of 0.508-0.874, all significant at P < .001. The composite reliability (CAC) of the CARAT10-C scale was 0.806, exceeding 0.8, indicating high reliability. Component 1 had a CAC of 0.834, and Component 2 had a CACs of 0.807, both exceeding 0.8, indicating high reliability for both components. Conclusion: The CARAT10-C scale demonstrates good reliability and validity in the preliminary assessment of AR. It holds potential value in the evaluation and management of AR in China, although the specific application effects still require further investigation.
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Asma , Rinite Alérgica , Humanos , Rinite Alérgica/diagnóstico , Masculino , Feminino , Adulto , Reprodutibilidade dos Testes , Asma/diagnóstico , Pessoa de Meia-Idade , China , Adulto Jovem , Inquéritos e Questionários/normas , Traduções , AdolescenteRESUMO
With the rapid development of China's railways, ensuring the safety of the operating environment of high-speed railways faces daunting challenges. In response to safety hazards posed by light and heavy floating objects during the operation of trains, we propose a dual-branch semantic segmentation network with the fusion of large models (SAMUnet). The encoder part of this network uses a dual-branch structure, in which the backbone branch uses a residual network for feature extraction and the large-model branch leverages the results of feature extraction generated by the segment anything model (SAM). Moreover, a decoding attention module is fused with the results of prediction of the SAM in the decoder part to enhance the performance of the network. We conducted experiments on the Inria Aerial Image Labeling (IAIL), Massachusetts, and high-speed railway hazards datasets to verify the effectiveness and applicability of the proposed SAMUnet network in comparison with commonly used semantic segmentation networks. The results demonstrated its superiority in terms of both the accuracies of segmentation and feature extraction. It was able to precisely extract hazards in the environment of high-speed railways to significantly improve the accuracy of semantic segmentation.
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ABC-stacked trilayer graphene on boron nitride (ABC-TLG/hBN) moiré superlattices provides a tunable platform for exploring Wigner crystal states in which the electron correlation can be controlled by electric and magnetic fields. Here we report the observation of magnetic field-stabilized Wigner crystal states in a ABC-TLG/hBN. We show that correlated insulating states emerge at multiple fractional and integer fillings corresponding to ν = 1/3, 2/3, 1, 4/3, 5/3, and 2 electrons per moiré lattice site under a magnetic field. These correlated insulating states can be attributed to generalized Mott states for the integer fillings and generalized Wigner crystal states for the fractional fillings. The generalized Wigner crystal states are stabilized by a vertical magnetic field and are strongest at one magnetic flux quantum per three moiré superlattices. The ν = 2 insulating state persists up to 30 T, which can be described by a Mott-Hofstadter transition at a high magnetic field.
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Phytochemicals and tryptophan (Trp) metabolites have been found to modulate gut function and health. However, whether these metabolites modulate gut ion transport and serotonin (5-HT) metabolism and signaling requires further investigation. The aim of this study was to investigate the effects of selected phytochemicals and Trp metabolites on the ion transport and 5-HT metabolism and signaling in the ileum of mice in vitro using the Ussing chamber technique. During the in vitro incubation, vanillylmandelic acid (VMA) reduced (p < 0.05) the short-circuit current, and 100 µM chlorogenic acid (CGA) (p = 0.12) and perillic acid (PA) (p = 0.14) had a tendency to reduce the short-circuit current of the ileum. Compared with the control, PA and N-acetylserotonin treatment upregulated the expression of tryptophan hydroxylase 1 (Tph1), while 100 µM cinnamic acid, indolelactic acid (ILA), and 10 µM CGA or indoleacetaldehyde (IAld) treatments downregulated (p < 0.05) the mRNA levels of Tph1. In addition, 10 µM IAld or 100 µM ILA upregulated (p < 0.05) the expression of monoamine oxidase A (Maoa). However, 10 µM CGA or 100 µM PA downregulated (p < 0.05) Maoa expression. All selected phytochemicals and Trp metabolites upregulated (p < 0.05) the expression of Htr4 and Htr7 compared to that of the control group. VMA and CGA reduced (p < 0.05) the ratios of Htr1a/Htr7 and Htr4/Htr7. These findings may help to elucidate the effects of phytochemicals and Trp metabolites on the regulation of gut ion transport and 5-HT signaling-related gut homeostasis in health and disease.
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Cinamatos , Íleo , Serotonina , Transdução de Sinais , Triptofano , Animais , Serotonina/metabolismo , Camundongos , Íleo/metabolismo , Íleo/efeitos dos fármacos , Triptofano/metabolismo , Transdução de Sinais/efeitos dos fármacos , Cinamatos/farmacologia , Cinamatos/metabolismo , Transporte de Íons/efeitos dos fármacos , Masculino , Triptofano Hidroxilase/metabolismo , Triptofano Hidroxilase/genética , Ácido Clorogênico/farmacologia , Ácido Clorogênico/metabolismoRESUMO
Leymus chinensis (Trin.) Tzvel., also known as the "Alkali Grass", is a major forage grass in the eastern and northeastern steppe vegetation in the Songnen Prairie. It is of great practical significance for grassland management to understand the influence of animal saliva on L. chinensis during animal feeding. In this study, we used clipping and daubing animal saliva to simulate responses to grazing by L. chinensis, and analyzed the physiological and metabolomic changes in response to simulated animal feeding. Results showed that the effects of animal saliva on physiological and metabolic processes of the treated plants produced a recovery phenomenon. Moreover, the effects of animal saliva produced a large number of differential metabolites related to several known metabolic pathways, among which the flavonoid biosynthesis pathway has undergone significant and persistent changes. We posit that the potential metabolic mechanisms of L. chinensis in response to simulated animal feeding are closely related to flavonoid biosynthesis.