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Topological electronic flattened bands near or at the Fermi level are a promising route towards unconventional superconductivity and correlated insulating states. However, the related experiments are mostly limited to engineered materials, such as moiré systems1-3. Here we present a catalogue of the naturally occuring three-dimensional stoichiometric materials with flat bands around the Fermi level. We consider 55,206 materials from the Inorganic Crystal Structure Database catalogued using the Topological Quantum Chemistry website4,5, which provides their structural parameters, space group, band structure, density of states and topological characterization. We combine several direct signatures and properties of band flatness with a high-throughput analysis of all crystal structures. In particular, we identify materials hosting line-graph or bipartite sublattices-in either two or three dimensions-that probably lead to flat bands. From this trove of information, we create the Materials Flatband Database website, a powerful search engine for future theoretical and experimental studies. We use the database to extract a curated list of 2,379 high-quality flat-band materials, from which we identify 345 promising candidates that potentially host flat bands with charge centres that are not strongly localized on the atomic sites. We showcase five representative materials and provide a theoretical explanation for the origin of their flat bands close to the Fermi energy using the S-matrix method introduced in a parallel work6.
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Activatable near-infrared (NIR) fluorescent probes possess advantages of high selectivity, sensitivity, and deep imaging depth, holding great potential in the early diagnosis and prognosis assessment of tumors. However, small-molecule fluorescent probes are largely limited due to the rapid diffusion and metabolic clearance of activated fluorophores in vivo. Herein, we propose an efficient and reproducible novel strategy to construct activatable fluorescent nanoprobes through bioorthogonal reactions and the strong gold-sulfur (Au-S) interactions to achieve an enhanced permeability and retention (EPR) effect, thereby achieving prolonged and high-contrast tumor imaging in vivo. To demonstrate the merits of this strategy, we prepared an activatable nanoprobe, hCy-ALP@AuNP, for imaging alkaline phosphatase (ALP) activity in vivo, whose nanoscale properties facilitate accumulation and long-term retention in tumor lesions. Tumor-overexpressed ALP significantly increased the fluorescence signal of hCy-ALP@AuNP in the NIR region. More importantly, compared with the small-molecule probe hCy-ALP-N3, the nanoprobe hCy-ALP@AuNP significantly improved the distribution and retention time in the tumor, thus improving the imaging window and accuracy. Therefore, this nanoprobe platform has great potential in the efficient construction of biomarker-responsive fluorescent nanoprobes to realize precise tumor diagnosis in vivo.
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Corantes Fluorescentes , Neoplasias , Humanos , Corantes Fluorescentes/metabolismo , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodosRESUMO
Zygotic genomic activation (ZGA) is a landmark event in the maternal-to-zygotic transition (MZT), and the regulation of ZGA by maternal factors remains to be elucidated. In this study, the depletion of maternal ring finger protein 114 (RNF114), a ubiquitin E3 ligase, led to developmental arrest of two-cell mouse embryos. Using immunofluorescence and transcriptome analysis, RNF114 was proven to play a crucial role in major ZGA. To study the underlying mechanism, we performed protein profiling in mature oocytes and found a potential substrate for RNF114, chromobox 5 (CBX5), ubiquitylation and degradation of which was regulated by RNF114. The overexpression of CBX5 prevented embryonic development and impeded major ZGA. Furthermore, TAB1 was abnormally accumulated in mutant two-cell embryos, which was consistent with the result of in vitro knockdown of Rnf114. Knockdown of Cbx5 or Tab1 in maternal RNF114-depleted embryos partially rescued developmental arrest and the defect of major ZGA. In summary, our study reveals that maternal RNF114 plays a precise role in degrading some important substrates during the MZT, the misregulation of which may impede the appropriate activation of major ZGA in mouse embryos.
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Desenvolvimento Embrionário/fisiologia , Genoma , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Zigoto/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/genética , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Fatores de Transcrição/metabolismo , TranscriptomaRESUMO
The poor efficiency and low immunogenicity of photodynamic therapy (PDT), and the immunosuppressive tumor microenvironment (ITM) lead to tumor recurrence and metastasis. In this work, TCPP-TER-Zn@RSV nanosheets (TZR NSs) that co-assembled from the endoplasmic reticulum (ER)-targeting photosensitizer TCPP-TER-Zn nanosheets (TZ NSs for short) and the autophagy promoting and indoleamine-(2, 3)-dioxygenase (IDO) inhibitor-like resveratrol (RSV) are fabricated to enhance antitumor PDT. TZR NSs exhibit improved therapeutic efficiency and amplified immunogenic cancer cell death (ICD) by ER targeting PDT and ER autophagy promotion. TZR NSs reversed the ITM with an increase of CD8+ T cells and reduce of immunosuppressive Foxp3 regulatory T cells, which effectively burst antitumor immunity thus clearing residual tumor cells. The ER-targeting TZR NSs developed in this paper presents a simple but valuable reference for high-efficiency tumor photodynamic immunotherapy.
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Autofagia , Retículo Endoplasmático , Imunoterapia , Fotoquimioterapia , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Fotoquimioterapia/métodos , Imunoterapia/métodos , Autofagia/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Nanoestruturas/química , Humanos , Linhagem Celular Tumoral , CamundongosRESUMO
OBJECTIVE: The purpose of this study is to investigate the role of high mobility group protein B1 (HMGB1) in placental development and fetal growth. METHODS: We employed the Cre-loxP recombination system to establish a placenta-specific HMGB1 knockout mouse model. Breeding HMGB1flox/flox mice with Elf5-Cre mice facilitated the knockout, leveraging Elf5 expression in extra-embryonic ectoderm, ectoplacental cone, and trophoblast giant cells at 12.5 days of embryonic development. The primary goal of this model was to elucidate the molecular mechanism of HMGB1 in placental development, assessing parameters such as placental weight, fetal weight, and bone development. Additionally, we utilized lentiviral interference and overexpression of HMGB1 in human trophoblast cells to further investigate HMGB1's functional role. RESULTS: Our findings indicate that the HMGB1flox/floxElf5cre/+ mouse displays fetal growth restriction, characterized by decreased placental and fetal weight and impaired bone development. The absence of HMGB1 inhibits autophagosome formation, impairs lysosomal degradation, and disrupts autophagic flux. Depletion of HMGB1 in human trophoblast cells also suppresses cell viability, proliferation, migration, and invasion by inhibiting the ERK signaling pathway. Overexpression of HMGB1 observed the opposite phenotypes. CONCLUSIONS: HMGB1 participates in the regulation of autophagy through the ERK signaling pathway and affects placental development.
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Autofagia , Proteína HMGB1 , Sistema de Sinalização das MAP Quinases , Placenta , Trofoblastos , Animais , Feminino , Trofoblastos/metabolismo , Trofoblastos/fisiologia , Autofagia/fisiologia , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Gravidez , Camundongos , Sistema de Sinalização das MAP Quinases/fisiologia , Placenta/metabolismo , Humanos , Camundongos Knockout , Placentação/fisiologiaRESUMO
STUDY QUESTION: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. STUDY DESIGN, SIZE, DURATION: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS: The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. WIDER IMPLICATIONS OF THE FINDINGS: Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
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In the context of measurement-induced entanglement phase transitions, the influence of quantum noises, which are inherent in real physical systems, is of great importance and experimental relevance. In this Letter, we present a comprehensive theoretical analysis of the effects of both temporally uncorrelated and correlated quantum noises on entanglement generation and information protection. This investigation reveals that entanglement within the system follows q^{-1/3} scaling for both types of quantum noises, where q represents the noise probability. The scaling arises from the Kardar-Parisi-Zhang fluctuation with effective length scale L_{eff}â¼q^{-1}. More importantly, the information protection timescales of the steady states are explored and shown to follow q^{-1/2} and q^{-2/3} scaling for temporally uncorrelated and correlated noises, respectively. The former scaling can be interpreted as a Hayden-Preskill protocol, while the latter is a direct consequence of Kardar-Parisi-Zhang fluctuations. We conduct extensive numerical simulations using stabilizer formalism to support the theoretical understanding. This Letter not only contributes to a deeper understanding of the interplay between quantum noises and measurement-induced phase transition but also provides a new perspective to understand the effects of Markovian and non-Markovian noises on quantum computation.
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Photocatalytic benzylic C-H oxidation/cyclization of enaminones was efficiently achieved to afford oxazole derivatives under mild conditions. The oxygen in the oxazole ring originated from green oxidant molecular oxygen. The synthetic protocol features broad substrate scopes and good functional group tolerance. The combined experimental and theoretical studies reveal that in suit benzylic C-H oxidation/cyclization is involved in the reaction transformations.
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Oxazóis , Oxigênio , Ciclização , Estrutura Molecular , Oxirredução , Oxigênio/químicaRESUMO
BACKGROUND: To find out the incidence and risk factors of opaque bubble layer (OBL) in eyes with myopia and myopic astigmatism following femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE). METHODS: A total of 1076 eyes from 569 patients who had FS-LASIK or SMILE were included in the retrospective research. For each kind of surgery, eyes were separated into two groups: "OBL" groups and "no OBL" groups. In the FS-LASIK group, eyes that developed OBL were split into "hard OBL" and "soft OBL" groups. The incidence and size of OBL were analyzed after watching the surgical procedure videotaped during the operation and taking screenshots. Surgical parameters, including sphere, cylinder, keratometry, corneal thickness, flap thickness, cap thickness, lenticule thickness, and visual acuity, were compared. RESULTS: In the FS-LASIK surgery, the incidence of OBL was 63.2% (347 eyes). A thicker central corneal thickness (CCT) was the only independent risk factor affecting the OBL area (ß = 0.126, P = 0.019). One hundred and thirty of these eyes had hard OBL, and the flap thickness of these eyes was thinner than that of those with soft OBL (P = 0.027). In the SMILE group, 26.6% (140 eyes) developed OBL. A higher flat keratometry (K) and a thicker residual stromal thickness (RST) were risk factors affecting the OBL area (ß = 0.195, P = 0.024; ß = 0.281, P = 0.001). CONCLUSION: The incidence of OBL differs between the FS-LASIK surgery and the SMILE surgery. There are differences in the factors influencing OBL between the two surgeries.
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The evolution of the manufacturing sector coupled with advancements in digital twin technology has precipitated the extensive integration of digital twin robotic arms within the industrial domain. Notwithstanding this trend, there exists a paucity of studies examining the interaction of these robotic arms in virtual reality (VR) contexts from the user's standpoint. This paper delves into the virtual interaction of digital twin robotic arms by concentrating on effective guidance methodologies for the input of their target motion trajectories. Such a focus is pivotal to optimize input precision and efficiency, thus contributing to research on the virtual interaction interfaces of these robotic arms. During empirical evaluations, metrics related to human-machine interaction, such as objective operational efficiency, precision, and subjective workload, were meticulously quantified. Moreover, the influence of disparate guidance methods on the interaction experience of digital twin robotic arms and their corresponding scenarios was investigated. Consequent findings offer pivotal insights regarding the efficacy of these guidance methods across various scenarios, thereby serving as an invaluable guide for future endeavors aiming to bolster interactive experiences in devices akin to digital twin robotic arms.
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Procedimentos Cirúrgicos Robóticos , Humanos , Benchmarking , Comércio , Tecnologia Digital , IndústriasRESUMO
Inflammatory bowel disease (IBD) is an autoimmune disease that leads to severe bowel symptoms and complications. Currently, there is no effective treatment, and the exact cause of IBD remains unclear. In the last decades, numerous studies have confirmed that flavonoids can have a positive impact on the treatment of IBD. Therefore, this study investigated the protective effect of a flavonoid combination of apigenin and epigallocatechin-3-gallate (EGCG) on IBD. In vitro studies in which Caco-2 cell monolayers were incubated with different concentrations of flavonoids found that the flavonoid-treated group exhibited increased transepithelial electrical resistance (TEER) at high concentrations, indicating a protective effect on the barrier function of the intestinal epithelium. In vivo studies showed that flavonoids significantly attenuated inflammatory levels in both chronic and acute hapten-mediated experimental colitis models in a time- and dose-dependent manner. In addition, the activity of myeloperoxidase (MPO) and the level of proinflammatory cytokines in the colon tissue were significantly reduced. Interestingly, the levels of anti-inflammatory cytokines were also dramatically increased. Finally, flavonoids were found to positively modulate the composition of the gut microbiota in the colon. Therefore, a combination of flavonoids could be a promising therapeutic agent for the future adjunctive treatment of IBD.
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Colite , Doenças Inflamatórias Intestinais , Humanos , Animais , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Apigenina/farmacologia , Apigenina/uso terapêutico , Células CACO-2 , Colite/induzido quimicamente , Colite/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Citocinas , Inflamação/tratamento farmacológico , Sulfato de Dextrana , Modelos Animais de DoençasRESUMO
Inflammatory bowel disease (IBD) is a group of disorders that cause chronic non-specific inflammation in the gastrointestinal (GI) tract, primarily affecting the ileum and colon. The incidence of IBD has risen sharply in recent years. Despite continuous research efforts over the past decades, the aetiology of IBD is still not fully understood and only a limited number of drugs are available for its treatment. Flavonoids, a ubiquitous class of natural chemicals found in plants, have been widely used in the prevention and treatment of IBD. However, their therapeutic efficacy is unsatisfactory due to poor solubility, instability, rapid metabolism, and rapid systemic elimination. With the development of nanomedicine, nanocarriers can efficiently encapsulate various flavonoids and subsequently form nanoparticles (NPs), which greatly improves the stability and bioavailability of flavonoids. Recently, progress has also been made in the methodology of biodegradable polymers that can be used to fabricate NPs. As a result, NPs can significantly enhance the preventive or therapeutic effects of flavonoids on IBD. In this review, we aim to evaluate the therapeutic effect of flavonoid NPs on IBD. Furthermore, we discuss possible challenges and future perspectives.
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Doenças Inflamatórias Intestinais , Nanopartículas , Humanos , Flavonoides/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colo , Polímeros/farmacologiaRESUMO
BACKGROUND: Aiming at unbalanced coordination of irrigation and fertilization of winter wheat in the eastern North China Plain, this study investigated the effect of fertigation on wheat grain yield, grain quality, and water use efficiency (WUE) and nitrogen use efficiency (NUE) in seven irrigation and nitrogen (N) fertilization treatments. Under the field conditions, the traditional irrigation and fertilization method (total N amount of 240 kg ha-1 , application of 90 kg ha-1 at sowing irrigation at jointing and anthesis, with topdressing N of 150 kg ha-1 at jointing) was used as the control (CK). There were six fertigation treatments to compare with CK. For the fertigation treatments, the total amount of N application was set to 180 kg ha-1 and 90 kg ha-1 was applied at sowing and the remaining N fertilizer was applied through fertigation. The fertigation treatments included the combination of three fertigation frequencies (S2: at jointing and anthesis; S3: at jointing, anthesis, and filling; S4: at jointing, booting, anthesis, and filling) and two soil water replenishment depths (M1: 0-10 cm; M2: 0-20 cm). The six treatments were S4M2, S4M1, S3M2, S3M1, S2M2, and S2M1. RESULT: Compared with CK, three and four irrigations (S3 and S4) maintained higher soil and plant analyzer development value and photosynthetic rate after anthesis. These treatments increased soil water extraction while reducing crop water consumption during the whole growing season, promoted the assimilation and translocation of dry matter into the grain after anthesis, and increased the 1000-grain weight. These fertigation treatments also significantly increased WUE and NUE. At the same time, the high grain protein content and grain protein yield were maintained. Compared with the CK, high wheat yield was maintained by S3M1 (drip irrigation fertilizer at the jointing, anthesis, and filling, and the depth of the moisture replenishment is 10 cm). This fertigation treatment significantly increased yield by 7.6%, WUE by 30%, NUE by 41.4%, and partial factor productivity from applied N by 25.8%; grain yield, grain protein content, and grain protein yield also performed well. CONCLUSION: Consequently, S3M1 treatment was suggested to be a good practice for reducing irrigation water and N input in the eastern North China Plain. © 2023 Society of Chemical Industry.
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Proteínas de Grãos , Triticum , Estações do Ano , Triticum/metabolismo , Água/análise , Nitrogênio/metabolismo , Fertilizantes , Irrigação Agrícola/métodos , Biomassa , Grão Comestível/química , China , Solo/químicaRESUMO
H2O2 and polarity are quite important in many physiological and pathological processes, and their relationship is complicated and obscure for researchers. Thus, it is vital and challenging to achieve simultaneous detection of H2O2 and polarity in vivo. Herein, the first naphthalimide-triphenylamine-based dual-site fluorescent probe NATPA is developed for simultaneously imaging intracellular H2O2 and polarity fluctuations. It exhibits excellent sensitivity (LOD = 44 nM), selectivity, and fast response (15 min) to H2O2 and a superior capacity for detecting polarity upon the intramolecular charge transfer (ICT) effect. Besides, the probe displays low cytotoxicity and lipid droplet targeting and is further applied in imaging H2O2 and polarity fluctuations in HepG2 and L-02 cells, so that NATPA is qualified to distinguish cancer cells from normal cells. This research contributes a new design principle for the construction of dual-site fluorescent probes for simultaneously detecting active molecules and polarity.
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Corantes Fluorescentes , Peróxido de Hidrogênio , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Gotículas Lipídicas , Naftalimidas/toxicidadeRESUMO
BACKGROUND: The purpose of this study was to investigate the ability of differential diagnosis of prostate specific antigen decline rate (PSADR) per week, degree of prostatic collapse (DPC) and tissue signal rate of prostate (TSRP) between prostatitis and prostate cancer. METHODS: The clinical data of 92 patients [prostate specific antigen (PSA) > 10 ng/mL] who underwent prostate biopsy in the Department of Urology, the Second Affiliated Hospital of Xi 'an Jiaotong University from May 2017 to April 2020 were reviewed retrospectively. They were divided into two groups, prostatitis group (n = 42) and prostate cancer (PCa) group (n = 50), according to pathological results. Parameters, like patient characteristics, PSADR, DPC, TSRP and infectious indicators, were compared and analyzed by t test or non-parametric test to identify if there were significant differences. The thresholds of parameters were determined by the receiver operating characteristic curve (ROC), and the data were analyzed to investigate the diagnostic value in distinguishing of prostatitis and prostate cancer. RESULTS: There were statistical differences in age, PSADR, DPC, TSRP, neutrophil percentage in serum, white blood cell (WBC) in urine and prostate volume between prostatitis group and PCa group (P < 0.001, < 0.001, = 0.001, 0.001, 0.024, 0.014, < 0.001 respectively). There was no statistical difference in serum WBC count, serum neutrophil count, monocyte percentage and urine bacterial count between two groups (P = 0.089, 0.087, 0.248, 0.119, respectively). Determined by ROC curve, when the thresholds of PSADR per week as 3.175 ng/mL/week, DPC as 1.113, TSRP as 2.708 were cutoffs of distinguishing prostatitis and prostate cancer. When combining these three indexes to diagnose, the accuracy rate of diagnosis of prostatitis was 78.85%, the accuracy rate of diagnosis of prostate cancer was 97.50%. Univariate analysis suggested that PSADR, DPC and TSRP played an important role in differentiating prostate cancer from prostatitis (P < 0.05), multivariate analysis suggested PSADR > 3.175 might be good indicators when distinguishing prostate disease with prostatitis (OR = 14.305, 95%CI = 3.779 ~ 54.147), while DPC > 1.113 and TSRP > 2.708 might be associated with a higher risk of prostate cancer (OR = 0.151, 95%CI = 0.039 ~ 0.588; OR = 0.012, 95%CI = 0.005 ~ 0.524, respectively). CONCLUSION: The combination of PSADR per week, DPC, and TSRP might be helpful to distinguish prostate cancer and prostatitis, and can reduce unnecessary invasive and histological procedure.
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Neoplasias da Próstata , Prostatite , Humanos , Masculino , Próstata/patologia , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Prostatite/diagnóstico , Prostatite/patologia , Estudos RetrospectivosRESUMO
Schizophrenia is a severe neuropsychiatric disorder with core features including hallucinations, delusions, and cognition deficits. Accumulating evidence has implicated abnormal DNA methylation in the development of schizophrenia. However, the mechanisms by which DNA methylation changes alter the risk for schizophrenia remain largely unknown. We recently carried out a DNA methylome study of peripheral blood samples from 469 first-episode patients with schizophrenia and 476 age- and gender-matched healthy controls of Han Chinese origin. Genomic DNA methylation patterns were quantified using an Illumina Infinium Human MethylationEPIC BeadChip. We identified multiple differentially methylated positions (DMPs) and regions between patients and controls. The most significant DMPs were annotated to genes C17orf53, THAP1 and KCNQ4 (KV7.4), with Bonferroni-adjusted P values of [Formula: see text], [Formula: see text], and [Formula: see text], respectively. In particular, KCNQ4 encodes a voltage-gated potassium channel of the KV7 family, which is linked to neuronal excitability. The genes associated with top-ranked DMPs also included many genes involved in nervous system development, such as LIMK2 and TMOD2. Gene ontology analysis of the differentially methylated genes further identified strong enrichment of neuronal networks, including neuron projection extension, axonogenesis and neuron apoptotic process. Finally, we provided evidence that schizophrenia-associated epigenetic alterations co-localize with genetic susceptibility loci. By focusing on first-episode schizophrenia patients, our investigation lends particularly strong support for an important role of DNA methylation in schizophrenia pathogenesis unconfounded by the effects of long-term antipsychotic medication or disease progression. The observed DNA methylation aberrations in schizophrenia patients could potentially provide a valuable resource for identifying diagnostic biomarkers and developing novel therapeutic targets to benefit schizophrenia patients.
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Metilação de DNA , Esquizofrenia , Povo Asiático , Células Sanguíneas , China , Ilhas de CpG/genética , Metilação de DNA/genética , Epigênese Genética , Humanos , Esquizofrenia/genéticaRESUMO
RESEARCH QUESTION: Does 4,4'-dimethoxychalcone (DMC), a natural antioxidant compound, effectively improve the quality of postovulatory ageing (POA) oocytes? DESIGN: Freshly ovulated MII oocytes were cultured in 10-µM DMC for 12 h in vitro. Reactive oxygen species (ROS) production, apoptosis rate, mitochondrial distribution, formation of the actin cap, and fertilization and development potential of POA oocytes, were studied. The change of autophagy level was detected, and the autophagy inhibitor 3-methyladenine (3-MA) was used to establish the relationship between DMC and autophagy. RESULTS: DMC supplementation eliminated the accumulated ROS (P < 0.0001) and ROS dependent 4 hydroxynonenal products (Pâ¯=â¯0.0399), and decreased apoptosis (Pâ¯=â¯0.0033), reduced abnormal mitochondrion distribution (Pâ¯=â¯0.0280), improved mitochondrial membrane potential (Pâ¯=â¯0.0135) and restored the formation of the actin cap (Pâ¯=â¯0.0487), thus improving fertilization ability (Pâ¯=â¯0.0156) and developmental potential (Pâ¯=â¯0.0130) in POA oocytes. The role autophagy plays in the effects of DMC supplementation was investigated. The immunofluorescence results showed that POA leads to the accumulation of SQSTM1/p62 (Pâ¯=â¯0.0083) but DMC supplementation could eliminate this (P < 0.0001). The western blot result of p62 protein was similar to the immunofluorescence results of the POA group (Pâ¯=â¯0.0441) and DMC supplementation group (Pâ¯=â¯0.0154). After inhibiting autophagy by 3-MA, the DMC supplementation group could no longer eliminate the accumulation of ROS (Pâ¯=â¯0.1704). CONCLUSIONS: DMC supplementation activates autophagy to protect oocytes from postovulatory ageing. This approach can feasibly improve the reproductive outcome of ART.
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Actinas , Oócitos , Actinas/metabolismo , Animais , Humanos , Potencial da Membrana Mitocondrial , Camundongos , Ovulação/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Axially chiral aldehydes have received increasing attention in enantioselective catalysis. However, only very few catalytic methods have been developed to construct structurally diverse axially chiral aldehydes. We herein describe an NHC-catalyzed atroposelective esterification of biaryl dialdehydes as a general and practical strategy for the construction of axially chiral aldehydes. Mechanistic studies indicate that coupling proceeds through a novel combination of NHC-catalyzed desymmetrization of the dialdehydes and kinetic resolution. This protocol features excellent enantioselectivity, mild conditions, good functional-group tolerance, and applicability to late-stage functionalization and provides a modular platform for the synthesis of axially chiral aldehydes and their derivatives.
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NOVELTY STATEMENT: AMF significantly increased the GRSP content and the macroaggregate proportion in soil, which contributed to reducing the Cd concentration in pore water and its leaching loss from soil.