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Alzheimer's disease (AD) represents a devastating form of neurodegeneration, hallmarked by a relentless erosion of memory and cognitive faculties. One key player in this complex pathology is hydrogen sulfide (H2S), a gaseous neurotransmitter that is highly concentrated in the brain. Its fluctuating levels have been compellingly linked to the onset and progression of AD. Despite the availability of numerous fluorescent probes for detecting H2S, targeted imaging of this neurotransmitter within AD models remains underexplored. To bridge this gap, we have engineered an innovative near-infrared (NIR) "turn-on" fluorescent probe, designated as probe 1. Crafted around a dicyanoisophorone scaffold, the probe incorporates a strategic methoxy modification to facilitate a bathochromic spectral shift. Impressively, upon binding with H2S, probe 1 exhibited a robust 46-fold enhancement in fluorescence at a wavelength of 680 nm. We successfully deployed this probe to visualize both exogenous and endogenous H2S in living cells and zebrafish. Further, our pathogenic investigations have corroborated that diminished H2S levels are intricately linked to an escalation in amyloid plaque formation. Most crucially, we employed probe 1 to capture real-time images of H2S concentrations within the hippocampal tissue of AD mouse models. This revealed a significant depletion in H2S levels, thereby underscoring the probe's immense potential as an effective tool for the diagnosis and prevention of Alzheimer's disease.
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Oysters that filter feed can accumulate numerous pathogens, including viruses, which can serve as a valuable viral repository. As oyster farming becomes more prevalent, concerns are mounting about diseases that can harm both cultivated and wild oysters. Unfortunately, there is a lack of research on the viruses and other factors that can cause illness in shellfish. This means that it is harder to find ways to prevent these diseases and protect the oysters. This is part of a previously started project, the Dataset of Oyster Virome, in which we further study 30 almost complete genomes of oyster-associated CRESS DNA viruses. The replication-associated proteins and capsid proteins found in CRESS DNA viruses display varying evolutionary rates and frequently undergo recombination. Additionally, some CRESS DNA viruses have the capability for cross-species transmission. A plethora of unclassified CRESS DNA viruses are detectable in transcriptome libraries, exhibiting higher levels of transcriptional activity than those found in metagenome libraries. The study significantly enhances our understanding of the diversity of oyster-associated CRESS DNA viruses, emphasizing the widespread presence of CRESS DNA viruses in the natural environment and the substantial portion of CRESS DNA viruses that remain unidentified. This study's findings provide a basis for further research on the biological and ecological roles of viruses in oysters and their environment.
Assuntos
Brassicaceae , Vírus , DNA Viral/genética , Viroma , Vírus de DNA/genética , Vírus/genética , Filogenia , Genoma ViralRESUMO
Pyrazole carboxamide is widely utilized in agricultural crop protection. In this research, we synthesized two classes of compounds, namely, pyrazole-5-carboxamide (4a) and pyrazole-4-carboxamide (4b), which are distinguished by the inclusion of the N-1-(6-aryloxypyridin-3-yl) ethylamine skeleton. This design was inspired by the frequent occurrence of diaryl ether modules in pesticide molecules. The bioassay results revealed that some compounds 4a exhibit higher insecticidal activity (IA) than 4b, while some compounds 4b display stronger fungicidal activity compared to 4a. This suggests that pyrazolyl plays a crucial role in determining the selectivity of these compounds toward different biological species. Notably, compound 4a-14 not only retains the potent activity of tolfenpyrad, the exact lead compound of 4a, against Lepidoptera pest Plutella xylostella and Thysanoptera pest Frankliniella occidentalis but also shows excellent IA against pests with piercing-sucking mouthparts, such as Aphis craccivora Koch and Nilaparvata lugens. This research has important implications for the control of pests with piercing-sucking mouthparts and the development of new insecticides and fungicides. The findings highlight the potential of inhibitory complex I as an effective control target for these pests, particularly those that have developed resistance to traditional insecticides. Additionally, it sheds light on the binding mode of 4b-11 and complex II, which serves as a negative reference for the design of SDHI fungicides. The study emphasizes the significance of pyrazolyl in determining selectivity in biological species and identifies avenues for future research in enhancing the biological activity of amino modules. The discovery of (S)-4a-14 not only presents a promising candidate compound for pesticide development but also provides valuable insights into the inhibitory effect of a respiratory chain complex on piercing-sucking insect pests. These findings have important implications in both theory and practice, offering new directions for pest control strategies and pesticide and fungicide development.
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Fungicidas Industriais , Inseticidas , Lepidópteros , Animais , Inseticidas/química , Estrutura Molecular , Fungicidas Industriais/química , Insetos , Pirazóis/química , Relação Estrutura-AtividadeRESUMO
In the present study, we conducted optimization of pyramoxadone and synthesized a series of novel oxazolidinediones. Antifungal assays showed that these compounds exhibited moderate to excellent antifungal activity against various pathogens. Further SAR analysis revealed that the introduction of substituents to the benzene ring of the phenoxy group or the inclusion of bulky groups, such as tert-butyl, on the aniline moiety, had a detrimental effect on the activity. However, the inclusion of fluorine atoms in the aniline moiety significantly enhanced the antifungal efficacy. Notably, compound 2-4 displayed significantly higher activity compared to both pyramoxadone and famoxadone against R. solani, B. cinerea, S. sclerotiorum, and P. oryzae, where it demonstrated EC50 values of 1.78, 2.47, 2.33, and 2.23 µg/mL, respectively. Furthermore, compound 2-4 exhibited potent protective and curative effects against the tomato gray mold in vivo. A mechanistic investigation revealed that compound 2-4 significantly impacted the mycelial morphology, inhibited spore germination, and impeded mycelial respiration, ultimately leading to the inhibition of pathogenic fungus growth. These findings indicate that compound 2-4 has the potential to serve as a cyt bc1 inhibitor and should be further investigated for development.
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Synaptotagmins (SYTs), constitute a family of 17 membrane-trafficking protein, palying crucial roles in the development and progression of human cancers. However, only very few studies have investigated the expression profile and prognostic values of SYTs family members in gastric cancer (GC). Therefore, we comprehensively evaluated the expression, methylation, prognosis and immune significance of SYTs family members through bioinformatics analysis from the online databases in GC. The expressions of SYT4, SYT9, and SYT14 were up-regulated, and negatively associated with their methylation levels in GC. Both the over-expression of SYT4, SYT9 and SYT14 and their hypomethylation levels contributed to an unsatisfactory overall survival (OS) and progression-free survival (PFS) in GC. Moreover, the low expressions of several methylation cg sites (cg02795029, cg07581146, cg15149095, cg19922137, cg25371503, cg26158959, cg02269161, cg03226737, cg08185661, cg16437728, cg22723056 and cg24678137) were significantly correlated with an unfavorable OS and PFS in GC. Furthermore, the expression of SYT4, SYT9 and SYT14 played a pivotal role in immune cells infiltration in GC. Collectively, our current finding suggested that SYT4, SYT9 and SYT14 might be potent prognostic indictors and promising immunotherapeutic targets for GC patients.
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Metilação de DNA/genética , Neoplasias Gástricas , Sinaptotagminas/genética , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Sinaptotagminas/química , Sinaptotagminas/metabolismo , Transcriptoma/genéticaRESUMO
Carbon monoxide (CO), a gaseous signal molecule, plays a crucial role in biological systems. With the aim of unraveling its biological functions, a novel fluorescent probe for sensing CO was rationally designed and synthesized based on a coumarin derivative fluorophore merging tetrahydroquinoxaline unit and five-membered pyrrolidine. This fluorescent probe demonstrated a large Stokes shift (Δλ = 132 nm), high quantum yield, red emission, high sensitivity and selectivity for CO with remarkable fluorescence turn-on. And the detection limit for CORM-3 is as low as 31.2 nM with the linear range of 0-30 µM. More importantly, this novel probe has been successfully applied to the fluorescence imaging of CO in HepG2 cells and zebrafish, providing a useful approach for the further understanding of the physiological and pathological roles of CO in living systems.
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Monóxido de Carbono , Corantes Fluorescentes , Animais , Cumarínicos , Fluorescência , Peixe-ZebraRESUMO
Worldwide, gastric cancer (GC) represents the fifth most common cancer for incidence and the third leading cause of death in developed countries. Despite the development of combination chemotherapies, the survival rates of GC patients remain unsatisfactory. The reprogramming of energy metabolism is a hallmark of cancer, especially increased dependence on aerobic glycolysis. In the present review, we summarized current evidence on how metabolic reprogramming in GC targets the tumor microenvironment, modulates metabolic networks and overcomes drug resistance. Preclinical and clinical studies on the combination of metabolic reprogramming targeted agents and conventional chemotherapeutics or molecularly targeted treatments [including vascular endothelial growth factor receptor (VEGFR) and HER2] and the value of biomarkers are examined. This deeper understanding of the molecular mechanisms underlying successful pharmacological combinations is crucial in finding the best-personalized treatment regimens for cancer patients.
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The monitoring of heavy transition metals has increasingly attracted great attention because they pollute the environment and have unique physiological functions. Chemosensors are useful tools for monitoring heavy transition metals due to their simple visualization, excellent sensitivity and high selectivity. Herein, we have developed a novel chemosensor for the detection of water-soluble Cu2+ and Ni2+ species with different mechanisms, and low detection limits of 2.1 nM for Cu2+ and 1.2 nM for Ni2+ were obtained. The colorimetric probe CPH has been applied to qualitative and quantitative detection of Cu2+ and Ni2+ species in real samples.
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Aminopiridinas/química , Cobre/sangue , Cumarínicos/química , Indicadores e Reagentes/química , Níquel/sangue , Poluentes Químicos da Água/análise , Aminopiridinas/síntese química , Colorimetria/métodos , Corantes/síntese química , Corantes/química , Cobre/química , Cumarínicos/síntese química , Água Potável/análise , Humanos , Indicadores e Reagentes/síntese química , Lagos/análise , Limite de Detecção , Níquel/química , Rios/química , Espectrofotometria/métodos , Poluentes Químicos da Água/químicaRESUMO
The aim of the study was to describe the refinements to the classic enlarged translabyrinthine approach (ETLA) by modifying the bony dissection range of temporal bone and to analyze the main outcomes achieved in a series of vestibular schwannoma (VS) cases submitted to microsurgery by ETLA. This was a retrospective study of 382 patients who underwent VS surgical removal via ETLA between January 2001 and December 2012. Among those cases, 332 were via classic ETLA, while 28 cases were via ETLA with blind sac technique and middle ear eradication and 22 via transotic approach. Total tumor removal was achieved in 368 cases, whereas near total removal in 11 patients and subtotal in 3 patients. In cases of large VS (>3 cm) via classic ETLA, good short-term and long-term facial nerve function (HB I-II) was gained in 27.8 % (32/115) and 42.6 % (49/115) cases, respectively, meanwhile in VS operated via blind sac technique, good short-term (p = 0.048) and long-term (p = 0.044) facial nerve function was reached in 44.0 % (22/50) and 60.0 % (30/50) cases, respectively. Postoperative facial nerve function was proved to be better in modified ETLA group. CSF leakage occurred in 16 (4.2 %) patients via classic ETLA. In 115 cases of large VS (>3 cm), postoperative CSF leakage occurred in 10 (8.7 %) patients. Whereas in 50 cases via blind sac technique, none developed CSF leakage (p = 0.03). The incidence of CSF leakage was lower in modified ETLA group. Our refinements to classic ETLA by changing the temporal bone resection range provide a wide surgical field, well prevention of CSF leakage and preservation of facial nerve function in large VS.
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Vazamento de Líquido Cefalorraquidiano/prevenção & controle , Tomada de Decisão Clínica , Dissecação/efeitos adversos , Microcirurgia/efeitos adversos , Neuroma Acústico/cirurgia , Osso Temporal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vazamento de Líquido Cefalorraquidiano/diagnóstico , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Dissecação/métodos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/patologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Osso Temporal/patologia , Adulto JovemRESUMO
OBJECTIVE: Cavernous hemangioma of the internal auditory canal (IAC) is an extremely rare type of tumor, and only 50 cases have been reported in the literature prior to this study. The aim in this study was to describe the symptomatology, radiological features, and surgical outcomes for patients with cavernous hemangioma of the IAC and to discuss the diagnostic criteria and treatment strategy for the disease. METHODS: The study included 6 patients with cavernous hemangioma of the IAC. All patients presented with sensorineural hearing loss and tinnitus, and 2 also suffered from vertigo. Five patients reported a history of facial symptoms with hemispasm or palsy: 3 had progressive facial weakness, 1 had a hemispasm, and 1 had a history of recovery from sudden facial paresis. All patients underwent CT and MRI to rule out intracanalicular vestibular schwannomas and facial nerve neuromas. Five patients had their tumors surgically removed, while 1 patient, who did not have facial problems, was followed up with a wait-and-scan approach. RESULTS: All patients had a presurgical diagnosis of cavernous hemangioma of the IAC, which was confirmed pathologically in the 5 patients who underwent surgical removal of the tumor. The translabyrinthine approach was used to remove the tumor in 4 patients, while the middle cranial fossa approach was used in the 1 patient who still had functional hearing. Tumors adhered to cranial nerves VII and/or VIII and were difficult to dissect from nerve sheaths during surgeries. Complete hearing loss occurred in all 5 patients. In 3 patients, the facial nerve could not be separated from the tumor, and primary end-to-end anastomosis was performed. Intact facial nerve preservation was achieved in 2 patients. Patients were followed up for at least 1 year after treatment, and MRI showed no evidence of tumor regrowth. All patients experienced some level of recovery in facial nerve function. CONCLUSIONS: Cavernous hemangioma of the IAC can be diagnosed preoperatively through analysis of clinical features and neuroimaging. Early surgical intervention may preserve the functional integrity of the facial nerve and provide a better outcome after nerve reconstruction. However, preservation of functional hearing may not be achieved, even with the retrosigmoid or middle cranial fossa approaches. The translabyrinthine approach seems to be the most appropriate approach overall, as the facial nerve can be easily located and reconstructed.
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Meato Acústico Externo , Neoplasias da Orelha/diagnóstico , Neoplasias da Orelha/terapia , Hemangioma Cavernoso/diagnóstico , Hemangioma Cavernoso/terapia , Adulto , Estudos de Coortes , Neoplasias da Orelha/patologia , Paralisia Facial/etiologia , Feminino , Perda Auditiva Neurossensorial/etiologia , Hemangioma Cavernoso/patologia , Humanos , Masculino , Zumbido/etiologia , Adulto JovemRESUMO
OBJECTIVE: To explore the effects of obstructive sleep apnea syndrome (OSAS) on children's growth by the study of identical twins. STUDY DESIGN: Seventeen cases of nonobese children with OSAS were included in this study. The control group was their identical twin sibling, who had no signs of OSAS. Data including height, weight, and serum insulin-like growth factor 1 levels were analyzed before tonsillectomy and adenoidectomy (T&A) and at 3, 6, and 12 months after surgery. RESULTS: The mean apnea hyponea index was 3.9 times/hour in patients with OSAS and became normal after surgery. Minimum oxygen saturation gradually increased after T&A. The height and weight of the OSAS group before T&A was lower than the control group. During the follow-up period, height and weight increased but were lower than the control group. Serum insulin-like growth factor 1 levels in the OSAS group before T&A were lower than the control group. The level was significantly increased 3 months after T&A. CONCLUSION: OSAS impairs growth and development. Significant growth recovery occurs after T&A, and early surgical intervention is an important factor for improvement in growth.
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Desenvolvimento Infantil/fisiologia , Doenças em Gêmeos , Apneia Obstrutiva do Sono/fisiopatologia , Gêmeos , Adenoidectomia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Polissonografia , Prognóstico , Estudos Retrospectivos , Apneia Obstrutiva do Sono/cirurgia , TonsilectomiaRESUMO
Patients who had uncontrolled pain with carbamazepine therapy and those who suffered adversely from its side effects were selected for this safe, simple and repeatable surgery. Pain-free periods were achieved for at least 2 years. Functional difficulty was not experienced in the affected numb areas. When it recurred, pain was less intense and was better controlled with a reduced dosage of carbamazepine. In four cases, after avulsion of the involved nerves, a suitable-sized titanium screw was inserted into the mental and infra-orbital foramina. Obturation of the foramen prevented nerve regeneration, which further prolonged the pain remission period.