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PURPOSE: To summarize the ultrasonographic features of head and neck Castleman disease (CD), and to clarify its diagnostic key points. METHODS: Seven patients with head and neck CD confirmed by histopathology were collected from Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The clinical features and ultrasound findings of the patients were evaluated. RESULTS: Of the 7 patients (1 male and 6 females), the mean age at diagnosis was 31.4 years (7-60 years). All the cases were hyaline vascular type. On ultrasound, 3 lesions (42.9%) were located in the parotid gland, 4 lesions(57.1%) in the neck. All the lesions presented as a solitary, well-defined and solid mass without calcification. The echogenicity was markedly hypoechoic in 1 case(14.3%) and hypoechoic in 6 cases (85.7%). Of the 7 CD cases, 4 cases (57.1%) were heterogeneous masses with linear echogenic septa. All lesions had mixed pattern in vascularity on color Doppler sonography. CONCLUSIONS: Most CDs in the head and neck represent as a markedly hypoechoic or hypoechoic lesion with mixed pattern in vascularity. The neoplasm may be characterized by the presence of linear echogenic septa within the mass.
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Hiperplasia do Linfonodo Gigante , Pescoço , Ultrassonografia , Humanos , Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Hiperplasia do Linfonodo Gigante/patologia , Masculino , Pescoço/diagnóstico por imagem , Adulto , Feminino , Ultrassonografia/métodos , Pessoa de Meia-Idade , Cabeça/diagnóstico por imagem , Criança , Adolescente , Ultrassonografia Doppler em Cores/métodos , Adulto Jovem , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/patologiaRESUMO
OBJECTIVE: To compare the differential impact of recombinant protein A immunoadsorption (PAIA) or therapeutic plasma exchange (TPE) on neurological functional improvement and quality of life in patients afflicted with severe acute neuroimmune diseases, including Guillain-Barré syndrome (GBS), myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), and anti-NMDA receptor encephalitis (NMDARE). METHODS: The retrospective study included 29 patients with moderate to severe disability (modified Rankin scale, mRS≥3) due to acute neuroimmune diseases at the second Xiangya hospital from January 2021 to January 2023. The clinical efficacy of PAIA and TPE in improving neurological function (ΔmRS≥1) and the difference in favorable functional outcomes (mRS 0-2) at three months were evaluated. The impact of both treatments on patients' health-related quality of life (HRQoL) was assessed using a visual analog scale (EQ-VAS) score ranging from 0 to 100. RESULTS: The findings revealed that the PAIA group exhibited a significantly higher rate of improvement in modified Rankin scale (mRS) scores (ΔmRS≥1) at the three-month follow-up compared to the TPE group (94.4 % vs. 54.5 %, p = 0.018). However, no statistically significant difference was observed between the two treatment modalities in terms of favorable neurological functional outcomes at the three-month mark. Furthermore, the PAIA group demonstrated a significantly higher EQ-VAS score at 14 days post-treatment compared to the TPE group (60.0 vs. 47.7, p = 0.017). CONCLUSION: In the short-term management of severe acute neuroimmune diseases, PAIA may present a greater probability of improving neurological function and facilitating an earlier enhancement of quality of life compared to TPE.
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Although messenger RNA translation is tightly regulated to preserve protein synthesis and cellular homeostasis, chronic exposure to interferon-γ (IFN-γ) in several cancers can lead to tryptophan (Trp) shortage via the indoleamine-2,3-dioxygenase (IDO)- kynurenine pathway and therefore promotes the production of aberrant peptides by ribosomal frameshifting and tryptophan-to-phenylalanine (W>F) codon reassignment events (substitutants) specifically at Trp codons. However, the effect of Trp depletion on the generation of aberrant peptides by ribosomal mistranslation in gastric cancer (GC) is still obscure. Here, it is shows that the abundant infiltrating lymphocytes in EBV-positive GC continuously secreted IFN-γ, upregulated IDO1 expression, leading to Trp shortage and the induction of W>F substitutants. Intriguingly, the production of W>F substitutants in EBV-positive GC is linked to antigen presentation and the activation of the mTOR/eIF4E signaling pathway. Inhibiting either the mTOR/eIF4E pathway or EIF4E expression counteracted the production and antigen presentation of W>F substitutants. Thus, the mTOR/eIF4E pathway exposed the vulnerability of gastric cancer by accelerating the production of aberrant peptides and boosting immune activation through W>F substitutant events. This work proposes that EBV-positive GC patients with mTOR/eIF4E hyperactivation may benefit from anti-tumor immunotherapy.
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Like all coronaviruses, infectious bronchitis virus, the causative agent of infectious bronchitis in chickens, exhibits a high mutation rate. Adaptive mutations that arise during the production of live attenuated vaccines against IBV often decrease virulence. The specific impact of these mutations on viral pathogenicity, however, has not been fully elucidated. In this study, we identified a mutation at the 3' end of the S gene in an IBV strain that was serially passaged in chicken embryos, and showed that this mutation resulted in a 9-aa truncation of the cytoplasmic tail (CT) of the S protein. This phenomenon of CT truncation has previously been observed in the production of attenuated vaccines against other coronaviruses such as the porcine epidemic diarrhea virus. We next discovered that the 9-aa truncation in the S protein CT resulted in the loss of the endoplasmic-reticulum-retention signal (KKSV). Rescue experiments with recombinant viruses confirmed that the deletion of the KKSV motif impaired the localization of the S protein to the endoplasmic-reticulum-Golgi intermediate compartment (ERGIC) and increased its expression on the cell surface. This significantly reduced the incorporation of the S protein into viral particles, impaired early subgenomic RNA and protein synthesis, and ultimately reduced viral invasion efficiency in CEK cells. In vivo experiments in chickens confirmed the reduced pathogenicity of the mutant IBV strains. Additionally, we showed that the adaptive mutation altered the TRS-B of ORF3 and impacted the transcriptional regulation of this gene. Our findings underscore the significance of this adaptive mutation in the attenuation of IBV infection and provide a novel strategy for the development of live attenuated IBV vaccines.
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Galinhas , Infecções por Coronavirus , Vírus da Bronquite Infecciosa , Doenças das Aves Domésticas , Glicoproteína da Espícula de Coronavírus , Vacinas Atenuadas , Animais , Vírus da Bronquite Infecciosa/genética , Vírus da Bronquite Infecciosa/patogenicidade , Embrião de Galinha , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Infecções por Coronavirus/virologia , Vacinas Atenuadas/genética , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/genética , Virulência , Vacinas Virais/genética , Vacinas Virais/imunologia , MutaçãoRESUMO
In this study, we present in vitro actions of pure commercial preparations of oxidized and/or dehydrated metabolites of cholesterol (OS) identified in the lipid fraction of Fraction B (FB) prepared from a catfish skin preparation on calcium transients and on the formation of human neutrophil extracellular traps (NETs). These investigations are part of an ongoing effort to understand the important roles these compounds play as components of FB when FB is applied to accelerate the healing of wounds and the healing of highly infected non-healing diabetic foot ulcers, without the use of antibiotics. Our aim was to determine potential therapeutic interventions for various disease states. Our results reveal interesting findings, demonstrating specific actions of the individual compounds. Compounds 7α-hydroxy-cholesterol (S3), Cholestane-3,5,6-triol (S5), 5-cholesten-3ß-ol-7-one (S8) and Cholesta-3,5 dien-7-one (S10) are inhibitory, while Cholesterol 5ß,6ß-epoxide (S4) and 5α-cholestane-3,6-dione (S11) activate the response for calcium influx in human neutrophils. A somewhat similar response is observed in dHL60 cell lines, where S3, S5, S7, S8, and cholesta-2,4-diene (S14) inhibit the calcium influx, although S4, S10, and S11 activate the response in this cell line. Furthermore, we observed a relationship between actions against NETosis and calcium transients. Interestingly, relative to the vehicle control, S3, Cholesta-3,5 diene (S9), and S14 appeared to significantly stimulate DNA release (NETosis), while S2, 7α-hydroxy-cholesterol (S6) and cholesta-3,5 dien-7-one (S10) caused lesser stimulation. We provide the IC50 activities for each compound tested in each assay. Calcium influx and NETs formation (NETosis) correlate with diseases exacerbation. These findings offer valuable insights into the potential therapeutic applications of individual OS for various diseases, highlighting their importance in future interventions.
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The microreactor with two types of immobilized enzymes, exhibiting excellent orthogonal performance, represents an effective approach to counteract the reduced digestion efficiency resulting from the absence of a single enzyme cleavage site, thereby impacting protein identification. In this study, we developed a hydrophilic dual-enzyme microreactor characterized by rapid mass transfer and superior enzymatic activity. Initially, we selected KIT-6 molecular sieve as the carrier for the dual-IMER due to its three-dimensional network pore structure. Modification involved co-deposition of polyethyleneimine (PEI) and acrylamide (AM) as amine donors, along with dopamine to enhance material hydrophilicity. Remaining amino and double bond functional groups facilitated stepwise immobilization of trypsin and Glu-C. Digestion times for bovine serum albumin (BSA) and bovine hemoglobin (BHb) on the dual-IMER were significantly reduced compared to solution-based digestion (1 min vs. 36 h), resulting in improved sequence coverage (91.30% vs. 82.7% for BSA; 90.24% vs. 89.20% for BHb). Additionally, the dual-IMER demonstrated excellent durability, retaining 96.08% relative activity after 29 reuse cycles. Enhanced protein digestion efficiency can be attributed to several factors: (1) KIT-6's large specific surface area, enabling higher enzyme loading capacity; (2) Its three-dimensional network pore structure, facilitating faster mass transfer and substance diffusion; (3) Orthogonality of trypsin and Glu-C enzyme cleavage sites; (4) The spatial effect introduced by the chain structure of PEI and glutaraldehyde's spacing arm, reducing spatial hindrance and enhancing enzyme-substrate interactions; (5) Mild and stable enzyme immobilization. The KIT-6-based dual-IMER offers a promising technical tool for protein digestion, while the PDA/PEI/AM-KIT-6 platform holds potential for immobilizing other proteins or active substances.
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Acrilamida , Dopamina , Enzimas Imobilizadas , Polietilenoimina , Soroalbumina Bovina , Tripsina , Polietilenoimina/química , Dopamina/química , Dopamina/metabolismo , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Acrilamida/química , Tripsina/química , Tripsina/metabolismo , Animais , Bovinos , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Porosidade , Interações Hidrofóbicas e Hidrofílicas , Hemoglobinas/química , Hemoglobinas/metabolismo , ProteóliseRESUMO
The nucleus tractus solitarii (NTS) plays a critical role in the homeostatic regulation of respiration, blood pressure, sodium consumption and metabolic processes. Despite their significance, the circuitry mechanisms facilitating these diverse physiological functions remain incompletely understood. In this study, we present a whole-brain mapping of both the afferent and efferent connections of Phox2b-expressing and GABAergic neurons within the NTS. Our findings reveal that these neuronal populations not only receive monosynaptic inputs primarily from the medulla oblongata, pons, midbrain, supra-midbrain and cortical areas, but also mutually project their axons to these same locales. Moreover, intense monosynaptic inputs are received from the central amygdala, the paraventricular nucleus of the hypothalamus, the parasubthalamic nucleus and the intermediate reticular nucleus, along with brainstem nuclei explicitly engaged in respiratory regulation. In contrast, both neuronal groups extensively innervate brainstem nuclei associated with respiratory functions, although their projections to regions above the midbrain are comparatively limited. These anatomical findings provide a foundational platform for delineating an anatomical framework essential for dissecting the specific functional mechanisms of these circuits.
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OBJECTIVE: Alzheimer's disease (AD) has become a significant global concern, but effective drugs able to slow down AD progression is still lacked. Electroacupuncture (EA) has been demonstrated to ameliorate cognitive impairment in individuals with AD. However, the underlying mechanisms remains poorly understood. This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD. METHODS: APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu (BL 23) and Baihui (GV 20). Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus (DRN). Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests. Golgi staining, western blot, and immunostaining were utilized to determine EA-induced neuroprotection. RESULTS: EA at Shenshu (BL 23) and Baihui (GV 20) effectively ameliorated learning and memory impairments in APP/PS1 mice. EA attenuated dendritic spine loss, increased the expression levels of PSD95, synaptophysin, and brain-derived neurotrophic factor in hippocampus. Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B. Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory. CONCLUSION: EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN. Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.
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Substituted tetrahydrofuran derivatives were designed and synthesized to serve as the P2 ligand for a series of potent HIV-1 protease inhibitors. Both enantiomers of the tetrahydrofuran derivatives were synthesized stereoselectivity in optically active forms using lipase-PS catalyzed enzymatic resolution as the key step. These tetrahydrofuran derivatives are designed to promote hydrogen bonding and van der Waals interactions with the backbone atoms in the S2 subsite of the HIV-1 protease active site. Several inhibitors displayed very potent HIV-1 protease inhibitory activity. A high-resolution X-ray crystal structure of an inhibitor-bound HIV-1 protease provided important insight into the ligand binding site interactions in the active site.
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In order to study the toxic effect and mechanism of triptolide(TP) on the reproductive system of female rats with â ¡ type collagen induced arthritis(CIA), 50 SD rats were randomly divided into normal control group, CIA model group, and three groups receiving TP tablets at clinically equivalent doses of 0. 5, 1, and 2 times, respectively(with TP dosages of 3. 75, 7. 5, and 15 µg·kg~(-1)·d~(-1)), each comprising 10 rats. Intragastric administration was started on the day after the first immunization, once a day, for 42 days.The results were taken on the 21st and 42nd days to calculate the uterine and ovarian organ indexes; pathological and morphological changes in uterus and ovaries were observed under a light microscope; and the levels of estradiol(E_2) and cytochrome P450A1(aromatase,CYP19A1) in ovarian homogenate were detected by ELISA. Furthermore, immunohistochemistry was employed to detect the expression levels of transforming growth factor ß3( TGFß3) pathway-related proteins, mothers against decapentaplegic homolog 3(Smad3) and steroidogenic factor-1(SF-1) in ovarian tissues. In vitro, the mouse Chinese hamster ovary(CHO) cell line was established, and after 24 hours of TP administration(30, 60, 120 nmol·L~(-1)), cell proliferation was detected by the thiazolyl blue tetrazolium bromide(MTT) method, apoptosis by the flow cytometry, and TGFß3, Smad3 and SF-1 protein expression in cells by the Western blot method, and the nuclear entry of SF-1 was detected by immunofluorescence. The results showed that compared with the CIA model group, all TP administration groups showed decreased number of uterine glands, total follicles, mature follicles, and corpus luteum on days 21 and 42 of administration, but there was no statistical difference, and only the administration of 2 times the clinically equivalent dose of TP could significantly increase the number of atretic follicles at 42 days of administration. TP at 3. 75 µg·kg-1·d-1significantly reduced the level of E_2 at 21 days of administration and the expression of TGFß3 and Smad3 factors in ovarian tissues,but had no significant effect on the rate-limiting enzyme in estrogen synthesis CYP19A1. TP at 7. 5 and 15 µg·kg~(-1)·d~(-1) significantly reduced the expression of SF-1 regardless of administration for 21 days or 42 days. TP can significantly promote ovarian cell apoptosis in vitro, with apoptosis mainly concentrated in the late stage of apoptosis after 24 hours of administration. In addition, 60 nmol·L~(-1) TP significantly reduced the protein expression of TGFß3, Smad3 and SF-1 in a dose-dependent manner. In summary, intragastric administration of TP at less than 2 times the clinically equivalent dose for 21 days and 42 days did not cause obvious reproductive damage to the uterus and ovarian tissues of CIA rats, and the number of atretic follicles changed significantly only when the 2 times the clinically equivalent dose was administered for 42 days. TP exerted reproductive toxicity in vivo on reproductive target organs and in vitro on ovarian cells by inhibiting the expression of TGFß3/Smad3/SF-1 pathway.
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Diterpenos , Compostos de Epóxi , Ovário , Fenantrenos , Ratos Sprague-Dawley , Útero , Animais , Feminino , Diterpenos/farmacologia , Fenantrenos/toxicidade , Ratos , Compostos de Epóxi/toxicidade , Compostos de Epóxi/administração & dosagem , Ovário/efeitos dos fármacos , Ovário/metabolismo , Útero/efeitos dos fármacos , Útero/metabolismo , Colágeno Tipo II/metabolismo , Proteína Smad3/metabolismo , Proteína Smad3/genética , Humanos , Reprodução/efeitos dos fármacos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , EstradiolRESUMO
Codonopsis convolvulacea is a highly valued Chinese medicinal plant containing diverse bioactive compounds. While roots/tubers have been the main medicinal parts used in practice, leaves and stems may also harbor valuable phytochemicals. However, research comparing volatiles across tissues is lacking. This study performed metabolomic profiling of leaves, stems, and tubers of C. convolvulacea to elucidate tissue-specific accumulation patterns of volatile metabolites. Ultra-high performance liquid chromatography-tandem mass spectrometry identified 302 compounds, belonging to 14 classes. Multivariate analysis clearly differentiated the metabolic profiles of the three tissues. Numerous differentially accumulated metabolites (DAMs) were detected, especially terpenoids and esters. The leaves contained more terpenoids, ester, and alcohol. The stems accumulated higher levels of terpenoids, heterocyclics, and alkaloids with pharmaceutical potential. The tubers were enriched with carbohydrates like sugars and starch, befitting their storage role, but still retained reasonable amounts of valuable volatiles. The characterization of tissue-specific metabolic signatures provides a foundation for the selective utilization of C. convolvulacea parts. Key metabolites identified include niacinamide, p-cymene, tridecanal, benzeneacetic acid, benzene, and carveol. Leaves, stems, and tubers could be targeted for antioxidants, drug development, and tonics/nutraceuticals, respectively. The metabolomic insights can also guide breeding strategies to enhance the bioactive compound content in specific tissues. This study demonstrates the value of tissue-specific metabolite profiling for informing the phytochemical exploitation and genetic improvement of medicinal plants.
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Codonopsis , Metabolômica , Compostos Fitoquímicos , Folhas de Planta , Caules de Planta , Tubérculos , Folhas de Planta/química , Folhas de Planta/metabolismo , Caules de Planta/química , Caules de Planta/metabolismo , Metabolômica/métodos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/metabolismo , Tubérculos/química , Tubérculos/metabolismo , Codonopsis/química , Codonopsis/metabolismo , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Metaboloma , Terpenos/metabolismo , Terpenos/análise , Plantas Medicinais/metabolismo , Plantas Medicinais/químicaRESUMO
Objective: This population-based study aims to assess the survival benefits of selective neck dissection (SND) compared to neck observation in patients with T1/T2N0M0 major salivary gland malignancy (MSGC). Methods: We conducted a retrospective review of T1/T2N0M0 MSGC patients who underwent primary tumor surgical extirpation with or without elective neck dissection in the Surveillance, Epidemiology, and End Results database (SEER) from 2004-2015. The impact of SND and clinical variables on overall survival (OS) and disease-specific survival (DSS) was evaluated using Univariate and Multivariate Cox proportional hazards regression models. Kaplan-Meier survival curves were generated, and survival rates were assessed via the log-rank test. Results: Of 3778 post-operative T1-T2N0M0 MSGC patients, 2305 underwent elective neck dissection, while 1473 did not. Median follow-up was 106 months. Univariate and Multivariate analysis identified SND as a prognostic factor for OS in all the study population. After stratified analysis, we found that in the poorly high-grade (differentiated and undifferentiated) patients, the survival showed a significant OS and DSS benefit after receiving SND compared with the neck observations [HR for OS (95%CI): 0.571(0.446-0.731), P<0.001] and [HR for DSS (95%CI): 0.564(0.385-0.826), P=0.003], other than in the well differentiated or moderately differentiated subgroup. Especially, when the pathological is squamous cell carcinoma, the results show that the people underwent SND had better prognosis, not only in OS [HR (95%CI): 0.532(0.322-0.876), P=0.013], but also in DSS [HR (95%CI): 0.330(0.136-0.797), P=0.014]. The multivariate analysis also yielded encouraging results, compared with neck observation, receiving SND bought about a significant independent OS (adjusted HR, 0.555; 95% CI, 0.328-0.941; P=0.029) and DSS (adjusted HR, 0.349; 95% CI, 0.142-0.858; P=0.022) advantage in high grade squamous cell carcinoma MSGC patients. The Kaplan-Meier survival curves also demonstrated that adjusted SND still had significantly better OS(P=0.029) and DSS(P=0.022) than the observation group in patients with high-grade squamous cell carcinoma of MSGC. Conclusion: Poorly differentiated and undifferentiated T1/T2N0M0 major salivary gland malignancy treated with selective neck dissection demonstrated superior survival compared to neck observation, especially in the pathological subtype of squamous cell carcinoma. These findings suggest the potential benefits of multimodal therapy for appropriately selected patients, emphasizing significant clinical implications.
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Generating multiple beams in distinct polarization states is promising in multi-mode wireless communication but still remains challenging in metasurface design. Here, we theoretically and experimentally demonstrate a concept of broadband receiving-transmitting metasurface and its application to the generation of multi-polarization multi-beam. By employing U-slot patch, an efficient receiving-transmitting element with full phase coverage is designed within a wide bandwidth. Based on this architecture, a methodology is proposed to generate dual spin-decoupled beams and then developed into the strategy of generating multiple beams at different linear polarizations. To verify our strategy, two lens antennas, respectively radiating dual-spin dual-beam and quad-polarization quad-beam, are devised. With multi-polarization multi-beam radiated, the two lens antennas are both with whole aperture efficiency above 40% within the bandwidth of 10.6-12.3â GHz (14.8%), firmly validating our strategy and design.
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Transglutaminase (EC 2.3.2.13, TGase), an enzyme that catalyzes the formation of covalent cross-links between protein or peptide molecules, plays a critical role in commercial food processing, medicine, and textiles. TGase from Streptomyces is the sole commercial enzyme preparation for cross-linking proteins. In this study, we revealed that the SOS response repressor protein LexA in Streptomyces mobaraensis not only triggers morphological development but also enhances TGase synthesis. The absence of lexA significantly diminished TGase production and sporulation. Although LexA does not bind directly to the promoter region of the TGase gene, it indirectly stimulates transcription of the tga gene, which encodes TGase. Furthermore, LexA directly enhances the expression of genes associated with protein synthesis and transcription factors, thus favorably influencing TGase synthesis at both the transcriptional and posttranscriptional levels. Moreover, LexA activates four crucial genes involved in morphological differentiation, promoting spore maturation. Overall, our findings suggest that LexA plays a dual role as a master regulator of the SOS response and a significant contributor to TGase regulation and certain aspects of secondary metabolism, offering insights into the cellular functions of LexA and facilitating the strategic engineering of TGase overproducers.
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As a typical RNA virus, the genetic information on HIV-1 is entirely stored in RNA. The reverse transcription activity of HIV-1 reverse transcriptase (RT) plays a crucial role in the replication and transmission of the virus. Non-nucleoside RT inhibitors (NNRTIs) block the function of RT by binding to the RNA binding site on RT, with very few targeting viral RNA. In this study, by transforming planar conjugated ligands into a spiro structure, we convert classical Ru(II) DNA intercalators into a nonintercalator. This enables selective binding to HIV-1 transactivation response (TAR) RNA on the outer side of nucleic acids through dual interactions involving hydrogen bonds and electrostatic attraction, effectively inhibiting HIV-1 RT and serving as a selective fluorescence probe for TAR RNA.
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Transcriptase Reversa do HIV , HIV-1 , Inibidores da Transcriptase Reversa , Rutênio , Transcriptase Reversa do HIV/antagonistas & inibidores , Transcriptase Reversa do HIV/metabolismo , Inibidores da Transcriptase Reversa/química , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/metabolismo , Ligantes , HIV-1/enzimologia , HIV-1/efeitos dos fármacos , Rutênio/química , Rutênio/farmacologia , RNA Viral/metabolismo , RNA Viral/química , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Compostos de Espiro/metabolismo , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Estrutura Molecular , Humanos , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Repetição Terminal Longa de HIV , Sítios de LigaçãoRESUMO
AIMS: Activation of central respiratory chemoreceptors provides excitatory drive to both respiratory and sympathetic outputs. The enhanced respiratory-sympathetic coupling contributes to the onset and development of hypertension. However, the specific central targets and molecular mechanisms involved in this process remain elusive. This study aimed to investigate the role of acid-sensing ion channel 1 (ASIC1) in nucleus tractus solitarii (NTS) neurons in CO2-stimulated cardiorespiratory effects in spontaneously hypertensive rats (SHRs). MAIN METHODS: Respiration and blood pressure of conscious rats were recorded by whole-body plethysmography and telemetry, respectively. Western blot was used to detect the expression difference of ASIC1 protein in NTS region between Wistar-Kyoto (WKY) rats and SHRs. Excitability of NTS neurons were assessed by extracellular recordings. KEY FINDINGS: Compared to WKY rats, the enhanced CO2-stimulated cardiopulmonary effect and up-regulation of ASIC1 in the NTS were already observed in 4-week-old prehypertensive SHRs. Furthermore, specific blockade of ASIC1 effectively attenuated the CO2-stimulated increase in firing rate of NTS neurons in anesthetized adult SHRs. Intracerebroventricular injections of the ASIC1a blocker PcTx1 or knockdown Asic1 in NTS neurons significantly reduced the heightened CO2-stimulated ventilatory response, and diminished the CO2-stimulated increase in arterial pressure and heart rate in adult SHRs. SIGNIFICANCE: These findings showed that dysregulated ASIC1 signaling in the NTS contribute to the exaggerated CO2-stimulated cardiorespiratory effects observed in SHRs.
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Canais Iônicos Sensíveis a Ácido , Pressão Sanguínea , Dióxido de Carbono , Hipertensão , Neurônios , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Núcleo Solitário , Animais , Canais Iônicos Sensíveis a Ácido/metabolismo , Núcleo Solitário/metabolismo , Ratos , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Masculino , Dióxido de Carbono/metabolismo , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Respiração/efeitos dos fármacos , Peptídeos , Venenos de AranhaRESUMO
OBJECTIVE: This study aimed to understand the health of workers exposed to occupational noise and explore the influencing factors related to workers' health, especially the impact of noise on workers' hearing. This work can provide a basis for formulating relevant measures for occupational noise prevention and control in the future. METHODS: On the basis of the key occupational disease monitoring project in Chongqing, China, in 2021, the data of 1125 workers exposed to occupational noise were analyzed. Data included demographic information, occupational history, clinical physical examination information, and noise detection information of the working environment. Chi-square test and multifactorial logistic regression were used for statistical analysis. RESULTS: The prevalence rates of abnormal electrocardiogram (ECG), blood pressure (BP), and pure tone audiometry (PTA) were 21.9% (246/1125), 27.8% (313/1125), and 18.0% (202/1125), respectively. Male workers accounted for 78.8%. Compared with male workers, female workers had a lower prevalence of abnormal PTA (OR = 0.28, 95% CI = 0.16-0.50). Workers working in medium enterprises had a lower prevalence of abnormal BP than workers in micro enterprises (OR = 0.36, 95% CI = 0.19-0.66). The prevalence of abnormal BP and PTA of workers increased with age. After adjusting for age, sex, and body mass index, the prevalence of abnormal ECG of mining workers was higher than that of manufacturing workers (OR = 1.54, 95% CI = 1.07-2.24), and the prevalence of abnormal PTA had a rising trend with the increase in noise exposure value. CONCLUSION: Noise-exposed workers have a high prevalence of abnormal ECG, BP, and PTA, and factors such as age, enterprise size, and workplace noise exposure are correlated with the aberrant health of workers. Governments, enterprises, and individuals need to attach great importance to the possible adverse effects of noise. They must also actively adopt various effective measures to protect the occupational safety and health of workers.
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Ruído Ocupacional , Exposição Ocupacional , Humanos , Ruído Ocupacional/efeitos adversos , Masculino , China/epidemiologia , Feminino , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Prevalência , Perda Auditiva Provocada por Ruído/epidemiologia , Perda Auditiva Provocada por Ruído/etiologia , Pressão Sanguínea , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Eletrocardiografia , Audiometria de Tons Puros , Adulto JovemRESUMO
OBJECTIVE: Phenylethanolamine N-methyltransferase (PNMT)-expressing neurons in the nucleus tractus solitarii (NTS) contribute to the regulation of autonomic functions. However, the neural circuits linking these neurons to other brain regions remain unclear. This study aims to investigate the connectivity mechanisms of the PNMT-expressing neurons in the NTS (NTSPNMT neurons). METHODS: The methodologies employed in this study included a modified rabies virus-based retrograde neural tracing technique, conventional viral anterograde tracing, and immunohistochemical staining procedures. RESULTS: A total of 43 upstream nuclei projecting to NTSPNMT neurons were identified, spanning several key brain regions including the medulla oblongata, pons, midbrain, cerebellum, diencephalon, and telencephalon. Notably, dense projections to the NTSPNMT neurons were observed from the central amygdaloid nucleus, paraventricular nucleus of the hypothalamus, area postrema, and the gigantocellular reticular nucleus. In contrast, the ventrolateral medulla, lateral parabrachial nucleus, and lateral hypothalamic area were identified as the primary destinations for axon terminals originating from NTSPNMT neurons. Additionally, reciprocal projections were evident among 21 nuclei, primarily situated within the medulla oblongata. CONCLUSION: Our research findings demonstrate that NTSPNMT neurons form extensive connections with numerous nuclei, emphasizing their essential role in the homeostatic regulation of vital autonomic functions.
Assuntos
Neurônios , Feniletanolamina N-Metiltransferase , Núcleo Solitário , Animais , Feniletanolamina N-Metiltransferase/metabolismo , Feniletanolamina N-Metiltransferase/genética , Núcleo Solitário/enzimologia , Núcleo Solitário/metabolismo , Núcleo Solitário/citologia , Neurônios/metabolismo , Neurônios/enzimologia , Masculino , Vias Eferentes/enzimologia , Vias Aferentes/enzimologia , Ratos Sprague-Dawley , Mapeamento Encefálico/métodos , RatosRESUMO
Developing technologies aimed at ecologically restoring is of great significance in addressing the problem of heavy metal pollution. In this study, NaA zeolites (FAZ) originated from fly ash with outstanding performance were prepared by alkali fusion hydrothermal method and used for the solidification and stabilization of heavy metals in soil. After systematic evaluation, it was found that FAZ may lower the leaching concentration of lead (Pb) in soil to <1 mg/kg and increase the stabilization rate of Pb to 80 % in the single Pb-contaminated soil, lower the leaching concentration of cadmium (Cd) in soil to <3 mg/kg and increase the stabilization rate of Cd to 60 % in the single Cd-contaminated soil, and lower the leaching concentration of Pb to 0.15 mg/kg and the leaching concentration of Cd to 0.74 mg/kg in PbCd complex polluted soil. Additionally, Pb stabilization rates reach 60 % and Cd stabilization rates reach 30 %, respectively. Ion exchange is primarily responsible for the adsorption and solidification of Pb and Cd in soil by FAZ. Generally, FAZ has a wide range of applications in the rehabilitation of contaminated soil and significantly lowers the level of heavy metal pollution in soil.