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The self-assembly of proteins into curved structures plays an important role in many cellular processes. One good example of this phenomenon is observed in the septum-forming protein (SepF), which forms polymerized structures with uniform curvatures. SepF is essential for regulating the thickness of the septum during bacteria cell division. In Bacillus subtilis, SepF polymerization involves two distinct interfaces, the ß-ß and α-α interfaces, which define the assembly unit and contact interfaces, respectively. However, the mechanism of curvature formation in this step is not yet fully understood. In this study, we employed solid-state NMR (SSNMR) to compare the structures of cyclic wild-type SepF assemblies with linear assemblies resulting from a mutation of G137 on the ß-ß interface. Our results demonstrate that while the sequence differences arise from the internal assembly unit, the dramatic changes in the shape of the assemblies depend on the α-α interface between the units. We further provide atomic-level insights into how the angular variation of the α2 helix on the α-α interface affects the curvature of the assemblies, using a combination of SSNMR, cryo-electron microscopy, and simulation methods. Our findings shed light on the shape control of protein assemblies and emphasize the importance of interhelical contacts in retaining curvature.
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Citocinese , Microscopia Crioeletrônica , Polimerização , Divisão Celular , MutaçãoRESUMO
Thoracic aortic aneurysm/dissection (TAAD) is a lethal vascular disease, and several pathological factors participate in aortic medial degeneration. We previously discovered that the complement C3a-C3aR axis in smooth muscle cells promotes the development of thoracic aortic dissection (TAD) through regulation of matrix metalloproteinase 2. However, discerning the specific complement pathway that is activated and elucidating how inflammation of the aortic wall is initiated remain unknown. We ascertained that the plasma levels of C3a and C5a were significantly elevated in patients with TAD and that the levels of C3a, C4a, and C5a were higher in acute TAD than in chronic TAD. We also confirmed the activation of the complement in a TAD mouse model. Subsequently, knocking out Cfb (Cfb) or C4 in mice with TAD revealed that the alternative pathway and Cfb played a significant role in the TAD process. Activation of the alternative pathway led to generation of the anaphylatoxins C3a and C5a, and knocking out their receptors reduced the recruitment of inflammatory cells to the aortic wall. Moreover, we used serum from wild-type mice or recombinant mice Cfb as an exogenous source of Cfb to treat Cfb KO mice and observed that it exacerbated the onset and rupture of TAD. Finally, we knocked out Cfb in the FBN1C1041G/+ Marfan-syndrome mice and showed that the occurrence of TAA was reduced. In summary, the alternative complement pathway promoted the development of TAAD by recruiting infiltrating inflammatory cells. Targeting the alternative pathway may thus constitute a strategy for preventing the development of TAAD.NEW & NOTEWORTHY The alternative complement pathway promoted the development of TAAD by recruiting infiltrating inflammatory cells. Targeting the alternative pathway may thus constitute a strategy for preventing the development of TAAD.
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Aneurisma da Aorta Torácica , Dissecção Aórtica , Azidas , Desoxiglucose/análogos & derivados , Humanos , Camundongos , Animais , Via Alternativa do Complemento , Metaloproteinase 2 da Matriz , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/metabolismo , Aneurisma da Aorta Torácica/patologia , Dissecção Aórtica/genética , InflamaçãoRESUMO
Peptide assemblies are promising nanomaterials, with their properties and technological applications being highly hinged on their supramolecular architectures. Here, how changing the chirality of the terminal charged residues of an amphiphilic hexapeptide sequence Ac-I4 K2 -NH2 gives rise to distinct nanostructures and supramolecular handedness is reported. Microscopic imaging and neutron scattering measurements show thin nanofibrils, thick nanofibrils, and wide nanotubes self-assembled from four stereoisomers. Spectroscopic and solid-state nuclear magnetic resonance (NMR) analyses reveal that these isomeric peptides adopt similar anti-parallel ß-sheet secondary structures. Further theoretical calculations demonstrate that the chiral alterations of the two C-terminal lysine residues cause the formation of diverse single ß-strand conformations, and the final self-assembled nanostructures and handedness are determined by the twisting direction and degree of single ß-strands. This work not only lays a useful foundation for the fabrication of diverse peptide nanostructures by manipulating the chirality of specific residues but also provides a framework for predicting the supramolecular structures and handedness of peptide assemblies from single molecule conformations.
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Lateralidade Funcional , Nanoestruturas , Peptídeos/química , Nanoestruturas/química , Isomerismo , Estrutura Secundária de ProteínaRESUMO
Global population growth and demographic restructuring are driving the food and agriculture sectors to provide greater quantities and varieties of food, of which protein resources are particularly important. Traditional animal-source proteins are becoming increasingly difficult to meet the demand of the current consumer market, and the search for alternative protein sources is urgent. Microbial proteins are biomass obtained from nonpathogenic single-celled organisms, such as bacteria, fungi, and microalgae. They contain large amounts of proteins and essential amino acids as well as a variety of other nutritive substances, which are considered to be promising sustainable alternatives to traditional proteins. In this review, typical approaches to microbial protein synthesis processes were highlighted and the characteristics and applications of different types of microbial proteins were described. Bacteria, fungi, and microalgae can be individually or co-cultured to obtain protein-rich biomass using starch-based raw materials, organic wastes, and one-carbon compounds as fermentation substrates. Microbial proteins have been gradually used in practical applications as foods, nutritional supplements, flavor modifiers, and animal feeds. However, further development and application of microbial proteins require more advanced biotechnological support, screening of good strains, and safety considerations. This review contributes to accelerating the practical application of microbial proteins as a promising alternative protein resource and provides a sustainable solution to the food crisis facing the world.
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Rapid advances in high-quality sequencing and bioinformatics have invalidated the argument that noncoding RNAs (ncRNAs) are junk transcripts that do not encode proteins. Increasing evidence suggests that small open reading frames (sORFs) in ncRNAs can encode micropeptides and polypeptides within 100 amino acids in length. Several micropeptides have been characterized and proven to have various functions in human physiology and pathology, particularly in cancer. The present review mainly highlights the latest studies on ncRNA-encoded micropeptides in different cancers and categorizes them based on their subcellular localization, thereby providing a theoretical basis for micropeptide applications in the early diagnosis and prognosis of cancer and as therapeutic targets. However, considering the inherent characteristics of micropeptides and the limitations of the assay technology methods, more detailed information is warranted.
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Neoplasias , RNA Longo não Codificante , Humanos , Proteínas , Peptídeos/genética , RNA não Traduzido , Neoplasias/genética , Fases de Leitura Aberta/genética , MicropeptídeosRESUMO
BACKGROUND: Avian influenza viruses (AIVs) constitute significant zoonotic pathogens encompassing a broad spectrum of subtypes. Notably, the H4 subtype of AIVs has a pronounced ability to shift hosts. The escalating prevalence of the H4 subtype heightens the concern for its zoonotic potential, signaling an urgent need for vigilance. METHODS: During the period from December 2021 to November 2023, we collected AIV-related environmental samples and assessed them using a comprehensive protocol that included nucleic acid testing, gene sequencing, isolation culture, and resequencing. RESULTS: In this study, a total of 934 environmental samples were assessed, revealing a remarkably high detection rate (43.66%, 289/662) of AIV in the live poultry market. Notably, the H4N1 subtype AIV (cs2301) was isolated from the live poultry market and its complete genome sequence was successfully determined. Subsequent analysis revealed that cs2301, resulting from a reassortment event between wild and domesticated waterfowl, exhibits multiple mutations and demonstrates potential for host transfer. CONCLUSIONS: Our research once again demonstrates the significant role of wild and domesticated waterfowl in the reassortment process of avian influenza virus, enriching the research on the H4 subtype of AIV, and emphasizing the importance of proactive monitoring the environment related to avian influenza virus.
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Vírus da Influenza A , Influenza Aviária , Animais , Influenza Aviária/epidemiologia , Filogenia , Vírus da Influenza A/genética , Aves Domésticas , China/epidemiologiaRESUMO
Oxidative stress (OS) and inflammation play essential roles in the development of diabetic nephropathy (DN). Tirzepatide (TZP) has a protective effect in diabetes. However, its underlying mechanism in DN remains unclear. DN model mice were induced by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg), followed by administration of different doses of TZP (3 and 10 nmol/kg) via intraperitoneal injection for 8 weeks. The effects of TZP on DN were evaluated by detecting DN-related biochemical indicators, kidney histopathology, apoptosis, OS, and inflammation levels. Additionally, to further reveal the potential mechanism, we investigated the role of TZP in modulating the IL-17 pathway. TZP reduced serum creatinine (sCR), blood urea nitrogen (BUN), and advanced glycosylation end products (AGEs) levels, while simultaneously promoting insulin secretion in diabetic mice. Additionally, TZP attenuated tubular and glomerular injury and reduced renal apoptosis levels. Further studies found that TZP increased the levels of SOD and CAT, and decreased MDA. Meanwhile, TZP also reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in both mouse serum and kidney homogenates. TZP effectively inhibited the IL-17 pathway, and subsequent intervention with an IL-17 pathway agonist (IL-17A) reversed the suppressive effects of TZP on OS and inflammation. TZP can improve DN by inhibiting OS and inflammation through the suppression of the IL-17 pathway.
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OBJECTIVES: Chronic hyperglycemia is considered as an important factor to promote the neurodegenerative process of brain, and the synaptic plasticity as well as heterogeneity of hippocampal cells are thought to be associated with cognitive dysfunction in the early process of neurodegeneration. To date, fibronectin type III domain-containing protein 5 (FNDC5) has been highlighted its protective role in multiple neurodegenerative diseases. However, the potential molecular and cellular mechanisms of FNDC5 on synaptic plasticity regulation in cognitive impairment (CI) induced by diabetics are still need to known. METHODS/DESIGN: To investigate the heterogeneity and synaptic plasticity of hippocampus in animals with CI state induced by hyperglycemia, and explore the potential role of FNDC5 involved in this process. Firstly, the single cell sequencing was performed based on the hippocampal tissue from db diabetic mice induced CI and normal health control mice by ex vivo experiments; and then the integrated analysis and observations validation using Quantitative Real-time PCR, western blot as well as other in vitro studies. RESULTS: We observed and clarified the sub-cluster of type IC spiral ganglion neurons expressed marker genes as Trmp3 and sub-cluster of astrocytes with marker gene as Atp1a2 in hippocampal cells from diabetic animals induced CI and the effect of those on neuron-glial communication. We also found that FNDC5\BDNF-Trk axis was involved in the synaptic plasticity regulation of hippocampus. In high glucose induced brain injury model in vitro, we investigated that FNDC5 significantly regulates BDNF expression and that over-expression of FNDC5 up-regulated BDNF expression (p < 0.05) and can also significantly increase the expression of synapsin-1 (p < 0.05), which is related to synaptic plasticity, In addition, the unbalanced methylation level between H3K4 and H3K9 in Fndc5 gene promoter correlated with significantly down-regulated expression of FNDC5 (p < 0.05) in the hyperglycemia state. CONCLUSION: The current study revealed that the synaptic plasticity of hippocampal cells in hyperglycemia might be regulated by FNDC5\BDNF-Trk axis, playing the protective role in the process of CI induced by hyperglycemia and providing a target for the early treatment of hyperglycemia induced cognitive dysfunction in clinic.
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Disfunção Cognitiva , Diabetes Mellitus Experimental , Fibronectinas , Hiperglicemia , Animais , Humanos , Camundongos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Fibronectinas/genética , Fibronectinas/metabolismo , Hipocampo , Hiperglicemia/metabolismo , Plasticidade Neuronal/fisiologia , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).
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Anestésicos Inalatórios , Anestésicos Intravenosos , Procedimentos Cirúrgicos Cardíacos , Desflurano , Complicações Pós-Operatórias , Propofol , Humanos , Propofol/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Anestésicos Intravenosos/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Idoso , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Adulto , Sevoflurano/efeitos adversos , Anestesia Intravenosa/métodos , China/epidemiologia , Tempo de Internação/estatística & dados numéricos , Anestesia por Inalação/métodos , Anestesia por Inalação/efeitos adversos , Resultado do TratamentoRESUMO
Angelicin has been reported to have antitumor effects on many types of cancer. However, few studies on angelicin in oral squamous cell carcinoma (OSCC) have been performed. We performed cell cycle and apoptosis analyses to assess the effect of angelicin on OSCC cells. We conducted RNA-seq studies to reveal differentially expressed genes (DEGs). Dual-specificity phosphatase 6 (DUSP6) and c-MYC were strongly down-regulated differential genes. Silencing RNA (siRNA) was used to knockdown DUSP6. The mouse xenograft model was used to mimic OSCC. Angelicin inhibited OSCC in vitro. We found that DUSP6 interacted with c-MYC. DUSP6 knockdown group and DUSP6 knockdown + angelicin group had similar effects of OSCC cells. Angelicin could reduce tumor formation, DUSP6, and c-MYC expression in vivo. Compared with paclitaxel, the tumor inhibition effect of the two drugs was similar. However, angelicin did not cause weight loss and had lower toxicity. In sum, Angelicin has antitumor effects on OSCC in vitro and vivo by negatively regulating the DUSP6 mediated c-MYC signaling pathway.
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Cancer is the most severe health problem facing most people today. Photodynamic therapy (PDT) for tumors has attracted attention because of its non-invasive nature, negligible adverse reactions, and high spatiotemporal selectivity. Developing biocompatible photosensitizers that can target, guide, and efficiently kill cancer cells is desirable in PDT. Here, two amphiphilic organic compounds, PS-I and PSS-II, were synthesized based on the D-π-A structure with a positive charge. The two AIEgens exhibited near-infrared emission, large Stokes shift, high 1O2 and O2-â generation efficiency, good biocompatibility, and photostability. They were co-incubated with cancer cells and eventually accumulated to lysosomes by cell imaging experiments. In vitro and in vivo experiments demonstrated that PS-I and PSS-II could effectively kill cancer cells and sufficiently inhibit tumor growth under light irradiation. PS-I had a higher fluorescence quantum yield in the aggregated state, which made it better for bio-imaging in imaging-guided photodynamic therapy. In contrast, PSS-II with a longer conjugated structure had more ROS generation to kill tumor cells under illumination, and the tumor growth inhibition of mice reached 71.95% during the treatment. No observable injury or undesirable outcomes were detected in the vital organs of the mice within the treatment group, suggesting that PSS-II/PS-I had a promising future in efficient imaging-guided PDT for cancer.
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Raios Infravermelhos , Lisossomos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Humanos , Animais , Camundongos , Estrutura Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Desenho de Fármacos , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/diagnóstico por imagem , Sobrevivência Celular/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , FemininoRESUMO
In this study, a UV-driven photocatalytic activation of peroxymonosulfate (PMS) system was constructed using bimetallic metal-organic frameworks to degrade pharmaceuticals and personal care products (PPCPs). Mn-MIL-53(Fe) was successfully synthesised by adjusting the doping ratio of Mn using solvothermal method. The removal of ibuprofen (IBP) by UV/Mn-MIL-53(Fe)/PMS process was as high as 79.7% in 30 min with a Mn doping ratio of 1.0 (molar ratio of Mn to Fe), and the reaction rate constant was 26.9% higher than undoped. Mn-MIL-53(Fe) had been systematically characterized in terms of its physical structure, microscopic morphology, surface functional groups and photoelectric properties. The mechanism investigation revealed that the cycling of Mn and Fe accelerated the rate of electron transfer in the system, which significantly increased the activation efficacy of PMS to generate more hydroxyl and sulfate radicals for IBP degradation. A total of 13 transformation products were detected during the degradation of IBP by the UV/Mn-MIL-53(Fe)/PMS process. Theoretical calculations were used to predict the sites on the IBP molecule that were vulnerable to attack, and four possible degradation pathways were deduced. The excellent stability and efficient catalytic properties of Mn-MIL-53(Fe) provided a promising solution to the problem of water treatment contaminated with PPCPs.
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Ibuprofeno , Peróxidos , Poluentes Químicos da Água , Ibuprofeno/química , Peróxidos/química , Poluentes Químicos da Água/química , Catálise , Manganês/química , Fotólise , Raios Ultravioleta , Estruturas Metalorgânicas/química , Ferro/químicaRESUMO
OBJECTIVE: To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO4)in women with preeclampsia (PE), and to determine the key covariates having an effect in magnesium pharmacokinetics in Chinese PE. METHODS: Pregnant women with PE prescribed MgSO4 were enrolled in this prospective study from April 2021 to April 2023. On the initial day of administration, the patients were administered a loading dose of 5 g in conjunction with 10 g of magnesium sulfate as a maintenance dose. On the second day, only the maintenance dose was administration, and maternal blood samples were taken at 0, 4, 5, and 12 h after the second day's 10 g maintenance dose. The software Phoenix was used to estimate PPK parameters of MgSO4, such as clearance (CL) and volume of distribution (V), and to model PPK models with patient demographic, clinical, and laboratory covariates. RESULTS: A total of 199 blood samples were collected from 51 women with PE and PPK profiles were analyzed. The PPK of MgSO4 is consistent with to a one-compartment model. The base model adequately described the maternal serum magnesium concentrations after magnesium administration. The population parameter estimates were as follows: CL was 2.98 L/h, V was 25.07 L. The model predictions changed significantly with covariates (BMI, creatinine clearance, and furosemide). Furosemide statistically influences V. The creatinine clearance, BMI and furosemide jointly affects CL. Monte Carlo simulation results showed that a loading dose combined with a maintenance dose would need to be administered daily to achieve the therapeutic blood magnesium concentrations. For the non-furosemide group, the optimal dosing regimen was a 5 g loading dose combined with a 10 g maintenance dose of MgSO4. For the furosemide group, the optimal dosing regimen was a 2.5 g loading dose combined with a 10 g maintenance dose of MgSO4. CONCLUSIONS: The magnesium PPK model was successfully developed and evaluated in Chinese preeclampsia population, and the dose optimization of MgSO4 was completed through Monte Carlo simulation.
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Sulfato de Magnésio , Pré-Eclâmpsia , Humanos , Feminino , Sulfato de Magnésio/administração & dosagem , Sulfato de Magnésio/farmacocinética , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/sangue , Gravidez , Adulto , Estudos Prospectivos , China , Adulto Jovem , Relação Dose-Resposta a Droga , População do Leste AsiáticoRESUMO
Hua-ju-hong (HJH) is a Chinese medicinal material obtained from Citrus grandis 'Tomentosa' (CGT) and Citrus grandis (L.) Osbeck (CG) with various commercial specifications. It is known for relieving cough and dispelling phlegm. To reveal the quality marker for distinguishing the various HJH, 215 batches of commercial HJH were studied systematically using multidimensional chemical analysis. Ten major components were identified by high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and quantified via high-performance liquid chromatography coupled with diode array detection. In this study, a rapid, efficient, and low-cost chromatographic method was established. Total coumarin-hemiterpene and total coumarin-monoterpene were first classified and analyzed in HJH. The result indicated that the main component, naringin, was not the quality marker for differentiating CGT from CG. For reflecting the unique medicinal and food value of HJH, coumarins should be the more potential quality markers. Flavonoids were the possible quality markers for distinguishing two growth stages of fruit-exocarp and young fruit. For the first time, two chemotypes of HJH were identified in CG. This study provides a convenient yet reliant chromatographic method and novel yet systematic strategies for overall quality control of commercial HJH.
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Citrus , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Citrus/química , Cumarínicos/análise , Cumarínicos/química , Espectrometria de Massas , Controle de Qualidade , Estrutura MolecularRESUMO
BACKGROUND: IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines. CASE PRESENTATION: A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz's disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size. CONCLUSION: Mikulicz's disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.
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Hipofisite Autoimune , Doença Relacionada a Imunoglobulina G4 , Doença de Mikulicz , Humanos , Idoso , Feminino , Doença de Mikulicz/tratamento farmacológico , Doença de Mikulicz/complicações , Doença de Mikulicz/diagnóstico , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Hipofisite Autoimune/complicações , Hipofisite Autoimune/tratamento farmacológico , Imunoglobulina G/sangue , Prednisolona/uso terapêutico , Prednisolona/administração & dosagem , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Even with advances in primary health care, depressive disorders remain a major global public health problem. We conducted an in-depth analysis of global, regional and national trends in depressive disorders incidence over the past 30 years. METHODS: Data on the incidence of depressive disorders were obtained by sex (female, male, and both), location (204 countries), age (5-84 years), year (1990-2019) from the Global Burden of Disease Study (GBD) 2019. Further, age-period-cohort modeling was used to estimate the net drift, local drift, age, period and cohort effects between 1990 and 2019. RESULTS: In 2019, although the incidence of depressive disorders has increased by 59.3% to 290 million (95% UI: 256, 328), the age-standardized incidence rate has decreased by 2.35% to 3588.25 per 100,000 people (3152.71, 4060.42) compared to 1990. There was an emerging transition of incidences from the young and middle-aged population to the old population. From 1990 to 2019, the net drift of incidence rate ranged from -0.54% (-0.61%, -0.47%) in low-middle Socio-demographic Index (SDI) regions to 0.52% (0.25%, 0.79%) in high SDI regions. Globally, the incidence rate of depressive disorders increases with age, period effects showing a decreasing risk and cohort effects beginning to decline after the 1960s. CONCLUSIONS: Our current findings reflect substantial health disparities and potential priority-setting of depressive disorders incidence in the three dimensions of age, period and cohort across SDI regions, countries. The scope of healthcare to improve the progression of depressive disorders events can be expanded to include males, females of all ages.
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BACKGROUND: Neuropeptides play a critical role in regulating pain and inflammation. Despite accumulating evidence has further uncovered the novel functions and mechanisms of different neuropeptides in orofacial pain sensation and transmission, there is deficient systematic description of neuropeptides' pain modulation in the orofacial region, especially in the trigeminal system. OBJECTIVES: The present review aims to summarise several key neuropeptides and gain a better understanding of their major regulatory roles in orofacial inflammation and pain. METHODS: We review and summarise current studies related to calcitonin gene-related peptide (CGRP), substance P (SP), opioid peptide (OP), galanin (GAL) and other neuropeptides' functions and mechanisms as well as promising targets for orofacial pain control. RESULTS: A number of neuropeptides are clearly expressed in the trigeminal sensory system and have critical functions in the transduction and pathogenesis of orofacial pain. The functions, possible cellular and molecular mechanisms have been introduced and discussed. Neuropeptides and their agonists or antagonists which are widely studied to be potential treatment options of orofacial pain has been evaluated. CONCLUSIONS: Various neuropeptides play important but distinct (pro-nociceptive or analgesic) roles in orofacial pain with different mechanisms. In summary, CGRP, SP, NPY, NKA, HK-1, VIP mainly play proinflammatory and pro-nociceptive effects while OP, GAL, OXT, OrxA mainly have inhibitory effects on orofacial pain.
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Peptídeo Relacionado com Gene de Calcitonina , Neuropeptídeos , Humanos , Dor Facial , Substância P , InflamaçãoRESUMO
The rapid development of green energy would render a profound impact on the non-ferrous metals markets in China. This paper adopts the quantile vector autoregression (QVAR) to investigate the spillover effects between China's green energy and non-ferrous metals markets as well as their dynamic pattern under normal and extreme conditions. Furthermore, GARCH-MIDAS model and quantile regression method are applied to examine the impact of China's climate policy uncertainty on the spillovers between the two markets. In doing so, we find that green energy markets mainly act as transmitters of return spillover effects to non-ferrous metals markets during normal market times and periods of downturns. However, in upturns, the non-ferrous metals markets would easily transit spillover effects to green energy ones. It is further indicated that China's climate policy uncertainty exacerbates the spillover effect, and the exacerbated effect of high uncertainty on the market relationship when the spillover effect is at high level is the most significant.
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Metais , China , Incerteza , Clima , Mudança Climática , Política AmbientalRESUMO
This study aimed to investigate the volatile flavor compounds and tastes of six kinds of sauced pork from the southwest and eastern coastal areas of China using gas chromatography-ion mobility spectroscopy (GC-IMS) combined with an electronic nose (E-nose) and electronic tongue (E-tongue). The results showed that the combined use of the E-nose and E-tongue could effectively identify different kinds of sauced pork. A total of 52 volatile flavor compounds were identified, with aldehydes being the main flavor compounds in sauced pork. The relative odor activity value (ROAV) showed that seven key volatile compounds, including 2-methylbutanal, 2-ethyl-3, 5-dimethylpyrazine, 3-octanone, ethyl 3-methylbutanoate, dimethyl disulfide, 2,3-butanedione, and heptane, contributed the most to the flavor of sauced pork (ROAV ≥1). Multivariate data analysis showed that 13 volatile compounds with the variable importance in projection (VIP) values > 1 could be used as flavor markers to distinguish six kinds of sauced pork. Pearson correlation analysis revealed a significant link between the E-nose sensor and alcohols, aldehydes, terpenes, esters, and hetero-cycle compounds. The results of the current study provide insights into the volatile flavor compounds and tastes of sauced pork. Additionally, intelligent sensory technologies can be a promising tool for discriminating different types of sauced pork.
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Carne de Porco , Carne Vermelha , Suínos , Animais , Nariz Eletrônico , China , Análise Espectral , Aldeídos , Cromatografia GasosaRESUMO
BACKGROUND: Pulmonary hypertension (PH) seriously affects the health of patients. We have found in clinical studies that PH has adverse effects on both maternal and offspring. OBJECTIVE: To establish a animal model of PH induced by hypoxia/SU5416 and observe the effects of PH on pregnant mice and their fetuses. METHODS: Twenty-four C57 mice aged 7-9 weeks were selected and divided into 4 groups with 6 mice in each group. â Female mice with normal oxygen; â¡ Female mice with hypoxia/SU5416; ⢠Pregnant mice with normal oxygen; ⣠Pregnant mice with hypoxia/SU5416. After 19 days, weight, right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) were compared in each group. Lung tissue and right ventricular blood were collected. The number and weight of fetal mice were also compared between the two pregnant groups. RESULTS: There was no significant difference in RVSP and RVHI between female and pregnant mice under the same condition. Compared with normal oxygen condition, two groups of mice in hypoxia/SU5416 had poor development, RVSP and RVHI were significantly increased, the number of fetal mice was small, hypoplasia, degeneration and even abortion. CONCLUSION: The model of mice PH was successfully established. PH affects the development and health of female and pregnant mice, and seriously affects the fetuses.