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1.
Sci Rep ; 14(1): 9235, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649718

RESUMO

Magnetic resonance-diffusion tensor imaging (MR-DTI) has been used in the microvascular decompression and gamma knife radiosurgery in trigeminal neuralgia (TN) patients; however, use of percutaneous stereotactic radiofrequency rhizotomy (PSR) to target an abnormal trigeminal ganglion (ab-TG) is unreported. Fractional anisotropy (FA), mean and radial diffusivity (MD and RD, respectively), and axial diffusivity (AD) of the trigeminal nerve (CNV) were measured in 20 TN patients and 40 healthy control participants immediately post PSR, at 6-months, and at 1 year. Longitudinal alteration of the diffusivity metrics and any correlation with treatment effects, or prognoses, were analyzed. In the TN group, either low FA (value < 0.30) or a decreased range compared to the adjacent FA (dFA) > 17% defined an ab-TG. Two-to-three days post PSR, all 15 patients reported decreased pain scores with increased FA at the ab-TG (P < 0.001), but decreased MD and RD (P < 0.01 each). Treatment remained effective in 10 of 14 patients (71.4%) and 8 of 12 patients (66.7%) at the 6-month and 1-year follow-ups, respectively. In patients with ab-TGs, there was a significant difference in treatment outcomes between patients with low FA values (9 of 10; 90%) and patients with dFA (2 of 5; 40%) (P < 0.05). MR-DTI with diffusivity metrics correlated microstructural CNV abnormalities with PSR outcomes. Of all the diffusivity metrics, FA could be considered a novel objective quantitative indicator of treatment effects and a potential indicator of PSR effectiveness in TN patients.

2.
Appl Environ Microbiol ; 90(4): e0208723, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38557137

RESUMO

Filamentous growth of streptomycetes coincides with the synthesis and deposition of an uncharacterized protective glucan at hyphal tips. Synthesis of this glucan depends on the integral membrane protein CslA and the radical copper oxidase GlxA, which are part of a presumably large multiprotein complex operating at growing tips. Here, we show that CslA and GlxA interact by forming a protein complex that is sufficient to synthesize cellulose in vitro. Mass spectrometry analysis revealed that the purified complex produces cellulose chains with a degree of polymerization of at least 80 residues. Truncation analyses demonstrated that the removal of a significant extracellular segment of GlxA had no impact on complex formation, but significantly diminished activity of CslA. Altogether, our work demonstrates that CslA and GlxA form the active core of the cellulose synthase complex and provide molecular insights into a unique cellulose biosynthesis system that is conserved in streptomycetes. IMPORTANCE: Cellulose stands out as the most abundant polysaccharide on Earth. While the synthesis of this polysaccharide has been extensively studied in plants and Gram-negative bacteria, the mechanisms in Gram-positive bacteria have remained largely unknown. Our research unveils a novel cellulose synthase complex formed by the interaction between the cellulose synthase-like protein CslA and the radical copper oxidase GlxA from Streptomyces lividans, a soil-dwelling Gram-positive bacterium. This discovery provides molecular insights into the distinctive cellulose biosynthesis machinery. Beyond expanding our understanding of cellulose biosynthesis, this study also opens avenues for exploring biotechnological applications and ecological roles of cellulose in Gram-positive bacteria, thereby contributing to the broader field of microbial cellulose biosynthesis and biofilm research.


Assuntos
Polissacarídeos , Streptomyces lividans , Streptomyces lividans/genética , Streptomyces lividans/metabolismo , Polissacarídeos/metabolismo , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Celulose/metabolismo
3.
Int J Biol Macromol ; 266(Pt 2): 131352, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38574926

RESUMO

Domain engineering, including domain truncation, fusion, or swapping, has become a common strategy to improve properties of enzymes, especially glycosyl hydrolases. However, there are few reports explaining the mechanism of increased activity from a protein structure perspective. Amy703 is an alkaline amylase with a unique N-terminal domain. Prior studies have shown that N-Amy, a mutant without an N-terminal domain, exhibits improved activity, stability, and calcium ion independence. In this study, we have used X-ray crystallography to determine the crystal structure of N-Amy and used AlphaFold2 to model the Amy703 structure, respectively. We further used size exclusion chromatography to show that Amy703 existed as a monomer, whereas N-Amy formed a unique dimer. It was found that the N-terminus of one monomer of N-Amy was inserted into the catalytic domain of its symmetrical subunit, resulting in the expansion of the catalytic pocket. This also significantly increased the pKa of the hydrogen donor Glu350, thereby enhancing substrate binding affinity and contributing to increased N-Amy activity. Meanwhile, two calcium ions were found to bind to N-Amy at different binding sites, which also contributed to the stability of protein. Therefore, this study provided new structural insights into the mechanisms of various glycosyl hydrolases.

4.
J Agric Food Chem ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38657166

RESUMO

Cytotoxic enzymes often exist as zymogens containing prodomains to keep them in an inactive state. Protein-glutaminase (PG), which can enhance various functional characteristics of food proteins, is an enzyme containing pro-PG and mature-PG (mPG). However, poor activity and stability limit its application while tedious purification and activation steps limit its high-throughput engineering. Here, based on structural analysis, we replaced the linker sequence between pro-PG and mPG with the HRV3C protease recognition sequence and then coexpressed it with HRV3C protease in Escherichia coli to develop an efficient one-step purification and activation method for PG. We then used this method to obtain several mutants designed by a combination of computer-aided approach and beneficial point mutations. The specific activity (131.6 U/mg) of the best variant D1 was 4.14-fold that of the wild type, and t1/2 and T5010 increased by 13 min and 7 °C, respectively. D1 could effectively improve the solubility and emulsification of wheat proteins, more than twice the effect of the wild type. We also discussed the mechanism underlying the improved properties of D1. In summary, we not only provide a universal one-step purification and activation method to facilitate zymogen engineering but also obtain an excellent PG mutant.

5.
Int J Mol Sci ; 25(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38612689

RESUMO

Intestinal epithelial cells (IECs) play crucial roles in forming an essential barrier, providing host defense against pathogens and regulating nutrients absorption. Milk-derived extracellular vesicles (EVs) within its miRNAs are capable of modulating the recipient cell function. However, the differences between colostrum and mature milk EVs and their biological function in attenuating intestinal epithelial cell injury remain poorly understood. Thus, we carried out the present study to characterize the difference between colostrum and mature milk-derived miRNA of EVs and the effect of colostrum and mature milk EVs on the proliferation, apoptosis, proinflammatory cytokines and intestinal epithelial barrier related genes in IEC-6 induced by LPS. Differential expression of 329 miRNAs was identified between colostrum and mature milk EVs, with 185 miRNAs being downregulated and 144 upregulated. In addition, colostrum contains a greater number and protein concentration of EVs than mature milk. Furthermore, compared to control, EVs derived from colostrum significantly inhibited the expression of apoptosis- (Bax, p53, and caspase-3) and proinflammatory-related genes (TNFα, IL6, and IL1ß). EVs derived from mature milk did not affect expression of apoptosis-related genes (Bax, p53, bcl2, and caspase-3). The EVs derived from mature milk significantly inhibited the expression of proinflammatory-related genes (TNFα and IL6). Western blot analysis also indicated that colostrum and mature milk EVs significantly decreased the apoptosis of IEC-6 cells. The EdU assay results showed that colostrum and mature milk EVs significantly increased the proliferation of IEC-6 cells. The expression of intestinal barrier-related genes (TJP1, CLDN1, OCLN, CDX2, MUC2, and IGF1R) was significantly promoted in IEC-6 cells after colostrum and mature milk EVs addition. Importantly, colostrum and mature milk EVs significantly relieved the LPS-induced inhibition of proliferation and intestinal barrier-related genes expression and attenuated apoptosis and proinflammatory responses induced by LPS in IEC-6 cells. Flow cytometry and Western blot analysis also indicated that colostrum and mature milk EVs significantly affect the apoptosis of IEC-6 cells induced by LPS. The results also indicated that EVs derived from colostrum had better effects on inhibiting the apoptosis- and proinflammatory cytokines-related genes expression. However, the EVs derived from mature milk exhibited beneficial effects on intestinal epithelial barrier protection. The present study will provide a better understanding of the role of EVs derived from colostrum and milk in dairy cows with different responses in the regulation of intestinal cells function, and also presents new evidence for the change of EVs cargos during various stages of lactation.


Assuntos
Vesículas Extracelulares , Leite , Animais , Feminino , Gravidez , Bovinos , Colostro , Lipopolissacarídeos/farmacologia , Caspase 3 , Fator de Necrose Tumoral alfa , Interleucina-6 , Proteína Supressora de Tumor p53 , Proteína X Associada a bcl-2 , Células Epiteliais
6.
ACS Chem Biol ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602492

RESUMO

The prevalence of multidrug-resistant (MDR) pathogens combined with a decline in antibiotic discovery presents a major challenge for health care. To refill the discovery pipeline, we need to find new ways to uncover new chemical entities. Here, we report the global genome mining-guided discovery of new lipopeptide antibiotics tridecaptin A5 and tridecaptin D, which exhibit unusual bioactivities within their class. The change in the antibacterial spectrum of Oct-TriA5 was explained solely by a Phe to Trp substitution as compared to Oct-TriA1, while Oct-TriD contained 6 substitutions. Metabolomic analysis of producer Paenibacillus sp. JJ-21 validated the predicted amino acid sequence of tridecaptin A5. Screening of tridecaptin analogues substituted at position 9 identified Oct-His9 as a potent congener with exceptional efficacy against Pseudomonas aeruginosa and reduced hemolytic and cytotoxic properties. Our work highlights the promise of tridecaptin analogues to combat MDR pathogens.

7.
Front Bioeng Biotechnol ; 12: 1363803, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481571

RESUMO

Introduction: Daunorubicin and doxorubicin, two anthracycline polyketides produced by S. peucetius, are potent anticancer agents that are widely used in chemotherapy, despite severe side effects. Recent advances have highlighted the potential of producing improved derivatives with reduced side effects by incorporating l-rhodosamine, the N,N-dimethyl analogue of the native amino sugar moiety. Method: In this study, we aimed to produce N,N-dimethylated anthracyclines by engineering the doxorubicin biosynthetic pathway in the industrial Streptomyces peucetius strain G001. To achieve this, we introduced genes from the aclarubicin biosynthetic pathway encoding the sugar N-methyltransferases AclP and AknX2. Furthermore, the native gene for glycosyltransferase DnrS was replaced with genes encoding the aclarubicin glycosyltransferases AknS and AknT. Additionally, the gene for methylesterase RdmC from the rhodomycin biosynthetic pathway was introduced. Results: A new host was engineered successfully, whereby genes from the aclarubicin pathway were introduced and expressed. LC-MS/MS analysis of the engineered strains showed that dimethylated sugars were efficiently produced, and that these were incorporated ino the anthracycline biosynthetic pathway to produce the novel dimethylated anthracycline N,N-dimethyldaunorubicin. Further downstream tailoring steps catalysed by the cytochrome P450 monooxygenase DoxA exhibited limited efficacy with N,N-dimethylated substrates. This resulted in only low production levels of N,N-dimethyldaunorubicin and no N,N-dimethyldoxorubicin, most likely due to the low affinity of DoxA for dimethylated substrates. Discussion: S. peucetius G001 was engineered such as to produce N,N-dimethylated sugars, which were incorporated into the biosynthetic pathway. This allowed the successful production of N,N-dimethyldaunorubicin, an anticancer drug with reduced cytotoxicity. DoxA is the key enzyme that determines the efficiency of the biosynthesis of N,N-dimethylated anthracyclines, and engineering of this enzyme will be a major step forwards towards the efficient production of more N,N-dimethylated anthracyclines, including N,N-dimethyldoxorubicin. This study provides valuable insights into the biosynthesis of clinically relevant daunorubicin derivatives, highlighting the importance of combinatorial biosynthesis.

8.
Biology (Basel) ; 13(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38534423

RESUMO

The prognosis for cancer patients has declined dramatically in recent years due to the challenges in treating malignant tumors. Tumor immunotherapy, which includes immune target inhibition and chimeric antigen receptor cell treatment, is currently evolving quickly. Among them, natural killer (NK) cells are gradually becoming another preferred cell immunotherapy after T cell immunotherapy due to their unique killing effects in innate and adaptive immunity. NK cell therapy has shown encouraging outcomes in clinical studies; however, there are still some problems, including limited efficacy in solid tumors, inadequate NK cell penetration, and expensive treatment expenses. Noteworthy benefits of nanomaterials include their chemical specificity, biocompatibility, and ease of manufacturing; these make them promising instruments for enhancing NK cell anti-tumor immune responses. Nanomaterials can promote NK cell homing and infiltration, participate in NK cell modification and non-invasive cell tracking and imaging modes, and greatly increase the effectiveness of NK cell immunotherapy. The introduction of NK cell-based immunotherapy research and a more detailed discussion of nanomaterial research in NK cell-based immunotherapy and molecular imaging will be the main topics of this review.

9.
Adv Mater ; : e2309172, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38391035

RESUMO

X-ray circular dichroism, arising from the contrast in X-ray absorption between opposite photon helicities, serves as a spectroscopic tool to measure the magnetization of ferromagnetic materials and identify the handedness of chiral crystals. Antiferromagnets with crystallographic chirality typically lack X-ray magnetic circular dichroism because of time-reversal symmetry, yet exhibit weak X-ray natural circular dichroism. Here, the observation of giant natural circular dichroism in the Ni L3-edge X-ray absorption of Ni3TeO6 is reported, a polar and chiral antiferromagnet with effective time-reversal symmetry. To unravel this intriguing phenomenon, a phenomenological model is proposed that classifies the movement of photons in a chiral crystal within the same symmetry class as that of a magnetic field. The coupling of X-ray polarization with the induced magnetization yields giant X-ray natural circular dichroism, revealing typical ferromagnetic behaviors allowed by the symmetry in an antiferromagnet, i.e., the altermagnetism of Ni3TeO6. The findings provide evidence for the interplay between magnetism and crystal chirality in natural optical activity. Additionally, the first example of a new class of magnetic materials exhibiting circular dichroism is established with time-reversal symmetry.

10.
Front Endocrinol (Lausanne) ; 15: 1326402, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323105

RESUMO

Background: Oxidative stress (OS) is considered one of the major factors affecting male fertility, and research in this field has seen constant growth year by year. Currently, around 700 relevant papers are published each year, with a trend of further growth. Therefore, this study systematically summarizes the literature published in the last decade from a bibliometric perspective, revealing the dynamic development of the field, identifying research hotspots, analyzing future trends, and providing reference for further research. Methods: Relevant literature on oxidative stress and male fertility was retrieved from the Web of Science Core Collection (WoSCC) database, covering the timespan from 2014 to 2023 and including two types, articles and reviews. CiteSpace and VOSviewer were used for bibliometric analysis, including cluster analysis, co-occurrence analysis, co-citation analysis, and burst analysis of countries/regions, institutions, journals, authors, references, and keywords. Results: This paper studied a total of 5,301 papers involving 107 countries/regions, with China having the highest number of publications (898 papers) and the United States having the highest centrality (0.62). Burst analysis of journal citations revealed the emergence of many new journals (e.g., Antioxidants-Basel, Front Endocrinol) after 2021, indicating continuous expansion and development in this field. Cluster analysis of co-cited references and co-occurring keywords divided the research into areas such as oxidative stress and male infertility, oxidative stress level detection, and antioxidants. The keywords associated with research hotspots shifted from oxidative stress detection, sperm DNA damage, apoptosis, and redox potential to DNA methylation, embryonic development, infection, polyunsaturated fatty acids, and antioxidants. Conclusion: Bibliometric methods provide an intuitive reflection of the development process in the field of oxidative stress and male fertility, as well as the analysis of research hotspots in different periods. Research on oxidative stress and embryonic development, as well as antioxidant health management, may become hotspots in future research.


Assuntos
Reconhecimento Automatizado de Padrão , Sêmen , Feminino , Gravidez , Humanos , Masculino , Estresse Oxidativo , Antioxidantes , Bibliometria , Fertilidade
11.
Environ Microbiol ; 26(2): e16589, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38356049

RESUMO

Ancient environmental samples, including permafrost soils and frozen animal remains, represent an archive with microbial communities that have barely been explored. This yet unexplored microbial world is a genetic resource that may provide us with new evolutionary insights into recent genomic changes, as well as novel metabolic pathways and chemistry. Here, we describe Actinomycetota Micromonospora, Oerskovia, Saccharopolyspora, Sanguibacter and Streptomyces species were successfully revived and their genome sequences resolved. Surprisingly, the genomes of these bacteria from an ancient source show a large phylogenetic distance to known strains and harbour many novel biosynthetic gene clusters that may well represent uncharacterised biosynthetic potential. Metabolic profiles of the strains display the production of known molecules like antimycin, conglobatin and macrotetrolides, but the majority of the mass features could not be dereplicated. Our work provides insights into Actinomycetota isolated from an ancient source, yielding unexplored genomic information that is not yet present in current databases.


Assuntos
Actinomycetales , Mamutes , Streptomyces , Animais , Filogenia , Genômica , Streptomyces/genética , Fezes
12.
BMC Pulm Med ; 24(1): 12, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178046

RESUMO

BACKGROUND: The new coronavirus Omicron variant strain spread rapidly worldwide and is currently the primary mutant strain prevalent in the world. OBJECTIVE: To explore the clinical features of severe central nervous system lesions in children infected with novel coronavirus Omicron mutant strain, so as to provide a reference for clinical diagnosis and treatment. MATERIALS AND METHODS: The clinical data of 13 children diagnosed with novel coronavirus Omicron variant strain complicated with severe central nervous system infection from December 13, 2022, to January 31, 2023, in the Children's Intensive Care Medicine Department of Shanxi Children's Hospital were retrospectively analyzed. RESULTS: Among the 13 children, there were 9 males (69%) and 4 females (31%); the ages ranged from 1-year-old 16 days to 13 years old, with a median age of 9 years old, and most of them were school-age children (84.6%). The 13 children were usually healthy, but this time they were all positive for the new coronavirus nucleic acid test. The 13 children had obvious signs of the abnormal nervous system when they were admitted to the hospital, among which 12 cases (92.3%) showed convulsions, 11 children had obvious disturbance of consciousness (84.6%) when they were admitted to the hospital, and 5 children had circulatory disorders (38.4%). Among the 13 children, 2 were cured (15.3%), 5 children had serious sequelae (38.4%) when they were discharged from the hospital, and 6 children died of severe illness (46.3%). CONCLUSION: This study illuminates the clinical characteristics of severe central nervous system complications in children with coronavirus variant infection, highlighting rapid onset, swift progression, relatively poor prognosis, and notable symptoms such as high fever, convulsions, altered consciousness, elevated interleukin-6 levels, increased cerebrospinal fluid lactate levels, and early imaging changes.


Assuntos
Sistema Nervoso Central , SARS-CoV-2 , Criança , Masculino , Feminino , Humanos , Recém-Nascido , Estudos Retrospectivos , Convulsões , Hospitais
13.
Genes Genomics ; 46(3): 323-332, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37831404

RESUMO

BACKGROUND: ACT001 is an anti-inflammatory agent that has been widely investigated for its role in tumors, intracranial diseases, and fibrotic diseases, but its effect on acute lung injury is less known. OBJECTIVE: The purpose of this study was to investigate the effect and mechanism of ACT001 on regulating inflammation and pyroptosis in lipopolysaccharide (LPS)-induced alveolar macrophages. METHODS: NR8383 alveolar macrophages treated with LPS were used to replicate the proinflammatory macrophage phenotype observed during acute lung injury. After ACT001 treatment, we measured the secretion and expression levels of critical inflammatory cytokines, the rate of pyroptosis, and the expression of NLRP3 inflammasome-associated proteins and pyroptosis-associated proteins. In addition, we assessed the role of the PPAR-γ/NF-κB signaling pathways and further validated the results with a PPAR-γ inhibitor. RESULTS: Our findings confirmed that ACT001 reduced the expression and release of inflammatory factors, attenuated cell pyroptosis, and downregulated the expression of NLRP3, ASC, caspase-1 p20, and GSDMD-N. These effects may be achieved by activating PPAR-γ expression and then inhibiting the NF-κB signaling pathway. When macrophages were treated with the PPAR-γ inhibitor, the protective effects of ACT001 were reversed. CONCLUSION: ACT001 significantly ameliorated inflammation and pyroptosis via the PPAR-γ/NF-κB signaling pathways in LPS-induced NR8383 alveolar macrophages.


Assuntos
Lesão Pulmonar Aguda , Furanos , NF-kappa B , Humanos , NF-kappa B/metabolismo , Macrófagos Alveolares/metabolismo , Lipopolissacarídeos/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores Ativados por Proliferador de Peroxissomo , Piroptose , Transdução de Sinais , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lesão Pulmonar Aguda/metabolismo
14.
Med Vet Entomol ; 38(1): 59-72, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37771128

RESUMO

Pederin, a defensive toxin in Paederus fuscipes, is produced by an uncultured Gram-negative symbiont, which establishes a stable symbiotic relationship with a female host before completion of metamorphosis. However, the transmission process of pederin-producing bacteria (PPB) in P. fuscipes at different life stages remains unknown. Herein, the PPB population dynamics and transcriptome atlas for P. fuscipes development (egg, first-instar larva, second-instar larva, pupa, and newly emerged female and male) were characterised. We found that a microbial layer containing PPB covered the eggshell, which could be sterilised by smearing the eggshell with streptomycin. Maternal secretions over the eggshell are likely the main PPB acquisition route for P. fuscipes offspring. The PPB density in eggs was significantly higher than that in other life stages (p < 0.05), which demonstrated that the beetle mothers gave more PPB than the larvae acquired. Physiological changes (hatching and eclosion) led to a decreased PPB density in P. fuscipes. Pattern recognition receptors related to Gram-negative bacteria recognition were identified from P. fuscipes transcriptomes across various life stages, which might be used to screen genes involved in PPB regulation. These results will help advance future efforts to determine the molecular mechanisms of PPB colonisation of P. fuscipes.


Assuntos
Besouros , Masculino , Feminino , Animais , Besouros/microbiologia , Besouros/fisiologia , Bactérias/genética , Larva , Piranos
15.
ACS Nano ; 18(4): 2828-2840, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38101421

RESUMO

Multiwalled carbon nanotubes (MWCNTs) have been widely used in many disciplines and raised great concerns about their negative health impacts, especially environmental and occupational exposure. MWCNTs have been reported to induce fibrotic responses; however, the underlying mechanisms remain largely veiled. Here, we reported that MWCNTs inhalation induced lung fibrosis together with decreased lung compliance, increased elastance in the mice model, and elevated surface tension in vitro. Specifically, MWCNTs increased surface tension by impairing the function of the pulmonary surfactant. Mechanistically, MWCNTs induced lamellar body (LB) dysfunction through autophagy dysfunction, which then leads to surface tension elevated by pulmonary surfactant dysfunction in the context of lung fibrosis. This is a study to investigate the molecular mechanism of MWCNTs-induced lung fibrosis and focus on surface tension. A direct mechanistic link among impaired LBs, surface tension, and fibrosis has been established. This finding elucidates the detailed molecular mechanisms of lung fibrosis induced by MWCNTs. It also highlights that pulmonary surfactants are expected to be potential therapeutic targets for the prevention and treatment of lung fibrosis induced by MWCNTs.


Assuntos
Doenças Pulmonares Intersticiais , Nanotubos de Carbono , Fibrose Pulmonar , Surfactantes Pulmonares , Camundongos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Tensão Superficial , Fibrose , Homeostase , Pulmão/patologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-38064616

RESUMO

Objective: This study was carried out to evaluate the clinical efficacy of proprotein convertase chymotrypsin 9 (PCSK9) inhibitors in multi-branch lesions in coronary artery disease with substandard lipid-lowering effects. Methods: This retrospective study collected the clinical data of 100 patients with multiple coronary artery diseases admitted to our hospital between May 2020 and August 2022 for analysis. The eligible patients were assigned to either a PCSK9 inhibitor group or a control group at a ratio of 1:1 by their dosing regimens, with 50 cases in each group. Outcome measures for the clinical efficacy of PCSK9 inhibitors included lipid levels, low-density lipoprotein cholesterol (LDL-C) changes, serum concentrations of coronary artery disease-related inflammatory factors, improvement of angina questionnaire scores, adverse reactions, and major cardiovascular adverse events. Results: PCSK9 inhibitors resulted in significantly lower serum concentrations of total cholesterol (TC), LDL-C, and ApoB and higher high-density lipoprotein cholesterol (HDL-C) levels versus conventional lipid-lowering medication (P < .05). The two arms exhibited similar serum concentrations of triglyceride (TG) and ApoA1 after treatment (P > .05). With LDL-C<1.4 mmol/L as the cut-off for desirable blood lipid levels, 47 (94%) patients reached the standard after in the PCSK9 inhibitors group, while no eligible cases were reported in the control group (P < .05). PCSK9 inhibitors provided a marked reduction in the serum concentrations of high-sensitivity C-reactive protein in the patients. Patients had higher angina stability (AS), angina flare (AF), physical limitation (PL), and treatment satisfaction (TS) scores after PCSK9 inhibitor administration versus after conventional medication (P < .05). PCSK9 inhibitors were associated with a significantly lower incidence of adverse cardiovascular events (10%) versus conventional medication (42%) (P < .05). Conclusion: PCSK9 inhibitors significantly improve the LDL-C concentrations of patients with multiple lesions of coronary artery disease who have failed to meet lipid-lowering targets, this enables physicians to more effectively manage patients' cholesterol levels, consequently reducing their cardiovascular risk. Moreover, these inhibitors have the potential to enhance patients' quality of life by alleviating relieve angina symptoms. These findings offer valuable insights into managing multi-branch coronary artery disease.

17.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(6): 695-697, 2023 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-38086731

RESUMO

This study introduced a time-delay exposure system independent of the mobile digital radiography equipment. The system consisted of lithium battery, delay control circuit, micro electric motor and related auxiliary facilities. When the starting time was reached through the delay circuit, the motor pushed out the rod to squeeze the exposure button and completed the exposure. The accessories used in this system were easy to purchase and cheap. At the same time, the technology was mature and had good compatibility. The exposure success rate was high and the exposure effect was satisfactory. This time-delay exposure system had good practicability and popularization value.


Assuntos
Intensificação de Imagem Radiográfica , Tecnologia , Fontes de Energia Elétrica
18.
Alzheimers Res Ther ; 15(1): 199, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957768

RESUMO

BACKGROUND: Understanding the pathological characteristics of various mild cognitive impairment (MCI) subtypes is crucial for the differential diagnosis of dementia. The purpose of this study was to feature divergent symptom-deficit profiles in amnestic MCI (aMCI) and non-amnestic MCI (naMCI). METHODS: T1 and DTI MRI data from a total of 158 older adults with 50 normal controls, 56 aMCI, and 52 naMCI were included. The voxel-wise gray matter volumes and the number of seed-based white matter fiber bundles were compared among these three groups. Furthermore, correlation and mediation analyses between the neuroimaging indices and cognitive measures were performed. RESULTS: The aMCI with specific memory abnormalities was characterized by volumetric atrophy of the left hippocampus but not by damage in the linked white matter fiber bundles. Conversely, naMCI was characterized by both the altered volume of the right inferior frontal gyrus and the significant damage to fiber bundles traversing the region in all three directions, not only affecting fibers around the atrophied area but also distant fibers. Mediation analyses of gray matter-white matter-cognition showed that gray matter atrophy affects the number of fiber bundles and further affects attention and executive function. Meanwhile, fiber bundle damage also affects gray matter volume, which further affects visual processing and language. CONCLUSIONS: The divergent structural damage patterns of the MCI subtypes and cognitive dysfunctions highlight the importance of detailed differential diagnoses in the early stages of pathological neurodegenerative diseases to deepen the understanding of dementia subtypes and inform targeted early clinical interventions.


Assuntos
Disfunção Cognitiva , Demência , Doenças Neurodegenerativas , Humanos , Idoso , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/diagnóstico , Córtex Cerebral/patologia , Doenças Neurodegenerativas/patologia , Demência/diagnóstico por imagem , Demência/patologia , Atrofia/patologia , Encéfalo/patologia , Testes Neuropsicológicos
19.
Food Res Int ; 174(Pt 1): 113567, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37986440

RESUMO

The circulating non-fried roast (CNR) technology was firstly applied to roast mutton. The formation of (non)volatile compounds in the mutton roasted for 0-15 min was investigated. The samples roasted at varying times were discriminated using GC-O-MS and multivariate data analysis. A total of 40 volatile compounds were observed, in which 17 compounds were considered as key odorants with odor activity values (OAVs) higher than 1, such as dimethyl trisulfide and 2-ethyl-3,5-dimethylpyrazine. Composition and concentrations of volatile compounds were significantly changed during the process. The key nonvolatile compounds that contributed to flavor were 5'-inosine monophosphate (5'-IMP) and glutamic acid based on taste active values (TAVs) greater than 1. The reduced concentrations of most free amino acids and 5'-nucleotides decreased the equivalent umami concentrations (EUC). The higher thermal conductivity, lower thermal diffusivity and water activity were responsible for the formation of volatile compounds with increased roasting times. The CNR technology was an efficient tool to roast meat products.


Assuntos
Temperatura Alta , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Aromatizantes/análise , Odorantes/análise , Cromatografia Gasosa-Espectrometria de Massas
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