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1.
Nature ; 578(7796): 577-581, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32076270

RESUMO

Hydrogen peroxide (H2O2) is a major reactive oxygen species in unicellular and multicellular organisms, and is produced extracellularly in response to external stresses and internal cues1-4. H2O2 enters cells through aquaporin membrane proteins and covalently modifies cytoplasmic proteins to regulate signalling and cellular processes. However, whether sensors for H2O2 also exist on the cell surface remains unknown. In plant cells, H2O2 triggers an influx of Ca2+ ions, which is thought to be involved in H2O2 sensing and signalling. Here, by using forward genetic screens based on Ca2+ imaging, we isolated hydrogen-peroxide-induced Ca2+ increases (hpca) mutants in Arabidopsis, and identified HPCA1 as a leucine-rich-repeat receptor kinase belonging to a previously uncharacterized subfamily that features two extra pairs of cysteine residues in the extracellular domain. HPCA1 is localized to the plasma membrane and is activated by H2O2 via covalent modification of extracellular cysteine residues, which leads to autophosphorylation of HPCA1. HPCA1 mediates H2O2-induced activation of Ca2+ channels in guard cells and is required for stomatal closure. Our findings help to identify how the perception of extracellular H2O2 is integrated with responses to various external stresses and internal cues in plants, and have implications for the design of crops with enhanced fitness.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Peróxido de Hidrogênio/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Cisteína/química , Cisteína/metabolismo , Ativação Enzimática , Proteínas de Membrana/química , Proteínas de Membrana/genética , Mutação , Oxirredução , Células Vegetais/metabolismo , Domínios Proteicos , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética
2.
Proc Natl Acad Sci U S A ; 120(29): e2218973120, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37428928

RESUMO

Antibiotics are among the most used weapons in fighting microbial infections and have greatly improved the quality of human life. However, bacteria can eventually evolve to exhibit antibiotic resistance to almost all prescribed antibiotic drugs. Photodynamic therapy (PDT) develops little antibiotic resistance and has become a promising strategy in fighting bacterial infection. To augment the killing effect of PDT, the conventional strategy is introducing excess ROS in various ways, such as applying high light doses, high photosensitizer concentrations, and exogenous oxygen. In this study, we report a metallacage-based PDT strategy that minimizes the use of ROS by jointly using gallium-metal organic framework rods to inhibit the production of bacterial endogenous NO, amplify ROS stress, and enhance the killing effect. The augmented bactericidal effect was demonstrated both in vitro and in vivo. This proposed enhanced PDT strategy will provide a new option for bacterial ablation.


Assuntos
Fotoquimioterapia , Humanos , Espécies Reativas de Oxigênio/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias
3.
Proc Natl Acad Sci U S A ; 119(49): e2215124119, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36454760

RESUMO

Munc18 chaperones assembly of three membrane-anchored soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) into a four-helix bundle to mediate membrane fusion between vesicles and plasma membranes, leading to neurotransmitter or insulin release, glucose transporter (GLUT4) translocation, or other exocytotic processes. Yet, the molecular mechanism underlying chaperoned SNARE assembly is not well understood. Recent evidence suggests that Munc18-1 and Munc18-3 simultaneously bind their cognate SNAREs to form ternary template complexes - Munc18-1:Syntaxin-1:VAMP2 for synaptic vesicle fusion and Munc18-3:Syntaxin-4:VAMP2 for GLUT4 translocation and insulin release, which facilitate the binding of SNAP-25 or SNAP-23 to conclude SNARE assembly. Here, we further investigate the structure, dynamics, and function of the template complexes using optical tweezers. Our results suggest that the synaptic template complex transitions to an activated state with a rate of 0.054 s-1 for efficient SNAP-25 binding. The transition depends upon the linker region of syntaxin-1 upstream of its helical bundle-forming SNARE motif. In addition, the template complex is stabilized by a poorly characterized disordered loop region in Munc18-1. While the synaptic template complex efficiently binds both SNAP-25 and SNAP-23, the GLUT4 template complex strongly favors SNAP-23 over SNAP-25, despite the similar stabilities of their assembled SNARE bundles. Together, our data demonstrate that a highly dynamic template complex mediates efficient and specific SNARE assembly.


Assuntos
Fusão de Membrana , Proteína 2 Associada à Membrana da Vesícula , Sintaxina 1 , Chaperonas Moleculares , Proteínas Qa-SNARE/genética , Insulina
4.
BMC Cancer ; 24(1): 690, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844891

RESUMO

INTRODUCTION: The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC. METHODS: This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC. RESULTS: Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455). CONCLUSION: Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.


Assuntos
Recidiva Local de Neoplasia , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Adolescente , Masculino , Feminino , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Criança , Prognóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Adulto Jovem , Metástase Linfática/patologia , Seguimentos , Tireoidectomia , Adulto , Pré-Escolar
5.
J Nanobiotechnology ; 22(1): 246, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38735970

RESUMO

Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal-organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.


Assuntos
Inflamação , Estruturas Metalorgânicas , Espécies Reativas de Oxigênio , Cicatrização , Cicatrização/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Camundongos , Superóxido Dismutase/metabolismo , Porosidade , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células RAW 264.7 , Masculino , Ferroptose/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Diabetes Mellitus Experimental , Nanopartículas/química , Humanos , Antioxidantes/farmacologia , Nanocompostos/química , Proteínas de Membrana
6.
Eur Spine J ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858266

RESUMO

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) caused by osteoporosis is a common clinical fracture type. There are many surgical treatment options for OVCF, but there is a lack of comparison among different options. Therefore, we counted a total of 104 cases of OVCF operations with different surgical plans, followed up the patients, and compared the surgical outcome indications before, after and during the follow-up. METHOD: 104 patients who underwent posterior osteotomy (Modified PSO, SPO, PSO, VCR) and kyphosis correction surgery at our hospital between April 2006 and August 2021 with a minimum follow-up period of 24 months were included. All cases were injuries induced by a fall incurred while standing or lifting heavy objects without high-energy trauma. The mean CT value was 71 HU, which was below 110 HU, indicating severe osteoporosis. The indications for surgery included gait disturbance due to severe pain with pseudarthrosis, increased kyphotic angle, and progressive neurological symptoms. Pre- and postoperative CL, TLK, TK, PrTK, TKmax, GK, LL, PI, SS, PT, SVA, TPA, were investigated radiologically. Additionally, We evaluated estimated blood loss, surgical time and perioperative symptom. RESULT: The results show, after operation, TLK (37.32 ± 10.61° vs. 11.01 ± 8.06°, P < 0.001), TK (35.42 ± 17.64° vs. 25.62 ± 12.24°, P < 0.001), TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001), SVA (44.91 ± 48.67 vs. 23.52 ± 30.21, P = 0.013), CL (20.23 ± 13.21° vs. 11.45 ± 9.85°, P = 0.024) and TPA (27.44 ± 12.76° vs. 13.91 ± 9.24°, P = 0.009) were improved significantly in modified Pedicle subtraction osteotomy (mPSO) after operation. During follow-up, TLK (37.32 ± 10.61° vs. 13.88 ± 10.02°, P < 0.001) and TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001) were improved significantly in Modified PSO group. In additon, estimated blood loss (790.0 ± 552.2 ml vs. 987.0 ± 638.5 ml, P = 0.038), time of operation (244.1 ± 63.0 min vs. 292.4 ± 87.6 min, P = 0.025) were favorable in Modified PSO group compared to control group. CONCLUSION: To conclude, mPSO could acquire a favorable degree of kyphosis correction as well as fewer follow-up complications. Compared with other surgical methods, it also has the advantages of less surgical trauma and shorter operation time. It can be an effective solution for the treatment of OVCF.

7.
Gut ; 72(5): 958-971, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35688610

RESUMO

OBJECTIVE: Innate immunity plays important roles in pancreatic ductal adenocarcinoma (PDAC), as non-T-cell-enriched tumour. Neutrophils are major players in innate immune system. Here, we aimed to explore the heterogeneity and pro-tumour mechanisms of neutrophils in PDAC. DESIGN: We analysed single-cell transcriptomes of peripheral blood polymorphonuclear leucocytes (PMNs) and tumour-infiltrating immune cells from five patients with PDAC, and performed immunofluorescence/immunohistochemistry staining, multi-omics analysis and in vitro experiments to validate the discoveries of bioinformatics analysis. RESULTS: Exploration of the heterogeneity of tumour-associated neutrophils (TANs) revealed a terminally differentiated pro-tumour subpopulation (TAN-1) associated with poor prognosis, an inflammatory subpopulation (TAN-2), a population of transitional stage that have just migrated to tumour microenvironment (TAN-3) and a subpopulation preferentially expressing interferon-stimulated genes (TAN-4). Glycolysis signature was upregulated along neutrophil transition trajectory, and TAN-1 was featured with hyperactivated glycolytic activity. The glycolytic switch of TANs was validated by integrative multi-omics approach of transcriptomics, proteomics and metabolomics analysis. Activation of glycolytic activity by LDHA overexpression induced immunosuppression and pro-tumour functions in neutrophil-like differentiated HL-60 (dHL-60) cells. Mechanistic studies revealed BHLHE40, downstream to hypoxia and endoplasmic reticulum stress, was a key regulator in polarisation of neutrophils towards TAN-1 phenotype, and direct transcriptional regulation of BHLHE40 on TAN-1 marker genes was demonstrated by chromatin immunoprecipitation assay. Pro-tumour and immunosuppression functions were observed in dHL-60 cells overexpressing BHLHE40. Importantly, immunohistochemistry analysis of PDAC tissues revealed the unfavourable prognostic value of BHLHE40+ neutrophils. CONCLUSION: The dynamic properties of TANs revealed by this study will be helpful in advancing PDAC therapy targeting innate immunity.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neutrófilos , Microambiente Tumoral , Análise da Expressão Gênica de Célula Única , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Proteínas de Homeodomínio/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Neoplasias Pancreáticas
8.
Small ; 19(25): e2300363, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36929568

RESUMO

Although assembled hollow architectures have received considerable attention as lightweight functional materials, their uncontrollable self-aggregation and tedious synthetic methods hinder precise construction and modulation. Therefore, this study proposes a bi-ion synergistic regulation strategy to design assembled hollow-shaped cobalt spinel oxide microspheres. Dominated by the coordination-etching effects of F- and the hydrolysis-complex contributions of NH4 + , the unique construction is formed attributed to the dynamic cycles between metal complexes and precipitates. Meanwhile, their basic structures are perfectly retained after reduction treatment, enabling FeCo/CoFe2 O4 bimagnetic system to be obtained. Subsequently, in-depth analyses are conducted. Investigations reveal that multiscale magnetic coupling networks and enriched air-material heterointerfaces contribute to the remarkable magnetic-dielectric behavior, supported by the advanced off-axis electron holography technique. Consequently, the obtained FeCo/CoFe2 O4 composites exhibit excellent microwave absorption performances with minimal reflection losses (RLmin ) as high as -51.6 dB, an effective absorption bandwidth (EAB) of 4.7 GHz, and a matched thickness of 1.4 mm. Thus, this work provides an informative guide for rationally assembling building blocks into hollow architectures as advanced microwave absorbers through bi-ion and even multi-ion synergistic engineering mechanisms.

9.
Small ; : e2308192, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072794

RESUMO

The single-atom sites (SAs) have achieved enhanced performance toward oxygen reduction reaction (ORR) with the effective utilization of the active sites. However, the excess adsorption of the intermediates and the limited stability hinders performance improvement. Metal clusters with promising stability and weak adsorption can be used as potential substitutions, but the lack of active sites is considered undesirable for catalytic reactions. Herein, a framework of Fe nanoclusters combined with SAs on One dimensional (1D) carbon nanotubes (Fe3 C-NCNTs 90 min CC-1 ) is synthesized to confirm the synergistic atom-cluster interaction. The composite exhibits strong polarization and electron redistribution between nanocluster and SAs. The electron redistribution will significantly boost the electron transport and the desorption of the intermediates, which is confirmed by off-axis holography and DFT calculation. The electrocatalytic performance is significantly enhanced as the half-wave potential of ORR increased 75 mV and the potential of OER increased 133 mV compared with the sample without nanoclusters. Furthermore, such a bifunctional catalyst endows homemade Zn-air batteries (ZABs) with high power density and long-term stability. This work paves a facile route to design bifunctional ORR/OER electrocatalysts consisting of 0D composite structures.

10.
Small ; : e2308129, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037491

RESUMO

Engineering phase transition in micro-nanomaterials to optimize the dielectric properties and further enhance the electromagnetic microwave absorption (EMA) performance is highly desirable. However, the severe synthesis conditions restrict the design of EMA materials featuring controllable phases, which hinders the tunability of effective absorption bandwidth (EAB) and leads to an unclear loss mechanism. Herein, a seed phase decomposition-controlled strategy is proposed to induct nickel sulfide (NiSx ) absorbers with controllable phases and hollow sphere nature. Transmission electron microscopy holography and theoretical calculations evidence that the reconstruction of atoms in phase transition induces numerous heterogeneous interfaces and lattice defects/sulfur vacancies to cause varied work functions and local electronic redistribution, which contributes to reinforced dielectric polarization. As a result, the optimized NiS2 /NiS heterostructure enables enhanced EM attenuation capability with a wide EAB of 5.04 GHz at only 1.6 mm, compared to that of NiS2 and NiS. Moreover, the correlation between EAB and NiS phase content is demonstrated as the "volcano" feature. This study on the concept of phase transition of micro-nanomaterials can offer a novel approach to constructing highly efficient absorbers for EMA and other functionalities.

11.
Artigo em Inglês | MEDLINE | ID: mdl-37000635

RESUMO

We isolated a paraffin oil-degrading bacterial strain from a mixture of oil-based drill cutting and paddy soil, and characterized the strain using a polyphasic approach. The Gram-positive, aerobic, rod-shaped and non-spore-forming strain (SCAU 2101T) grew optimally at 50 °C, pH 7.0 and 0.5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequence indicated that the strain represented a distinct clade in the genus Chelativorans, neighbouring Chelativorans intermedius LMG 28482T (97.1 %). The genome size and DNA G+C content of the strain were 3 969 430 bp and 63.1 mol%, respectively. Whole genome based phylogenomic analyses showed that the average nucleotide identity and digital DNA-DNA hybridization values between strain SCAU 2101T and C. intermedius LMG 28482T were 77.5 and 21.2 %, respectively. The major respiratory quinone was Q-10. The dominant fatty acids were C19 : 0 cyclo ω8c (50.6 %), summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c; 22.5 %) and C18 : 0 (13.8 %). The polar lipids of the strain included phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylglycerol, phosphatidylcholine and diphosphatidylglycerol. Based on the results, strain SCAU 2101T was considered to represent a novel species in the genus Chelativorans, for which the name Chelativorans petroleitrophicus sp. nov. is proposed. The type strain is SCAU 2101T (= CCTCC AB 2021125T=KCTC 92067T).


Assuntos
Ácidos Graxos , Phyllobacteriaceae , Ácidos Graxos/química , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Ubiquinona/química , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Phyllobacteriaceae/genética
12.
Eur Radiol ; 33(7): 4513-4523, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36622410

RESUMO

OBJECTIVE: To evaluate the diagnostic performance of a commercial artificial intelligence (AI)-assisted ultrasonography (US) for thyroid nodules and to validate its value in real-world medical practice. MATERIALS AND METHODS: From March 2021 to July 2021, 236 consecutive patients with 312 suspicious thyroid nodules were prospectively enrolled in this study. One experienced radiologist performed US examinations with a real-time AI system (S-Detect). US images and AI reports of the nodules were recorded. Nine residents and three senior radiologists were invited to make a "benign" or "malignant" diagnosis based on recorded US images without knowing the AI reports. After referring to AI reports, the diagnosis was made again. The diagnostic performance of AI, residents, and senior radiologists with and without AI reports were analyzed. RESULTS: The sensitivity, accuracy, and AUC of the AI system were 0.95, 0.84, and 0.753, respectively, and were not statistically different from those of the experienced radiologists, but were superior to those of the residents (all p < 0.01). The AI-assisted resident strategy significantly improved the accuracy and sensitivity for nodules ≤ 1.5 cm (all p < 0.01), while reducing the unnecessary biopsy rate by up to 27.7% for nodules > 1.5 cm (p = 0.034). CONCLUSIONS: The AI system achieved performance, for cancer diagnosis, comparable to that of an average senior thyroid radiologist. The AI-assisted strategy can significantly improve the overall diagnostic performance for less-experienced radiologists, while increasing the discovery of thyroid cancer ≤ 1.5 cm and reducing unnecessary biopsies for nodules > 1.5 cm in real-world medical practice. KEY POINTS: • The AI system reached a senior radiologist-like level in the evaluation of thyroid cancer and could significantly improve the overall diagnostic performance of residents. • The AI-assisted strategy significantly improved ≤ 1.5 cm thyroid cancer screening AUC, accuracy, and sensitivity of the residents, leading to an increased detection of thyroid cancer while maintaining a comparable specificity to that of radiologists alone. • The AI-assisted strategy significantly reduced the unnecessary biopsy rate for thyroid nodules > 1.5 cm by the residents, while maintaining a comparable sensitivity to that of radiologists alone.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/patologia , Estudos Prospectivos , Inteligência Artificial , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/patologia , Ultrassonografia/métodos
13.
BMC Infect Dis ; 23(1): 443, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37391716

RESUMO

BACKGROUND: Negative conversion of nucleic acid was a key factor in deciding discharge or the end of isolation of asymptomatic or mild COVID-19 patients. We aimed to explore the effect of vaccination on the time to negative conversion after Omicron infection. METHODS: This retrospective cohort study included asymptomatic or mild patients with COVID-19 admitted to Fangcang shelter Hospital from November 10, 2022 to December 2, 2022. The relationship between vaccination status and the time to negative conversion was analyzed by multiple linear regression. RESULTS: A total of 2,104 asymptomatic or mild COVID-19 patients were included in the analysis, of whom 1,963 were vaccinated. The mean time to negative conversion of no vaccination, one dose, two doses, and three doses were 12.57 (5.05), 12.18 (3.46), 11.67 (4.86) and 11.22 (4.02) days, respectively (p = 0.002). Compared with no vaccination, two doses (ß=-0.88, 95% CI: -1.74, -0.02, p = 0.045), and three doses (ß=-1.51, 95% CI: -2.33, -0.70, p < 0.001) were both associated with shorter time to negative conversion. Comparing with two doses, booster dose was associated significantly with shorter time to negative conversion (ß=-0.63, 95% CI: -1.07, -0.20, p = 0.004). Age was positively correlated with the time to negative conversion (ß = 0.04, 95% CI: 0.02, 0.05, p < 0.001). CONCLUSION: Vaccination with inactivated vaccine and booster dose can shorten the time to negative conversion of asymptomatic or mild COVID-19 patients. The significant prolongation of time to negative conversion with increasing age suggests the promotion of vaccination, especially booster dose, particularly in the elderly.


Assuntos
COVID-19 , Ácidos Nucleicos , Idoso , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Hospitais Especializados , Estudos Retrospectivos , Unidades Móveis de Saúde
14.
Crit Care ; 27(1): 366, 2023 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-37742018

RESUMO

BACKGROUND: Critical care patients often require central venous cannulation (CVC). We hypothesized that real-time biplane ultrasound-guided CVC would improve first-puncture success rate and reduce mechanical complications. The purpose of this study was to compare the success rate and safety of single-plane and real-time biplane approaches for ultrasound-guided CVC. METHODS: From October 2022 to March 2023, 256 participants with critical illness requiring CVC were randomized to either the single-plane (n = 128) or biplane (n = 128) ultrasound-guided cannulation groups. The success rate, number of punctures, procedure duration, incidence of catheterization-related complications, and confidence score of operators were documented. RESULTS: The central vein was successfully cannulated in all 256 participants (163 [64%] man and 93 [36%] women; mean age 69 ± 19 [range 13-104 years]), including 182 and 74 who underwent internal jugular vein cannulation (IJVC) and femoral vein cannulation (FVC), respectively. The incidence of successful puncture on the first attempt was higher in the biplane group than that in the single-plane group (91.6% vs. 74.7%; relative risk (RR), 1.226; 95% confidence interval (CI), 1.069-1.405; P = 0.002 for the IJVC and 90.9% vs. 68.3%; RR, 1.331; 95% CI, 1.053-1.684; P = 0.019 for the FVC). The biplane group was also associated with a higher first-puncture single-pass catheterization success rate (87.4% vs. 69.0% and 90.9% vs. 68.3%), fewer undesired punctures (1[1-1(1-2)] vs. 1[1-2(1-4)] and 1[1-1(1-3)] vs. 1[1-2(1-4)]), shorter cannulation time (205 s [162-283 (66-1,526)] vs. 311 s [243-401 (136-1,223)] and 228 s [193-306 (66-1,669)] vs. 340 s [246-499 (130-944)]), and fewer immediate complications (10.5% vs. 28.7% and 9.1% vs. 34.1%) for both IJVC and FVC (all P < 0.05). CONCLUSION: Real-time biplane imaging of ultrasound-guided CVCs offers advantages over the single-plane approach for critically ill patients. TRIAL REGISTRATION: This prospective RCT was registered at Chinese Clinical Trial Registry (ChiCTR2200064843). Registered 19 October 2022.


Assuntos
Cateterismo Venoso Central , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Cateterismo Venoso Central/métodos , Ultrassonografia de Intervenção/métodos , Estudos Prospectivos , Ultrassonografia , Veias Jugulares/diagnóstico por imagem , Estado Terminal/terapia , Cuidados Críticos
15.
Clin Exp Pharmacol Physiol ; 50(6): 463-475, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36809521

RESUMO

Osteosarcoma (OS) is the most common bone tumour with a high risk of metastatic progression and recurrence after treatment. Circular RNA hsa_circ_0000591 (circ_0000591) plays a compelling role in OS aggressiveness. However, the function and regulatory mechanism of circ_0000591 need to be further elucidated. As a subject of this study, a differential circRNA circ_0000591 was screened by circRNA microarray expression profiling (GSE96964). Expression changes of circ_0000591 were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Effects of circ_0000591 silencing on OS cell viability, proliferation, colony formation, apoptosis, invasion, and glycolysis were determined via functional experiments. The mechanism by which circ_0000591 functions as a molecular sponge for miRNAs was predicted using bioinformatics analysis and validated using dual-luciferase reporter and RNA pull-down assays. Xenograft assay was done to validate the function of circ_0000591. Circ_0000591 was strongly expressed in OS samples and cells. Silencing of circ_0000591 lessened cell viability, repressed cell proliferation, invasion, glycolysis, and promoted cell apoptosis. Importantly, circ_0000591 regulated HK2 expression by serving as a miR-194-5p molecular sponge. MiR-194-5p silencing impaired circ_0000591 downregulation-mediated suppression of OS cell malignancy and glycolysis. HK2 overexpression weakened the inhibiting impacts of miR-194-5p on OS cell malignancy and glycolysis. Also, circ_0000591 silencing decreased xenograft tumour growth in vivo. Circ_0000591 drove OS glycolysis and growth by upregulating HK2 by sequestering miR-194-5p. The study highlighted the tumour-promoting function of circ_0000591 in OS.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Humanos , RNA Circular , Proliferação de Células , Glicólise , Linhagem Celular Tumoral
16.
BMC Musculoskelet Disord ; 24(1): 870, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946195

RESUMO

OBJECTIVE: Acute traumatic Spinal cord injury (TSCI) is a devastating event that causes severe sensory and motor impairments as well as autonomic dysfunction in patients, yet relevant clinical biomarkers have not been established. This study aimed to determine the significance of the serum glucose/potassium ratio (GPR) in evaluating TSCI severity and predicting prognosis. METHODS: An analysis of 520 clinical records of acute TSCI patients from January 2012 to June 2022 was conducted. The relationships between serum GPR and The American Spinal Injury Association Impairment Scale (AIS) grade 6-month post-trauma prognosis and the admission AIS grade were analyzed. To evaluate the discriminatory ability, a receiver operating characteristic curve (ROC) analysis was used. All methods were performed in accordance with the relevant guidelines and regulations. RESULTS: Based on the initial assessment of AIS grade, 256 (49.2%) patients were categorized into the severe TSCI group (AIS A-B), and there was a significant correlation between the severe TSCI group and serum GPR (p < 0.001). Serum GPR was reduced in an AIS grade-dependent manner (R = - 0.540, p < 0.001). Of the 520 patients, 262 (50.4%) patients were classified as having a poor prognosis according to the AIS grade at discharge. Serum GPR was also reduced in an AIS grade at discharge-dependent manner (R = - 0.599, p < 0.001), and was significantly higher in the poor prognosis group compared to the good prognosis group (p < 0.001). Poor prognosis was significantly associated with sex (p = 0.009), severity of TSCI (p < 0.001), location of TSCI (p < 0.001), surgical decompression (p < 0.018), body temperature (p < 0.001), heart rate (p < 0.001), systolic arterial pressure (SAP) (p < 0.001), diastolic arterial pressure (DAP) (p < 0.001), serum GPR (p < 0.001), serum glucose (p < 0.001), serum potassium (p < 0.001), and white blood cell count (p = 0.003). Multivariate logistic regression analysis showed a significant correlation between poor prognosis and serum GPR (p = 0.023). The ROC analysis showed the area under the curve of serum GPR to be a poor predictor of prognosis in TSCI patients at 0.842 (95% confidence interval, 0.808-0.875). CONCLUSION: There was a significant relationship between serum GPR and admission injury severity and the 6-month prognosis of acute TSCI patients. Serum GPR serves as a readily available clinical risk factor for predicting the severity and 6-month prognosis of acute traumatic spinal cord injury, which holds potential clinical significance for patients with TSCI.


Assuntos
Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Humanos , Glucose , Potássio , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/complicações , Prognóstico , Fatores de Risco , Estudos Retrospectivos
17.
Microsurgery ; 43(2): 185-195, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36086933

RESUMO

BACKGROUND: Perforator-based free perforator flaps have become an important tool for the reconstruction of tissue defects. The effect of the number of perforators on the outcomes of perforator flaps has been widely debated. This study aimed to compare the outcomes of single- and multiple-perforator-based free perforator flaps in free-flap reconstruction. METHODS: We searched PubMed, Web of Science, EMBASE, Chinese BioMedical Literature Database (CBM), Cochrane Library, and clinicaltrials.gov between January 2000 and June 2021 to identify studies that reported data on the outcomes of free perforator flaps. Two authors individually extracted data and performed quality assessment. Outcomes, including partial flap loss, total loss, fat necrosis, arterial insufficiency, venous insufficiency, hemorrhage and hematoma, wound dehiscence at recipient sites and donor site complications, were evaluated. RESULTS: Thirty-two studies with 2498 flaps were included in our analysis. No significant difference was found in the rates of partial loss and arterial insufficiency of flaps, hemorrhage and hematoma, wound dehiscence at recipient sites and donor site complications. However, the multiple-perforator group showed significantly lower rates of total loss (relative risk [RR] = 1.08, 95% confidence interval [CI]: 0.78-1.79, p = .754), fat necrosis (RR = 1.79, 95% [CI]: 1.36-2.36, p = .000) and venous insufficiency (RR = 1.72, 95% CI: 1.07-2.79, p = .026) than the single-perforator group. CONCLUSION: The rates of total loss, fat necrosis and venous insufficiency in the multiple-perforator group were lower than those in the single-perforator group. Hence, we recommend that multiple perforators be included in the free perforator flap when appropriate, to yield better clinical outcomes in reconstruction.


Assuntos
Necrose Gordurosa , Retalhos de Tecido Biológico , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Humanos , Complicações Pós-Operatórias/etiologia , Hematoma
18.
Mol Genet Genomics ; 297(1): 87-99, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34786637

RESUMO

The type of myofiber is related to the quality of meat. The slow oxidized myofiber helps to increase the tenderness and juiciness of muscle. Numerous studies have shown that circRNA plays a key role in skeletal muscle development. However, the role of circRNA in porcine skeletal myofiber types is unclear. In this study, we performed high-throughput RNA sequencing to study the differential expression of circRNA in the longissimus dorsi and the soleus muscle. A total of 40,757 circRNAs were identified, of which 181 were significantly different. Interestingly, some circRNAs were involved in metabolism pathways, AMPK, FoxO, and PI3K-Akt signaling pathways. Besides, we focused on a novel circRNA-circMYLK4. By injecting circMYLK4-AAV into piglets, we found that circMYLK4 significantly increased the mRNA and protein levels of the slow muscle marker genes. In summary, our study laid an essential foundation for further research of circRNA in myofiber type conversion and higher meat quality.


Assuntos
Desenvolvimento Muscular/genética , Músculo Esquelético/crescimento & desenvolvimento , RNA Circular/fisiologia , Suínos , Animais , Animais Geneticamente Modificados , Diferenciação Celular/genética , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Fibras Musculares de Contração Rápida/fisiologia , Fibras Musculares de Contração Lenta/fisiologia , Músculo Esquelético/fisiologia , RNA Circular/análise , RNA Circular/genética , Suínos/genética , Suínos/crescimento & desenvolvimento
19.
Soft Matter ; 18(20): 4031, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35543092

RESUMO

Correction for 'Efficient and stable electrorheological fluids based on chestnut-like cobalt hydroxide coupled with surface-functionalized carbon dots' by Yudai Liang et al., Soft Matter, 2022, DOI: 10.1039/D2SM00176D.

20.
Soft Matter ; 18(20): 3845-3855, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35416233

RESUMO

Intrinsically polarized electrorheological fluids (ERFs) have better thermal stability than ERFs with polar molecules, so they have a broader application prospect. However, the electrorheological efficiency of the common intrinsically polarized ERF is still lower than 1500, which is related to the poor wettability between polarized materials and the continuous phase. Carbon dots (CDs) exhibit good stability, semiconductor properties and low toxicity. We prepared biomimetic chestnut-like cobalt hydroxide coupled with surface-functionalized CD particles (Co(OH)2@CDs) by a simple hydrothermal method. Then we prepared an ERF by mixing Co(OH)2@CDs with silicone oil and studied the effect of CDs on its rheology and electrorheology properties. The synergistic effect of the lipophilic groups on the surface of CDs and the biomimetic chestnut-like structure makes Co(OH)2@CDs exhibit good wettability with silicone oil, and the optimal zero-field viscosity of Co(OH)2@CDs-ERF is only 0.46 Pa s (particle mass fraction of 40%). Exceptional electrorheological efficiency (about 10 000, shear rate 0.1 s-1, 5 kV mm-1) and dynamic shear stress stability of optimal Co(OH)2@CDs-ERF can be attributed to the dielectric enhancement of the biomimetic chestnut-like structure coupled with the semiconductor properties of CDs. In addition, Co(OH)2@CDs-ERF has excellent anti-settling performance, outstanding thermal stability and low current density.


Assuntos
Carbono , Óleos de Silicone , Carbono/química , Cobalto/química , Hidróxidos , Óleos de Silicone/química
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