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1.
Clin Spine Surg ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38723028

RESUMO

STUDY DESIGN: Intraoperative neurophysiological monitoring (IONM) as a guide to bone layer estimation was examined during posterior cervical spine lamina grinding. OBJECTIVE: To explore the feasibility of IONM to estimate bone layer thickness. SUMMARY OF BACKGROUND DATA: Cervical laminoplasty is a classic operation for cervical spondylosis. To increase safety and accuracy, surgery-assistant robots are currently being studied. It combines the advantages of various program awareness methods to form a feasible security strategy. In the field of spinal surgery, robots have been successfully used to help place pedicle screws. IONM is used to monitor intraoperative nerve conditions in spinal surgery. This study was designed to explore the feasibility of adding IONM to robot safety strategies. METHODS: Chinese miniature pig model was used. Electrodes were placed on the lamina, and the minimum stimulation threshold of DNEP for each lamina was measured (Intact lamina, IL). The laminae were ground to measure the DNEP threshold after incomplete grinding (Inner cortical bone preserved, ICP) and complete grinding (Inner cortical bone grinded, ICG). Subsequently, the lateral cervical mass screw canal drilling was performed, and the t-EMG threshold of the intact and perforated screw canals was measured and compared. RESULT: The threshold was significantly lower than that of the recommended threshold of DENP via percutaneous cervical laminae measurement. The DNEP threshold decreases with the process of laminae grinding. The DNEP threshold of the IL group was significantly higher than ICP and ICG group, while there was no significant difference between the ICP group and the ICG group. There was no significant relationship between the integrity of the cervical spine lateral mass screw path and t-EMG threshold. CONCLUSIONS: It is feasible to use DENP threshold to estimate lamina thickness. Cervical lateral mass screw canals by t-EMG showed no help to evaluate the integrity.

2.
Ear Nose Throat J ; : 1455613241249540, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738381

RESUMO

Objectives: This project aims to explore the relationship between the air quality index (AQI), the concentration of 6 air pollutants, and the incidence of epistaxis in Yangzhou. Also, to provide reference information for the prevention and treatment of epistaxis. Methods: Data of patients with epistaxis admitted to the Northern Jiangsu People's Hospital Affiliated to Yangzhou University from January 2017 to December 2021 were collected. In addition, the local AQI and the concentrations of 6 air pollutants, namely particulate matter (PM2.5, PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3), were analyzed at the time of onset. Furthermore, the correlation with the incidence of epistaxis has been analyzed. Results: From 2017 to 2021, there were 24,721 patients with epistaxis aged from 0 to 17 years old while male patients were more than females. The incidence was higher in April, May, and June. There was a statistically significant difference in the number of daily epistaxis in different months and under AQI conditions (P < .05). Spearman's correlation analysis showed that there was a positive correlation between the number of daily epistaxis and the concentrations of AQI, CO, NO2, O3, PM2.5, PM10, and SO2 in Yangzhou, in which O3, PM10, and SO2 were highly correlated with the average number of daily epistaxis, and there was no obvious time lag effect of air pollutants on epistaxis. Conclusion: Epistaxis in the Yangzhou area is more common in males, mostly occurs in 0 to 17 years old, with seasonal. There was also a positive correlation between the incidence of epistaxis and air pollutants in Yangzhou. Therefore, by reducing the AQI index in daily life, and reducing the concentration of environmental pollutants in the air, the occurrence of epistaxis could be prevented and reduced to a certain extent.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38769195

RESUMO

BACKGROUND: High-resolution mapping offers superior accuracy in delineating conduction features; however, certain characteristics are still linked to elevated recurrence rates of atrial tachycardia (AT), suggesting the influence of additional mechanisms. This study systematically assessed the substrate of functional conduction block (FCB) regions in relation to the mechanisms of multiple ATs. METHODS: In this study, the Carto system facilitated the mapping of ATs in 13 patients undergoing ablation, each presenting with more than two AT variants. FCB regions were marked and further analyzed. RESULTS: A total of 33 sustained ATs were mapped across the patient cohort. FCB regions showed convertibility in 7 of 13 patients (54%). Three kinds of presentations can be summarized by the FCB region: Firstly, the FCB region could act as the main obstacle sustaining the localized reentrant pathway, for which rounding obviously has a direct correlation with the mechanism of the AT (27%). Secondly, the FCB regions could act as obstacle lines to reorganize the propagation of the reentry in localized AT and macroreentrant AT (55%). Lastly, the FCB region could act as a bystander and may not be related to the mechanism of the ATs (18%). The potentials in FCB regions mostly performed low voltages or fragmented potentials (FPs) in the ATs which they did not perform the conduction block (90%). CONCLUSION: In multiple ATs, FCB regions may not be uncommon. The participation of FCB regions in the mechanism of ATs showed three different kinds of performance. The dynamic nature of this substrate may provide insight into the reasons for the high recurrence of related ATs.

4.
Bioorg Med Chem ; 106: 117753, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749342

RESUMO

The expression of prostate-specific membrane antigen (PSMA) in prostate cancer is 100-1000 times higher than that in normal tissues, and it has shown great advantages in the diagnosis and treatment of prostate cancer. The combination of PSMA and PET imaging technology based on the principle of metabolic imaging can achieve high sensitivity and high specificity for diagnosis. Due to its suitable half-life (109 min) and good positron abundance (97%), as well as its cyclotron accelerated generation, 18F has the potential to be commercialize, which has attracted much attention. In this article, we synthesized a series of fluorosulfate PET tracers targeting PSMA. All four analogues have shown high affinity to PSMA (IC50 = 1.85-5.15 nM). After the radioisotope exchange labeling, [18F]L9 and [18F]L10 have PSMA specific cellular uptake (0.65 ± 0.04% AD and 1.19 ± 0.03% AD) and effectively accumulated in 22Rv1 xenograft mice model. This study demonstrates that PSMA-1007-based PSMA-targeted aryl [18F]fluorosulfate novel tracers have the potential for PET imaging in tumor tissues.


Assuntos
Antígenos de Superfície , Desenho de Fármacos , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Animais , Humanos , Masculino , Radioisótopos de Flúor/química , Camundongos , Antígenos de Superfície/metabolismo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Estrutura Molecular , Linhagem Celular Tumoral , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismo , Relação Estrutura-Atividade
5.
Hepatology ; 79(6): 1324-1336, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38758104

RESUMO

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.


Assuntos
Neoplasias do Sistema Biliar , Café , Chá , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias do Sistema Biliar/epidemiologia , Neoplasias do Sistema Biliar/etiologia , Idoso , Incidência , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/etiologia , Neoplasias da Vesícula Biliar/prevenção & controle , Fatores de Risco , Adulto , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/etiologia
6.
Carbohydr Polym ; 337: 122146, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710570

RESUMO

Diabetic wounds remain a global challenge due to disordered wound healing led by inflammation, infection, oxidative stress, and delayed proliferation. Therefore, an ideal wound dressing for diabetic wounds not only needs tissue adhesiveness, injectability, and self-healing properties but also needs a full regulation of the microenvironment. In this work, adhesive wound dressings (HA-DA/PRP) with injectability were fabricated by combining platelet rich plasma (PRP) and dopamine-modified-hyaluronic acid (HA-DA). The engineered wound dressings exhibited tissue adhesiveness, rapid self-healing, and shape adaptability, thereby enhancing stability and adaptability to irregular wounds. The in vitro experiments demonstrated that HA-DA/PRP adhesives significantly promoted fibroblast proliferation and migration, attributed to the loaded PRP. The adhesives showed antibacterial properties against both gram-positive and negative bacteria. Moreover, in vitro experiments confirmed that HA-DA/PRP adhesives effectively mitigated oxidative stress and inflammation. Finally, HA-DA/PRP accelerated the healing of diabetic wounds by inhibiting bacterial growth, promoting granulation tissue regeneration, accelerating neovascularization, facilitating collagen deposition, and modulating inflammation through inducing M1 to M2 polarization, in an in vivo model of infected diabetic wounds. Overall, HA-DA/PRP adhesives with the ability to comprehensively regulate the microenvironment in diabetic wounds may provide a novel approach to expedite the diabetic wounds healing in clinic.


Assuntos
Antibacterianos , Diabetes Mellitus Experimental , Ácido Hialurônico , Hidrogéis , Plasma Rico em Plaquetas , Cicatrização , Ácido Hialurônico/química , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Plasma Rico em Plaquetas/química , Antibacterianos/farmacologia , Antibacterianos/química , Diabetes Mellitus Experimental/tratamento farmacológico , Camundongos , Ratos , Bandagens , Masculino , Proliferação de Células/efeitos dos fármacos , Humanos , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Dopamina/química , Fibroblastos/efeitos dos fármacos , Adesivos/química , Adesivos/farmacologia
7.
Gene ; 922: 148562, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754567

RESUMO

BACKGROUND: Previously, we discovered a strain of Kunming mice, referred to as the KMush/ush strain, that exhibited notably abnormal electroretinogram (ERG) readings and elevated thresholds for auditory brainstem responses (ABRs), which resembled the characteristics of Usher Syndrome (USH). We successfully identified the pathogenic genes, Pde6b and Adgrv1, after KMush/ush crossbred with CBA/CaJ mice, referred to as CBA-1ush/ush, CBA-2ush/ush or CBA-2ush/ush. In this investigation, we crossbred KMush/ush and CBA/J mice to establish novel recombinant inbred lines and analysed their phenotypic and genotypic characteristics. METHODS: ERG readings, ABR testing, fundus morphology, histological examination of the retina and inner ear, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, western blotting, DNA sequence analysis and behavioural experiments were performed to assess the phenotypes and genotypes of the progeny lines. RESULTS: No obvious waveforms in the ERG were detected in F1 hybrid mice while normal ABR results were recorded. The F2 hybrids, which were called J1ush/ush or J2ush/ush, exhibited segregated hearing-loss phenotypes. J1ush/ush mice had a retinitis pigmentosa (RP) phenotype with elevated ABR thresholds, whereas J2ush/ush mice exhibited only the RP phenotype. Interestingly, J1ush/ush mice showed significantly higher ABR thresholds than wild-type mice at 28 days post born (P28), and RT-qPCR and DNA-sequencing analysis showed that Adgrv1 gene expression was significantly altered in J1ush/ush mice, but histological analysis showed no significant structural changes in the organ of Corti or spiral ganglia. Further elevation of ABR-related hearing thresholds by P56 manifested only as a reduced density of spiral ganglion cells, which differed significantly from the previous pattern of cochlear alterations in CBA-2ush/ush mice. CONCLUSIONS: We successfully introduced the hearing-loss phenotype of inbred mice with USH into CBA/J mice, which provides a good animal model for future studies on the important physiological roles of the Adgrv1 gene in inner-ear structure and for therapeutic studies targeting Adgrv1-mutated USH.

8.
Inorg Chem ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38752554

RESUMO

The combination of piezoelectric catalysis and photocatalysis could effectively enhance the carrier separation efficiency and further improve the hydrogen production activity. However, piezoelectric polarization always suffers from a low polarization strength, which severely restricts its actual applications. In this study, we successfully synthesized a novel sulfur vacancy-rich Bi2S3/ZnSn (OH)6 (BS-12/ZSH) piezo-photocatalyst for hydrogen evolution through water splitting. Notably, the piezo-photocatalytic hydrogen generation rate of the 8% BS-12/ZSH catalyst (336.21 µmol/g/h) was superior to that of pristine ZSH (29.71 µmol/g/h) and BS-12 (21.66 µmol/g/h). In addition, the hydrogen generation for 8% BS-12/ZSH (336.21 µmol/g/h) under ultrasonic coupling illumination was significantly higher than that under single illumination (52.09 µmol/g/h) and ultrasound (121.90 µmol/g/h), owing to the cooperative interaction of the sulfur vacancy and piezoelectric field. Various characterization analyses confirmed that (1) the introduction of sulfur vacancies in BS-12 provided more active sites, (2) BS-12 with sulfur vacancies acted as a co-catalyst to accelerate the hydrogen production rate, and (3) the piezoelectric field eliminated the electrostatic shielding and offered an additional driving force, which effectively promoted the separation of electron-hole pairs. This research clearly reveals the synergistic effect between piezocatalysis and photocatalysis as well as offers a promising sight for the rational design of high-efficiency piezo-photocatalysts.

9.
Medicine (Baltimore) ; 103(20): e38100, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758908

RESUMO

Numerous studies related to esophagogastric junction cancer (EGC) have been published, and bibliometric analysis of these publications may be able to identify research hotspots and frontiers of EGC. Studies published on EGC between 2002 and 2021 were retrieved from the Web of Science Core Collection. The collaboration network of countries/regions, institutions, authors, co-citation network of journals, co-occurrence network, and overlay visualization of keywords were analyzed using the VOSviewer software. Cluster and timeline analyses of references were performed using the CiteSpace software. A total of 5109 English articles were published across 691 journals by authors affiliated with 4727 institutions from 81 countries/regions. The annual number of publications related to EGC research has exhibited an increasing trend. The United States, China, and Japan emerged as the top 3 prolific countries/regions. Institutions in the United States, Japan, and South Korea exhibited significant collaboration with one another. Diseases of the Esophagus was the most prolific journal, and Annals of Surgical Oncology, World Journal of Gastroenterology, and Gastric Cancer had also published more than 100 studies. Jaffer A Ajani was the most productive author while David Cunningham ranked the first in terms of total citations and average citations per article. Barrett's esophagus, gastroesophageal reflux disease, Helicobacter pylori, and obesity were common topics in earlier research, and recent years had seen a shift towards the topics of immunotherapy, targeted therapy, and neoadjuvant chemotherapy. In conclusion, growing attention is paid to EGC research, especially in terms of immunotherapy, targeted therapy, and neoadjuvant chemotherapy.


Assuntos
Bibliometria , Neoplasias Esofágicas , Junção Esofagogástrica , Neoplasias Gástricas , Humanos , Junção Esofagogástrica/patologia , Neoplasias Esofágicas/terapia , Neoplasias Gástricas/terapia , Pesquisa Biomédica/estatística & dados numéricos
10.
J Colloid Interface Sci ; 669: 804-815, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38749219

RESUMO

Herein, a novel copper selenide/zinc selenide/Nitrogen-doped carbon (Cu2Se/ZnSe/NC) sphere was constructed via a combination of cation exchange, selenization and carbonization approaches with zinc-based metal-organic frameworks (ZIF-8) as precursor for sulfadiazine (SDZ) removal. Compared with the ZnSe/NC, the defective Cu2Se/ZnSe interface in the optimizing Cu-ZnSe/NC2 sample caused a remarkably improved adsorption performance. Notably, the adsorption capacity of 129.32 mg/g was better than that of mostly reported adsorbents for SDZ. And the adsorption referred to multiple-layer physical-chemical process that was spontaneous and exothermic. Besides, the Cu-ZnSe/NC2 displayed fast adsorption equilibrium of about 20 min and significant anti-interference ability for inorganic ions. Specially, the adsorbent possessed excellent stability and reusability, which could also be applied for rhodamine B (RhB), methylene blue (MB), and methyl orange (MO) dyes removal. Ultimately, the charge redistribution of Cu2Se/ZnSe interface greatly contributes the superior adsorption performance for SDZ, in which electrostatic attraction occupied extremely crucial status as compared to π-π electron-donor-acceptor (π-π EDA) interaction and hydrogen bonding (H-bonding), as revealed by the density function theory (DFT) calculations and experimental results. This study can provide a guideline for design of high-efficient adsorbent with interfacial charge redistribution.

11.
Comput Biol Med ; 176: 108530, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38749324

RESUMO

As an autoimmune-mediated inflammatory demyelinating disease of the central nervous system, multiple sclerosis (MS) is often confused with cerebral small vessel disease (cSVD), which is a regional pathological change in brain tissue with unknown pathogenesis. This is due to their similar clinical presentations and imaging manifestations. That misdiagnosis can significantly increase the occurrence of adverse events. Delayed or incorrect treatment is one of the most important causes of MS progression. Therefore, the development of a practical diagnostic imaging aid could significantly reduce the risk of misdiagnosis and improve patient prognosis. We propose an interpretable deep learning (DL) model that differentiates MS and cSVD using T2-weighted fluid-attenuated inversion recovery (FLAIR) images. Transfer learning (TL) was utilized to extract features from the ImageNet dataset. This pioneering model marks the first of its kind in neuroimaging, showing great potential in enhancing differential diagnostic capabilities within the field of neurological disorders. Our model extracts the texture features of the images and achieves more robust feature learning through two attention modules. The attention maps provided by the attention modules provide model interpretation to validate model learning and reveal more information to physicians. Finally, the proposed model is trained end-to-end using focal loss to reduce the influence of class imbalance. The model was validated using clinically diagnosed MS (n=112) and cSVD (n=321) patients from the Beijing Tiantan Hospital. The performance of the proposed model was better than that of two commonly used DL approaches, with a mean balanced accuracy of 86.06 % and a mean area under the receiver operating characteristic curve of 98.78 %. Moreover, the generated attention heat maps showed that the proposed model could focus on the lesion signatures in the image. The proposed model provides a practical diagnostic imaging aid for the use of routinely available imaging techniques such as magnetic resonance imaging to classify MS and cSVD by linking DL to human brain disease. We anticipate a substantial improvement in accurately distinguishing between various neurological conditions through this novel model.

12.
Artigo em Chinês | MEDLINE | ID: mdl-38563167

RESUMO

Objective:To study the characteristics of Mismatch negativity(MMN) in normal hearing patients of different ages, and to compare the MMN of normal hearing subjects at different ages to explore the differences in MMN between different ages. Methods:MMN test was performed on both ears using the classic Oddball mode. A frequency of 1 000 Hz(standard stimuli) and 2 000 Hz(deviant stimuli) was used to evoked the MMN. According to different age groups: the juvenile group(7-17 years old), the youth group(18-44 years old), the middle-aged group(45-59 years old), and the elderly group(60-75 years old), with 25 cases in each group. The MMN characteristics of normal hearing subjects in different age groups were analyzed statistically and the differences between groups were compared. All subjects underwent pure tone threshold test, tympanic reactance test and ABR test before MMN test. Results:MMN waveform could be elicited from both ears of 100 subjects. Among them, the average latency of the juvenile group was(159.70±20.34) ms while the average amplitude was(4.34±2.26) µV, For the youth group, the average latency was(166.01±28.67) ms and the average amplitude was(3.70±2.28) µV. Then in the middle-aged group, the average latency was(175.16±37.24) ms, meanwhile, the average amplitude was(2.69±0.84) µV. Finally, the elderly group has an average latency of(178.03±14.37) ms and an average amplitude of(2.11±0.70) µV. Therefore, there was no statistical difference in latency and amplitude between all groups(P>0.05), and there was no statistical difference in latency and amplitude between left and right ears among all subjects as a whole(P>0.05). However, when the left and right ears of all groups were compared, it was found that the latency between the left and right ears of the Juvenile group had statistical significance(P<0.05), and the amplitude difference was not statistically significant(P>0.05), while the latency and amplitude differences between the left and right ears of other groups had no statistical significance(P>0.05). There were also no significant differences in latency and amplitude between men and women(P>0.05). Conclusion:There was no statistically significant difference in the latency and amplitude of mismatched negative among normal hearing subjects of different ages, and no statistically significant difference in the MMN latency and amplitude between the left and right ears of subjects and between men and women. Therefore, the study inferred that the auditory cerebral cortex of subjects aged 7-75 years old maintained a stable state for a long time after maturity, and the latency and amplitude of mismatched negative waves were relatively stable. It is not affected by age, gender and ear side, and can stably reflect the auditory cortex function of the subjects. It has broad application prospects in clinical practice, and provides a reliable detection means for future research on the changes of the auditory cerebral cortex of patients, which is worthy of our further research and clinical promotion.


Assuntos
Córtex Auditivo , Audição , Masculino , Pessoa de Meia-Idade , Idoso , Adolescente , Humanos , Feminino , Criança , Adulto Jovem , Adulto , Audição/fisiologia , Orelha Média , Potenciais Evocados Auditivos/fisiologia , Estimulação Acústica
13.
Urolithiasis ; 52(1): 55, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564006

RESUMO

The formation of calcium oxalate (CaOx) crystals in the kidneys leads to renal epithelial damage and the progression of crystalline nephropathy. This study investigated the role of STIP1 homology and U-box protein 1 (STUB1), an E3 ubiquitin ligase, and cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel, in CaOx-related renal damage and autophagy regulation. HK-2 cells were treated with various doses of CaOx monohydrate (COM) to simulate kidney injury in vitro. Cell viability, reactive oxygen species (ROS) production, and apoptosis were assessed. The regulation of CFTR ubiquitination by STUB1 was confirmed by immunoprecipitation. An in vivo model was established by injecting mice with glyoxylate. COM treatment dose-dependently decreased cell viability, increased TNF-α and ROS production, and induced apoptotic cell death in HK-2 cells. COM-treated cells also showed decreased CFTR protein expression. CFTR overexpression improved cell viability and reduced ROS production in COM-stimulated HK-2 cells. Bioinformatics analysis predicted CFTR's ubiquitination binding site for STUB1. Further analysis confirmed the role of STUB1 as a ubiquitin ligase in CFTR degradation. Knockdown of STUB1 upregulated CFTR expression, while STUB1 overexpression had the opposite effect. Knockdown of CFTR reversed the impact of STUB1 deficiency on autophagy. The in vivo experiments showed that CFTR overexpression attenuated kidney tissue damage and CaOx deposition in mice. STUB1-mediated CFTR ubiquitination plays a crucial role in mitigating calcium oxalate-related renal damage by regulating autophagy. Targeting the STUB1/CFTR axis may hold therapeutic potential for treating kidney injury associated with calcium oxalate deposition.


Assuntos
Oxalato de Cálcio , Regulador de Condutância Transmembrana em Fibrose Cística , Animais , Camundongos , Espécies Reativas de Oxigênio , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Rim , Autofagia , Ubiquitinação , Oxalatos
14.
Int Wound J ; 21(4): e14851, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563121

RESUMO

Scarring following oral and maxillofacial trauma can have significant aesthetic and functional repercussions. Recombinant human epidermal growth factor (rhEGF) has emerged as a potential therapeutic agent to enhance wound healing and minimise scar formation. This retrospective study analysed data from March 2020 to June 2023 at a single institution. A total of 105 patients were divided into a control group (n = 70) receiving standard treatment and an observation group (n = 35) receiving standard treatment plus rhEGF. The primary outcomes were the incidence of scar hyperplasia and infection rates, with the secondary outcome being scar aesthetics measured by the visual analogue scale (VAS). No significant differences were found in baseline characteristics between the two groups. The observation group showed a significant reduction in scar hyperplasia (14.3% vs. 57.1%, χ2 = 20.98, p < 0.01) and infection rates (5.7% vs. 21.4%, χ2 = 4.246, p < 0.05) compared to the control group. VAS scores indicated a superior aesthetic outcome in the observation group at all post-treatment timepoints (p < 0.01). rhEGF treatment in oral and maxillofacial trauma patients resulted in favourable healing outcomes and reduced scar formation, improving aesthetic results. These findings highlight the therapeutic potential of rhEGF and underscore the need for larger-scale trials to further investigate its benefits.


Assuntos
Cicatriz , Traumatismos Maxilofaciais , Humanos , Cicatriz/tratamento farmacológico , Hiperplasia/tratamento farmacológico , Estudos Retrospectivos , Proteínas Recombinantes/uso terapêutico , Fator de Crescimento Epidérmico/uso terapêutico , Cicatrização , Traumatismos Maxilofaciais/tratamento farmacológico
15.
Anesthesiol Res Pract ; 2024: 4660422, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586152

RESUMO

Purpose: Preoperative oral carbohydrate (CHO) is a rapid postoperative rehabilitation protocol that improves perioperative outcomes and is widely used in adult surgical patients. However, pregnant women are excluded because of the possibility of aspiration due to delayed gastric emptying. This meta-analysis was conducted to evaluate the efficacy of preoperative oral CHO in elective cesarean section. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to July 2023. Randomized controlled trials were included. The risk of bias was assessed using the Cochrane tool. Risk ratios and 95% confidence intervals were calculated. Meta-analysis was performed using random-effects models to estimate risk ratios and mean differences (MDs) with 95% confidence intervals (CIs). The outcomes included thirst and hunger scores, incidence of vomiting and nausea, time to flatus, and homeostatic model assessment of insulin resistance (HOMA-IR). Results: A total of nine studies with 1211 patients were included in the analysis. The levels of thirst and hunger were evaluated using a 10-point visual analog scale, with 0 representing the best and 10 representing the worst. The severity of hunger (weighted mean difference (WMD: -2.34, 95% CI: -3.13 to -1.54), time to flatus (WMD: -3.51 hours, 95% CI: -6.85 to -0.17), and HOMA-IR (WMD: -1.04, 95% CI: -1.31 to -0.77) were significantly lower in the CHO group compared to the control group. However, there were no significant differences in the severity of thirst or the incidence of vomiting and nausea between the CHO and control groups. Conclusion: Preoperative oral CHO during cesarean section alleviates thirst and hunger, shortens the time of postoperative flatus, and reduces HOMA-IR. However, the available evidence is insufficient to reach a clear consensus on the benefits or harms of preoperative oral CHO during cesarean section. Therefore, it is premature to make a definitive recommendation for or against its routine use.

16.
Plants (Basel) ; 13(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38611479

RESUMO

Acyl carrier proteins (ACPs) have been reported to play a crucial role in responding to biotic and abiotic stresses, regulating growth and development. However, the biological function of the ACP gene family in the Brassica genus has been limited until now. In this study, we conducted a comprehensive analysis and identified a total of 120 ACP genes across six species in the Brassica genus. Among these, there were 27, 26, and 30 ACP genes in the allotetraploid B. napus, B. juncea, and B. carinata, respectively, and 14, 13, and 10 ACP genes in the diploid B. rapa, B. oleracea, and B. nigra, respectively. These ACP genes were further classified into six subclades, each containing conserved motifs and domains. Interestingly, the majority of ACP genes exhibited high conservation among the six species, suggesting that the genome evolution and polyploidization processes had relatively minor effects on the ACP gene family. The duplication modes of the six Brassica species were diverse, and the expansion of most ACPs in Brassica occurred primarily through dispersed duplication (DSD) events. Furthermore, most of the ACP genes were under purifying selection during the process of evolution. Subcellular localization experiments demonstrated that ACP genes in Brassica species are localized in chloroplasts and mitochondria. Cis-acting element analysis revealed that most of the ACP genes were associated with various abiotic stresses. Additionally, RNA-seq data revealed differential expression levels of BnaACP genes across various tissues in B. napus, with particularly high expression in seeds and buds. qRT-PCR analysis further indicated that BnaACP genes play a significant role in salt stress tolerance. These findings provide a comprehensive understanding of ACP genes in Brassica plants and will facilitate further functional analysis of these genes.

17.
bioRxiv ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617360

RESUMO

APOBEC enzymes are part of the innate immunity and are responsible for restricting viruses and retroelements by deaminating cytosine residues1,2. Most solid tumors harbor different levels of somatic mutations attributed to the off-target activities of APOBEC3A (A3A) and/or APOBEC3B (A3B)3-6. However, how APOBEC3A/B enzymes shape the tumor evolution in the presence of exogenous mutagenic processes is largely unknown. Here, by combining deep whole-genome sequencing with multi-omics profiling of 309 lung cancers from smokers with detailed tobacco smoking information, we identify two subtypes defined by low (LAS) and high (HAS) APOBEC mutagenesis. LAS are enriched for A3B-like mutagenesis and KRAS mutations, whereas HAS for A3A-like mutagenesis and TP53 mutations. Unlike APOBEC3A, APOBEC3B expression is strongly associated with an upregulation of the base excision repair pathway. Hypermutation by unrepaired A3A and tobacco smoking mutagenesis combined with TP53-induced genomic instability can trigger senescence7, apoptosis8, and cell regeneration9, as indicated by high expression of pulmonary healing signaling pathway, stemness markers and distal cell-of-origin in HAS. The expected association of tobacco smoking variables (e.g., time to first cigarette) with genomic/epigenomic changes are not observed in HAS, a plausible consequence of frequent cell senescence or apoptosis. HAS have more neoantigens, slower clonal expansion, and older age at onset compared to LAS, particularly in heavy smokers, consistent with high proportions of newly generated, unmutated cells and frequent immuno-editing. These findings show how heterogeneity in mutational burden across co-occurring mutational processes and cell types contributes to tumor development, with important clinical implications.

18.
Nat Microbiol ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649411

RESUMO

The cyclic-oligonucleotide-based anti-phage signalling system (CBASS) is a type of innate prokaryotic immune system. Composed of a cyclic GMP-AMP synthase (cGAS) and CBASS-associated proteins, CBASS uses cyclic oligonucleotides to activate antiviral immunity. One major class of CBASS contains a homologue of eukaryotic ubiquitin-conjugating enzymes, which is either an E1-E2 fusion or a single E2. However, the functions of single E2s in CBASS remain elusive. Here, using biochemical, genetic, cryo-electron microscopy and mass spectrometry investigations, we discover that the E2 enzyme from Serratia marcescens regulates cGAS by imitating the ubiquitination cascade. This includes the processing of the cGAS C terminus, conjugation of cGAS to a cysteine residue, ligation of cGAS to a lysine residue, cleavage of the isopeptide bond and poly-cGASylation. The poly-cGASylation activates cGAS to produce cGAMP, which acts as an antiviral signal and leads to cell death. Thus, our findings reveal a unique regulatory role of E2 in CBASS.

19.
Orthop Surg ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654387

RESUMO

OBJECTIVE: The reported date in the repeat surgical intervention for adolescent lumbar disc herniation (ALDH) after percutaneous endoscopic lumbar discectomy (PELD) was quite scarce. This study aims to introduce cases of repeat surgeries after PELD for ALDH and assess the incidence, chief causes, repeat surgery methods, and surgical outcomes of repeat surgeries after PELD for ALDH. METHODS: A retrospective multicenter observational study was conducted on patients undergoing repeat surgeries after PELD for ALDH at four tertiary referral hospitals from January 2014 through August 2022. The incidence of repeat surgeries, chief causes, strategies for repeat surgeries, and timing of repeat surgeries were recorded and analyzed. The clinical outcomes were evaluated by the Numeric Rating Scales (NRS) scores and the modified MacNab criteria. Statistical analyses were performed with the Wilcoxon signed-rank test. RESULTS: A total of 23 patients who underwent repeat surgeries after PELD for ALDH were included. The chief causes were re-herniation (homo-lateral re-herniation at the same level, new disc herniation of adjacent level). The repeat surgery methods were revision PELD, micro-endoscopic discectomy (MED), open discectomy and instrumented lumbar inter-body fusion. The NRS scores decreased significantly in follow-up evaluations and these scores demonstrated significant improvement at the last follow-up (p < 0.002). For the modified MacNab criteria, at the last follow-up, 18 patients (78.26%) had an excellent outcome, and the overall success rate was 86.95%. CONCLUSION: This study's data suggest that young patients who underwent repeat surgery improved significantly compared to baseline. The chief cause was re-herniation. Revision PELD was the main surgical procedure, which provides satisfactory clinical results in young patients who underwent repeat surgeries.

20.
Nucleic Acids Res ; 52(9): 5257-5272, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38634805

RESUMO

It has been proposed that coronavirus nsp15 mediates evasion of host cell double-stranded (ds) RNA sensors via its uracil-specific endoribonuclease activity. However, how nsp15 processes viral dsRNA, commonly considered as a genome replication intermediate, remains elusive. Previous research has mainly focused on short single-stranded RNA as substrates, and whether nsp15 prefers single-stranded or double-stranded RNA for cleavage is controversial. In the present work, we prepared numerous RNA substrates, including both long substrates mimicking the viral genome and short defined RNA, to clarify the substrate preference and cleavage pattern of SARS-CoV-2 nsp15. We demonstrated that SARS-CoV-2 nsp15 preferentially cleaved pyrimidine nucleotides located in less thermodynamically stable areas in dsRNA, such as AU-rich areas and mismatch-containing areas, in a nicking manner. Because coronavirus genomes generally have a high AU content, our work supported the mechanism that coronaviruses evade the antiviral response mediated by host cell dsRNA sensors by using nsp15 dsRNA nickase to directly cleave dsRNA intermediates formed during genome replication and transcription.


Assuntos
RNA de Cadeia Dupla , RNA Viral , SARS-CoV-2 , Proteínas não Estruturais Virais , RNA de Cadeia Dupla/metabolismo , RNA de Cadeia Dupla/genética , SARS-CoV-2/genética , SARS-CoV-2/enzimologia , RNA Viral/metabolismo , RNA Viral/genética , RNA Viral/química , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/genética , Humanos , Endorribonucleases/metabolismo , Endorribonucleases/genética , Replicação Viral/genética , Especificidade por Substrato , Genoma Viral , COVID-19/virologia
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