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1.
Orthod Craniofac Res ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629950

RESUMO

OBJECTIVES: This study was aimed to clarify the incidence, severity, and clinical risk factors for white spot lesions (WSLs) in adolescent patients treated with clear aligners. METHODS: Pre-treatment and post-treatment intraoral photographs of 203 adolescent patients undergoing clear aligner therapy were retrospectively evaluated to assess the occurrence and severity of WSLs. Information on patients' general oral condition and orthodontic treatment was collected from clinical medical documents, retrospective questionnaires, and ClinCheck® software. Independent risk factors and model performance were determined by multivariate logistic regression and receiver operating characteristic curve analysis. RESULTS: Thirty-five percent of adolescent patients developed WSLs during clear aligner treatment. Logistic regression analysis revealed that the presence of WSLs before treatment (OR 2.484, 95% CI 1.245-4.957), frequency of drinking carbonated beverages (OR 1.508, 95% CI 1.045-2.177), and number of anterior attachments (OR 2.192, 95% CI 1.502-3.198) were risk factors for the occurrence of WSLs in adolescent patients treated with clear aligners (P < .05), whereas the number of times they brushed each day (OR 0.656, 95% CI 0.454-0.947) and frequency of aligner cleaning after eating while wearing them (OR 0.611, 95% CI 0.433-0.861) were protective factors against WSLs (P < .05). CONCLUSIONS: The incidence of WSLs was high in adolescent patients treated with clear aligners. Few brushings each day, pre-treatment WSLs, a high frequency of drinking carbonated beverages, a low frequency of aligner cleaning after eating while wearing them, and a high number of anterior attachments are strongly associated with the development of WSLs in adolescent patients treated with clear aligners.

2.
Arch Oral Biol ; 162: 105964, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582010

RESUMO

OBJECTIVE: This study aimed to explore the effects of small extracellular vesicles derived from lipopolysaccharide-preconditioned dental follicle cells (L-D-sEV) on periodontal ligament cells from periodontitis affected teeth (p-PDLCs) in vitro and experimental periodontitis in mice. DESIGN: In vitro, the biological function of p-PDLCs and the underlying molecular mechanism were investigated by flow cytometry, Western blot, and quantitative real-time PCR (qRT-PCR) analysis. Eighteen-eight-week-old male C57BL/6 mice were randomly divided into three groups: control (Con), periodontitis (Peri), and L-D-sEV groups. Mice periodontitis model was induced by placing the 5-0 silk thread (around the maxillary second molar) and P.gingivalis (1 ×107 CFUs per mouse). In vivo, the alveolar bone loss, osteoclast activity, and macrophage polarization were measured by micro-computed tomography and histological analysis. RESULTS: In vitro, the RANKL/OPG ratio and phosphorylation of JNK and P38 protein levels of p-PDLCs were significantly decreased after L-D-sEV administration. Besides, flow cytometry and qRT-PCR analysis showed that L-D-sEV reduced apoptosis of p-PDLCs, down-regulated apoptosis-related genes Caspase-3 and BCL-2-Associated X expression, and up-regulated B-cell lymphoma-2 gene levels. In vivo, L-D-sEV administration significantly reduced alveolar bone loss, inhibited osteoclast activity, and induced M2 polarization. The histological analysis showed that iNOS/CD206, RANKL/OPG, p-JNK/JNK, and p-P38/P38 ratios were significantly lower in the L-D-sEV group than in the Peri group. CONCLUSIONS: L-D-sEV administration alleviated alveolar bone loss by mediating RANKL/OPG-related osteoclast activity and M2 macrophage polarization, alleviating p-PDLCs apoptosis and proliferation via the JNK and P38 pathways.


Assuntos
Perda do Osso Alveolar , Periodontite , Camundongos , Masculino , Animais , Perda do Osso Alveolar/patologia , Lipopolissacarídeos/farmacologia , Microtomografia por Raio-X , Saco Dentário/metabolismo , Camundongos Endogâmicos C57BL , Periodontite/metabolismo , Apoptose , Modelos Animais de Doenças
3.
J Nanobiotechnology ; 22(1): 189, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632615

RESUMO

Although gene expression signatures offer tremendous potential in diseases diagnostic and prognostic, but massive gene expression signatures caused challenges for experimental detection and computational analysis in clinical setting. Here, we introduce a universal DNA-based molecular classifier for profiling gene expression signatures and generating immediate diagnostic outcomes. The molecular classifier begins with feature transformation, a modular and programmable strategy was used to capture relative relationships of low-concentration RNAs and convert them to general coding inputs. Then, competitive inhibition of the DNA catalytic reaction enables strict weight assignment for different inputs according to their importance, followed by summation, annihilation and reporting to accurately implement the mathematical model of the classifier. We validated the entire workflow by utilizing miRNA expression levels for the diagnosis of hepatocellular carcinoma (HCC) in clinical samples with an accuracy 85.7%. The results demonstrate the molecular classifier provides a universal solution to explore the correlation between gene expression patterns and disease diagnostics, monitoring, and prognosis, and supports personalized healthcare in primary care.

4.
Polymers (Basel) ; 16(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38611179

RESUMO

As a promising candidate for high-energy-density rechargeable lithium metal batteries, Li/FeS2 batteries still suffer from the large volume change and severe shuttle effect of lithium polysulfides during cycling. To improve the electrochemical performance, great efforts have been made to modify FeS2 cathodes by constructing various nanocomposites. However, energy density is sacrificed, and these materials are not applicable at a large scale. Herein, we report that the electrochemical performance of commercial FeS2 can be greatly enhanced with the application of a double-layer MoS2-CNTs-PVA (MCP)/PVA separator fabricated by electrospinning. The assembled Li/FeS2 batteries can still deliver a high discharge capacity of 400 mAh/g after 200 cycles at a current density of 0.5 C. The improved cycling stability can be attributed to the strong affinity towards lithium polysulfides (LiPSs) of the hydroxyl-rich PVA matrix and the unique double-layer structure, in which the bottom layer acts as an electrical insulation layer and the top layer coupled with MoS2/CNTs provides catalytic sites for LiPS conversion.

5.
Foods ; 13(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38611301

RESUMO

The objective of our study was to analyze and identify enzymatic peptides from straw mushrooms that can enhance salty taste with the aim of developing saltiness enhancement peptides to reduce salt intake and promote dietary health. We isolated taste-related peptides from the straw mushroom extract using ultrafiltration and identified them using UPLC-Q-TOF-MS/MS. The study found that the ultrafiltration fraction (500-2000 Da) of straw mushroom peptides had a saltiness enhancement effect, as revealed via subsequent E-tongue and sensory analyses. The ultrafiltration fractions (500-2000 Da) were found to contain 220 peptides, which were identified through UPLC-Q-TOF-MS/MS analysis. The interaction of these peptides with the T1R1/T1R3 receptor was also assessed. The investigation highlighted the significant involvement of Asp223, Gln243, Leu232, Asp251, and Pro254 in binding peptides from triple-enzymatically hydrolyzed straw mushrooms to T1R1/T1R3. Based on the binding energy and active site analysis, three peptides were selected for synthesis: DFNALPFK (-9.2 kcal/mol), YNEDNGIVK (-8.8 kcal/mol), and VPGGQEIKDR (-8.9 kcal/mol). Importantly, 3.2 mmol of VPGGQEIKDR increased the saltiness level of a 0.05% NaCl solution to that of a 0.15% NaCl solution. Additionally, the addition of 0.8 mmol of YNEDNGIVK to a 0.05% NaCl solution resulted in the same level of saltiness as a 0.1% NaCl solution.

6.
J Phys Chem A ; 128(15): 2989-2996, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38572621

RESUMO

The wavelength-dependent dynamics of the O(1D2) channel, formed by photoexcitation of CO2 to the 1Δu state at 143.53-153.03 nm, is investigated by using the time-sliced velocity-mapped ion imaging method. The measured ionic peaks of the O(1D2) images are analyzed to determine the total kinetic energy release (TKER) spectra and image anisotropy parameters. The structures observed in the TKER spectra can be directly assigned to the ro-vibrational state distributions of the counter CO photofragments. Compared to those observed at 157 and 155 nm, the highly rotationally excited CO photofragments still obviously appear in v = 0 and 1, but the fraction of rotational excitations is significantly reduced. Conversely, the CO photofragments exhibit substantially higher vibrational excitations, implying that the nearly linear 21A' state also contributes to dissociation in addition to the bend configuration. The image anisotropy parameters display an extremely slow decreasing trend with an increase of the CO ro-vibrational state besides those for the highest ro-vibrationally excited CO photofragments. Nevertheless, the nonaxial recoil effect, suggested in previous photodissociation studies of CO2 and other triatomic molecular systems, is still appropriate to explain the observations of internal energy dependences of image anisotropy parameters.

7.
Physiol Mol Biol Plants ; 30(2): 153-166, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38623162

RESUMO

Leguminosae is one of the three largest families of angiosperms after Compositae and Orchidaceae. It is widely distributed and grows in a variety of environments, including plains, mountains, deserts, forests, grasslands, and even waters where almost all legumes can be found. It is one of the most important sources of starch, protein and oil in the food of mankind and also an important source of high-quality forage material for animals, which has important economic significance. In our study, the codon usage patterns and variation sources of the chloroplast genome of nine important forage legumes were systematically analyzed. Meanwhile, we also constructed a phylogenetic tree based on the whole chloroplast genomes and protein coding sequences of these nine forage legumes. Our results showed that the chloroplast genomes of nine forage legumes end with A/T bases, and seven identical high-frequency (HF) codons were detected among the nine forage legumes. ENC-GC3s mapping, PR2 analysis, and neutral analysis showed that the codon bias of nine forage legumes was influenced by many factors, among which natural selection was the main influencing factor. The codon usage frequency showed that the Nicotiana tabacum and Saccharomyces cerevisiae can be considered as receptors for the exogenous expression of chloroplast genes of these nine forage legumes. The phylogenetic relationships of the chloroplast genomes and protein coding genes were highly similar, and the nine forage legumes were divided into three major clades. Among the clades Melilotus officinalis was more closely related to Medicago sativa, and Galega officinalis was more closely related to Galega orientalis. This study provides a scientific basis for the molecular markers research, species identification and phylogenetic studies of forage legumes. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01421-0.

8.
Open Med (Wars) ; 19(1): 20240951, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38623457

RESUMO

Objective: In the present study, we investigated the impact of left atrial appendage closure (LAAC) following catheter ablation (CA) on the left atrial structure and functioning of patients with paroxysmal atrial fibrillation (AF). Methods: Patients with paroxysmal AF were enrolled in this single-center prospective cohort study between April 2015 and July 2021; 353 patients received CA alone, while 93 patients received CA in combination with Watchman LAAC. We used age, gender, CHA2DS2-VASc, and HAS-BLED scores as well as other demographic variables to perform propensity score matching. Patients with paroxysmal AF were randomly assigned to the CA combined with Watchman LAAC group (combined treatment group) and the simple CA group, with 89 patients in each group. The left atrial structure, reserve, ventricular diastole, and pump functions and their changes in patients were assessed using routine Doppler echocardiography and 2D speckle tracking echocardiography over the course of a 1-year follow-up. Results: At 1-week follow-up, the reserve, ventricular diastole, and pump functions of the left atrium (LA) increased in both groups; these functions were gradually restored at the 1- to 3-month follow-up; they were close to or returned to their pre-operative levels at the 3-month follow-up; and no significant differences were found compared with the pre-operative levels at the 12-month follow-up. In the first 3 months, the reserve (Ƹ, SRs) and pump functions (SRa) in the combined treatment group decreased significantly when compared with the simple CA group, and the differences were statistically significant. Conclusion: Patients with paroxysmal AF may experience a short term, partial effect of LAAC on LA reserve and pump functions, which are gradually restored and the effect disappears by 12 months.

9.
Meat Sci ; 213: 109511, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38598966

RESUMO

This study primarily aimed to investigate the influence of seaweed dietary fibre (SDF), as a potential alternative to phosphates, on the quality profiles and flavour attributes of frankfurters. The results revealed that SDF addition can significantly improve the cooking yield and texture characteristics of phosphate-free frankfurters (P < 0.05), and 1.00% SDF proved to be the optimal concentration for replacing phosphates in frankfurters. Moreover, electronic nose and electronic tongue analyses demonstrated that SDF incorporation potentially influences the aroma and taste of phosphate-free frankfurters. Furthermore, volatile compound analysis revealed that SDF addition potentially compensates for the decrease in volatile flavour compound content caused by phosphate deficiency. Generally, our results indicate that SDF can be successfully applied as a potential alternative to phosphates and subsequently improve the quality profiles and flavour attributes of phosphate-free frankfurters. Moreover, they provide valuable theoretical guidance for the processing of phosphate-free emulsified meat products.

10.
Emerg Microbes Infect ; : 2341972, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597192

RESUMO

Staphylococcus aureus (S. aureus) is a notorious pathogen that cause metastatic or complicated infections. Hypervirulent ST398 clonotype strains, remarkably increased in recent years, dominated Community-associated S. aureus (CA-SA) infections in the past decade in China. Small RNAs like RNAIII have been demonstrated to play important roles in regulating the virulence of S. aureus, however, the regulatory roles played by many of these sRNAs in the ST398 clonotype strains are still unclear. Through transcriptome screening and combined with knockout phenotype analysis, we have identified a highly transcribed sRNA, RSaX28, in the ST398 clonotype strains. Sequence analysis revealed that RSaX28 is highly conserved in the most epidemic clonotypes of S. aureus, but its high transcription level is particularly prominent in the ST398 clonotype strains. Characterization of RSaX28 through RACE and Northern blot revealed its length to be 533nt. RSaX28 is capable of promoting the hemolytic ability, reducing biofilm formation capacity, and enhancing virulence of S. aureus in the in vivo murine infection model. Through IntaRNA prediction and EMSA validation, we found that RSaX28 can specifically interact with RNAIII, promoting its stability and positively regulating the translation of downstream alpha-toxin while inhibiting the translation of Sbi, thereby regulating the virulence and biofilm formation capacity of the ST398 clonotype strains. RSaX28 is an important virulence regulatory factor in the ST398 clonotype S. aureus and represents a potential important target for future treatment and immune intervention against S. aureus infections.

11.
Eur J Neurol ; : e16296, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588211

RESUMO

BACKGROUND AND PURPOSE: The ratio of serum uric acid (SUA) to serum creatinine (SCr), representing normalized SUA for renal function, is associated with functional outcome in acute ischaemic stroke (AIS) patients. However, its effect on AIS patients undergoing mechanical thrombectomy (MT) remains unknown. This study aimed to investigate the influence of the SUA/SCr ratio on clinical outcome in MT-treated AIS patients. METHODS: Acute ischaemic stroke patients who underwent MT were continuously enrolled from January 2018 to June 2023. Upon admission, SUA and SCr levels were recorded within the initial 24 h. Stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS) score. Clinical outcome included poor functional outcome (modified Rankin Scale score >2) at 90 days, symptomatic intracranial haemorrhage and death. RESULTS: Amongst 734 patients, 432 (58.8%) exhibited poor functional outcome at 90 days. The SUA/SCr ratio exhibited a negative correlation with NIHSS score (ρ = -0.095, p = 0.010). Univariate analysis revealed a significant association between SUA/SCr ratio and poor functional outcome. After adjusting for confounders, the SUA/SCr ratio remained an independent predictor of functional outcome (adjusted odds ratio 0.348, 95% confidence interval 0.282-0.428, p < 0.001). Receiver operating characteristic curve analysis highlighted the ability of the SUA/SCr ratio to predict functional outcome, with a cutoff value of 3.62 and an area under the curve of 0.757 (95% confidence interval 0.724-0.788, p < 0.001). CONCLUSION: The SUA/SCr ratio is correlated with stroke severity and may serve as a predictor of 90-day functional outcome in AIS patients undergoing MT.

12.
Adv Mater ; : e2401221, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563723

RESUMO

Renewable electricity-powered nitrate/carbon dioxide co-reduction reaction toward urea production paves an attractive alternative to industrial urea processes and offers a clean on-site approach to closing the global nitrogen cycle. However, its large-scale implantation is severely impeded by challenging C-N coupling and requires electrocatalysts with high activity/selectivity. Here, cobalt-nanoparticles anchored on carbon nanosheet (Co NPs@C) are proposed as a catalyst electrode to boost yield and Faradaic efficiency (FE) toward urea electrosynthesis with enhanced C-N coupling. Such Co NPs@C renders superb urea-producing activity with a high FE reaching 54.3% and a urea yield of 2217.5 µg h-1 mgcat. -1, much superior to the Co NPs and C nanosheet counterparts, and meanwhile shows strong stability. The Co NPs@C affords rich catalytically active sites, fast reactant diffusion, and sufficient catalytic surfaces-electrolyte contacts with favored charge and ion transfer efficiencies. The theoretical calculations reveal that the high-rate formation of *CO and *NH2 intermediates is crucial for facilitating urea synthesis.

13.
Medicine (Baltimore) ; 103(14): e37723, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579029

RESUMO

INTRODUCTION: Transseptal punctures (TSPs) are widely used in left atrium and left ventricle surgery. Accidental puncture of the puncture needle into the aorta is a rare complication that is rarely reported but has serious consequences. The appropriate management of this complication remains unclear. PATIENT CONCERNS: This report describes a case of a male with the chief complaint: paroxysmal palpitation for 1 year, aggravated for 1 month. DIAGNOSIS: The electrophysiological diagnosis was atrioventricular reentrant tachycardia caused by left-side bypass. INTERVENTIONS: Radiofrequency ablation of the heart was a necessary treatment and a TSP operation was needed, in which a puncture was mistakenly believed to have entered the aorta, a series of measures were taken urgently. Although the surgical procedure in this case was a false alarm, we still initiated a series of emergency plans. Emergency measures to address the complications were effectively implemented, and the emergency measures were promptly terminated after it was clear that complications had been misjudged. OUTCOMES: At last, it was confirmed that the angiogram was a pulmonary artery image, not an aorta image. Then the atrial septal puncture operation was successfully completed, and under the guidance of the Carto system, the ablation was successfully completed. Postoperative fluoroscopy showed no complications, such as pericardial effusion. After 2 years of follow-up, there was no reoccurrence of tachycardia, and there were no complications. It is crucial that emergency procedures are terminated in a timely manner after a clear miscarriage of performance. Although accidental puncture into the aorta is urgent and serious, performing a blockage or even thoracotomy in an emergency if complications are not clearly confirmed can cause further damage to the patient and would be a definitively wrong strategy. CONCLUSION: Strict and standardized TSP operations can avoid complications. Correct judgment of the authenticity of complications is crucial, and remedial measures that may cause further damage should not be blindly adopted. The retention of the aortic guide wire can provide convenient access for further differential diagnosis and remedial treatment.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Comunicação Interatrial , Ablação por Radiofrequência , Humanos , Masculino , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Estudos Retrospectivos , Punções/efeitos adversos , Punções/métodos , Aorta/cirurgia , Comunicação Interatrial/cirurgia , Fibrilação Atrial/cirurgia
14.
Nat Commun ; 15(1): 2950, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580635

RESUMO

Seawater electroreduction is attractive for future H2 production and intermittent energy storage, which has been hindered by aggressive Mg2+/Ca2+ precipitation at cathodes and consequent poor stability. Here we present a vital microscopic bubble/precipitate traffic system (MBPTS) by constructing honeycomb-type 3D cathodes for robust anti-precipitation seawater reduction (SR), which massively/uniformly release small-sized H2 bubbles to almost every corner of the cathode to repel Mg2+/Ca2+ precipitates without a break. Noticeably, the optimal cathode with built-in MBPTS not only enables state-of-the-art alkaline SR performance (1000-h stable operation at -1 A cm-2) but also is highly specialized in catalytically splitting natural seawater into H2 with the greatest anti-precipitation ability. Low precipitation amounts after prolonged tests under large current densities reflect genuine efficacy by our MBPTS. Additionally, a flow-type electrolyzer based on our optimal cathode stably functions at industrially-relevant 500 mA cm-2 for 150 h in natural seawater while unwaveringly sustaining near-100% H2 Faradic efficiency. Note that the estimated price (~1.8 US$/kgH2) is even cheaper than the US Department of Energy's goal price (2 US$/kgH2).

15.
J Texture Stud ; 55(2): e12823, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38613313

RESUMO

In 2017, the International Dysphagia Diet Standardisation Initiative (IDDSI) introduced the IDDSI flow test which enables patients, clinicians, caregivers, food service professionals and researchers to classify liquid thickness into five levels based on the volume of liquid remaining in a standard 10 mL slip tip syringe after 10 s of flow under gravity. Within a few months of publishing the IDDSI flow test instructions, several barriers emerged: (1) the preferred model of syringe (BD 303134) was not equally accessible around the world, causing some users to perform flow tests with alternate models of syringe; (2) differences in syringe geometry across models led to variations in IDDSI flow test results; and (3) the need to use a second syringe for sample loading added complexity and cost to end users. To address these barriers, IDDSI designed the IDDSI funnel, a novel device, which combines the geometry of the BD 303134 syringe with a kitchen funnel to facilitate easy loading of liquid samples without need for a second syringe. In this report, we compare the IDDSI flow test results across two devices: syringe BD 303134 and IDDSI funnel. IDDSI level classifications were in complete agreement with the syringe reference test results in 67/73 (92%) of the test fluids and temperature conditions with mean difference of residual liquid across devices of 0.2 (2% full scale). These results demonstrate excellent correspondence between the two devices.


Assuntos
Transtornos de Deglutição , Serviços de Alimentação , Humanos , Fenômenos Físicos , Temperatura
16.
Microb Pathog ; : 106644, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38616001

RESUMO

OBJECTIVE: To assess and compare the composition of tongue coating microbiota among patients at different stages of rheumatoid arthritis (RA). METHODS: A total of 47 patients diagnosed with RA, as per the American College of Rheumatology criteria, and 10 healthy individuals were enrolled in this study. The RA patients were stratified considering their Disease Activity Score 28 (DAS28), a composite measure based on the 28 tender and swollen joint count and erythrocyte sedimentation rate (ESR). The study population was further categorized into active phase group (LMH group) and inactive phase group (RE group) according to their DAS28 values. DNA extraction was extracted from tongue coating samples. Subsequently, the V3-V4 16S rDNA region was selectively amplified and sequenced through high-throughput 16S rDNA analysis. The resulting data were then utilized to ascertain the microbial contents. RESULTS: Significant variations were observed in the tongue coating microbiota of patients with RA during active and inactive phases, in comparison to healthy individuals (p < 0.05). At the genus level, the presence of Prevotellan, Veillonella, Rothia, and Neisseria in RA patients was notably more evident than in the healthy control (HC) group. These disparities find support in existing research on gut and oral microbiota. During the active phase of RA, the relative abundance of Veillonella, Rothia, and Neisseria in the tongue coating microbiota of patients was significantly higher than in those with inactive RA. These findings underscore the need for further and in-depth research on the potential impact of these microorganisms on the progression of RA disease. CONCLUSION: The results substantiate the hypothesis that tongue coating microbes actively contribute to the progression of RA.

17.
MedComm (2020) ; 5(4): e516, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38617433

RESUMO

At present, diabetes mellitus (DM) has been one of the most endangering healthy diseases. Current therapies contain controlling high blood sugar, reducing risk factors like obesity, hypertension, and so on; however, DM patients inevitably and eventually progress into different types of diabetes complications, resulting in poor quality of life. Unfortunately, the clear etiology and pathogenesis of diabetes complications have not been elucidated owing to intricate whole-body systems. The immune system was responsible to regulate homeostasis by triggering or resolving inflammatory response, indicating it may be necessary to diabetes complications. In fact, previous studies have been shown inflammation plays multifunctional roles in the pathogenesis of diabetes complications and is attracting attention to be the meaningful therapeutic strategy. To this end, this review systematically concluded the current studies over the relationships of susceptible diabetes complications (e.g., diabetic cardiomyopathy, diabetic retinopathy, diabetic peripheral neuropathy, and diabetic nephropathy) and inflammation, ranging from immune cell response, cytokines interaction to pathomechanism of organ injury. Besides, we also summarized various therapeutic strategies to improve diabetes complications by target inflammation from special remedies to conventional lifestyle changes. This review will offer a panoramic insight into the mechanisms of diabetes complications from an inflammatory perspective and also discuss contemporary clinical interventions.

18.
Nano Lett ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588010

RESUMO

Hampered by their susceptibility to nucleophilic attack and chemical bleaching, electron-deficient squaraine dyes have long been considered unsuitable for biological imaging. This study unveils a surprising twist: in aqueous environments, bleaching is not irreversible but rather a reversible spontaneous quenching process. Leveraging this new discovery, we introduce a novel deep-red squaraine probe tailored for live-cell super-resolution imaging. This probe enables single-molecule localization microscopy (SMLM) under physiological conditions without harmful additives or intense lasers and exhibits spontaneous blinking orchestrated by biological nucleophiles, such as glutathione or hydroxide anion. With a low duty cycle (∼0.1%) and high-emission rate (∼6 × 104 photons/s under 400 W/cm2), the squaraine probe surpasses the benchmark Cy5 dye by 4-fold and Si-rhodamine by a factor of 1.7 times. Live-cell SMLM with the probe reveals intricate structural details of cell membranes, which demonstrates the high potential of squaraine dyes for next-generation super-resolution imaging.

19.
Biochem Biophys Res Commun ; 709: 149836, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38564937

RESUMO

Mitochondria are essential cellular organelles; detecting mitochondrial damage is crucial in cellular biology and toxicology. Compared with existing chemical probe detection methods, genetically encoded fluorescent protein sensors can directly indicate cellular and molecular events without involving exogenous reagents. In this study, we introduced a molecular sensor system, MMD-Sensor, for monitoring mitochondrial membrane damage. The sensor consists of two molecular modules. Module I is a fusion structure of the mitochondrial localization sequence (MLS), AIF cleavage site sequence (CSS), nuclear localization sequence (NLS), N-terminus of mNeonGreen and mCherry. Module II is a fusion structure of the C-terminus of mNeonGreen, NLS sequence, and mtagBFP2. Under normal condition, Module I is constrained in the inner mitochondrial membrane anchored by MLS, while Module II is restricted to the nucleus by its NLS fusion component. If the mitochondrial membrane is damaged, CSS is cut from the inner membrane, causing Module I to shift into the nucleus guided by the NLS fusion component. After Module I enters the nucleus, the N- and C-terminus of mNeonGreen meet each other and rebuild its intact 3D structure through fragment complementation and thus generates green fluorescence in the nucleus. Dynamic migration of red fluorescence from mitochondria to the nucleus and generation of green fluorescence in the nucleus indicate mitochondrial membrane damage. Using the MMD-Sensor, mitochondrial membrane damage induced by various reagents, such as uncoupling agents, ATP synthase inhibitors, monovalent cationic carriers, and ROS, in HeLa and 293T cells are directly observed and evaluated.


Assuntos
Mitocôndrias , Membranas Mitocondriais , Humanos , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Células HeLa
20.
Heliyon ; 10(6): e28244, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38560689

RESUMO

Background: The immune microenvironment and oxidative stress of melanoma show significant heterogeneity, which affects tumor growth, invasion and treatment response. Single-cell and bulk RNA-seq data were used to explore the heterogeneity of the immune microenvironment and oxidative stress of melanoma. Methods: The R package Seurat facilitated the analysis of the single-cell dataset, while Harmony, another R package, was employed for batch effect correction. Cell types were classified using Uniform Manifold Approximation and Projection (UMAP). The Secreted Signaling algorithm from CellChatDB.human was applied to elucidate cell-to-cell communication patterns within the single-cell data. Consensus clustering analysis for the skin cutaneous melanoma (SKCM) samples was executed with the R package ConsensusClusterPlus. To quantify immune infiltrating cells, we utilized CIBERSORT, ESTIMATE, and TIMERxCell algorithms provided by the R package Immuno-Oncology Biological Research (IOBR). Single nucleotide variant (SNV) analysis was conducted using Maftools, an R package specifically designed for this purpose. Subsequently, the expression levels of PXDN and PAPSS2 genes were assessed in melanoma tissues compared to adjacent normal tissues. Furthermore, in vitro experiments were conducted to evaluate the proliferation and reactive oxygen species expression in melanoma cells following transfection with siRNA targeting PXDN and PAPSS2. Results: Malignant tumor cell populations were reclassified based on a comprehensive single-cell dataset analysis, which yielded six distinct tumor subsets. The specific marker genes identified for these subgroups were then used to interrogate the Cancer Genome Atlas Skin Cutaneous Melanoma (TCGA-SKCM) cohort, derived from bulk RNA sequencing data, resulting in the delineation of two immune molecular subtypes. Notably, patients within the cluster2 (C2) subtype exhibited a significantly more favorable prognosis compared to those in the cluster1 (C1) subtype. An alignment of immune characteristics was observed between the C2 subtype and unique immune functional tumor cell subsets. Genes differentially expressed across these subtypes were subsequently leveraged to construct a predictive risk model. In vitro investigations further revealed elevated expression levels of PXDN and PAPSS2 in melanoma tissue samples. Functional assays indicated that modulation of PXDN and PAPSS2 expression could influence the production of reactive oxygen species (ROS) and the proliferative capacity of melanoma cells. Conclusion: The constructed six-gene signature can be used as an immune response and an oxidative stress marker to guide the clinical diagnosis and treatment of melanoma.

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