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1.
Adv Healthc Mater ; : e2401567, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38962848

RESUMO

Copper is indispensable to organisms, while its homeostatic imbalance may interference normal cellular physiological processes and even induce cell death. Artificially regulating cellular copper content provides a viable strategy to activate antineoplastic effect. In light of this, a copper ions homeostasis perturbator (CuP-CL) with cinnamaldehyde (Cin) packaging and thermosensitive liposome coating is reported. Following laser exposure, the doping of Cu2+ in polydopamine initiates enhanced photothermal therapy (PTT) and unlocks the outer layer of liposome, leading to the release of copper ions and Cin in tumor microenvironment with mild acidity and high glutathione (GSH) levels. The liberative Cu2+ can evoke cuproptosis and chemodynamic therapy (CDT). Meanwhile, leveraging the merits of H2O2 supply and GSH consumption, Cin serves as a tumor microenvironment regulator to amplify Cu2+ mediated cuproptosis and CDT. Additionally, the positive feedback effects of "laser-triggered PTT, PTT accelerates reactive oxygen species (ROS) generation, ROS amplifies lipid peroxide (LPO) accumulation, LPO mediates heat shock proteins (HSPs) clearance, down-regulated HSPs promote PTT" entailed the overall benefit to therapeutic outcomes. Both in vitro and in vivo results corroborate the remarkable antineoplastic performance of CuP-CL by the synergy of cuproptosis/CDT/PTT. Collectively, based on the three-pronged approach, this work plots a viable multimodal regimen for cancer therapy.

2.
BMC Pulm Med ; 24(1): 291, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909192

RESUMO

OBJECTIVE: To investigate the association between meteorological data three days before admission and the status of sputum pathogens culture in hospitalized patients with Acute exacerbation of Chronic obstructive pulmonary disease (AECOPD) and respiratory infections. METHODS: Data from 1,370 AECOPD patients (80.66% males, approximately 80% age > 70) with respiratory infections hospitalized in Fujian Provincial Hospital between December 2013 and December 2019 were collected. This cohort comprised, along with concurrent meteorological data from Fuzhou. Group differences were analyzed to compare the meteorological data three days prior to admission between patients with positive sputum pathogen cultures and those without. Logistic regression models were employed to investigate the association between meteorological parameters and the status of sputum pathogen cultures in patients with AECOPD and respiratory infections. Sensitivity analyses was conducted among the hospitalized patients from 2013 to 2016 and 2017-2019. Stratified analysis was performed to explore the factors affecting the effect of temperature differences and their interactions. RESULTS: 578(42.19%) cases had a positive sputum culture report indicating pathogen growth. 323 cases were found with Gram-negative bacteria, 160 with Gram-positive bacteria, and 114 with fungi. Uni-variate analysis revealed statistical differences in DTD three days prior to admission (DTD-3d) between the positive and negative sputum culture groups (p = 0.019). Multivariate analysis indicated that an increase in the risk of positive sputum pathogen cultures was associated with greater DTD three days before admission (DTD-3d), with OR1.657 (95%CI [ 1.328-1.981]). The risk of positive sputum pathogen cultures was higher in groups with greater DTD-3d. The findings were consistent across different admission periods. Stratified analysis showed that patients without respiratory failure were more affected by DTD-3d, and an interaction effect was observed (p < 0.001). CONCLUSION: In coastal areas, the diurnal temperature difference three days prior to admission affects the sputum pathogen status in AECOPD patients with respiratory infections.


Assuntos
Hospitalização , Doença Pulmonar Obstrutiva Crônica , Escarro , Temperatura , Humanos , Escarro/microbiologia , Masculino , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Estudos Retrospectivos , Idoso , Feminino , China , Pessoa de Meia-Idade , Infecções Respiratórias/microbiologia , Infecções Respiratórias/diagnóstico , Idoso de 80 Anos ou mais , Progressão da Doença , Bactérias Gram-Negativas/isolamento & purificação , Modelos Logísticos , Bactérias Gram-Positivas/isolamento & purificação
3.
World J Clin Cases ; 12(16): 2789-2795, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38899280

RESUMO

BACKGROUND: Vitamin deficiencies are linked to various eye diseases, and the influence of vitamin D on cataract formation has been noted in prior research. However, detailed investigations into the causal relationship between 25-(OH)D status and cataract development remain scarce. AIM: To explore a possible causal link between cataracts and vitamin D. METHODS: In this study, we explored the causal link between 25-(OH)D levels and cataract development using Mendelian randomization. Our analytical approach included inverse-variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. The primary analyses utilized IVW with random effects, supplemented by sensitivity and heterogeneity tests using both IVW and MR-Egger. MR-Egger was also applied for pleiotropy testing. Additionally, a leave-one-out analysis helped identify potentially impactful single-nucleotide polymorphisms. RESULTS: The analysis revealed a positive association between 25-(OH)D levels and the risk of developing cataracts (OR = 1.11, 95%CI: 1.00-1.22; P = 0.032). The heterogeneity test revealed that our IVW analysis exhibited minimal heterogeneity (P > 0.05), and the pleiotropy test findings confirmed the absence of pleiotropy within our IVW analysis (P > 0.05). Furthermore, a search of the human genotype-phenotype association database failed to identify any potentially relevant risk-factor single nucleotide polymorphisms. CONCLUSION: There is a potential causal link between 25-(OH)D levels and the development of cataracts, suggesting that greater 25-(OH)D levels may be a contributing risk factor for cataract formation. Further experimental research is required to confirm these findings.

4.
Front Microbiol ; 15: 1364517, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832114

RESUMO

This study aimed to investigate the effect of prickly ash seeds (PAS) on the microbial community found in rumen microbes of Hu sheep by adding different percentages of prickly ash seeds and to carry out research on the relation between rumen flora and production performance. Twenty-seven male lambs of Hu sheep were classified into three groups based on the content of prickly ash seeds (PAS) fed for 90 days, i.e., 0%, 3%, and 6%. At the end of the feeding trial, rumen fluid samples were collected from six sheep in each group for 16S amplicon sequencing. The results showed that the addition of prickly ash seeds significantly increased both Chao1 and ACE indices (P < 0.05), and the differences between groups were greater than those within groups. The relative content of Bacteriodota decreased, and the relative content of Fusobacteriota, Proteobacteria, Acidobacteriota, and Euryarchaeota increased. The relative content of Papillibacter and Saccharofermentans was increased at the genus level, and the relative content of Bacteroides and Ruminococcus was decreased. The test group given 3% of prickly ash seeds was superior to the test group given 6% of prickly ash seeds. In addition, the addition of 3% of prickly ash seeds improved the metabolism or immunity of sheep. Fusobacteriota and Acidobacteriota were positively correlated with total weight, dressing percentage, and average daily gain (ADG) and negatively correlated with average daily feed intake (ADFI), feed-to-gain ratio (F/G), and lightness (L*). Methanobrevibacter and Saccharofermentans were positively correlated with ADG and negatively correlated with ADFI and L*. In conclusion, under the present experimental conditions, the addition of prickly ash seeds increased the abundance and diversity of rumen microorganisms in Hu sheep and changed the relative abundance of some genera. However, the addition of 6% prickly ash seeds may negatively affect the digestive and immune functions in sheep rumen.

5.
J Obstet Gynaecol ; 44(1): 2363515, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38864487

RESUMO

BACKGROUND: Cystatin SA (CST2) plays multiple roles in different types of malignant tumours; however, its role in serous ovarian cancer (SOC) remains unclear. Therefore, we aimed to investigate the expression levels, survival outcomes, immune cell infiltration, proliferation, cell cycle, and underlying molecular mechanisms associated with the CST2 signature in SOC. METHODS: The Cancer Genome Atlas database was used to acquire clinical information and CST2 expression profiles from patients with SOC. Wilcoxon rank-sum tests were used to compare CST2 expression levels between SOC and normal ovarian tissues. A prognostic assessment of CST2 was conducted using Cox regression analysis and the Kaplan-Meier method. Differentially expressed genes were identified using functional enrichment analysis. Immune cell infiltration was examined using a single-sample gene set enrichment analysis. Cell cycle characteristics and proliferation were assessed using a colony formation assay, flow cytometry, and a cell counting kit-8 assay. Western blots and quantitative reverse transcription PCR analyses were employed to examine CST2 expressions and related genes involved in the cell cycle and the Wnt-ß-catenin signalling pathway. RESULTS: Our findings revealed significant upregulation of CST2 in SOC, and elevated CST2 expression was correlated with advanced clinicopathological characteristics and unfavourable prognoses. Pathway enrichment analysis highlighted the association between the cell cycle and the Wnt signalling pathway. Moreover, increased CST2 levels were positively correlated with immune cell infiltration. Functionally, CST2 played vital roles in promoting cell proliferation, orchestrating the G1-to-S phase transition, and driving malignant SOC progression through activating the Wnt-ß-catenin signalling pathway. CONCLUSIONS: The elevated expression of CST2 may be related to the occurrence and progression of SOC by activating the Wnt-ß-catenin pathway. Additionally, our findings suggest that CST2 is a promising novel biomarker with potential applications in therapeutic, prognostic, and diagnostic strategies for SOC.


Serous ovarian cancer is a type of gynecological malignant tumour with high mortality rates. Understanding this disease is crucial for improving treatments and enhancing patient survival. In our study, we investigated a protein called CST2 and its role in serous ovarian cancer. We found that CST2 levels vary among patients and are associated with the progression of cancer and the prognosis of the patient, which could be valuable for future diagnosis and treatment strategies. However, further research is needed to validate these findings. Despite its limitations, our findings suggest that CST2 holds promise as a potential biomarker for detecting serous ovarian cancer and as a therapeutic target in the management of patients with this type of cancer.


Assuntos
Ciclo Celular , Proliferação de Células , Neoplasias Ovarianas , Via de Sinalização Wnt , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Via de Sinalização Wnt/genética , Proliferação de Células/genética , Ciclo Celular/genética , Pessoa de Meia-Idade , Prognóstico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Regulação para Cima
6.
Comput Methods Programs Biomed ; 254: 108292, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38936152

RESUMO

BACKGROUND AND OBJECTIVES: The exploration of various neuroimaging techniques have become focal points within the field of neuroscience research. Magnetoencephalography based on optically pumped magnetometers (OPM-MEG) has shown significant potential to be the next generation of functional neuroimaging with the advantages of high signal intensity and flexible sensor arrangement. In this study, we constructed a 31-channel OPM-MEG system and performed a preliminary comparison of the temporal and spatial relationship between magnetic responses measured by OPM-MEG and blood-oxygen-level-dependent signals detected by functional magnetic resonance imaging (fMRI) during a grasping task. METHODS: For OPM-MEG, the ß-band (15-30 Hz) oscillatory activities can be reliably detected across multiple subjects and multiple session runs. To effectively localize the inhibitory oscillatory activities, a source power-spectrum ratio-based imaging method was proposed. This approach was compared with conventional source imaging methods, such as minimum norm-type and beamformer methods, and was applied in OPM-MEG source analysis. Subsequently, the spatial and temporal responses at the source-level between OPM-MEG and fMRI were analyzed. RESULTS: The effectiveness of the proposed method was confirmed through simulations compared to benchmark methods. Our demonstration revealed an average spatial separation of 10.57 ± 4.41 mm between the localization results of OPM-MEG and fMRI across four subjects. Furthermore, the fMRI-constrained OPM-MEG localization results indicated a more focused imaging extent. CONCLUSIONS: Taken together, the performance exhibited by OPM-MEG positions it as a potential instrument for functional surgery assessment.

7.
Ann Thorac Surg ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936593

RESUMO

BACKGROUND: Although adverse technical events during aortic root replacement (ARR) are not uncommon and are extremely challenging, there is little literature to help surgeons prepare for such situations. We describe our experience of outstanding technical events during ARR. METHODS: This is a retrospective study of 830 consecutive ARR at a single center from 2012-2022. Technical events were defined as intraoperative events that led to an unplanned cardiac procedure, need for mechanical circulatory support, or additional aortic cross-clamping. Logistic regression identified factors associated with operative mortality and technical events. RESULTS: Technical events occurred in 90 (10.8%) patients, and were attributed to bleeding (n=26), nonischemic ventricular dysfunction (n=23), residual valve disease (n=20), myocardial ischemia (n=19), and iatrogenic dissection (n=2). Prior sternotomy (OR 2.38 [1.36-4.19], p=0.002) and complex aortic valve disease (OR 3.09 [1.09-8.75], p=0.03) were associated with technical events. Patients with technical events had higher rates of operative mortality (6.7% vs 2.3%, p=0.03) and all major postoperative complications. Surgical indications of dissection (OR 13.57 [4.95-37.23], p<0.001) and complex aortic valve disease (OR 14.09 [3.67-54.02], p<0.001) but not adverse technical events (OR 2.42 [0.81-7.26], p=0.11) were associated with operative mortality. CONCLUSIONS: Adverse technical events occur in 10.8% of ARR and were associated with reoperative sternotomies. Technical events are associated with increased postoperative complications.

8.
Animals (Basel) ; 14(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731263

RESUMO

The purpose of this experiment was to investigate the differences in rumen tissue morphology, volatile fatty acid content, and rumen microflora between Tianhua mutton sheep and Gansu alpine fine wool sheep under the same grazing conditions. Twelve 30-day-old lambs were randomly selected from two different flocks in Duolong Village and grazed together for a period of 150 days. The rumen tissue was fixed with 4% paraformaldehyde and brought back to the laboratory for H&E staining, the volatile fatty acid content of the rumen contents was detected by gas chromatography, and the rumen flora structure was sequenced by full-length sequencing of the bacterial 16S rRNA gene using the PacBio sequencing platform. The acetic acid and total acid contents of the rumen contents of Tianhua mutton sheep were significantly higher than those of Gansu alpine fine wool sheep (p < 0.05). The rumen papillae height of Tianhua mutton sheep was significantly higher than that of Gansu alpine fine wool sheep (p < 0.05). The diversity and richness of the rumen flora of Tianhua mutton sheep were higher than those of Gansu alpine fine wool sheep, and Beta analysis showed that the microflora structure of the two fine wool sheep was significantly different. At the phylum level, Firmicutes and Bacteroidetes dominated the rumen flora of Tianhua mutton sheep and Gansu alpine fine wool sheep. At the genus level, the dominant strains were Christensenellaceae_R_7_group and Rikenellaceae_RC9_gut_group. LEfSe analysis showed that Prevotella was a highly abundant differential species in Tianhua mutton sheep and lachnospiraccac was a highly abundant differential species in Gansu alpine fine wool sheep. Finally, both the KEGG and COG databases showed that the enrichment of biometabolic pathways, such as replication and repair and translation, were significantly higher in Tianhua mutton sheep than in Gansu alpine fine wool sheep (p < 0.05). In general, there were some similarities between Tianhua mutton sheep and Gansu alpine fine wool sheep in the rumen tissue morphology, rumen fermentation ability, and rumen flora structure. However, Tianhua mutton sheep had a better performance in the rumen acetic acid content, rumen papillae height, and beneficial bacteria content. These differences may be one of the reasons why Tianhua mutton sheep are more suitable for growing in alpine pastoral areas than Gansu alpine fine wool sheep.

9.
Adv Mater ; : e2404761, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38796773

RESUMO

Long-term continuous monitoring (LTCM) of physiological electrical signals is an effective means for detecting several cardiovascular diseases. However, the integrated challenges of stable adhesion, low impedance, and robust durability under different skin conditions significantly hinder the application of flexible electrodes in LTCM. This paper proposes a structured electrode inspired by the treefrog web, comprising dispersed pillars at the bottom and asymmetric cone holes at the top. Attachment structures with a dispersed pillar improve the contact stability (adhesion increases 2.79/13.16 times in dry/wet conditions compared to an electrode without structure). Improved permeable duct structure provides high permeability (12 times compared to cotton). Due to high adhesion and permeability, the electrode's durability is 40 times larger than commercial Ag/AgCl electrodes. The treefrog web-like electrode has great advantages in permeability, adhesion, and durability, resulting in prospects for application in physiological electrical signal detection and a new design idea for LTCM wearable dry electrodes.

10.
PeerJ ; 12: e17264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803580

RESUMO

Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) with heterogeneous clinical presentations. There are no clear testing parameters for its diagnosis, and the complex pathophysiology of IBS and the limited time that doctors have to spend with patients makes it difficult to adequately educate patients in the outpatient setting. An increased awareness of IBS means that patients are more likely to self-diagnose and self-manage IBS based on their own symptoms. These factors may make patients more likely to turn to Internet resources. Wikipedia is the most popular online encyclopedia among English-speaking users, with numerous validations. However, in Mandarin-speaking regions, the Baidu Encyclopedia is most commonly used. There have been no studies on the reliability, readability, and objectivity of IBS information on the two sites. This is an urgent issue as these platforms are accessed by approximately 1.45 billion people. Objective: We compared the IBS content on Wikipedia (in English) and Baidu Baike (in Chinese), two online encyclopedias, in terms of reliability, readability, and objectivity. Methods: The Baidu Encyclopedia (in Chinese) and Wikipedia (in English) were evaluated based on the Rome IV IBS definitions and diagnoses. All possible synonyms and derivatives for IBS and IBS-related FGIDs were screened and identified. Two gastroenterology experts evaluated the scores of articles for both sites using the DISCERN instrument, the Journal of the American Medical Association scoring system (JAMA), and the Global Quality Score (GQS). Results: Wikipedia scored higher overall with DISCERN (p < .0001), JAMA (p < .0001) and GQS (p < .05) than the Baidu Encyclopedia. Specifically, Wikipedia scored higher in DISCERN Section 1 (p < .0001), DISCERN Section 2 (p < .01), DISCERN Section 3 (p < .001), and the General DISCERN score (p < .0001) than the Baidu Encyclopedia. Both sites had low DISCERN Section 2 scores (p = .18). Wikipedia also had a larger percentage of high quality scores in total DISCERN, DISCERN Section 1, and DISCERN Section 3 (p < .0001, P < .0001, P < .0004, respectively, based on the above 3 (60%) rule). Conclusions: Wikipedia provides more reliable, higher quality, and more objective IBS-related health information than the Baidu Encyclopedia. However, there should be improvements in the information quality for both sites. Medical professionals and institutions should collaborate with these online platforms to offer better health information for IBS.


Assuntos
Internet , Síndrome do Intestino Irritável , Síndrome do Intestino Irritável/diagnóstico , Humanos , Compreensão , Enciclopédias como Assunto , Reprodutibilidade dos Testes , Informação de Saúde ao Consumidor/normas
11.
Adv Sci (Weinh) ; : e2403645, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720473

RESUMO

High spatial-resolution detection is essential for biomedical applications and human-machine interaction. However, as the sensor array density increases, the miniaturization will lead to interference between adjacent units and deterioration in sensing performance. Here, inspired by the cochlea's sensing structure, a high-density flexible pressure sensor array featuring with suspended sensing membrane with sensitivity-enhanced customized channels is presented for crosstalk-free and high-resolution detection. By imitating the basilar membrane attached to spiral ligaments, a sensing membrane is fixed onto a high-stiffness substrate with cavities, forming a stable braced isolation to provide an excellent crosstalk-free capability (crosstalk coefficient: 47.24 dB) with high-density integration (100 units within 1 cm2). Similar to the opening of ion channels in hair cells, the wedge-type expansion of the embedded cracks introduced by stress concentration structures enables a high sensitivity (0.19 kPa-1) and a large measuring range (400 kPa). Finally, it demonstrates promising applications in distributed displays and the condition monitoring of medical-surgical intubation.

12.
ACS Biomater Sci Eng ; 10(6): 3923-3934, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38766805

RESUMO

The repair of critical-sized bone defects continues to pose a challenge in clinics. Strontium (Sr), recognized for its function in bone metabolism regulation, has shown potential in bone repair. However, the underlying mechanism through which Sr2+ guided favorable osteogenesis by modulating macrophages remains unclear, limiting their application in the design of bone biomaterials. Herein, Sr-incorporated bioactive glass (SrBG) was synthesized for further investigation. The release of Sr ions enhanced the immunomodulatory properties and osteogenic potential by modulating the polarization of macrophages toward the M2 phenotype. In vivo, a 3D-printed SrBG scaffold was fabricated and showed consistently improved bone regeneration by creating a prohealing immunological microenvironment. RNA sequencing was performed to explore the underlying mechanisms. It was found that Sr ions might enhance the mitochondrial function of macrophage by activating PI3K/AKT/mTOR signaling, thereby favoring osteogenesis. Our findings demonstrate the relationship between the immunomodulatory role of Sr ions and the mitochondrial function of macrophages. By focusing on the mitochondrial function of macrophages, Sr2+-mediated immunomodulation sheds light on the future design of biomaterials for tissue regenerative engineering.


Assuntos
Vidro , Macrófagos , Mitocôndrias , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Estrôncio , Serina-Treonina Quinases TOR , Serina-Treonina Quinases TOR/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Estrôncio/farmacologia , Estrôncio/química , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Células RAW 264.7 , Vidro/química , Osteogênese/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Alicerces Teciduais/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Microambiente Celular/efeitos dos fármacos
13.
Microbiol Immunol ; 68(7): 213-223, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38747013

RESUMO

Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed that L. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.


Assuntos
Injúria Renal Aguda , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Probióticos , Microbioma Gastrointestinal/efeitos dos fármacos , Limosilactobacillus reuteri/fisiologia , Limosilactobacillus reuteri/metabolismo , Animais , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/metabolismo , Camundongos , Lipopolissacarídeos/metabolismo , Masculino , Rim/microbiologia , Rim/metabolismo , Fezes/microbiologia , Modelos Animais de Doenças , Creatinina/sangue , Camundongos Endogâmicos C57BL , Apoptose/efeitos dos fármacos
14.
Biomaterials ; 309: 122574, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38670032

RESUMO

As an iron dependent regulatory cell death process driven by excessive lipid peroxides (LPO), ferroptosis is recognized as a powerful weapon for pancreatic cancer (PC) therapy. However, the tumor microenvironment (TME) with hypoxia and elevated glutathione (GSH) expression not only inhibits LPO production, but also induces glutathione peroxidase 4 (GPX4) mediated LPO clearance, which greatly compromise the therapeutic outcomes of ferroptosis. To address these issues, herein, a novel triple-enhanced ferroptosis amplifier (denoted as Zal@HM-PTBC) is rationally designed. After intravenous injection, the overexpressed H2O2/GSH in TME induces the collapse of Zal@HM-PTBC and triggers the production of oxygen and reactive oxygen species (ROS), which synergistically amplify the degree of lipid peroxidation (broaden sources). Concurrently, GSH consumption because of the degradation of the hollow manganese dioxide (HM) significantly weakens the activity of GPX4, resulting in a decrease in LPO clearance (reduce expenditure). Moreover, the loading and site-directed release of zalcitabine further promotes autophagy-dependent LPO accumulation (enhance effectiveness). Both in vitro and in vivo results validated that the ferroptosis amplifier demonstrated superior specificity and favorable therapeutic responses. Overall, this triple-enhanced LPO accumulation strategy demonstrates the ability to facilitate the efficacy of ferroptosis, injecting vigorous vitality into the treatment of PC.


Assuntos
Ferroptose , Glutationa , Peróxidos Lipídicos , Neoplasias Pancreáticas , Ferroptose/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Animais , Peróxidos Lipídicos/metabolismo , Humanos , Linhagem Celular Tumoral , Glutationa/metabolismo , Camundongos , Compostos de Manganês/química , Óxidos/química , Espécies Reativas de Oxigênio/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Camundongos Nus , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos BALB C
15.
Appl Opt ; 63(10): A86-A97, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38568515

RESUMO

Pulsed light detecting and ranging (Lidar) is capable of acquiring comprehensive target information within a single pulse, including distance and intensity data. Intensity data reflects the target's backscattered intensity and is commonly regarded as a crucial observational parameter associated with target reflectivity information. Multiple studies have indicated the potential of intensity data in various applications within pulsed Lidar contexts. However, the intensity data is influenced by the incident angle and distance; hence it cannot directly manifest target characteristics. Consequently, a prerequisite for its usage is the implementation of intensity calibration. This paper presents a target intensity correction method based on an improved tail model, designed for preprocessing intensity data. First, the pulse echo signal equation is derived by incorporating the improved tail model with the detected target. On this foundation, a target echo intensity correction model is established to correct the intensities at various incident angles to those at the normal direction. Lastly, the derived approach is validated through simulation analysis, and practical experiments are conducted on a constructed pulsed Lidar system. These experiments meticulously investigate the influences of incident angle and distance, two prominent factors, on echo intensity. In the context of incident angle correction experiments, the mean absolute errors (MAEs) in calibrated values for diverse targets all remain within 0.04 V. Prior to correction, the maximum MAE for the cystosepiment is 0.505 V; after the correction it is reduced to merely 0.02 V, indicating a 96% reduction in error. Furthermore, all discrepancies exhibit an error standard deviation (ESD) of 0.03 V or less, showcasing favorable stability. For distance correction, under normal incidence conditions, a diverse set of targets is measured at different distances to achieve corrected MAE and ESD within 0.05 V. Consequently, the proposed method effectively achieves intensity correction concerning incident angles and distances. To achieve this, a reflectivity lookup table for the relevant targets was established. Combining this with the corrected intensity information enabled target identification in the three-dimensional imaging of pulsed Lidar.

16.
Psych J ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618757

RESUMO

Subitizing is the ability to appraise a number of small quantities (up to four) rapidly and precisely. This system, however, can be impaired by distractors presented along with targets to be enumerated. To better understand whether this limitation arises in perceptual circuits or in the response selection stage, we investigated whether subitizing can endure in simultaneous comparison tasks. Participants were asked to compare the number of dots in two sets on the left and right sides of the screen, presented either simultaneously or sequentially. For comparing within the numerosity range (6-32 dots), both the error rate and reaction time increased steadily as the ratio between the two numbers compared approached "1." Namely, a phenomenon labeled the ratio effect was revealed. For comparison with small numbers (<5), the sequential comparison task was errorless despite the ratio, suggesting the feature of subitizing. Individual efficiency (measured by the inverse efficiency score [IES]) did not correlate between number ranges in sequential comparison, suggesting that distinct mechanisms were involved. However, we found that in simultaneous tasks, error rate and efficiency showed an increase as the ratios of the two numbers compared approached "1." This is similar to the ratio effect revealed in the comparison for moderate numbers. Individual efficiency within these two ranges correlated, indicating that the enumeration within these two ranges was based on a single mechanism. These results suggest that subitizing cannot process sets in parallel, and numerosity takes the job whenever subitizing fails.

17.
IEEE Trans Med Imaging ; PP2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669168

RESUMO

Many of the tissues/lesions in the medical images may be ambiguous. Therefore, medical segmentation is typically annotated by a group of clinical experts to mitigate personal bias. A common solution to fuse different annotations is the majority vote, e.g., taking the average of multiple labels. However, such a strategy ignores the difference between the grader expertness. Inspired by the observation that medical image segmentation is usually used to assist the disease diagnosis in clinical practice, we propose the diagnosis-first principle, which is to take disease diagnosis as the criterion to calibrate the inter-observer segmentation uncertainty. Following this idea, a framework named Diagnosis-First segmentation Framework (DiFF) is proposed. Specifically, DiFF will first learn to fuse the multi-rater segmentation labels to a single ground-truth which could maximize the disease diagnosis performance. We dubbed the fused ground-truth as Diagnosis-First Ground-truth (DF-GT). Then, the Take and Give Model (T&G Model) to segment DF-GT from the raw image is proposed. With the T&G Model, DiFF can learn the segmentation with the calibrated uncertainty that facilitate the disease diagnosis. We verify the effectiveness of DiFF on three different medical segmentation tasks: optic-disc/optic-cup (OD/OC) segmentation on fundus images, thyroid nodule segmentation on ultrasound images, and skin lesion segmentation on dermoscopic images. Experimental results show that the proposed DiFF can effectively calibrate the segmentation uncertainty, and thus significantly facilitate the corresponding disease diagnosis, which outperforms previous state-of-the-art multi-rater learning methods.

18.
Talanta ; 274: 126055, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38626695

RESUMO

Direct analysis of solid samples is always challenging for ionic sensors due to solidified elemental presence and matrix interference. In this work, a "three-phase transforming" technique was first established to make solid sampling elemental sensors and visual detection possible in the future. For Cd transforming from soil samples, a metal ceramic heater (MCH) electrothermal vaporizer (ETV) coupled with a dielectric barrier discharge quartz trap (DBD-QT) was first utilized to fulfill the solid sampling and preconcentration of Cd in soil; for on-site analysis, a colorimetric sensor based on the trithiocyanuric acid (TMT) functionalized gold nanoparticles (AuNPs) was chosen as a chromogenic analysis model. The portable and miniature ETV-DBD apparatus directly introduced Cd from soil and then captured Cd, consuming only <130 W and 4.5 kg weight; finally, only 200 µL water was injected as eluent to dissolve Cd for the following colorimetric detection. Herein, the Cd analyte underwent a "three-phase transforming" from solid (Cd compounds in soil), to aerosol (vaporization and transportation), to solid (Cd oxides trapped on quartz surface) and to liquid (Cd2+ in eluate). Under optimized conditions, the method limit of detection (LOD) reached 0.04 mg/kg Cd (50 mg sample), fulfilling fast monitoring of Cd contamination in soil, with <20 % relative standard deviations (RSDs). The analysis time was <10 min excluding sample digestion and acid application, as well as the interference of Pb2+ on the AuNPs sensor can be eliminated via the "three-phase transforming" process, proving an excellent anti-interference for solid analysis. This "three-phase transforming" processing technique coupled with colorimetric sensor holds a great potential for direct and on-site analysis in solid samples without complicated handling, providing a fantastic methodology for the application of ionic sensors and making solid sampling elemental sensor and visual detection possible.

19.
World J Gastroenterol ; 30(9): 1108-1120, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577179

RESUMO

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.


Assuntos
Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Úlcera Gástrica , Humanos , Mucosa Gástrica/patologia , Gastrite/diagnóstico , Gastrite/tratamento farmacológico , Gastrite/epidemiologia , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/patologia , Gastroscopia , Infecções por Helicobacter/patologia , Estilo de Vida , Dor , Úlcera Gástrica/patologia
20.
J Gastrointest Surg ; 28(3): 259-266, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38445918

RESUMO

BACKGROUND: Diversion colitis (DC) is a prevalent complication of colostomy characterized by intestinal inflammation. This study aimed to investigate the therapeutic potential of somatostatin (SST) in managing DC. METHODS: After establishing a rat DC model, SST was administered via Mini Osmotic Pumps 2001W at a pumping rate of 1.0 µL/h. Various techniques, including hematoxylin and eosin staining, periodic acid-Schiff staining, immunofluorescence staining, and electron microscopy were employed to assess the effects of SST. Intestinal barrier functions were evaluated using Evans blue, enzyme-linked immunosorbent assay, and MacConkey agar. RESULTS: After SST treatment, the significant weight loss and associated high mortality in the DC group were successfully mitigated. Upregulation of claudin-3 and claudin-4 restored mechanical barriers in colon epithelial tissue, whereas protection of goblet cells and stimulation of mucus secretion enhanced mucus barriers. SST effectively reduced leaky gut and alleviated systemic inflammation. CONCLUSION: This study provides initial evidence supporting the efficacy of SST in the treatment of DC. It offers insights into the role of SST in DC by elucidating its ability to restore damaged intestinal barriers.


Assuntos
Colite , Colostomia , Animais , Ratos , Colostomia/efeitos adversos , Rios , Colite/tratamento farmacológico , Colite/cirurgia , Somatostatina/uso terapêutico , Inflamação
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