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Recently, two-photon fluorescent probes based on anthocyanidin molecules have attracted extensive attention due to their outstanding photophysical properties. However, there are only a few two-photon excited fluorescent probes that really meet the requirements of relatively long emission wavelengths (>600 nm), large two-photon absorption (TPA) cross-sections (300 GM), significant Stokes shift (>80 nm), and high fluorescence intensity. Herein, the photophysical properties of a series of anthocyanidins with the same substituents but different fluorophore skeletons are investigated in detail. Compared with b-series molecules, a-series molecules with a six-membered ring in the backbone have a slightly higher reorganization energy. This results in more energy loss upon light excitation, enabling the reaction products to detect NTR through a larger Stokes shift. More importantly, there is very little decrease in fluorescence intensity as the Stokes shift increases. These features are extremely valuable for high-resolution NTR detection. In light of this, novel 2a-n (n = 1-5) compounds are designed, which are accomplished by inhibiting the twisted intramolecular charge transfer (TICT) effect through alkyl cyclization, azetidine ring and extending π conjugation. Among them, 2a-3 gains a long emission spectrum (λem = 691.4 nm), noticeable TPA cross-section (957 GM), and large Stokes shift (110 nm), indicating that it serves as a promising candidate for two-photon fluorescent dyes. It is hoped that this work will offer some insightful theoretical direction for the development of novel high performance anthocyanin fluorescent materials.
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The benzofuran core inhibitors HCV-796, BMS-929075, MK-8876, compound 2, and compound 9B exhibit good pan-genotypic activity against various genotypes of NS5B polymerase. To elucidate their mechanism of action, multiple molecular simulation methods were used to investigate the complex systems of these inhibitors binding to GT1a, 1b, 2a, and 2b NS5B polymerases. The calculation results indicated that these five inhibitors can not only interact with the residues in the palm II subdomain of NS5B polymerase, but also with the residues in the palm I subdomain or the palm I/III overlap region. Interestingly, the binding of inhibitors with longer substituents at the C5 position (BMS-929075, MK-8876, compound 2, and compound 9B) to the GT1a and 2b NS5B polymerases exhibits different binding patterns compared to the binding to the GT1b and 2a NS5B polymerases. The interactions between the para-fluorophenyl groups at the C2 positions of the inhibitors and the residues at the binding pockets, together with the interactions between the substituents at the C5 positions and the residues at the reverse ß-fold (residues 441-456), play a key role in recognition and the induction of the binding. The relevant studies could provide valuable information for further research and development of novel anti-HCV benzofuran core pan-genotypic inhibitors.
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Antivirales , Benzofuranos , Genotipo , Hepacivirus , Proteínas no Estructurales Virales , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/química , Benzofuranos/química , Benzofuranos/farmacología , Hepacivirus/efectos de los fármacos , Hepacivirus/enzimología , Hepacivirus/genética , Antivirales/farmacología , Antivirales/química , Simulación de Dinámica Molecular , Simulación del Acoplamiento Molecular , Sitios de Unión , Unión Proteica , Humanos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , ARN Polimerasa Dependiente del ARNRESUMEN
BACKGROUND: The oscillometrically measured ankle-brachial index (omABI), which is determined by the ratio of ankle to brachial systolic blood pressure measured through oscillography, has been demonstrated as a robust predictor of cardiovascular events. However, the reliability of mean arterial pressure measured by oscillography may be higher than that of systolic blood pressure based on the principle of oscillographic oscillation. We aimed to compare the predictive value of oscillometrically measured ankle-tobrachial mean arterial pressure ratio (omMAPR) and omABI for cardiovascular events and all-cause mortality. METHODS: The observation cohort consisted of a total of 37 803 employees from the Chinese Kailuan Group who underwent limb blood pressure measurements during their participation in physical examination between 2010 and 2017. RESULTS: After an average follow-up period of 3 years, a total of 589 cardiovascular events and 570 cases of all-cause mortality were observed. The predictive performance of omMAPR was found to be slightly superior to omABI in terms of cardiovascular events (C-statistics: 0.55 vs. 0.51, P < .001) and all-cause mortality (C-statistics: 0.60 vs. 0.55, P <.001). After adjusting for confounders, within a specific range (omMAPR ≤ 1.06 or omABI ≤ 1.12), each 0.1-unit increase in omMAPR was associated with reductions of 14% (HR = 0.86, 95% CI: 0.77-0.96) and 23% (HR = 0.77, 95% CI: 0.70-0.84) in cardiovascular events and all cause mortality, respectively, while each 0.1-unit increase in omABI was associated with reductions of 12% (HR = 0.88, 95% CI: 0.79-0.97) and 22% (HR = 0.78, 95% CI: 0.72-0.85) in cardiovascular events and all-cause mortality, respectively. However, once out of that range (omMAPR > 1.06 or omABI > 1.12), neither omMAPR nor omABI was significantly associated with cardiovascular events or all-cause mortality. CONCLUSION: Both omMAPR and omABI within specific ranges (omMAPR ≤ 1.06 or omABI ≤ 1.12) were independent predictors for cardiovascular events and all-cause mortality. Moreover, omMAPR exhibited a slightly superior predictive ability compared to omABI in relation to cardiovascular events and all-cause mortality. The trial registration number is ChiCTR-TNRC-11001489.
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Cardiac fibrosis is a prevalent pathological process observed in the progression of numerous cardiovascular diseases and is associated with an increased risk of sudden cardiac death. Although the BRD4 inhibitor JQ1 has powerful antifibrosis properties, its clinical application is extremely limited due to its side effects. There remains an unmet need for effective, safe, and low-cost treatments. Here, we present a multifunctional biomimetic nanoparticle drug delivery system (PM&EM nanoparticles) assembled by platelet membranes and erythrocyte membranes for targeted JQ1 delivery in treating cardiac fibrosis. The platelet membrane endows PM&EM nanoparticles with the ability to target cardiac myofibroblasts and collagen, while the participation of the erythrocyte membrane enhances the long-term circulation ability of the formulated nanoparticles. In addition, PM&EM nanoparticles can deliver sufficient JQ1 with controllable release, achieving excellent antifibrosis effects. Based on these advantages, it is demonstrated in both pressures overloaded induced mouse cardiac fibrosis model and MI-induced mouse cardiac fibrosis that injection of the fusion membrane biomimetic nanodrug carrier system effectively reduced fibroblast activation, collagen secretion, and improved cardiac fibrosis. Moreover, it significantly mitigated the toxic and side effects of long-term JQ1 treatment on the liver, kidney, and intestinal tract. Mechanically, bioinformatics prediction and experimental validation revealed that PM&EM/JQ1 NPs reduced liver and kidney damage via alleviated oxidative stress and mitigated cardiac fibrosis via the activation of oxidative phosphorylation activation. These results highlight the potential value of integrating native platelet and erythrocyte membranes as a multifunctional biomimetic drug delivery system for treating cardiac fibrosis and preventing drug side effects.
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Biopolymers-based food packaging materials have drawn attention as potential candidates for substitution of petroleum-based materials. In this study, composite alginate films were developed by incorporating Zn-based antimicrobials to overcome the intrinsic disadvantages of alginates that hinder their wide applications. Antimicrobials with different morphologies (nanoplatelets, nanorods, and nanospheres) were employed to investigate the effects of antimicrobials' morphology on antibacterial, thermal, mechanical, and barrier performance of composite alginate films. Meanwhile, morphological and structural characterizations were carried out to explore the interactions between antimicrobials and alginate matrix. Results indicated that films with nanospheres exhibited superior antibacterial property, while those with one-dimensional nanorods possessed better mechanical and barrier performance. Besides, preliminary test on fresh-cut potatoes and chicken breasts indicated that the composite films showed potential in extending shelf life of foods. By incorporating antimicrobials with three different morphologies, this study provides particular insights into improving properties of composite packaging materials.
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BACKGROUND: Accumulating evidences indicate regional grey matter (GM) morphology alterations in pediatric growth hormone deficiency (GHD); however, large-scale morphological brain networks (MBNs) undergo these patients remains unclear. OBJECTIVE: To investigate the topological organization of individual-level MBNs in pediatric GHD. METHODS: Sixty-one GHD and 42 typically developing controls (TDs) were enrolled. Inter-regional morphological similarity of GM was taken to construct individual-level MBNs. Between-group differences of topological parameters and network-based statistics analysis were compared. Finally, association relationship between network properties and clinical variables was analyzed. RESULTS: Compared to TDs, GHD indicated a disturbance in the normal small-world organization, reflected by increased Lp, γ, λ, σ and decreased Cp, Eglob (all PFDR < 0.017). Regarding nodal properties, GHD exhibited increased nodal profiles at cerebellum 4-5, central executive network-related left inferior frontal gyrus, limbic regions-related right posterior cingulate gyrus, left hippocampus, and bilateral pallidum, thalamus (all PFDR < 0.05). Meanwhile, GHD exhibited decreased nodal profiles at sensorimotor network -related bilateral paracentral lobule, default-mode network-related left superior frontal gyrus, visual network -related right lingual gyrus, auditory network-related right superior temporal gyrus and bilateral amygdala, right cerebellum 3, bilateral cerebellum 10, vermis 1-2, 3, 4-5, 6 (all PFDR < 0.05). Furthermore, serum markers and behavior scores in GHD group were correlated with altered nodal profiles (P ≤ 0.046, uncorrected). CONCLUSION: GHD undergo an extensive reorganization in large-scale individual-level MBNs, probably due to abnormal cortico-striatal-thalamo-cerebellum loops, cortico-limbic-cerebellum, dorsal visual-sensorimotor-striatal, and auditory-cerebellum circuitry. This study highlights the crucial role of abnormal morphological connectivity underlying GHD, which might result in their relatively slower development in motor, cognitive, and linguistic functional within behavior problem performance.
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Imagen por Resonancia Magnética , Red Nerviosa , Humanos , Masculino , Femenino , Niño , Red Nerviosa/fisiopatología , Red Nerviosa/patología , Red Nerviosa/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Gris/diagnóstico por imagen , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Enanismo Hipofisario/fisiopatología , Enanismo Hipofisario/patología , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/sangre , AdolescenteRESUMEN
BACKGROUND: Whether endobiliary radiofrequency ablation (EB-RFA) changes the standard role of stent placement in treating unresectable malignant biliary obstruction (MBO) remains unclear. The aim of this study is to compare percutaneous EB-RFA and metal stent placement (RFA-Stent) with metal stent placement alone (Stent) in treating unresectable MBO using a propensity score matching (PSM) analysis. METHODS: From June 2013 to June 2018, clinical data from 163 patients with malignant biliary obstruction who underwent percutaneous RFA-Stent or stenting alone were retrospectively analyzed using a nearest-neighbor algorithm to one-to-one PSM analysis to compare primary and secondary stent patency (PSP, SSP), overall survival (OS) and complications between the two groups. RESULTS: Before matching, for whole patients, RFA-Stent resulted in longer median PSP (8.0 vs. 5.1 months, P = 0.003), SSP (9.8 vs. 5.1 months, P < 0.001) and OS (7.0 vs. 4.5 months, P = 0.034) than the Stent group. After matching (54 pairs), RFA-Stent also resulted in better median PSP (8.5 vs. 5.1 months, P < 0.001), SSP (11.0 vs. 6.0 months, P < 0.001), and OS (8.0 vs. 4.0 months, P = 0.007) than Stent. RFA-Stent was comparable with Stent for complication rates. In Cox analysis, RFA-Stent modality and serum total bilirubin level were independent prognostic factors for PSP. RFA-Stent modality, performance status score and combination therapy after stent were independent prognostic factors for OS. CONCLUSION: Percutaneous RFA-Stent was superior to Stent in terms of PSP, SSP, and OS in selected patients with unresectable MBO.
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Colestasis , Puntaje de Propensión , Ablación por Radiofrecuencia , Stents , Humanos , Estudios Retrospectivos , Masculino , Femenino , Anciano , Colestasis/etiología , Colestasis/cirugía , Ablación por Radiofrecuencia/métodos , Persona de Mediana Edad , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/cirugía , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
Mammalian preimplantation development culminates in the formation of a blastocyst which undergoes extensive gene expression regulation to successfully implant into the maternal endometrium. Zinc-finger HIT domain-containing (ZNHIT) 1 and 2 are members of a highly conserved family, yet they have been identified as subunits of distinct complexes. Here we report that knockout of either Znhit1 or Znhit2 results in embryonic lethality during peri-implantation stages. Znhit1 and Znhit2 mutant embryos have overlapping phenotypes, including reduced proportion of SOX2-positive ICM cells, a lack of Fgf4 expression and aberrant expression of NANOG and SOX17. Furthermore, we find that the similar phenotypes are caused by distinct mechanisms. Specifically, embryos lacking ZNHIT1 likely fail to incorporate sufficient H2A.Z at the promoter region of Fgf4 and other genes involved in cell projection organization resulting in impaired invasion of trophoblast cells during implantation. In contrast, Znhit2 mutant embryos display a complete lack of nuclear EFTUD2, a key component of U5 spliceosome, indicating a global splicing deficiency. Our findings unveil the indispensable yet distinct roles of ZNHIT1 and ZNHIT2 in early mammalian embryonic development.
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OBJECTIVE: We aimed to evaluate the efficacy of decitabine consolidation after treatment with CD19/CD22 chimeric antigen receptor T-cell (CAR-T) for patients with relapsed/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL). METHODS: We retrospectively analysed 48 patients with r/r B-ALL who received CD19/CD22 CAR-T therapy between September 2017 and May 2021. Sixteen patients received decitabine consolidation (20â¯mg/m2/day for 5 days at 3-month intervals) after CAR-T therapy (DAC group), while 32 patients did not receive decitabine consolidation (CON group). Overall survival (OS), leukaemia-free survival (LFS), and cumulative incidence of relapse (CIR) were evaluated in both groups. Time-to-event analysis was performed using the Kaplan-Meier method. RESULTS: The median follow-up periods in the DAC and CON groups were 41.2 months and 28.6 months, respectively. The 4-year OS and 4-year LFS rates in both groups were 93.3â¯% and 64.3â¯% (P=0.029) and 87.5â¯% and 55.9â¯% (P=0.059), respectively. The 1-year CIR was 6.25â¯% and 28.6â¯%, respectively. Univariate and multivariate Cox regression analyses showed that decitabine consolidation after CAR-T therapy was significantly associated with superior OS (hazard ratio [HR]: 0.121, 95â¯% confidence interval [CI]: 0.015-0.947, P=0.044), and bridging to haematopoietic stem cell transplantation after CAR-T therapy was significantly associated with superior LFS (HR: 0.279, 95â¯%CI: 0.093-0.840, P=0.023). CONCLUSIONS: Our study recommends decitabine consolidation after CD19/CD22 CAR-T therapy as a novel maintenance strategy to improve the survival outcomes of patients with r/r B-ALL.
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BACKGROUND AND OBJECTIVES: The objective of this study was to examine the effects of nutritional therapy in adult patients with severe burns. METHODS AND STUDY DESIGN: Sixty adult patients with severe burns were enrolled. Data on nutritional intake through enteral nutrition (EN) or parenteral nutrition (PN) on days 7, 14, 21, and 28 post-injury were collected. Patients were divided into target and non-target groups according to whether their energy or protein intake reached the target. Age, length of ventilation, and total bilirubin (TBIL), albumin (ALB), prealbumin (pALB), and C-reactive protein (CRP) concentrations of patients were recorded. RESULTS: The percentage of protein targets with protein delivery was lower than that of energy target with energy delivery. The ratio of PN protein to total protein was lower than that of PN energy to total energy on days 7, 14, 21, and 28 (p<0.001, p<0.001, p=0.001, and p=0.003, respectively). Compared to the non-target group on day 21, the target group was younger, had lower TBIL on day 7, higher ALB and pALB on day 21, and lower CRP on day 14 (p=0.025, p=0.021, p=0.028, p=0.029, and p=0.049, respectively). Multivariate logistic regression analysis showed that older age and longer ventilation were independent risk factors in patients who did not meet the nutritional target on day 21 (p=0.026 and p=0.043, respectively). CONCLUSIONS: The protein intake of adult patients with severe burns was low. Compared to the non-target group, the target group had better laboratory test results. Older age and longer ventilation were independent risk factors for patients not meeting the nutritional target.
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Quemaduras , Humanos , Quemaduras/terapia , Masculino , Femenino , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Ingestión de Energía , Nutrición Parenteral/métodos , Nutrición Enteral/métodos , Estado Nutricional , Proteína C-Reactiva/análisis , Prealbúmina/análisis , Prealbúmina/metabolismo , Proteínas en la Dieta/administración & dosificación , Anciano , Adulto Joven , Bilirrubina/sangreRESUMEN
PURPOSE: Oral mucositis is a frequent adverse reaction in cancer treatment. Probiotics exhibit anti-inflammatory and immunomodulatory properties that could prevent the occurrence of severe oral mucositis (SOM) induced by chemotherapy or radiation therapy in patients. This meta-analysis aimed to investigate the influence of probiotics on the incidence of SOM in cancer patients undergoing chemotherapy and/or radiotherapy. METHODS: We conducted a comprehensive search in PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure (CNKI) from their inception to September 2023. Dichotomous variables are analyzed with odds ratios (ORs) with 95% CIs, and statistical significance was set at a two-tailed Pâ<0â.05. The primary outcome indicator was the effect of probiotics on SOM. Secondary outcome indicators included the effect of probiotics on oral mucositis and the ratio of diarrhoea. Statistical analysis was conducted using RevMan (5.4) and Stata 17.0 software. RESULTS: The study included a total of 12 articles and involved 1055 patients. All patients had undergone either radiotherapy or chemotherapy. Our findings revealed that the experimental group, which received probiotics for treatment, exhibited a lower ratio of SOM compared to the control group that received traditional placebo treatment (OR=0.37, 95%CI [0.28, 0.50], P<0.01). Subgroup analysis revealed variations in the ratio of SOM based on therapeutic regimen, tumor type, and region. The overall ratio of oral mucositis was significantly lower in the experimental group compared to the control group (OR=0.19, 95%CI [0.09-0.39], P<0.01). The ratio of diarrhea in the two patient groups showed no significant difference (OR=0.85, 95%CI [0.24, 3.01], P>0.05). CONCLUSION: The results of this meta-analysis suggest that probiotics could decrease the occurrence of SOM.
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Mitochondrial DNA (mtDNA) is an important genetic marker for degraded biological sample identification, maternal pedigree tracing, and population genetic structure study owing to its characteristics of high copy number, anti-degradable ring structure, and maternal inheritance. Whole mtDNA genome sequencing is an optimal method for the analysis of mtDNA polymorphism and heterogeneity because it allows for the comprehensive use of maternal genetic information. However, because of lacking quantitative evaluations for sequencing data, the scientific interpretation standards for mtDNA sequencing results of the previously used sequencing systems are often different, and false positive or false negative results are prone to occur when faced with the interference of nuclear genomic DNA, or the heterogeneities of mtDNA sequence and structure. In this study, we evaluated a novel mtDNA whole genome sequencing system using long fragment amplification strategy on the DNA nanoball (DNB) sequencing platform. This system demonstrated high sequencing quality and specific mtDNA sequencing efficiencies on positive control DNA and FTA bloodstain samples, as the average Q20 and Q30 values of the corresponding samples were 97.17â¯% and 91.93â¯%; 97.37â¯% and 92.48â¯%, respectively. The mean mapping percentages for the reference sequences of whole genome DNA (wgDNA), mtDNA, and nuclear genomic DNA (ngDNA) in the corresponding samples were 99.98â¯%, 99.97â¯%, 0.03â¯%, and 99.91â¯%, 99.40â¯%, 0.60â¯%; respectively. The average error calling rates for the bases A, C, G, and T of the whole mtDNA genome were 0.2519â¯%, 0.2550â¯%, 0.2906â¯%; and 0.2392â¯%, respectively. The efficacy of heteroplasmy identification was assessed using a set of theoretical sites with predetermined rates. These sites were created by combining the samples with known mtDNA haplotypes in certain proportions. The absolute errors between observed and theoretical heteroplasmy values were 89.59â¯%, 74.68â¯%, 50.20â¯%, 12.65â¯%, 8.31â¯%, and 4.85â¯%, while the theoretical heteroplasmy values were 5â¯%, 10â¯%, 20â¯%, 80â¯%, 90â¯%, and 95â¯%, respectively. The absolute error exhibited relative stability when the mtDNA sequencing depth exceeded 500×. Furthermore, the system sequencing efficiency was also confirmed among different kinds of samples, and these samples included natural samples (e.g., peripheral blood samples preserved on FTA cards for 2 and 11 years, and on filter paper for 6 and 9 years), degraded samples, sensitivity samples, samples derived from various bodily fluids, and maternal pedigree samples. In summary, the whole mtDNA genome sequencing system used for forensic identification demonstrated high performance in analyzing mtDNA sequence information, and showed significant prospects for forensic application and maternal genetic research.
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The accumulation of the active pharmaceutical chemical in the environment usually results in environmental pollution to increase the risk to human health. Indomethacin is a non-steroidal anti-inflammatory drug that potentially causes systemic and developmental toxicity in various tissues. However, there have been few studies for its potential effects on cardiac development. In this study, we systematically determined the cardiotoxicity of acute indomethacin exposure in zebrafish at different concentrations with morphological, histological, and molecular levels. Specifically, the malformation and dysfunction of cardiac development, including pericardial oedema, abnormal heart rate, the larger distance between the venous sinus and bulbus arteriosus (SV-BA), enlargement of the pericardial area, and aberrant motor capability, were determined after indomethacin exposure. In addition, further investigation indicated that indomethacin exposure results in myocardial apoptosis in a dose-dependent manner in zebrafish at early developmental stage. Mechanistically, our results revealed that indomethacin exposure mainly regulates key cardiac development-related genes, especially genes related to the cardiac muscle contraction-related signaling pathway, in zebrafish embryos. Thus, our findings suggested that acute indomethacin exposure might cause cardiotoxicity by disturbing the cardiac muscle contraction-related signaling pathway and inducing myocardial apoptosis in zebrafish embryos.
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We evaluated the efficacy of indocyanine green fluorescence imaging compared to that of traditional nanocarbon dyes in assessing peri-intestinal lymph node metastasis in patients with colorectal cancer, which is a key prognostic factor. The relationship between indocyanine green fluorescence imaging and histopathological outcomes in patients with colon cancer has also been explored. A retrospective analysis was conducted on 30 patients with colon cancer (from May to October 2023) confirmed by surgical pathology. Tumors were marked with indocyanine green (ICG) or nanocarbon via colonoscopy 16 to 24 hours before surgery. Within 15 minutes after surgery, peri-intestinal lymph node fluorescence imaging and hematoxylin and eosin staining were used to assess the distribution of cancer foci. The correlation between cancer foci distribution, fluorescence intensity, and area under the receiver operating characteristic curve was measured. Among 243 metastatic lymph nodes from 30 patients, 18 were found. After the patients were divided into metastatic and nonmetastatic groups, significant differences in tumor differentiation and stage were noted (Pâ <â .001). The fluorescence intensity was strongly correlated with the presence and proportion of metastasis (area under the receiver operating characteristic curveâ =â 0.931), whereas nanocarbon staining showed no significant correlation (Pâ =â .81). All P values were two-sided, with Pâ <â .05 indicating statistical significance. Lymph nodes with malignant intestinal tumor metastasis displayed weaker ICG fluorescence than did nonmetastatic nodes. Combining ICG and nanocarbon staining techniques enhances intraoperative lymph node dissection and postoperative analysis, indicating their potential utility in colorectal cancer surgery.
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Verde de Indocianina , Ganglios Linfáticos , Metástasis Linfática , Imagen Óptica , Humanos , Verde de Indocianina/administración & dosificación , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Imagen Óptica/métodos , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Colorantes/administración & dosificación , Curva ROC , Neoplasias del Colon/patología , Neoplasias del Colon/diagnóstico por imagen , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/diagnóstico por imagen , Anciano de 80 o más Años , Colonoscopía/métodosRESUMEN
Co-cultivation of isopod-associated fungi Herpotrichia sp. SF09 and Trametes versicolor SF09A led to the reciprocal induction of thirteen new compounds (1-7 and 9-13) with diverse architectures. Importantly, compounds 1 and 2 are rare fungal sesquiterpene-saccharide hybrids incorporating a xylopyranose moiety, compound (±)-3 represents the first example of a natural linear sesquiterpene racemate, and compound 7 is a rare α-pyrone derivative with a xylopyranose motif. Their structures were elucidated by analysis of NMR and mass spectrometry data, and their absolute configurations were determined by Mosher's method, microscale derivatization, and single-crystal X-ray diffraction, as well as ECD calculations. All the isolated compounds ameliorated MPP+-induced oxidative damage in PC12 cells in a dose-dependent fashion. Among them, compounds 5 and 15 showed significant protective action against neuronal injury by MPP+ at 5 µM. Meanwhile, transcriptome sequencing was performed to evaluate the molecular mechanism of the neuroprotective activity for compound 5. Results indicated that compound 5 might mitigate MPP+-induced neuronal injury through the regulation of multiple signaling pathways, including the PI3K-Akt and MAPK pathways. Our findings suggested that compound 5 could be a promising neuroprotective agent for the treatment of Parkinson's disease.
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PURPOSE: To evaluate the efficacy of retinal massage combined with autologous blood covering in the treatment of persistent macular holes following vitrectomy in eyes with high myopia. SETTINGS AND DESIGN: Retrospective, consecutive case series in a tertiary eye center. METHODS: A total of 12 highly myopic eyes with persistent macular holes after vitrectomy and internal limiting membrane peeling received combined retinal massage, air/fluid exchange, autologous blood covering, and gas/silicone oil tamponade. Best-corrected visual acuity, axial length, and optical coherence tomographic images before and after the treatment were compared. RESULTS: The mean hole diameter before this intervention was 931.58 ± 244.58 Symbolm (range, 508-1270), and the axial length was 30.39 ± 2.13 mm (range, 27.08-34.64). During the 6-month follow-up period, hole closure was achieved in eight eyes (66.67%). The mean best-corrected visual acuity improved significantly from 1.40 ± 0.50 logarithm of the minimum angle of resolution (logMAR) at baseline to 1.10 ± 0.30 logMAR (P < 0.05). No complications were observed. CONCLUSIONS: Combined retinal massage and autologous blood covering, which is easy to manipulate, can promote the closure of persistent macular holes after vitrectomy and improve vision in high myopia with an axial length less than 29 mm.
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For the sake of realizing the safety detection of natural gas and petroleum pipeline welds, this paper designs a ferromagnetic pipeline weld magnetic flux leakage detector based on the calculation of the magnetic circuit of the detection probe, with the magnetization direction perpendicular to the traveling direction. The traditional pipeline magnetic flux leakage detection device uses a detection system mode in which the magnetization direction is parallel to the direction of travel. However, due to the structural characteristics of the weld, the traditional detection system mode is not applicable. Since the weld magnetic flux leakage detector needs to travel along the direction of the weld, the detector designed in this paper rotates the magnetizer 90 degrees along the direction of the weld seam so that the magnetization direction is perpendicular to the direction of travel, breaking through the technical barrier that make traditional magnetic flux leakage detection devices unsuitable for weld detection. The detection device includes a magnetizing structure, a data sampling device, and a driving and traveling device. The magnetic flux leakage signal collected by the detector is converted into a digital image in the form of a grayscale matrix. Using mathematical morphology and chain code algorithms in image processing technology, a pipeline weld defect inversion software system is developed, and a preliminary quantitative analysis of pipeline weld defects is achieved. The application of this technology enables the inspection and protection of oil and gas pipeline welds throughout their life cycle, broadens the scope of existing inspection objects, and is of great safety significance for ensuring national public security.
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BACKGROUND: Research in functional asymmetry of Major Depressive Disorder (MDD) under different tasks is crucial for clinical diagnose. METHODS: Fifty individuals with MDD and twenty healthy controls (HCS) were recruited for hemodynamic data collection under four fNIRS tasks (Emotional picture, Verbal fluency, Fingering and Negative emotional picture description task). Integral values and functional connectivity strength were employed to probe neural activation and functional connectivity in frontal and temporal lobes in MDD. Following, asymmetry characteristic of the frontal cortex between MDD and HCS under four tasks were carefully analyzed and compared. RESULTS: Individuals with MDD demonstrated heightened connectivity between the frontal and right temporal lobes and reduced connectivity between the frontal and left temporal lobes compared to HCS in all tasks. Additionally, MDD exhibited attenuated activation in the left frontal lobes and exaggerated activation in the right frontal lobes, diverging from HCS. Furthermore, the disparities in left-right asymmetry characteristic of frontal cortex activation between MDD and HCS were more pronounced during the combined task. LIMITATIONS: Further research is required to grasp the neurophysiological mechanisms governing left-right asymmetry across various tasks and the influence of task-induced brain fatigue on cerebral cortex hemodynamics in MDD. CONCLUSION: The left-right asymmetry feature provides valuable neurophysiological insights for diagnosing MDD clinically. Variations in activation patterns and functional connectivity features between MDD and HCS are closely tied to the task chosen. Thus, in clinical practice, carefully selecting appropriate fNIRS tasks and relevant features can significantly improve the diagnostic accuracy of MDD.