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1.
Shock ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38813918

RESUMEN

OBJECTIVE: To explore the association of serum transactive response DNA binding protein 43 (TDP-43) with 28-day poor neurologic outcome in patients with return of spontaneous circulation (ROSC) after cardiac arrest. METHODS: We performed a study between January and December, 2023. Eligible patients with ROSC following cardiac arrest were enrolled. Their baseline characteristics were collected and serum levels of TDP-43, tumor necrosis factor-α, interleukin-6 and -10, C-reactive protein, and neuron-specific enolase (NSE) at 24 h after ROSC were measured. The neurological function was assessed by the cerebral performance category scores on day 28 after ROSC. RESULTS: A total of 92 patients were included, with 51 and 41 patients in the good and poor neurological outcome groups, respectively. Serum TDP-43 was significantly higher in the poor than the good neurologic outcome group (P < 0.05). Univariate and multivariate logistic regression analyses showed that TDP-43, Witnessed CA, IL-6, and NSE were associated with poor 28-day neurologic outcome (all P < 0.05). Restricted cubic spline analysis revealed that TDP-43 at the serum level of 11.64 pg/mL might be an ideal cutoff value for distinguishing between good and poor neurologic outcomes. Area Under Curve of serum TDP-43 (AUC = 0.78) was close to that of serum NSE (AUC = 0.82). A dynamic nomogram prediction model that combined TDP-43, Witnessed CA, IL-6, and NSE was constructed and validated. CONCLUSION: Elevated serum TDP-43 level was associated with and could be used together with Witnessed CA, IL-6, and NSE to predict poor 28-day neurologic outcome in patients after ROSC following cardiac arrest.

2.
Adv Mater ; : e2313971, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38573651

RESUMEN

Large-area flexible transparent conductive films (TCFs) are highly desired for future electronic devices. Nanocarbon TCFs are one of the most promising candidates, but some of their properties are mutually restricted. Here, a novel carbon nanotube network reorganization (CNNR) strategy, that is, the facet-driven CNNR (FD-CNNR) technique, is presented to overcome this intractable contradiction. The FD-CNNR technique introduces an interaction between single-walled carbon nanotube (SWNT) and Cu─-O. Based on the unique FD-CNNR mechanism, large-area flexible reorganized carbon nanofilms (RNC-TCFs) are designed and fabricated with A3-size and even meter-length, including reorganized SWNT (RSWNT) films and graphene and RSWNT (G-RSWNT) hybrid films. Synergistic improvement in strength, transmittance, and conductivity of flexible RNC-TCFs is achieved. The G-RSWNT TCF shows sheet resistance as low as 69 Ω sq-1 at 86% transmittance, FOM value of 35, and Young's modulus of ≈45 MPa. The high strength enables RNC-TCFs to be freestanding on water and easily transferred to any target substrate without contamination. A4-size flexible smart window is fabricated, which manifests controllable dimming and fog removal. The FD-CNNR technique can be extended to large-area or even large-scale fabrication of TCFs and can provide new insights into the design of TCFs and other functional films.

3.
Foods ; 13(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38672908

RESUMEN

To investigate the gelation process of direct ultra-high-temperature (UHT) milk, a pilot-scale steam infusion heat treatment was used to process milk samples over a wide temperature of 142-157 °C for 0.116-6 s, followed by storage at 4 °C, 25 °C, and 37 °C. The results of the physicochemical properties of milk showed that the particle sizes and plasmin activities of all milk samples increased during storage at 25 °C, but age gelation only occurred in three treated samples, 147 °C/6 s, 142 °C/6 s, and 142 °C/3 s, which all had lower plasmin activities. Furthermore, the properties of formed gels were further compared and analyzed by the measures of structure and intermolecular interaction. The results showed that the gel formed in the 147 °C/6 s-treated milk with a higher C* value had a denser network structure and higher gel strength, while the 142 °C/6 s-treated milk had the highest porosity. Furthermore, disulfide bonds were the largest contributor to the gel structure, and there were significant differences in disulfide bonds, hydrophobic interaction forces, hydrogen bonds, and electrostatic force among the gels. Our results showed that the occurrence of gel was not related to the thermal load, and the different direct UHT treatments produced different age gels in the milk.

4.
Anim Sci J ; 95(1): e13944, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38549501

RESUMEN

The objective of this study was to investigate the effects of two different organic selenium (Se) supplements, selenomethionine (Se-Met) and selenohomolanthionine (Se-Hlan), on the serum biochemical parameters and Se status of dairy cows. Different dietary Se supplementation treatments were set as follows: a control group (CON, adding sodium selenite at 0.3 mg Se/kg dry matter [DM]), 0.3 and 0.5 Se-Met (adding Se-Met at 0.3 and 0.5 mg Se/kg DM, respectively), as well as 0.3 and 0.5 Se-Hlan (adding Se-Hlan at 0.3 and 0.5 mg Se/kg DM, respectively). The experiment lasted 8 weeks. The serum measurements showed that both organic Se treatments resulted in higher uric acid than CON. Se-Met produced higher aspartate aminotransferase, glucose, urea, low-density lipoprotein cholesterol, and lactate dehydrogenase than Se-Hlan. Regarding the Se status, the highest milk Se values appeared in 0.5 Se-Met, with intermediate values in 0.3 Se-Met and 0.5 Se-Hlan, whereas the highest and lowest serum Se levels were presented in 0.5 Se-Met and 0.3 Se-Hlan, respectively. Our results suggest that Se-Hlan was not as efficient in boosting serum or milk Se as Se-Met and differences in serum biomarkers between Se-Met and Se-Hlan may be associated with distinct metabolic pathways for different forms of organic Se.


Asunto(s)
Selenio , Femenino , Bovinos , Animales , Suplementos Dietéticos , Leche/metabolismo , Selenometionina/metabolismo , Alimentación Animal/análisis , Biomarcadores/metabolismo , Dieta/veterinaria
5.
Small ; 20(23): e2400303, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38501842

RESUMEN

High-efficiency extraction of long single-wall carbon nanotubes (SWCNTs) with excellent optoelectronic properties from SWCNT solution is critical for enabling their application in high-performance optoelectronic devices. Here, a straightforward and high-efficiency method is reported for length separation of SWCNTs by modulating the concentrations of binary surfactants. The results demonstrate that long SWCNTs can spontaneously precipitate for binary-surfactant but not for single-surfactant systems. This effect is attributed to the formation of compound micelles by binary surfactants that squeeze the free space of long SWCNTs due to their large excluded volumes. With this technique, it can readily separate near-pure long (≥500 nm in length, 99% in content) and short (≤500 nm in length, 98% in content) SWCNTs with separation efficiencies of 26% and 64%, respectively, exhibiting markedly greater length resolution and separation efficiency than those of previously reported methods. Thin-film transistors fabricated from extracted semiconducting SWCNTs with lengths >500 nm exhibit significantly improved electrical properties, including a 10.5-fold on-state current and 14.7-fold mobility, compared with those with lengths <500 nm. The present length separation technique is perfectly compatible with various surfactant-based methods for structure separations of SWCNTs and is significant for fabrication of high-performance electronic and optoelectronic devices.

6.
Nano Lett ; 24(5): 1494-1501, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38264980

RESUMEN

The rapid progress in nanopore sensing has sparked interest in protein sequencing. Despite recent notable advancements in amino acid recognition using nanopores, chemical modifications usually employed in this process still need further refinements. One of the challenges is to enhance the chemical specificity to avoid downstream misidentification of amino acids. By employing adamantane to label proteinogenic amino acids, we developed an approach to fingerprint individual amino acids using the wild-type α-hemolysin nanopore. The unique structure of adamantane-labeled amino acids (ALAAs) improved the spatial resolution, resulting in distinctive current signals. Various nanopore parameters were explored using a machine-learning algorithm and achieved a validation accuracy of 81.3% for distinguishing nine selected amino acids. Our results not only advance the effort in single-molecule protein characterization using nanopores but also offer a potential platform for studying intrinsic and variant structures of individual molecules.


Asunto(s)
Proteínas Hemolisinas , Nanoporos , Proteínas Hemolisinas/química , Aminoácidos/química , Secuencia de Aminoácidos , Algoritmos
7.
Sensors (Basel) ; 23(20)2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37896462

RESUMEN

Ensuring road safety, structural stability and durability is of paramount importance, and detecting road cracks plays a critical role in achieving these goals. We propose a GM-ResNet-based method to enhance the precision and efficacy of crack detection. Leveraging ResNet-34 as the foundational network for crack image feature extraction, we consider the challenge of insufficient global and local information assimilation within the model. To overcome this, we incorporate the global attention mechanism into the architecture, facilitating comprehensive feature extraction across the channel and the spatial width and height dimensions. This dynamic interaction across these dimensions optimizes feature representation and generalization, resulting in a more precise crack detection outcome. Recognizing the limitations of ResNet-34 in managing intricate data relationships, we replace its fully connected layer with a multilayer fully connected neural network. We fashion a deep network structure by integrating multiple linear, batch normalization and activation function layers. This construction amplifies feature expression, stabilizes training convergence and elevates the performance of the model in complex detection tasks. Moreover, tackling class imbalance is imperative in road crack detection. Introducing the focal loss function as the training loss addresses this challenge head-on, effectively mitigating the adverse impact of class imbalance on model performance. The experimental outcomes on a publicly available crack dataset emphasize the advantages of the GM-ResNet in crack detection accuracy compared to other methods. It is worth noting that the proposed method has better evaluation indicators in the detection results compared with alternative methodologies, highlighting its effectiveness. This validates the potency of our method in achieving optimal crack detection outcomes.

8.
ACS Nano ; 17(21): 21093-21104, 2023 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-37643288

RESUMEN

Nanopore sensing of proteomic biomarkers lacks accuracy due to the ultralow abundance of targets, a wide variety of interferents in clinical samples, and the mismatch between pore and analyte sizes. By converting antigens to DNA probes via click chemistry and quantifying their characteristic signals, we show a nanopore assay with several amplification mechanisms to achieve an attomolar level limit of detection that enables quantitation of the circulating Mycobacterium tuberculosis (Mtb) antigen ESAT-6/CFP-10 complex in human serum. The assay's nonsputum-based feature and low-volume sample requirements make it particularly well-suited for detecting pediatric tuberculosis (TB) disease, where establishing an accurate diagnosis is greatly complicated by the paucibacillary nature of respiratory secretions, nonspecific symptoms, and challenges with sample collection. In the clinical assessment, the assay was applied to analyze ESAT-6/CFP-10 levels in serum samples collected during baseline investigation for TB in 75 children, aged 0-12 years, enrolled in a diagnostic study conducted in Cape Town, South Africa. This nanopore assay showed superior sensitivity in children with confirmed TB (94.4%) compared to clinical "gold standard" diagnostic technologies (Xpert MTB/RIF 44.4% and Mtb culture 72.2%) and filled the diagnostic gap for children with unconfirmed TB, where these traditional technologies fell short. We envision that, in combination with automated sample processing and portable nanopore devices, this methodology will offer a powerful tool to support the diagnosis of pulmonary TB in children.


Asunto(s)
Mycobacterium tuberculosis , Nanoporos , Tuberculosis Pulmonar , Tuberculosis , Humanos , Niño , Sudáfrica , Proteómica , Sensibilidad y Especificidad , Tuberculosis Pulmonar/diagnóstico , Tuberculosis/diagnóstico
9.
ACS Nano ; 17(17): 16369-16395, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37490313

RESUMEN

Biotechnological innovations have vastly improved the capacity to perform large-scale protein studies, while the methods we have for identifying and quantifying individual proteins are still inadequate to perform protein sequencing at the single-molecule level. Nanopore-inspired systems devoted to understanding how single molecules behave have been extensively developed for applications in genome sequencing. These nanopore systems are emerging as prominent tools for protein identification, detection, and analysis, suggesting realistic prospects for novel protein sequencing. This review summarizes recent advances in biological nanopore sensors toward protein sequencing, from the identification of individual amino acids to the controlled translocation of peptides and proteins, with attention focused on device and algorithm development and the delineation of molecular mechanisms with the aid of simulations. Specifically, the review aims to offer recommendations for the advancement of nanopore-based protein sequencing from an engineering perspective, highlighting the need for collaborative efforts across multiple disciplines. These efforts should include chemical conjugation, protein engineering, molecular simulation, machine-learning-assisted identification, and electronic device fabrication to enable practical implementation in real-world scenarios.


Asunto(s)
Nanoporos , Péptidos , Secuencia de Aminoácidos , Péptidos/química , Proteínas , Secuencia de Bases , Aminoácidos/química
10.
ACS Nano ; 17(9): 8393-8402, 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37092905

RESUMEN

High-purity enantiomer separation of chiral single-wall carbon nanotubes (SWCNTs) remains a challenge compared with electrical type and chirality separations due to the limited selectivities for both chirality and handedness, which is important for an exploration of their properties and practical applications. Here, we performed length fractionation for enantiomer-purified SWCNTs and found a phenomenon in which the enantioselectivities were higher for longer nanotubes than for shorter nanotubes due to length-dependent interactions with the gel medium, which provided an effective strategy of controlling nanotube length for high-purity enantiomer separation. Furthermore, we employed a gentler pulsed ultrasonication instead of traditional vigorous ultrasonication for preparation of a low-defect long SWCNT dispersion and achieved the enantiomer separation of single-chirality (6,5) SWCNTs with an ultrahigh enantiomeric purity of up to 98%, which was determined by using the linear relationship between the normalized circular dichroism intensity and the enantiomeric purity. Compared with all results reported previously, the present enantiomeric purity was significantly higher and reached the highest level reported to date. Due to the ultrahigh selectivity in both chirality and handedness, the two obtained enantiomers exhibited perfect symmetry in their circular dichroism spectra, which offers standardization for characterizations and evaluations of SWCNT enantiomers.

11.
Nat Commun ; 14(1): 2491, 2023 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-37120644

RESUMEN

Industrial production of single-chirality carbon nanotubes is critical for their applications in high-speed and low-power nanoelectronic devices, but both their growth and separation have been major challenges. Here, we report a method for industrial separation of single-chirality carbon nanotubes from a variety of raw materials with gel chromatography by increasing the concentration of carbon nanotube solution. The high-concentration individualized carbon nanotube solution is prepared by ultrasonic dispersion followed by centrifugation and ultrasonic redispersion. With this technique, the concentration of the as-prepared individualized carbon nanotubes is increased from about 0.19 mg/mL to approximately 1 mg/mL, and the separation yield of multiple single-chirality species is increased by approximately six times to the milligram scale in one separation run with gel chromatography. When the dispersion technique is applied to an inexpensive hybrid of graphene and carbon nanotubes with a wide diameter range of 0.8-2.0 nm, and the separation yield of single-chirality species is increased by more than an order of magnitude to the sub-milligram scale. Moreover, with present separation technique, the environmental impact and cost of producing single-chirality species are greatly reduced. We anticipate that this method promotes industrial production and practical applications of single-chirality carbon nanotubes in carbon-based integration circuits.

12.
Nat Commun ; 14(1): 1672, 2023 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-36966164

RESUMEN

Establishing the relationship between the electrical transport properties of single-wall carbon nanotubes (SWCNTs) and their structures is critical for the design of high-performance SWCNT-based electronic and optoelectronic devices. Here, we systematically investigated the effect of the chiral structures of SWCNTs on their electrical transport properties by measuring the performance of thin-film transistors constructed by eleven distinct (n, m) single-chirality SWCNT films. The results show that, even for SWCNTs with the same diameters but different chiral angles, the difference in the on-state current or carrier mobility could reach an order of magnitude. Further analysis indicates that the electrical transport properties of SWCNTs have strong type and family dependence. With increasing chiral angle for the same-family SWCNTs, Type I SWCNTs exhibit increasing on-state current and mobility, while Type II SWCNTs show the reverse trend. The differences in the electrical properties of the same-family SWCNTs with different chiralities can be attributed to their different electronic band structures, which determine the contact barrier between electrodes and SWCNTs, intrinsic resistance and intertube contact resistance. Our present findings provide an important physical basis for performance optimization and application expansion of SWCNT-based devices.

13.
J Am Soc Cytopathol ; 12(3): 206-215, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36792408

RESUMEN

INTRODUCTION: Fine-needle aspiration biopsy (FNAB) plays a critical role in the management of patients with salivary gland lesions. A specific diagnosis can be difficult due to the wide range of lesions with overlapping morphologic features, potentially leading to interpretation errors. We analyzed the cytologic-histologic discrepancies identified in the quality assurance program of a major cancer center in cases of salivary gland FNAB and performed a root cause analysis. MATERIALS AND METHODS: Salivary gland FNAB specimens performed during a 12-year period at a major tertiary cancer center were reviewed. The inclusion criteria for this study included FNAB cases of salivary glands with subsequent histologic or flow cytometry follow up. The cytologic diagnoses for these cases were recategorized according to the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) based on the original reports. The risk of neoplasm and malignancy based on the cases with subsequent resection or flow cytometry and the most common causes of discrepancy were analyzed. RESULTS: The risk of neoplasm ranged from 41% to 99% and the risk of malignancy ranged from 22% to 99% among the different MSRSGC categories. Lymphoid and myoepithelial rich lesions were the most common miscategorized lesions using the MSRSGC. Reactive changes due to inflammation were associated with overcalls. The most common malignancy in the atypical category was mucoepidermoid carcinomas. CONCLUSIONS: Myoepithelial and lymphoid rich lesions arising in the salivary gland are associated with a higher risk of misclassification. The use of category IVB in the MSRSGC is appropriate for lesions with abundant myoepithelial cells. Reactive atypia seen in sialadenitis was the most common feature associated with overcall.


Asunto(s)
Carcinoma Mucoepidermoide , Neoplasias de las Glándulas Salivales , Humanos , Neoplasias de las Glándulas Salivales/patología , Biopsia con Aguja Fina/métodos , Glándulas Salivales/patología , Carcinoma Mucoepidermoide/patología , Citología
14.
Cancer Cytopathol ; 131(5): 325-336, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36650420

RESUMEN

BACKGROUND: Pancreatic cyst cytology evaluates for neoplastic mucin and epithelial grade. This study describes cytological features of low- and high-grade mucinous neoplasms (MNs) using gastrointestinal contaminants for comparison. METHODS: Histologically confirmed pancreatic cystic neoplasms were reviewed by a panel of cytopathologists to identify which, among 26 selected cytologic features, correlate significantly with low- and high-grade MN. A test for greater than or equal to four of eight high-grade features (three-dimensional architecture, high nuclear:cytoplasmic ratio, moderate nuclear membrane abnormalities, loss of nuclear polarity, hyperchromasia, >4:1 nuclear size variation in one cluster, karyorrhexis, and necrosis) was assessed for identifying a high-grade neoplasms. Additional characteristics of the cohort such as cyst fluid carcinoembryonic antigen results, molecular testing, Papanicolaou Society of Cytopathology classification, and select high-risk clinical features are described. RESULTS: Endoscopic ultrasound fine-needle aspirations from 134 MN and 17 serous cystadenomas containing gastrointestinal contaminants were included. The MN consisted of 112 (84%) intraductal papillary MNs (low-grade = 69, 62%; high-grade = 24, 21%; and invasive = 19, 17%) and mucinous cystic neoplasms (low-grade = 20, 90%; high-grade = 2, 10%). Half had greater than five clusters of epithelium for analysis. Compared with gastrointestinal contaminants, mucin from MN was thick and colloid-like (40% vs. 6%, p < .01), covered >20% of the smear area (32% vs. none, p < .01), and contained histiocytes (46% vs. 18%, p = .04). Greater than or equal to four of eight select high-grade features was present in 36% of high-grade MN with sensitivity 37% and 98% specificity. CONCLUSION: Colloid-like features, >20% of smear, and histiocytes correlated with MN. Testing for greater than or equal to four high-grade features had low sensitivity and high specificity for high-grade MN.


Asunto(s)
Neoplasias Quísticas, Mucinosas y Serosas , Quiste Pancreático , Neoplasias Pancreáticas , Humanos , Biopsia con Aguja Fina , Quiste Pancreático/diagnóstico , Quiste Pancreático/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Mucinas , Líquido Quístico
15.
Sci Adv ; 8(50): eabq3515, 2022 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-36516257

RESUMEN

Although individual carbon nanotubes (CNTs) are superior to polymer chains, the mechanical and thermal properties of CNT fibers (CNTFs) remain inferior to synthetic fibers because of the failure of embedding CNTs effectively in superstructures. Conventional techniques resulted in a mild improvement of target properties while degrading others. Here, a double-drawing technique is developed to rearrange the constituent CNTs. Consequently, the mechanical and thermal properties of the resulting CNTFs can simultaneously reach their highest performances with specific strength ~3.30 N tex-1 (4.60 GPa), work of rupture ~70 J g-1, and thermal conductivity ~354 W m-1 K-1 despite starting from low-crystallinity materials (IG:ID ~ 5). The processed CNTFs are more versatile than comparable carbon fiber, Zylon and Dyneema. On the basis of evidence of load transfer efficiency on individual CNTs measured with in situ stretching Raman, we find that the main contributors to property enhancements are the increasing of the effective tube contribution.

16.
Nat Commun ; 13(1): 6852, 2022 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-36369146

RESUMEN

Despite major advances in HIV testing, ultrasensitive detection of early infection remains challenging, especially for the viral capsid protein p24, which is an early virological biomarker of HIV-1 infection. Here, To improve p24 detection in patients missed by immunological tests that dominate the diagnostics market, we show a click chemistry amplified nanopore (CAN) assay for ultrasensitive quantitative detection. This strategy achieves a 20.8 fM (0.5 pg/ml) limit of detection for HIV-1 p24 antigen in human serum, demonstrating 20~100-fold higher analytical sensitivity than nanocluster-based immunoassays and clinically used enzyme-linked immunosorbent assay, respectively. Clinical validation of the CAN assay in a pilot cohort shows p24 quantification at ultra-low concentration range and correlation with CD4 count and viral load. We believe that this strategy can improve the utility of p24 antigen in detecting early infection and monitoring HIV progression and treatment efficacy, and also can be readily modified to detect other infectious diseases.


Asunto(s)
Infecciones por VIH , VIH-1 , Nanoporos , Humanos , Química Clic , Proteína p24 del Núcleo del VIH , Prueba de VIH , Ensayo de Inmunoadsorción Enzimática , Sensibilidad y Especificidad
17.
Front Oncol ; 12: 937403, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36439444

RESUMEN

Circadian dysregulation can be involved in the development of malignant tumors, though its relationship with the progression of hepatocellular carcinoma is not yet fully understood. We identified genes related to circadian rhythms from the Cancer Genome Atlas (TCGA), measured gene expression, and conducted genomic difference analysis to construct a circadian rhythm-related signature. The resulting prognosis model proved to be an effective biomarker, as demonstrated by Kaplan-Meier survival analysis for both the training (n = 370, P = 2.687e-10) and external validation cohorts (n = 230, P = 1.45e-02). Further, we found that patients considered 'high risk', with an associated poor prognosis, displayed elevated levels of immune checkpoint genes and immune filtration. We also conducted functional enrichment, which indicated that the risk model showed a significant positive correlation with certain malignant phenotypes, including G2M checkpoint, MYC targets, and the MTORC1 signaling pathway. In summary, we identified a novel circadian rhythm-related signature allowing assessment of prognosis for hepatocellular carcinoma patients, and further can be used to predict immune infiltration sensitivity.

18.
Front Oncol ; 12: 897527, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35865481

RESUMEN

Background: DNA mismatch repair (MMR) deficiency (dMMR) has been recognized as an important biomarker for immunotherapy in esophageal squamous cell carcinoma (ESCC), along with programmed death ligand 1 (PD-L1) expression and/or tumor-infiltrated lymphocytes (TILs). However, in ESCC, MMR protein assessment has not been well studied at present. Methods: A total of 484 ESCC tissues treated between 2007 and 2010, in our hospital, were enrolled. Immunohistochemical expression of MLH1, MSH2, MSH6, PMS2, and PD-L1 on tissue microarray specimens and clinicopathological features, including TILs, were analyzed retrospectively. Results: Out of the 484 studied cases, loss of MLH1, MSH2, MSH6, and PMS2 expression were found in 6.8%, 2.1%, 8.7%, and 4.8% patients, respectively. dMMR was found in 65 patients, 37 cases involved in one MMR protein, 17 cases involved in two proteins, 7 cases involved in three proteins, and 4 cases involved in four proteins. There was no significant survival difference between pMMR (MMR-proficient) and dMMR patients (P>0.05). However, 224 patients with low PMS2 expression had better DFS and OS than 260 patients with high PMS2 expression (P=0.006 for DFS and 0.008 for OS), which was identified as an independent prognostic factor in multivariate analyses. Positive PD-L1 expression was detected in 341 (70.5%) samples. In stage I-II disease, patients with PD-L1 expression had better DFS and OS than those without PD-L1 expression(P<0.05), which was not found in stage III-IV disease. With the ITWG system, 40.1% of cases were classified as high TILs. Patients in the high-TILs group tended to have better DFS (P=0.055) and OS (P=0.070) than those in the low-TILs group and the differences were statistically significant in pMMR, high MSH6, or PMS2 expression cases (P<0.05). Also, high PMS2 expression patients with both PD-L1 expression and high TILs, had similar DFS and OS compared with low PMS2 expression patients (P>0.05), which were much better than other high PMS2 expression patients. Conclusion: The expression level of MMR proteins could also be used as a prognostic factor in ESCC and PMS2 expression outperformed other MMR proteins for predicting survival. The combination of PD-L1 expression and TILs may lead to more efficient risk stratification of ESCC.

19.
Ann Transl Med ; 10(8): 468, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35571402

RESUMEN

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was introduced in 2007. The current study explored the mechanisms of rapid liver hypertrophy after ALPPS in cirrhotic rats. Methods: A cirrhotic rat model was constructed and portal vein ligation (PVL) or ALPPS treatments were administered. The liver hyperplasia rate of the rats was calculated, and hepatic function was evaluated using biochemical factors and the indocyanine green excretion test. Subsequently, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and hematoxylin and eosin (HE) staining were performed to determine the degree of liver regeneration. Differentially expressed genes during the rapid liver hypertrophy were detected by bioinformatics analysis, followed verification using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Results: The body weight of rats that underwent PVL and ALPPS changed during the first 1-4 days postoperatively, and the alterations were more pronounced in rats receiving ALPPS. The recovery of body weight in cirrhotic rats was slower than that in normal rats. The levels of biochemical factors and the indocyanine green retention rate increased 1 day after PVL and ALPPS, and then decreased gradually. PVL and ALPPS elevated the levels of cytokines, inflammatory factors, and proliferating cell nuclear antigen (PCNA) in rats at 1 day postoperatively. HE observation of rat liver condition showed that rats recovered faster within the first 4 days postoperatively. ALPPS surgery resulted in a significant downregulation of matrix metalloproteinase (MMP)2/9 expression in cirrhotic rats at postoperative day 4. Conclusions: Liver function was partially recovered in cirrhotic rats after ALPPS, and the underlying mechanisms may involve PCNA and MMP2/9.

20.
J Electrochem Soc ; 169(5)2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35599744

RESUMEN

DNAs have been used as probes for nanopore sensing of noncharged biomacromolecules due to its negative phosphate backbone. Inspired by this, we explored the potential of diblock synthetic polyelectrolytes as more flexible and inexpensive nanopore sensing probes by investigating translocation behaviors of PEO-b-PSS and PEO-b-PVBTMA through commonly used alpha-hemolysin (α-HL) and Mycobacterium smegmatis porin A (MspA) nanopores. Translocation recordings in different configurations of pore orientation and testing voltage indicated efficient PEO-b-PSS translocations through α-HL and PEO-b-PVBTMA translocations through MspA. This work provides insight into synthetic polyelectrolyte-based probes to expand probe selection and flexibility for nanopore sensing.

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