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1.
Mol Cell ; 83(14): 2493-2508.e5, 2023 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-37343553

RESUMEN

Type IV CRISPR-Cas systems, which are primarily found on plasmids and exhibit a strong plasmid-targeting preference, are the only one of the six known CRISPR-Cas types for which the mechanistic details of their function remain unknown. Here, we provide high-resolution functional snapshots of type IV-A Csf complexes before and after target dsDNA binding, either in the absence or presence of CasDinG, revealing the mechanisms underlying CsfcrRNA complex assembly, "DWN" PAM-dependent dsDNA targeting, R-loop formation, and CasDinG recruitment. Furthermore, we establish that CasDinG, a signature DinG family helicase, harbors ssDNA-stimulated ATPase activity and ATP-dependent 5'-3' DNA helicase activity. In addition, we show that CasDinG unwinds the non-target strand (NTS) and target strand (TS) of target dsDNA from the CsfcrRNA complex. These molecular details advance our mechanistic understanding of type IV-A CRISPR-Csf function and should enable Csf complexes to be harnessed as genome-engineering tools for biotechnological applications.


Asunto(s)
Proteínas Asociadas a CRISPR , ADN , ADN/genética , ADN de Cadena Simple/genética , Sistemas CRISPR-Cas , Proteínas Asociadas a CRISPR/metabolismo
2.
Nat Chem Biol ; 20(4): 503-511, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37932528

RESUMEN

Argonaute proteins (Agos), which use small RNAs or DNAs as guides to recognize complementary nucleic acid targets, mediate RNA silencing in eukaryotes. In prokaryotes, Agos are involved in immunity: the short prokaryotic Ago/TIR-APAZ (SPARTA) immune system triggers cell death by degrading NAD+ in response to invading plasmids, but its molecular mechanisms remain unknown. Here we used cryo-electron microscopy to determine the structures of inactive monomeric and active tetrameric Crenotalea thermophila SPARTA complexes, revealing mechanisms underlying SPARTA assembly, RNA-guided recognition of target single-stranded DNA (ssDNA) and subsequent SPARTA tetramerization, as well as tetramerization-dependent NADase activation. The small RNA guides Ago to recognize its ssDNA target, inducing SPARTA tetramerization via both Ago- and TIR-mediated interactions and resulting in a two-stranded, parallel, head-to-tail TIR rearrangement primed for NAD+ hydrolysis. Our findings thus identify the molecular basis for target ssDNA-mediated SPARTA activation, which will facilitate the development of SPARTA-based biotechnological tools.


Asunto(s)
ADN de Cadena Simple , NAD+ Nucleosidasa , NAD , Microscopía por Crioelectrón , ARN , Sistema Inmunológico
3.
Proc Natl Acad Sci U S A ; 120(4): e2213727120, 2023 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-36656854

RESUMEN

The myophage possesses a contractile tail that penetrates its host cell envelope. Except for investigations on the bacteriophage T4 with a rather complicated structure, the assembly pattern and tail contraction mechanism of myophage remain largely unknown. Here, we present the fine structure of a freshwater Myoviridae cyanophage Pam3, which has an icosahedral capsid of ~680 Å in diameter, connected via a three-section neck to an 840-Å-long contractile tail, ending with a three-module baseplate composed of only six protein components. This simplified baseplate consists of a central hub-spike surrounded by six wedge heterotriplexes, to which twelve tail fibers are covalently attached via disulfide bonds in alternating upward and downward configurations. In vitro reduction assays revealed a putative redox-dependent mechanism of baseplate assembly and tail sheath contraction. These findings establish a minimal myophage that might become a user-friendly chassis phage in synthetic biology.


Asunto(s)
Myoviridae , Ensamble de Virus , Bacteriófago T4/química , Cápside , Proteínas de la Cápside/química , Microscopía por Crioelectrón , Myoviridae/química
4.
Biochem Biophys Res Commun ; 705: 149733, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38442446

RESUMEN

Osteoarthritis (OA) is a common chronic inflammatory degenerative disease. Since chondrocytes are the only type of cells in cartilage, their survival is critical for maintaining cartilage morphology. This review offers a comprehensive analysis of how reactive oxygen species (ROS), including superoxide anions, hydrogen peroxide, hydroxyl radicals, nitric oxide, and their derivatives, affect cartilage homeostasis and trigger several novel modes of regulated cell death, including ferroptosis, parthanatos, and oxeiptosis, which may play roles in chondrocyte death and OA development. Moreover, we discuss potential therapeutic strategies to alleviate OA by scavenging ROS and provide new insight into the research and treatment of the role of regulated cell death in OA.


Asunto(s)
Ferroptosis , Osteoartritis , Parthanatos , Humanos , Condrocitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Osteoartritis/metabolismo
5.
Small ; : e2403845, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940392

RESUMEN

As the anode reaction of proton exchange membrane water electrolysis (PEMWE), the acidic oxygen evolution reaction (OER) is one of the main obstacles to the practical application of PEMWE due to its sluggish four-electron transfer process. The development of high-performance acidic OER electrocatalysts has become the key to improving the reaction kinetics. To date, although various excellent acidic OER electrocatalysts have been widely researched, Ir-based nanomaterials are still state-of-the-art electrocatalysts. Hence, a comprehensive and in-depth understanding of the reaction mechanism of Ir-based electrocatalysts is crucial for the precise optimization of catalytic performance. In this review, the origin and nature of the conventional adsorbate evolution mechanism (AEM) and the derived volcanic relationship on Ir-based electrocatalysts for acidic OER processes are summarized and some optimization strategies for Ir-based electrocatalysts based on the AEM are introduced. To further investigate the development strategy of high-performance Ir-based electrocatalysts, several unconventional OER mechanisms including dual-site mechanism and lattice oxygen mediated mechanism, and their applications are introduced in detail. Thereafter, the active species on Ir-based electrocatalysts at acidic OER are summarized and classified into surface Ir species and O species. Finally, the future development direction and prospect of Ir-based electrocatalysts for acidic OER are put forward.

6.
Crit Rev Food Sci Nutr ; : 1-15, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38841814

RESUMEN

Mineral elements including calcium, iron, and zinc play crucial roles in human health. Their deficiency causes public health risk globally. Commercial mineral supplements have limitations; therefore, alternatives with better solubility, bioavailability, and safety are needed. Chelates of food-derived peptides and mineral elements exhibit advantages in terms of stability, absorption rate, and safety. However, low binding efficiency limits their application. Extensive studies have focused on understanding and enhancing the chelating activity of food-derived peptides with mineral elements. This includes obtaining peptides with high chelating activity, elucidating interaction mechanisms, optimizing chelation conditions, and developing techniques to enhance the chelating activity. This review provides a comprehensive theoretical basis for the development and utilization of food-derived peptide-mineral element chelates in the food industry. Efforts to address the challenge of low binding rates between peptides and mineral elements have yielded promising results. Optimization of peptide sources, enzymatic hydrolysis processes, and purification schemes have helped in obtaining peptides with high chelating activity. The understanding of interaction mechanisms has been enhanced through advanced separation techniques and molecular simulation calculations. Optimizing chelation process conditions, including pH and temperature, can help in achieving high binding rates. Methods including phosphorylation modification and ultrasonic treatment can enhance the chelating activity.

7.
J Nanobiotechnology ; 22(1): 360, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38907233

RESUMEN

Osteosarcoma (OS) derived small extracellular vesicles (OS-sEVs) have been shown to induce the formation of cancer-associated fibroblasts (CAFs), characterized by elevated pro-inflammatory factor expression and enhanced migratory and contractile abilities. These CAFs play a crucial role in priming lung metastasis by orchestrating the pre-metastatic niche (PMN) in the lung. Disrupting the communication between OS-sEVs and lung fibroblasts (LFs) emerges as a potent strategy to hinder OS pulmonary metastasis. Our previously established saponin-mediated cargo-elimination strategy effectively reduces the cancer-promoting ability of tumor-derived small extracellular vesicles (TsEVs) while preserving their inherent targeting capability. In this study, we observed that cargo-eliminated OS-sEVs (CE-sEVs) display minimal pro-tumoral and LFs activation potential, yet retain their ability to target LFs. The uptake of OS-sEVs by LFs can be concentration-dependently suppressed by CE-sEVs, preventing the conversion of LFs into CAFs and thus inhibiting PMN formation and pulmonary metastasis of OS. In summary, this study proposes a potential strategy to prevent LFs activation, PMN formation in the lung, and OS pulmonary metastasis through competitive inhibition of OS-sEVs' function by CE-sEVs.


Asunto(s)
Vesículas Extracelulares , Neoplasias Pulmonares , Osteosarcoma , Osteosarcoma/patología , Osteosarcoma/metabolismo , Vesículas Extracelulares/metabolismo , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Animales , Humanos , Ratones , Línea Celular Tumoral , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Neoplasias Óseas/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Ratones Endogámicos BALB C , Saponinas/farmacología , Ratones Desnudos , Movimiento Celular/efectos de los fármacos , Pulmón/patología
8.
J Nanobiotechnology ; 22(1): 105, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38468249

RESUMEN

Chemotherapy is an important therapeutic approach for malignant tumors for it triggers apoptosis of cancer cells. However, chemotherapy also induces senescence of stromal cells in the tumor microenvironment to promote tumor progression. Strategies aimed at killing tumor cells while simultaneously eliminating senescent stromal cells represent an effective approach to cancer treatment. Here, we developed an engineered Src-siRNA delivery system based on small extracellular vesicles (sEVs) to simultaneously eliminate senescent stromal cells and tumor cells for cancer therapy. The DSPE-PEG-modified urokinase plasminogen activator (uPA) peptide was anchored to the membranes of induced mesenchymal stem cell-derived sEVs (uPA-sEVs), and Src siRNA was loaded into the uPA-sEVs by electroporation (uPA-sEVs-siSrc). The engineered uPA-sEVs-siSrc retained the basic sEVs properties and protected against siSrc degradation. uPA peptide modification enhanced the sEVs with the ability to simultaneously target doxorubicin-induced senescent stromal cells and tumor cells. Src silencing by uPA-sEVs-siSrc induced apoptosis of both senescent stromal cells and tumor cells. The uPA-sEVs-siSrc displayed preferential tumor accumulation and effectively inhibited tumor growth in a tumor xenograft model. Furthermore, uPA-sEVs-siSrc in combination with doxorubicin significantly reduced the senescence burden and enhanced the therapeutic efficacy of chemotherapy. Taken together, uPA-sEVs-siSrc may serve as a promising therapy to kill two birds with one stone, not only killing tumor cells to achieve remarkable antitumor effect, but also eliminating senescent cells to enhance the efficacy of chemotherapeutic agent in tumor regression.


Asunto(s)
Vesículas Extracelulares , Neoplasias , Humanos , Activador de Plasminógeno de Tipo Uroquinasa/genética , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Neoplasias/tratamiento farmacológico , ARN Interferente Pequeño , Células del Estroma/metabolismo , Vesículas Extracelulares/metabolismo , Doxorrubicina/farmacología , Péptidos , Microambiente Tumoral
9.
BMC Ophthalmol ; 24(1): 38, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38267915

RESUMEN

BACKGROUND: To report a case of retinitis with multiple intraocular viral infections after second haematopoietic stem cell transplantation. CASE PRESENTATION: A 39-year-old female patient developed retinitis after a second haematopoietic stem cell transplant. Right eye was tested for three viral infections- cytomegalovirus, Epstein‒Barr virus and herpes simplex virus, while left was infected with cytomegalovirus. The patient was subsequently treated with vitreous cavity ganciclovir injections, and 1 week later both eyes tested negative for aqueous humour viruses. DISCUSSION AND CONCLUSION: CMV, EBV and HSV belong to the herpes virus family. They are all commonly observed in the body and represent opportunity infectious viruses. The retinitis they cause have different characteristics. But simultaneous infection of the eye by multiple viruses is quite rare. In this case, three viruses were detected in the patient's eye, but whether the retina was caused by all three viruses at the same time could not be determined. A satisfactory outcome was achieved after treatment with vitreous cavity ganciclovir injection.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Retinitis , Virosis , Femenino , Humanos , Adulto , Herpesvirus Humano 4 , Citomegalovirus , Simplexvirus , Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Retina , Ganciclovir/uso terapéutico
10.
Nano Lett ; 23(24): 11827-11834, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38079388

RESUMEN

Local electric field induced by the lightning-rod effect attracts great attention for regulating the local microenvironment and electronic properties of active sites. Nevertheless, local electric-field-assisted applications are mainly limited to metals with strong surface plasmonic resonance properties (e.g., Au, Ag, and Cu). Herein, we fabricate RuCu snow-like nanosheets (SNSs) with high-curvature nanotips for enhancing the hydrogen oxidation reaction (HOR) and hydrogen evolution reaction (HER). Theoretical simulations show that RuCu SNSs can induce a strong local electric field around the sharp nanotips, which favors the accumulation of OH- for HOR and H+ for HER. Cu incorporation can modulate the binding strength of OH* and H*, leading to significantly enhanced HOR and HER performance. Impressively, the mass activity of RuCu SNSs for alkaline HOR is 31.3 times higher than that of RuCu nanocrystals without sharp tips. Besides, the required overpotential for reaching 10 mA cm-2 during HER over RuCu SNSs is 14.0 mV.

11.
Microbiology (Reading) ; 169(4)2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37068121

RESUMEN

Penicillium brocae strain P6 is a phosphate-solubilizing fungus isolated from farmland in Guangdong Province, China. To gain better insights into the phosphate solubilization mechanisms of strain P6, a T-DNA insertion population containing approximately 4500 transformants was generated by Agrobacterium tumefaciens-mediated transformation. The transformation procedure was optimized by using a Hybond N membrane for co-cultivation of A. tumefaciens and P. brocae. A mutant impaired in phosphate solubilization (named MT27) was obtained from the T-DNA insertion population. Thermal asymmetric interlaced PCR was then used to identify the nucleotide sequences flanking the T-DNA insertion site. The T-DNA in MT27 was inserted into the fourth exon of an enolase gene, which shows 90.8 % nucleotide identity with enolase mRNA from Aspergillus neoniger. Amino acid sequence homology analysis indicated that the enolase is well conserved among filamentous fungi and Saccharomyces cerevisiae. Complementation tests with the MT27 mutant confirmed that the enolase gene is involved in phosphate solubilization. Analysis of organic acids in culture supernatants indicated reduced levels of oxalic acid and lactic acid for the MT27 mutant compared to the parent strain P6 or the complementation strain. In conclusion, we suggest that the identified enolase gene of P. brocae is involved in production of specific organic acids, which, when secreted, act as phosphate solubilizing agents.


Asunto(s)
Fosfatos , Fosfopiruvato Hidratasa , Fosfatos/metabolismo , Fosfopiruvato Hidratasa/genética , Mutagénesis Insercional , Agrobacterium tumefaciens/genética , Transformación Genética
12.
Small ; 19(19): e2207038, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36755212

RESUMEN

Crystal-phase-engineering provides a powerful strategy for regulating the catalytic performance yet remains great challenge. Herein, the kinetic-modulated crystal-phase-control of Ru nanosheet assemblies (Ru NAs) is demonstrated by simply altering the concentration of citric acid (CA). Detailed experimental results reveal that high concentration of CA retards the growth kinetics and thus leads to the formation of metastable face-centered cubic (fcc) Ru NAs, while low concentration of CA results in the fast growth kinetics and the preferential formation of Ru NAs with stable hexagonal close packed (hcp) phase. Moreover, Ru NAs with different phases are used as catalyst for hydrogen oxidation reaction (HOR) to evaluate the effects of crystal phase on catalytic performance. Impressively, Ru NAs with fcc phase display a mass activity of 2.75 A mgRu -1 at 50 mV, which is much higher than those of Ru NAs with fcc/hcp (1.02 A mgRu -1 ) and hcp (0.74 A mgRu -1 ) phases. Theoretical calculations show that fcc Ru NAs display weaker adsorption toward * H and lower energy barrier toward the rate-determining step (RDS) during HOR. This work provides a facile strategy for regulating the crystal phase of Ru nanocrystals, which may attract rapid interests of researchers in materials, chemistry, and catalysis.

13.
Opt Express ; 31(23): 38640-38652, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-38017964

RESUMEN

In this paper, we propose a high-security three-dimensional optical transmission system utilizing time-frequency-space interleaving chaos, which simultaneously enhances the reliability and security of the system. The four-wing 3D chaos model encrypts the time-frequency space interleaved modulation domain of a orthogonal time-frequency space (OTFS) modulation signal and the modulated phase information simultaneously, improving the system's security. We also experimentally validate the proposed high-security 3D-OTFS method, utilizing the hexadecimal modulation technique. The modulated OTFS signal achieves a transmission rate of 34.1 Gb/s over a 2-km seven-core fiber link, with the OTFS signal exhibiting a maximum of 1.31 dB receiver sensitivity gain compared to orthogonal frequency division multiplexing (OFDM) signals under the forward error correction threshold of the bit error rate. The achieved keyspace is equal to 5 × 1048. The findings demonstrate that the proposed high-security three-dimensional optical transmission mechanism, based on time-frequency-space interleaved disruption, exhibits excellent anti-interference ability and confidentiality performance. Consequently, it holds promising prospects for future applications in optical communications.

14.
Opt Lett ; 48(16): 4408-4411, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37582044

RESUMEN

In this paper, an artificial-intelligence-based secure semantic optical communication scheme is proposed. The semantic features of the original text information are extracted using Transformer. Compared with other networks, Transformer reduces the complexity of the structure and the associated training cost by using the multi-head attention mechanism. To solve the security problem, the encryption scheme is applied to an orthogonal frequency division multiplexed passive optical network (OFDM-PON). The proposed scheme applies chaotic sequences to produce masking vectors. We encrypt the constellation and frequency, achieving a large key space of 1 × 10270. To prove that Transformer can effectively extract the semantic features of text, we have computed the values of ROUGE-1, ROUGE-2, and ROUGE-L, which are 40.9, 18.02, and 37.17, respectively. An encrypted 16 quadrature amplitude modulation (16QAM) OFDM signal transmission over a 2 km seven-core fiber with a data rate of 78.5 Gbits/s was experimentally demonstrated. During the experiments, the bit error rate (BER) was analyzed and the results show that the proposed system improves efficiency and security in an OFDM-PON system.

15.
J Magn Reson Imaging ; 58(6): 1930-1941, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37177868

RESUMEN

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is difficult to predict and carries high mortality. This study utilized radiomic techniques with clinical examinations to assess recurrence in HCC. PURPOSE: To develop a Cox nomogram to assess the risk of postoperative recurrence in HCC using radiomic features of three volumes of interest (VOIs) in preoperative dynamic contrast-enhanced MRI (DCE-MRI), along with clinical findings. STUDY TYPE: Retrospective. SUBJECTS: 249 patients with pathologically proven HCCs undergoing surgical resection at three institutions were selected. FIELD STRENGTH/SEQUENCE: Fat saturated T2-weighted, Fat saturated T1-weighted, and DCE-MRI performed at 1.5 T and 3.0 T. ASSESSMENT: Three VOIs were generated; the tumor VOI corresponds to the area from the tumor core to the outer perimeter of the tumor, the tumor +10 mm VOI represents the area from the tumor perimeter to 10 mm distal to the tumor in all directions, finally, the background liver parenchyma VOI represents the hepatic tissue outside the tumor. Three models were generated. The total radiomic model combined information from the three listed VOI's above. The clinical-radiological model combines physical examination findings with imaging characteristics such as tumor size, margin features, and metastasis. The combined radiomic model includes features from both models listed above and showed the highest reliability for assessing 24-month survival for HCC. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) Cox regression, univariable, and multivariable Cox regression, Kmeans clustering, and Kaplan-Meier analysis. The discrimination performance of each model was quantified by the C-index. A P value <0.05 was considered statistically significant. RESULTS: The combined radiomic model, which included features from the radiomic VOI's and clinical imaging provided the highest performance (C-index: training cohort = 0.893, test cohort = 0.851, external cohort = 0.797) in assessing the survival of HCC. CONCLUSION: The combined radiomic model provides superior ability to discern the possibility of recurrence-free survival in HCC over the total radiomic and the clinical-radiological models. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Nomogramas , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética/métodos
16.
Pharmacol Res ; 193: 106820, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37315822

RESUMEN

Nuciferine aporphine alkaloid mainly exists in Nelumbo nucifera Gaertn and is a beneficial to human health, such as anti-obesity, lowering blood lipid, prevention of diabetes and cancer, closely associated with inflammation. Importantly, nuciferine may contribute to its bioactivities by exerting intense anti-inflammatory activities in multiple models. However, no review has summarized the anti-inflammatory effect of nuciferine. This review critically summarized the information regarding the structure-activity relationships of dietary nuciferine. Moreover, biological activities and clinical application on inflammation-related diseases, such as obesity, diabetes, liver, cardiovascular diseases, and cancer, as well as their potential mechanisms, involving oxidative stress, metabolic signaling, and gut microbiota has been reviewed. The current work provides a better understanding of the anti-inflammation properties of nuciferine against multiple diseases, thereby improving the utilization and application of nuciferine-containing plants across functional food and medicine.


Asunto(s)
Aporfinas , Hígado , Humanos , Hígado/metabolismo , Aporfinas/farmacología , Aporfinas/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Relación Estructura-Actividad
17.
Eur Radiol ; 33(9): 6608-6618, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37012548

RESUMEN

OBJECTIVES: The aim of the study was to evaluate the association between the radiomics-based intratumoral heterogeneity (ITH) and the recurrence risk in hepatocellular carcinoma (HCC) patients after liver transplantation (LT), and to assess its incremental to the Milan, University of California San Francisco (UCSF), Metro-Ticket 2.0, and Hangzhou criteria. METHODS: A multicenter cohort of 196 HCC patients were investigated. The endpoint was recurrence-free survival (RFS) after LT. A CT-based radiomics signature (RS) was constructed and assessed in the whole cohort and in the subgroups stratified by the Milan, UCSF, Metro-Ticket 2.0, and Hangzhou criteria. The R-Milan, R-UCSF, R-Metro-Ticket 2.0, and R-Hangzhou nomograms which combined RS and the four existing risk criteria were developed respectively. The incremental value of RS to the four existing risk criteria in RFS prediction was evaluated. RESULTS: RS was significantly associated with RFS in the training and test cohorts as well as in the subgroups stratified by the existing risk criteria. The four combined nomograms showed better predictive capability than the existing risk criteria did with higher C-indices (R-Milan [training/test] vs. Milan, 0.745/0.765 vs. 0.677; R-USCF vs. USCF, 0.748/0.767 vs. 0.675; R-Metro-Ticket 2.0 vs. Metro-Ticket 2.0, 0.756/0.783 vs. 0.670; R-Hangzhou vs. Hangzhou, 0.751/0.760 vs. 0.691) and higher clinical net benefit. CONCLUSIONS: The radiomics-based ITH can predict outcomes and provide incremental value to the existing risk criteria in HCC patients after LT. Incorporating radiomics-based ITH in HCC risk criteria may facilitate candidate selection, surveillance, and adjuvant trial design. KEY POINTS: • Milan, USCF, Metro-Ticket 2.0, and Hangzhou criteria may be insufficient for outcome prediction in HCC after LT. • Radiomics allows for the characterization of tumor heterogeneity. • Radiomics adds incremental value to the existing criteria in outcome prediction.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/etiología , Trasplante de Hígado/efectos adversos , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos
18.
Int J Hyperthermia ; 40(1): 2184397, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36888994

RESUMEN

OBJECTIVE: To develop and validate a radiomics nomogram for predicting the survival of patients with pancreatic ductal adenocarcinoma (PDAC) after receiving high-intensity focused ultrasound (HIFU) treatment. METHODS: A total of 52 patients with PDAC were enrolled. To select features, the least absolute shrinkage and selection operator algorithm were applied, and the radiomics score (Rad-Score) was obtained. Radiomics model, clinics model, and radiomics nomogram model were constructed by multivariate regression analysis. The identification, calibration, and clinical application of nomogram were evaluated. Survival analysis was performed using Kaplan-Meier (K-M) method. RESULTS: According to conclusions made from the multivariate Cox model, Rad-Score, and tumor size were independent risk factors for OS. Compared with the clinical model and radiomics model, the combination of Rad-Score and clinicopathological factors could better predict the survival of patients. Patients were divided into high-risk and low-risk groups according to Rad-Score. K-M analysis showed that the difference between the two groups was statistically significant (p < 0.05). In addition, the radiomics nomogram model indicated better discrimination, calibration, and clinical practicability in training and validation cohorts. CONCLUSION: The radiomics nomogram effectively evaluates the prognosis of patients with advanced pancreatic cancer after HIFU surgery, which could potentially improve treatment strategies and promote individualized treatment of advanced pancreatic cancer.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Ultrasónicos , Humanos , Nomogramas , Pronóstico , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas
19.
J Nanobiotechnology ; 21(1): 25, 2023 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-36681851

RESUMEN

BACKGROUND: Hematogenous metastasis is essential for the progression of advanced hepatocellular carcinoma (HCC) and can occur even after patients receive multidisciplinary therapies, including immunotherapy and hepatectomy; circulating tumor cells (CTCs) are one of the dominant components of the metastatic cascade. However, the CTC capture efficiency for HCC is low due to the low sensitivity of the detection method. In this study, epithelial cell adhesion molecule (EpCAM)/vimentin/Glypican-3 (GPC3) antibody-modified lipid magnetic spheres (LMS) were used to capture tumor cells with epithelial phenotype, mesenchymal phenotype and GPC3 phenotype, respectively, in order to capture more CTCs with a more comprehensive phenotype for monitoring tumor metastasis. RESULTS: The novel CTC detection system of Ep-LMS/Vi-LMS/GPC3-LMS was characterized by low toxicity, strong specificity (96.94%), high sensitivity (98.12%) and high capture efficiency (98.64%) in vitro. A sudden increase in CTC counts accompanied by the occurrence of lung metastasis was found in vivo, which was further validated by a clinical study. During follow-up, the rapid increase in CTCs predicted tumor progression in HCC patients. Additionally, genetic testing results showed common genetic alterations in primary tumors, CTCs and metastatic tissues. The proportion of patients predicted to benefit from immunotherapy with the CTC detection method was higher than that for the tissue detection method (76.47% vs. 41.18%, P = 0.037), guiding the application of clinical individualized therapy. CONCLUSIONS: The Ep-LMS/Vi-LMS/GPC3-LMS sequential CTC capture system is convenient and feasible for the clinical prediction of HCC progression. CTCs captured by this system could be used as a suitable alternative to HCC tissue detection in guiding immunotherapy, supporting the clinical application of CTC liquid biopsy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Neoplásicas Circulantes , Humanos , Carcinoma Hepatocelular/patología , Células Neoplásicas Circulantes/patología , Neoplasias Hepáticas/patología , Molécula de Adhesión Celular Epitelial/metabolismo , Hepatectomía , Biomarcadores de Tumor/metabolismo , Glipicanos
20.
Int Orthop ; 47(8): 2065-2071, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37270455

RESUMEN

PURPOSE: The purpose of this study is to compare the effect of buttress plate and cannulated screw in the treatment of anteromedial coronoid fracture with posteromedial rotatory instability (PMRI). METHODS: We retrospectively evaluated patients who were diagnosed with O'Driscoll type 2 fractures combined with elbow posteromedial rotatory instability and underwent surgery for anteromedial coronoid fracture between August 2014 and March 2019. They were divided into buttress plate (n=16) and cannulated screw (n=11) groups. The elbow range of motion, visual analog scale (VAS), Mayo elbow performance score (MEPS), and disabilities of the arm, shoulder, and hand score (DASH) were used for clinical outcome assessment. RESULT: There were no significant differences in clinical outcomes. However, the surgical time was significantly shorter in cannulated screw group (85.45±4.156) compared to the buttress plate group (93.81±8.863, P=0.008), and the surgical time was associated with internal fixation (P=0.008). CONCLUSION: Although there was selection of cases in that small fragments were treated with buttress plate and large fragments with cannulated screw, the buttress plate and cannulated screw have comparable functional outcomes on fixation of the anteromedial coronoid fracture with elbow PMRI. The fixation of the anteromedial coronoid fracture with large fragments using the cannulated screw has a shorter operation time.


Asunto(s)
Articulación del Codo , Fracturas Óseas , Fracturas del Cúbito , Humanos , Codo , Fracturas del Cúbito/complicaciones , Fracturas del Cúbito/diagnóstico por imagen , Fracturas del Cúbito/cirugía , Estudios Retrospectivos , Fracturas Óseas/complicaciones , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/cirugía , Fijación Interna de Fracturas/efectos adversos , Tornillos Óseos , Rango del Movimiento Articular , Resultado del Tratamiento
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