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1.
Nat Immunol ; 25(3): 552-561, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38263463

RESUMO

The steady flow of lactic acid (LA) from tumor cells to the extracellular space via the monocarboxylate transporter symport system suppresses antitumor T cell immunity. However, LA is a natural energy metabolite that can be oxidized in the mitochondria and could potentially stimulate T cells. Here we show that the lactate-lowering mood stabilizer lithium carbonate (LC) can inhibit LA-mediated CD8+ T cell immunosuppression. Cytoplasmic LA increased the pumping of protons into lysosomes. LC interfered with vacuolar ATPase to block lysosomal acidification and rescue lysosomal diacylglycerol-PKCθ signaling to facilitate monocarboxylate transporter 1 localization to mitochondrial membranes, thus transporting LA into the mitochondria as an energy source for CD8+ T cells. These findings indicate that targeting LA metabolism using LC could support cancer immunotherapy.


Assuntos
Antimaníacos , Ácido Láctico , Carbonato de Lítio , Mitocôndrias , Neoplasias , Humanos , Linfócitos T CD8-Positivos , Ácido Láctico/metabolismo , Carbonato de Lítio/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias/metabolismo , Antimaníacos/farmacologia
2.
Cell ; 163(7): 1783-1795, 2015 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-26687362

RESUMO

Touch perception begins with activation of low-threshold mechanoreceptors (LTMRs) in the periphery. LTMR terminals exhibit tremendous morphological heterogeneity that specifies their mechanical receptivity. In a survey of mammalian skin, we found a preponderance of neurofilament-heavy-chain(+) circumferential endings associated with hair follicles, prompting us to develop a genetic strategy to interrogate these neurons. Targeted in vivo recordings revealed them to be Aß field-LTMRs, identified 50 years ago but largely elusive thereafter. Remarkably, while Aß field-LTMRs are highly sensitive to gentle stroking of the skin, they are unresponsive to hair deflection, and they encode skin indentation in the noxious range across large, spotty receptive fields. Individual Aß field-LTMRs form up to 180 circumferential endings, making them the most anatomically expansive LTMR identified to date. Thus, Aß field-LTMRs are a major mammalian LTMR subtype that forms circumferential endings in hairy skin, and their sensitivity to gentle skin stroking arises through integration across many low-sensitivity circumferential endings.


Assuntos
Mecanorreceptores/metabolismo , Tato , Animais , Axônios/metabolismo , Tronco Encefálico/metabolismo , Fenômenos Eletrofisiológicos , Folículo Piloso/metabolismo , Filamentos Intermediários/metabolismo , Camundongos , Células Receptoras Sensoriais/metabolismo , Pele/citologia , Pele/metabolismo , Corno Dorsal da Medula Espinal/metabolismo
3.
Nature ; 633(8028): 71-76, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39198651

RESUMO

Majorana zero modes (MZMs) are emergent zero-energy topological quasiparticles that are their own antiparticles1,2. Detected MZMs are spatially separated and electrically neutral, so producing hybridization between MZMs is extremely challenging in superconductors3,4. Here, we report the magnetic field response of vortex bound states in superconducting topological crystalline insulator SnTe (001) films. Several MZMs were predicted to coexist in a single vortex due to magnetic mirror symmetry. Using a scanning tunnelling microscope equipped with a three-axis vector magnet, we found that the zero-bias peak (ZBP) in a single vortex exhibits an apparent anisotropic response even though the magnetic field is weak. The ZBP can robustly extend a long distance of up to approximately 100 nm at the (001) surface when the magnetic field is parallel to the ( 1 1 ¯ 0 )-type mirror plane, otherwise it displays an asymmetric splitting. Our systematic simulations demonstrate that the anisotropic response cannot be reproduced with trivial ZBPs. Although the different MZMs cannot be directly distinguished due to the limited energy resolution in our experiments, our comparisons between experimental measurements and theoretical simulations strongly support the existence and hybridization of symmetry-protected multiple MZMs. Our work demonstrates a way to hybridize different MZMs by controlling the orientation of the magnetic field and expands the types of MZM available for tuning topological states.

4.
Mol Cell ; 73(5): 1015-1027.e7, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30711376

RESUMO

TCRs recognize cognate pMHCs to initiate T cell signaling and adaptive immunity. Mechanical force strengthens TCR-pMHC interactions to elicit agonist-specific catch bonds to trigger TCR signaling, but the underlying dynamic structural mechanism is unclear. We combined steered molecular dynamics (SMD) simulation, single-molecule biophysical approaches, and functional assays to collectively demonstrate that mechanical force induces conformational changes in pMHCs to enhance pre-existing contacts and activates new interactions at the TCR-pMHC binding interface to resist bond dissociation under force, resulting in TCR-pMHC catch bonds and T cell activation. Intriguingly, cancer-associated somatic mutations in HLA-A2 that may restrict these conformational changes suppressed TCR-pMHC catch bonds. Structural analysis also indicated that HLA polymorphism might alter the equilibrium of these conformational changes. Our findings not only reveal critical roles of force-induced conformational changes in pMHCs for activating TCR-pMHC catch bonds but also have implications for T cell-based immunotherapy.


Assuntos
Imunidade Adaptativa , Antígeno HLA-A2/imunologia , Mecanotransdução Celular , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Animais , Células HEK293 , Antígeno HLA-A2/química , Antígeno HLA-A2/genética , Antígeno HLA-A2/metabolismo , Humanos , Hibridomas , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Simulação de Dinâmica Molecular , Mutação , Ligação Proteica , Conformação Proteica , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Imagem Individual de Molécula/métodos , Relação Estrutura-Atividade , Linfócitos T/metabolismo
5.
EMBO J ; 41(2): e107739, 2022 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34913508

RESUMO

Stimulatory immune receptor NKG2D binds diverse ligands to elicit differential anti-tumor and anti-virus immune responses. Two conflicting degeneracy recognition models based on static crystal structures and in-solution binding affinities have been considered for almost two decades. Whether and how NKG2D recognizes and discriminates diverse ligands still remain unclear. Using live-cell-based single-molecule biomechanical assay, we characterized the in situ binding kinetics of NKG2D interacting with different ligands in the absence or presence of mechanical force. We found that mechanical force application selectively prolonged NKG2D interaction lifetimes with the ligands MICA and MICB, but not with ULBPs, and that force-strengthened binding is much more pronounced for MICA than for other ligands. We also integrated steered molecular dynamics simulations and mutagenesis to reveal force-induced rotational conformational changes of MICA, involving formation of additional hydrogen bonds on its binding interface with NKG2D, impeding MICA dissociation under force. We further provided a kinetic triggering model to reveal that force-dependent affinity determines NKG2D ligand discrimination and its downstream NK cell activation. Together, our results demonstrate that NKG2D has a discrimination power to recognize different ligands, which depends on selective mechanical force-induced ligand conformational changes.


Assuntos
Subfamília K de Receptores Semelhantes a Lectina de Células NK/química , Sítios de Ligação , Células Cultivadas , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Células K562 , Ligantes , Fenômenos Mecânicos , Simulação de Dinâmica Molecular , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Ligação Proteica , Imagem Individual de Molécula
6.
Nano Lett ; 24(35): 10957-10963, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39171725

RESUMO

Logic-in-memory (LIM) architecture holds great potential to break the von Neumann bottleneck. Despite the extensive research on novel devices, challenges persist in developing suitable engineering building blocks for such designs. Herein, we propose a reconfigurable strategy for efficient implementation of Boolean logics based on a hafnium oxide-based ferroelectric field effect transistor (HfO2-based FeFET). The logic results are stored within the device itself (in situ) during the computation process, featuring the key characteristics of LIM. The fast switching speed and low power consumption of a HfO2-based FeFET enable the execution of Boolean logics with an ultralow energy of lower than 8 attojoule (aJ). This represents a significant milestone in achieving aJ-level computing energy consumption. Furthermore, the system demonstrates exceptional reliability with computing endurance exceeding 108 cycles and retention properties exceeding 1000 s. These results highlight the remarkable potential of a FeFET for the realization of high performance beyond the von Neumann LIM computing architectures.

7.
Proteomics ; : e2300491, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39126236

RESUMO

State-of-the-art mass spectrometers combined with modern bioinformatics algorithms for peptide-to-spectrum matching (PSM) with robust statistical scoring allow for more variable features (i.e., post-translational modifications) being reliably identified from (tandem-) mass spectrometry data, often without the need for biochemical enrichment. Semi-specific proteome searches, that enforce a theoretical enzymatic digestion to solely the N- or C-terminal end, allow to identify of native protein termini or those arising from endogenous proteolytic activity (also referred to as "neo-N-termini" analysis or "N-terminomics"). Nevertheless, deriving biological meaning from these search outputs can be challenging in terms of data mining and analysis. Thus, we introduce TermineR, a data analysis approach for the (1) annotation of peptides according to their enzymatic cleavage specificity and known protein processing features, (2) differential abundance and enrichment analysis of N-terminal sequence patterns, and (3) visualization of neo-N-termini location. We illustrate the use of TermineR by applying it to tandem mass tag (TMT)-based proteomics data of a mouse model of polycystic kidney disease, and assess the semi-specific searches for biological interpretation of cleavage events and the variable contribution of proteolytic products to general protein abundance. The TermineR approach and example data are available as an R package at https://github.com/MiguelCos/TermineR.

8.
J Cell Mol Med ; 28(5): e18101, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38165009

RESUMO

Bladder cancer is one of the most common malignant tumours of the urogenital system, with high morbidity and mortality. In most cases, surgery is considered the first choice of treatment, followed by adjuvant chemotherapy. However, the 5-year recurrence rate is still as high as 65% in patients with non-invasive or in situ tumours and up to 73% in patients with slightly more advanced disease at initial diagnosis. Various treatment methods for bladder cancer have been developed, and hundreds of new immunotherapies are being tested. To date, only a small percentage of people have had success with new treatments, though studies have suggested that the combination of immunotherapy with other therapies improves treatment efficiency and positive outcomes for individuals, with great hopes for the future. In this article, we summarize the origins, therapeutic mechanisms and current status of research on immunotherapeutic agents for bladder cancer.


Assuntos
Imunoterapia , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/imunologia , Humanos , Imunoterapia/métodos , Animais , Terapia Combinada
9.
J Biol Chem ; 299(11): 105302, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37777155

RESUMO

Immune checkpoint blockades have made huge breakthrough among some cancer types including lung cancer. However, only a small proportion of patients will benefit from immune checkpoint blockades; other patients have no or minor response to immunotherapy. The underlying mechanisms and efficient biomarkers to predict immunotherapy resistances remain unclear and lacking. In this study, BATF2 knockout mice, human xenograft mice, were used for in vivo studies. Relevant RNA and protein levels were analyzed by RT-quantitative PCR and Western blotting. As a result, we found that the expression of BATF2 is negatively correlated with expression of programmed death-ligand 1 in the plasma of patients. Mechanically, we showed that BATF2 inhibits programmed death-ligand 1 expression in cancer cells by inhibiting the PI3K-AKT pathway where ZEB2 plays an important role in this process. Based on bioinformatics analysis, we found that the function of BATF2 in promoting antitumor immune response in patients with non-small cell lung cancer, which is mediated by BATF2, enhances CD8+ T-cell infiltration as well as activation. The expression of BATF2 from circulating tumor cells and tissues can be serve as an efficient biomarker to predict diagnosis, prognosis, and immunotherapy efficacy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linfócitos T CD8-Positivos , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral
10.
Mol Med ; 30(1): 88, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879491

RESUMO

BACKGROUND: Macrophages play a crucial role in the development of cardiac fibrosis (CF). Although our previous studies have shown that glycogen metabolism plays an important role in macrophage inflammatory phenotype, the role and mechanism of modifying macrophage phenotype by regulating glycogen metabolism and thereby improving CF have not been reported. METHODS: Here, we took glycogen synthetase kinase 3ß (GSK3ß) as the target and used its inhibitor NaW to enhance macrophage glycogen metabolism, transform M2 phenotype into anti-fibrotic M1 phenotype, inhibit fibroblast activation into myofibroblasts, and ultimately achieve the purpose of CF treatment. RESULTS: NaW increases the pH of macrophage lysosome through transmembrane protein 175 (TMEM175) and caused the release of Ca2+ through the lysosomal Ca2+ channel mucolipin-2 (Mcoln2). At the same time, the released Ca2+ activates TFEB, which promotes glucose uptake by M2 and further enhances glycogen metabolism. NaW transforms the M2 phenotype into the anti-fibrotic M1 phenotype, inhibits fibroblasts from activating myofibroblasts, and ultimately achieves the purpose of treating CF. CONCLUSION: Our data indicate the possibility of modifying macrophage phenotype by regulating macrophage glycogen metabolism, suggesting a potential macrophage-based immunotherapy against CF.


Assuntos
Fibrose , Macrófagos , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Camundongos , Glicogênio Sintase Quinase 3 beta/metabolismo , Miofibroblastos/metabolismo , Glicogênio/metabolismo , Cálcio/metabolismo , Lisossomos/metabolismo , Fibroblastos/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Masculino , Camundongos Endogâmicos C57BL
11.
Plant Physiol ; 192(4): 3134-3151, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37165714

RESUMO

Gummosis is 1 of the most common and destructive diseases threatening global peach (Prunus persica) production. Our previous studies have revealed that ethylene and methyl jasmonate enhance peach susceptibility to Lasiodiplodia theobromae, a virulent pathogen inducing gummosis; however, the underlying molecular mechanisms remain obscure. Here, 2 ethylene response factors (ERFs), PpERF98 and PpERF1, were identified as negative regulators in peach response to L. theobromae infection. Expression of 2 putative paralogs, PpERF98-1/2, was dramatically induced by ethylene and L. theobromae treatments and accumulated highly in the gummosis-sensitive cultivar. Silencing of PpERF98-1/2 increased salicylic acid (SA) content and pathogenesis-related genes PpPR1 and PpPR2 transcripts, conferring peach resistance to L. theobromae, whereas peach and tomato (Solanum lycopersicum) plants overexpressing either of PpERF98-1/2 showed opposite changes. Also, jasmonic acid markedly accumulated in PpERF98-1/2-silenced plants, but reduction in PpPR3, PpPR4, and PpCHI (Chitinase) transcripts indicated a blocked signaling pathway. PpERF98-1 and 2 were further demonstrated to directly bind the promoters of 2 putative paralogous PpERF1 genes and to activate the ERF branch of the jasmonate/ethylene signaling pathway, thus attenuating SA-dependent defenses. The lesion phenotypes of peach seedlings overexpressing PpERF1-1/2 and PpERF98-1/2 were similar. Furthermore, PpERF98-1/2 formed homodimers/heterodimers and interacted with the 2 PpERF1 proteins to amplify the jasmonate/ethylene signaling pathway, as larger lesions were observed in peach plants cooverexpressing PpERF98 with PpERF1 relative to individual PpERF98 overexpression. Overall, our work deciphers an important regulatory network of ethylene-mediated peach susceptibility to L. theobromae based on a PpERF98-PpERF1 transcriptional cascade, which could be utilized as a potential target for genetic engineering to augment protection against L. theobromae-mediated diseases in crops and trees.


Assuntos
Prunus persica , Prunus persica/genética , Prunus persica/metabolismo , Etilenos/metabolismo , Plantas
12.
Plant Physiol ; 193(1): 519-536, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37224514

RESUMO

Citrus, 1 of the largest fruit crops with global economic and nutritional importance, contains fruit known as hesperidium with unique morphological types. Citrus fruit ripening is accompanied by chlorophyll degradation and carotenoid biosynthesis, which are indispensably linked to color formation and the external appearance of citrus fruits. However, the transcriptional coordination of these metabolites during citrus fruit ripening remains unknown. Here, we identified the MADS-box transcription factor CsMADS3 in Citrus hesperidium that coordinates chlorophyll and carotenoid pools during fruit ripening. CsMADS3 is a nucleus-localized transcriptional activator, and its expression is induced during fruit development and coloration. Overexpression of CsMADS3 in citrus calli, tomato (Solanum lycopersicum), and citrus fruits enhanced carotenoid biosynthesis and upregulated carotenogenic genes while accelerating chlorophyll degradation and upregulating chlorophyll degradation genes. Conversely, the interference of CsMADS3 expression in citrus calli and fruits inhibited carotenoid biosynthesis and chlorophyll degradation and downregulated the transcription of related genes. Further assays confirmed that CsMADS3 directly binds and activates the promoters of phytoene synthase 1 (CsPSY1) and chromoplast-specific lycopene ß-cyclase (CsLCYb2), 2 key genes in the carotenoid biosynthetic pathway, and STAY-GREEN (CsSGR), a critical chlorophyll degradation gene, which explained the expression alterations of CsPSY1, CsLCYb2, and CsSGR in the above transgenic lines. These findings reveal the transcriptional coordination of chlorophyll and carotenoid pools in the unique hesperidium of Citrus and may contribute to citrus crop improvement.


Assuntos
Citrus , Solanum lycopersicum , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Citrus/genética , Citrus/metabolismo , Clorofila/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Carotenoides/metabolismo , Solanum lycopersicum/genética , Frutas/metabolismo
13.
BMC Cancer ; 24(1): 728, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877514

RESUMO

BACKGROUND: Circular RNA (circRNAs) have been found to play major roles in the progression of colorectal cancer (CRC). However, the functions of circ_0008345 (transcribed by PTK2) in regulating CRC development remain undefined. In this study, we aimed to explore the roles and underlying mechanisms of circ_0008345 in CRC. METHODS: RNase R-treated total cellular RNA was used to verify the circular structure of circ_0008345, and a subcellular fractionation assay was performed to detect the subcellular localization of circ_0008345. RNA pull-down and dual-luciferase assays were used to verify the binding relation between microRNA (miR)-182-5p and circ_0008345 and/or CYP1A2. Colony formation assay, EdU, and Transwell assays were performed to detect the biological behavior of CRC cells in vitro, and CRC cells were injected into mice to observe the tumor formation. m6A immunoprecipitation was used to detect the m6A modification of circ_0008345 in CRC cells. RESULTS: Circ_0008345, upregulated in CRC tissues and cells, was mainly present in the cytoplasm. Circ_0008345 bound to miR-182-5p, and miR-182-5p targeted CYP1A2, an oncogene in CRC. The colony formation, mobility, EdU-positive cell rate in vitro, and tumor growth in mice were inhibited after the knockdown of circ_0008345. However, the suppressing effects of sh-circ_0008345 on CRC and CYP1A2 expression were significantly reversed after further knockdown of miR-182-5p. METTL3 was the m6A modifier mediating circ_0008345 expression, and the suppression of METTL3 reduced the expression of circ_0008345. CONCLUSIONS: METTL3-dependent m6A methylation upregulated circ_0008345, which blocked the inhibitory effect of miR-182-5p on CYP1A2, thereby exacerbating the malignant phenotype of CRC cells.


Assuntos
Neoplasias Colorretais , Citocromo P-450 CYP1A2 , Progressão da Doença , Metiltransferases , MicroRNAs , RNA Circular , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Humanos , Animais , Camundongos , Metiltransferases/metabolismo , Metiltransferases/genética , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Linhagem Celular Tumoral , Masculino , Feminino , Transdução de Sinais , Camundongos Nus
14.
BMC Cancer ; 24(1): 727, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877445

RESUMO

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Hepatectomia , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Idoso , Curva ROC , Estudos Retrospectivos , Estimativa de Kaplan-Meier , Adulto , Fatores de Risco
15.
BMC Cancer ; 24(1): 985, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39123182

RESUMO

BACKGROUND: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). METHODS: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. RESULTS: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). CONCLUSIONS: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas , Micro-Ondas , Veia Porta , Ablação por Radiofrequência , Humanos , Hepatectomia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirurgia , Quimioembolização Terapêutica/métodos , Ablação por Radiofrequência/métodos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirurgia , Idoso , Adulto , Fígado/cirurgia , Fígado/irrigação sanguínea , Embolização Terapêutica/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Taxa de Sobrevida , China/epidemiologia , Terapia Combinada
16.
Inorg Chem ; 63(9): 4168-4175, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38373068

RESUMO

In order to help understand the structural stability of KCoO2-type ternary nitrides AMN2, referring to perovskite structure, a tolerance factor t is proposed to describe the size effect on the phase/symmetry options of the experimentally accessible AMN2 nitrides. This leads to a range of t values above 0.946 for structurally stable KCoO2-type AMN2 nitrides with t values around 0.970 for the orthorhombic and tetragonal phase boundary. In contrast, most of AMN2 nitrides exhibit α-NaFeO2-type structure with t ∼ 0.898-0.946 and cations ordered or disordered rocksalt structure while t below 0.898. Employing the proposed criterion, the structure formation for other ternary AMN2 compositions with lanthanum and alkaline earth cations for the A sites were predicted, which was testified through the synthesis attempts and complemented by formation energy evaluations. The efforts to synthesize the ternary Lanthanide and alkaline earth-based AMN2 nitrides were unsuccessful, which could associate the structural instability with the large formation energies of lanthanide nitrides LaMN2 and the greater tolerance factor of 1.048 for BaTiN2. The experimentally already synthesized AMN2 nitrides could be categorized into three types with different tolerance factors, and scarce AMN2 nitrides with lower formation energies would be accessible using different synthetic routes beyond the traditional solid-state synthesis method.

17.
Nature ; 555(7698): 638-642, 2018 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-29555992

RESUMO

The kagome lattice is a two-dimensional network of corner-sharing triangles that is known to host exotic quantum magnetic states. Theoretical work has predicted that kagome lattices may also host Dirac electronic states that could lead to topological and Chern insulating phases, but these states have so far not been detected in experiments. Here we study the d-electron kagome metal Fe3Sn2, which is designed to support bulk massive Dirac fermions in the presence of ferromagnetic order. We observe a temperature-independent intrinsic anomalous Hall conductivity that persists above room temperature, which is suggestive of prominent Berry curvature from the time-reversal-symmetry-breaking electronic bands of the kagome plane. Using angle-resolved photoemission spectroscopy, we observe a pair of quasi-two-dimensional Dirac cones near the Fermi level with a mass gap of 30 millielectronvolts, which correspond to massive Dirac fermions that generate Berry-curvature-induced Hall conductivity. We show that this behaviour is a consequence of the underlying symmetry properties of the bilayer kagome lattice in the ferromagnetic state and the atomic spin-orbit coupling. This work provides evidence for a ferromagnetic kagome metal and an example of emergent topological electronic properties in a correlated electron system. Our results provide insight into the recent discoveries of exotic electronic behaviour in kagome-lattice antiferromagnets and may enable lattice-model realizations of fractional topological quantum states.

18.
J Sep Sci ; 47(17): e2400369, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39252170

RESUMO

Epoxy resins, as important thermosetting polymers, exhibit excellent adhesion to various substrates. In view of this, reticulate coating of triglycidyl isocyanate with triethylenetetramine was introduced onto the surface of poly(styrene-divinylbenzene) utilizing amine curing reaction to obtain poly(styrene-divinylbenzene)@triglycidyl isocyanate-triethylenetetramine composite microspheres. The amino groups and epoxy groups of triglycidyl isocyanate-triethylenetetramine endowed poly(styrene-divinylbenzene) with good reactivity, which could be quaternized under mild conditions to obtain an anion exchange chromatographic stationary phase. The quaternized poly(styrene-divinylbenzene)@triglycidyl isocyanate-triethylenetetramine was characterized by scanning electron microscope, Fourier-transform infrared spectroscopy, N2 adsorption-desorption experiment, et al. The chromatographic performance of the customized column was evaluated by separating seven conventional anions, organic weak acids, and carbohydrates. Poly(styrene-divinylbenzene)@triglycidyl isocyanate-triethylenetetramine possesses the uniform size of poly(styrene-divinylbenzene) microspheres and good reactivity of triglycidyl isocyanate-triethylenetetramine, which offers a flexible strategy for the preparation of anion exchange stationary phase. The column exhibits excellent chemical and mechanical stability and chromatographic performance. Finally, the column was successfully applied for the determination of nitrite in pickles.

19.
BMC Urol ; 24(1): 9, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172803

RESUMO

BACKGROUND: Duplication of the bladder with duplication of the posterior urethra is a relatively rare congenital malformation. Cases of sagittal septum duplication of the bladder with duplication of the posterior urethra have rarely been reported. Furthermore, the combination thereof with congenital megacolon is rare. CASE PRESENTATION: A 21-year-old male was admitted to our hospital because of frequent urination for two months. He presented to another hospital first with frequent urination and underwent computed tomography (CT) and testicular biopsy. Anti-inflammatory therapy was administered by the doctor to the patient. For further diagnosis and treatment, the patient went to the outpatient department in our hospital on June 6, 2022. After admission, the patient underwent ultrasound, CT, MRI, cystoscopy, and other related examinations and tests. The examination results suggested that the patient had duplication of the bladder with duplication of the posterior urethra. In addition, the patient's mother reported that he had suffered from long-term constipation with abdominal distension before the age of 5 years. At the time, he was admitted to the local hospital and was diagnosed with congenital megacolon based on the relevant examinations. After the patient was diagnosed with duplication of bladder and urethra, the doctor recommended surgical treatment to the patient. However, he considered that he only had frequent urination symptoms, and chose conservative treatment rather than to undergo surgical treatment. Thus, the doctor prescribed anti-inflammatory treatment. Four months later, the patient reported that frequent urination symptoms persisted, and was also considering fertility-related problems. The outpatient follow-up will be continued. CONCLUSIONS: In this article, we summarize the imaging findings of duplication of the bladder with duplication of the posterior urethra and propose the advantages and disadvantages of each type of imaging examination. We also review the relevant literature on cases of bladders with duplication of the posterior urethra. The related differential diagnosis is summarized, and the significance of guiding clinical treatment and diagnosis is discussed.


Assuntos
Doença de Hirschsprung , Bexiga Urinária , Masculino , Humanos , Pré-Escolar , Adulto Jovem , Adulto , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/cirurgia , Bexiga Urinária/anormalidades , Uretra/diagnóstico por imagem , Uretra/cirurgia , Intestinos , Anti-Inflamatórios
20.
BMC Surg ; 24(1): 148, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734630

RESUMO

BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.


Assuntos
Laparoscopia , Hepatopatias , Complicações Pós-Operatórias , Impressão Tridimensional , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Hepatopatias/cirurgia , Idoso , Doenças Biliares/prevenção & controle , Doenças Biliares/cirurgia , Doenças Biliares/etiologia , Hepatectomia/métodos , Hepatectomia/efeitos adversos , Adulto , Estudos Retrospectivos , Estudos de Coortes
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