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1.
Glob Chang Biol ; 29(4): 1144-1159, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36349544

RESUMEN

Specific leaf area (SLA) is one of the most important plant functional traits. It integrates multiple functions and reflects strategies of plants to obtain resources. How plants employ different strategies (e.g., through SLA) to respond to dynamic environmental conditions remains poorly understood. This study aimed to explore the spatial variation in SLA and its divergent adaptation through the lens of biogeographic patterns, evolutionary history, and short-term responses. SLA data for 5424 plant species from 76 natural communities in China were systematically measured and integrated with meta-analysis of field experiments (i.e., global warming, drought, and nitrogen addition). The mean value of SLA across all species was 21.8 m2  kg-1 , ranging from 0.9 to 110.2 m2  kg-1 . SLA differed among different ecosystems, temperature zones, vegetation types, and functional groups. Phylogeny had a weak effect on SLA, but plant species evolved toward higher SLA. Furthermore, SLA responded nonlinearly to environmental change. Unexpectedly, radiation was one of the main factors determining the spatial variation in SLA on a large scale. Conversely, short-term manipulative experiments showed that SLA increased with increased resource availability and tended to stabilize with treatment duration. However, different species exhibited varying response patterns. Overall, variation in long-term adaptation of SLA to environmental gradients and its short-term response to resource pulses jointly improve plant adaptability to a changing environment. Overall SLA-environment relationships should be emphasized as a multidimensional strategy for elucidating environmental change in future research.


Asunto(s)
Ecosistema , Plantas , Aclimatación , Temperatura , Hojas de la Planta/fisiología
2.
BMC Cancer ; 23(1): 465, 2023 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-37210519

RESUMEN

AIM: To understand the proportion of uHCC (unresectable hepatocellular carcinoma) patients who achieve successful conversion resection in a high-volume setting with state of the art treatment options. METHODS: We retrospectively reviewed all HCC patients hospitalized to our center from June 1st, 2019 to June 1st, 2022. Conversion rate, clinicopathological features, response to systemic and/or loco-regional therapy and surgical outcomes were analyzed. RESULTS: A total of 1,904 HCC patients were identified, with 1672 patients receiving anti-HCC treatment. 328 patients were considered up-front resectable. Of the remaining 1344 uHCC patients, 311 received loco-regional treatment, 224 received systemic treatment, and the remainder (809) received combination systemic plus loco-regional treatment. Following treatment, one patient from the systemic group and 25 patients from the combination group were considered to have resectable disease. A high objective response rate (ORR) was observed in these converted patients (42.3% under RECIST v1.1 and 76.9% under mRECIST criteria). The disease control rate (DCR) reached 100%. 23 patients underwent curative hepatectomy. Major post-operative morbidity was equivalent in the both groups (P=0.76). Pathologic complete response (pCR) was 39.1%. During conversion treatment, grade 3 or higher treatment-related adverse events (TRAEs) were observed in 50% of patients. The median follow-up time was 12.9 months (range, 3.9~40.6) from index diagnosis and 11.4 months (range, 0.9~26.9) from resection. Three patients experienced disease recurrence following conversion surgery. CONCLUSIONS: By intensive treatment, a small sub-group of uHCC patients (2%) may potentially be converted to curative resection. Loco-regional combined with systemic modality was relative safe and effective in the conversion therapy. Short-term outcomes are encouraging, but long-term follow-up in a larger patient population are required to fully understand the utility of this approach.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/patología , Terapia Combinada
3.
Hepatology ; 73(4): 1381-1398, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32609900

RESUMEN

BACKGROUND AND AIMS: Transarterial chemoembolization (TACE) is a standard locoregional therapy for patients with hepatocellular carcinoma (HCC) patients with a variable overall response in efficacy. We aimed to identify key molecular signatures and related pathways leading to HCC resistance to TACE, with the hope of developing effective approaches in preselecting patients with survival benefit from TACE. APPROACH AND RESULTS: Four independent HCC cohorts with 680 patients were used. MicroRNA (miRNA) transcriptome analysis in patients with HCC revealed a 41-miRNA signature related to HCC recurrence after adjuvant TACE, and miR-125b was the top reduced miRNA in patients with HCC recurrence. Consistently, patients with HCC with low miR-125b expression in tumor had significantly shorter time to recurrence following adjuvant TACE in two independent cohorts. Loss of miR-125b in HCC noticeably activated the hypoxia inducible factor 1 alpha subunit (HIF1α)/pAKT loop in vitro and in vivo. miR-125b directly attenuated HIF1α translation through binding to HIF1A internal ribosome entry site region and targeting YB-1, and blocked an autocrine HIF1α/platelet-derived growth factor ß (PDGFß)/pAKT/HIF1α loop of HIF1α translation by targeting the PDGFß receptor. The miR-125b-loss/HIF1α axis induced the expression of CD24 and erythropoietin (EPO) and enriched a TACE-resistant CD24-positive cancer stem cell population. Consistently, patients with high CD24 or EPO in HCC had poor prognosis following adjuvant TACE therapy. Additionally, in patients with HCC having TACE as their first-line therapy, high EPO in blood before TACE was also noticeably related to poor response to TACE. CONCLUSIONS: MiR-125b loss activated the HIF1α/pAKT loop, contributing to HCC resistance to TACE and the key nodes in this axis hold the potential in assisting patients with HCC to choose TACE therapy.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Resistencia a Antineoplásicos/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas/terapia , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/genética , Células A549 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Estudios de Cohortes , Femenino , Técnicas de Inactivación de Genes , Células HEK293 , Humanos , Neoplasias Hepáticas/genética , Masculino , Ratones , MicroARNs/genética , Persona de Mediana Edad , Células Madre Neoplásicas/metabolismo , Transcriptoma , Transfección , Adulto Joven
4.
Chem Pharm Bull (Tokyo) ; 68(10): 971-980, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32999149

RESUMEN

Inhibition of the epidermal growth factor receptor (EGFR) has been proved to be one of the most promising strategies for the treatment of non-small cell lung cancers. A series of 2-aryl-4-amino substituted quinazoline derivatives were designed and synthesized with the purpose to overcome L858R/T790M/C797S (CTL) triple mutant drug resistance and the biological activity for inhibition of CTL kinases and EGFR wild type (WT) were evaluated. Three compounds (20, 24 and 27) showed excellent inhibitory activities against EGFR kinases triple mutant CTL (IC50 < 1 µM) and high selectivity (IC50: WT/CTL >10000). Cell line evaluation showed that the most potent compound 27 was significantly potent against H1975-EGFR L858R/T790M (IC50 = 3.3 µM) and H1975-EGFR L858R/T790M/C797S (IC50 = 1.2 µM). Compound 27 also exhibited good microsomes stabilities in human, rat and mouse liver species, but low bioavailability. This work would be very useful for discovering new quinazoline derivatives as tyrosine kinase inhibitors targeting triple mutant L858R/T790M/C797S.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/síntesis química , Quinazolinas/síntesis química , Administración Oral , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB/antagonistas & inhibidores , Hígado , Masculino , Simulación del Acoplamiento Molecular , Mutación , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/farmacocinética , Quinazolinas/administración & dosificación , Quinazolinas/farmacocinética , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad
5.
Org Biomol Chem ; 17(3): 683-691, 2019 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-30601533

RESUMEN

A series of novel dipeptidyl boronic acid compounds were designed, synthesized and biologically investigated for the inhibition of the ß5 subunit of 20S proteasome and several compounds showed high activities with IC50 values of less than 10 nM. Some of these compounds potently inhibited the multiple myeloma (MM) cancer cell lines with IC50 values of less than 10 nM. It was reported that the inhibition of both ß2 and ß5 subunits strongly increased the cytotoxicity of proteasome inhibitors in solid tumor cells, so some of the compounds were evaluated for the inhibition of the ß2 subunit and the solid tumor triple-negative breast cancer cell line MDA-MB-231. The results showed that three compounds were active for both the ß2 subunit and the triple-negative breast cancer cell line MDA-MB-231. The in vivo pharmacokinetic results showed that compound 8t had good biological parameters for both ig and iv administrations. An in vivo pharmacodynamic experiment showed that compound 8t inhibited the ß5 subunit in whole blood more greatly than the marketed MLN9708 with the same dose at different time periods. A pathological analysis indicated that the injection of compound 8t in the tumor of a triple-negative breast cancer xenograft mice model led to tumor cell necrosis, nucleus condensation, deep staining, cell fragmentation, dissolution and neutrophil infiltration compared with the control group. The data in hand showed that compound 8t might be an effective candidate for the treatment of both MM and triple-negative breast cancer.


Asunto(s)
Antineoplásicos/farmacología , Ácidos Borónicos/farmacología , Descubrimiento de Drogas , Mieloma Múltiple/tratamiento farmacológico , Complejo de la Endopetidasa Proteasomal/metabolismo , Inhibidores de Proteasoma/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Administración Oral , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Ácidos Borónicos/administración & dosificación , Ácidos Borónicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Masculino , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Estructura Molecular , Mieloma Múltiple/patología , Inhibidores de Proteasoma/administración & dosificación , Inhibidores de Proteasoma/química , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Neoplasias de la Mama Triple Negativas/patología
6.
Bioorg Med Chem ; 27(18): 4151-4162, 2019 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-31383629

RESUMEN

A series of novel tetrapeptidyl epoxyketone inhibitors of 20S proteasome was designed and synthesized. To fully understand the SAR, various groups at R1, R2, R3, R4 and R5 positions, including aromatic and aliphatic substituents were designed, synthesized and biologically assayed. Based on the enzymatic results, seven compounds were selected to evaluate their cellular activities and soluble compound 36 showed strong potency against human multiple myeloma (MM) cell lines. Microsomal stability results indicated that compound 36 was more stable in mice, rat and human microsomes than marketed carfilzomib. The in vivo activities of this compound were evaluated with the xenograft mice models of MM cell lines ARH77 and RPMI-8226 with luciferase expression and the T/C value of the two models were 49.5% and 37.6%, respectively. To evaluate the potential cardiovascular toxicity, inhibition of hERG ion channel in HEK293 cells by compound 36 and carfilzomib was carried out. The results indicated that 36 had no binding affinity for the hERG ion channel while carfilzomib could bind it with IC50 of 92.1 µM.


Asunto(s)
Inhibidores de Proteasoma/uso terapéutico , Animales , Diseño de Fármacos , Humanos , Ratones , Inhibidores de Proteasoma/farmacología , Relación Estructura-Actividad
7.
Bioorg Med Chem ; 27(3): 533-544, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30606672

RESUMEN

Valosine containing protein (VCP/p97) is a member of the AAA ATPase family involved in several essential cellular functions and plays an important role in the ubiquitin-mediated degradation of misfolded proteins. P97 has a significant role in maintaining the cellular protein homeostasis for tumor cell growth and survival and has been found overexpressed in many tumor types. No new molecule entities based on p97 target were approved in clinic. Herein, a series of novel pyrimidine structures as p97 inhibitors were designed and synthesized. After enzymatic evaluations, structure-activity relationships (SAR) were discussed in detailed. Among the screened compounds, derivative 35 showed excellent enzymatic inhibitory activity (IC50, 36 nM). The cellular inhibition results showed that compound 35 had good antiproliferative activity against the non-small cell lung cancer A549 cells (IC50, 1.61 µM). Liver microsome stability showed that the half-life of compound 35 in human liver microsome was 42.3 min, which was more stable than the control CB-5083 (25.8 min). The in vivo pharmacokinetic results showed that the elimination phase half-lives of compound 35 were 4.57 h for ig and 3.64 h for iv, respectively and the oral bioavailability was only 4.5%. These results indicated that compound 35 could be effective for intravenous treatment of non-small cell lung cancer.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Descubrimiento de Drogas , Inhibidores Enzimáticos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Proteína que Contiene Valosina/antagonistas & inhibidores , Células A549 , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/química , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Microsomas Hepáticos/química , Microsomas Hepáticos/metabolismo , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Células Tumorales Cultivadas , Proteína que Contiene Valosina/metabolismo
8.
Bioorg Med Chem ; 26(14): 3975-3981, 2018 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-29934218

RESUMEN

A series of novel dipeptidyl boronic acid inhibitors of 20S proteasome were designed and synthesized. Aliphatic groups at R1 position were designed for the first time to fully understand the SAR (structure-activity relationship). Among the screened compounds, novel inhibitor 5c inhibited the CT-L (chymotrypsin-like) activity with IC50 of 8.21 nM and the MM (multiple myeloma) cells RPMI8226, U266B and ARH77 proliferations with the IC50 of 8.99, 6.75 and 9.10 nM, respectively, which showed similar in vitro activities compared with the compound MLN2238 (biologically active form of marketed MLN9708). To investigate the oral availability, compound 5c was esterified to its prodrug 6a with the enzymatic IC50 of 6.74 nM and RPMI8226, U266B and ARH77 cell proliferations IC50 of 2.59, 4.32 and 3.68 nM, respectively. Furthermore, prodrug 6a exhibited good pharmacokinetic properties with oral bioavailability of 24.9%, similar with MLN9708 (27.8%). Moreover, compound 6a showed good microsomal stabilities and displayed stronger in vivo anticancer efficacy than MLN9708 in the human ARH77 xenograft mouse model. Finally, cell cycle results showed that compound 6a had a significant inhibitory effect on CT-L and inhibited cell cycle progression at the G2M stage.


Asunto(s)
Antineoplásicos/farmacología , Ácidos Borónicos/farmacología , Dipéptidos/farmacología , Diseño de Fármacos , Mieloma Múltiple/tratamiento farmacológico , Inhibidores de Proteasoma/farmacología , Administración Oral , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Ácidos Borónicos/administración & dosificación , Ácidos Borónicos/química , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dipéptidos/administración & dosificación , Dipéptidos/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Ratones , Ratones Desnudos , Microsomas Hepáticos/química , Microsomas Hepáticos/metabolismo , Estructura Molecular , Mieloma Múltiple/patología , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Inhibidores de Proteasoma/administración & dosificación , Inhibidores de Proteasoma/química , Relación Estructura-Actividad , Células Tumorales Cultivadas
9.
Bioorg Med Chem Lett ; 26(8): 1958-62, 2016 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-26965867

RESUMEN

A series of novel dipeptidyl boronic acid proteasome inhibitors constructed from αα- and αß-amino acids were designed and synthesized. Their structures were elucidated by (1)H NMR, (13)C NMR, LC-MS and HRMS. These compounds were evaluated for their ß5 subunit inhibitory activities of human proteasome. The results showed that dipeptidyl boronic acid inhibitors composed of αα-amino acids were as active as bortezomib. Interestingly, the activities of those derived from αß-amino acids lost completely. Of all the inhibitors, compound 22 (IC50=4.82 nM) was the most potent for the inhibition of proteasome activity. Compound 22 was also the most active against three MM cell lines with IC50 values less than 5 nM in inhibiting cell growth assays. Molecular docking studies displayed that 22 fitted very well in the ß5 subunit active pocket of proteasome.


Asunto(s)
Aminoácidos/química , Aminoácidos/farmacología , Ácidos Borónicos/farmacología , Dipéptidos/farmacología , Diseño de Fármacos , Simulación del Acoplamiento Molecular , Complejo de la Endopetidasa Proteasomal/metabolismo , Inhibidores de Proteasoma/síntesis química , Inhibidores de Proteasoma/farmacología , Ácidos Borónicos/síntesis química , Ácidos Borónicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dipéptidos/síntesis química , Dipéptidos/química , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Inhibidores de Proteasoma/química , Relación Estructura-Actividad
10.
Bioorg Med Chem ; 24(11): 2576-88, 2016 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-27117691

RESUMEN

Proteasome had been clinically validated as an effective target for the treatment of cancers. Up to now, many structurally diverse proteasome inhibitors were discovered. And two of them were launched to treat multiple myeloma (MM) and mantle cell lymphoma (MCL). Based on our previous biological results of dipeptidyl boronic acid proteasome inhibitors, robust 3D-QSAR models were developed and structure-activity relationship (SAR) was summarized. Several structurally novel compounds were designed based on the theoretical models and finally synthesized. Biological results showed that compound 12e was as active as the standard bortezomib in enzymatic and cellular activities. In vivo pharmacokinetic profiles suggested compound 12e showed a long half-life, which indicated that it could be administered intravenously. Cell cycle analysis indicated that compound 12e inhibited cell cycle progression at the G2M stage.


Asunto(s)
Ácidos Borónicos/farmacología , Diseño de Fármacos , Complejo de la Endopetidasa Proteasomal/metabolismo , Inhibidores de Proteasoma/farmacología , Relación Estructura-Actividad Cuantitativa , Ácidos Borónicos/síntesis química , Ácidos Borónicos/química , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Humanos , Modelos Moleculares , Estructura Molecular , Inhibidores de Proteasoma/síntesis química , Inhibidores de Proteasoma/química
11.
Macromol Rapid Commun ; 35(19): 1668-72, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25168858

RESUMEN

Different techniques are being developed for fabricating microcapsules; it is still a challenge to fabricate them in an efficient and environment-friendly process. Here, a one-step green route to synthesize silk protein sericin-based microcapsules without any assistance of organic solvents is reported. By carefully changing the concentration of calcium ions accompanied with stirring, the morphology of the microcapsules can easily be regulated to form either discoidal, biconcave, cocoon-like, or tubular structures. The chelation of Ca(2+) and shearing force from agitation may induce the conformational transformation of sericin, which possibly results in the formation of microcapsules through the self-assembly of the protein subsequently. The as-prepared cocoon-like microcapsules exhibit pH-dependent stability. A potential application of microcapsules being fabricated from natural water-soluble silk protein sericin for controlled bioactive molecules loading and release system by a pH-triggered manner is quite feasible.


Asunto(s)
Cápsulas , Sericinas/química , Seda/química , Calcio/química , Quelantes/química , Microscopía Electrónica de Rastreo , Conformación Molecular
12.
Cell Mol Gastroenterol Hepatol ; 18(2): 101351, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38724007

RESUMEN

BACKGROUND & AIMS: Both nonalcoholic fatty liver disease (NAFLD) and colorectal cancer (CRC) are prevalent worldwide. The effects of concomitant NAFLD on the risk of colorectal liver metastasis (CRLM) and its mechanisms have not been definitively elucidated. METHODS: We observed the effect of concomitant NAFLD on CRLM in the mouse model and explored the underlying mechanisms of specific myeloid-derived suppressor cells (MDSCs) recruitment and then tested the therapeutic application based on the mechanisms. Finally we validated our findings in the clinical samples. RESULTS: Here we prove that in different mouse models, NAFLD induces F4/80+ Kupffer cells to secret chemokine CXCL5 and then recruits CXCR2+ MDSCs to promote the growth of CRLM. CRLM with NAFLD background is refractory to the anti-PD-1 monoclonal antibody treatment, but when combined with Reparixin, an inhibitor of CXCR1/2, dual therapy cures the established CRLM in mice with NAFLD. Our clinical studies also indicate that fatty liver diseases increase the infiltration of CXCR2+ MDSCs, as well as the hazard of liver metastases in CRC patients. CONCLUSIONS: Collectively, our findings highlight the significance of selective CXCR2+/CD11b+/Gr-1+ subset myeloid cells in favoring the development of CRLM with NAFLD background and identify a pharmaceutical medicine that is already available for the clinical trials and potential treatment.

13.
Nat Commun ; 15(1): 3260, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627377

RESUMEN

Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 × Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirugia , Humanos , Terapia Neoadyuvante , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Radiocirugia/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Estadificación de Neoplasias , Adyuvantes Inmunológicos
14.
Front Plant Sci ; 14: 1060066, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36844101

RESUMEN

Drylands dominate the trend and variability of the land carbon (C) sink. A better understanding of the implications of climate-induced changes in the drylands for C sink-source dynamics is urgently needed. The effect of climate on ecosystem C fluxes (gross primary productivity (GPP), ecosystem respiration (ER), and net ecosystem productivity (NEP)) in drylands has been extensively explored, but the roles of other concurrently changing factors, such as vegetation conditions and nutrient availability, remain unclear. We used eddy-covariance C-flux measurements from 45 ecosystems with concurrent information on climate (mean annual temperature (MAT) and mean annual precipitation (MAP)), soil (soil moisture (SM) and soil total nitrogen content (soil N)), and vegetation (leaf area index (LAI) and leaf nitrogen content (LNC)) factors to assess their roles in C fluxes. The results showed that the drylands in China were weak C sinks. GPP and ER were positively correlated with MAP, while they were negatively correlated with MAT. NEP first decreased and then increased with increasing MAT and MAP, and 6.6 °C and 207 mm were the boundaries for the NEP response to MAT and MAP, respectively. SM, soil N, LAI, and MAP were the main factors affecting GPP and ER. However, SM and LNC had the most important influence on NEP. Compared with climate and vegetation factors, soil factors (SM and soil N) had a greater impact on C fluxes in the drylands. Climate factors mainly affected C fluxes by regulating vegetation and soil factors. To accurately estimate the global C balance and predict the response of ecosystems to environmental change, it is necessary to fully consider the discrepant effects of climate, vegetation, and soil factors on C fluxes, as well as the cascade relationships between different factors.

15.
Front Plant Sci ; 14: 1084355, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37008469

RESUMEN

Aims: Drought stress is one of the most limiting factors for agriculture and ecosystem productivity. Climate change exacerbates this threat by inducing increasingly intense and frequent drought events. Root plasticity during both drought and post-drought recovery is regarded as fundamental to understanding plant climate resilience and maximizing production. We mapped the different research areas and trends that focus on the role of roots in plant response to drought and rewatering and asked if important topics were overlooked. Methods: We performed a comprehensive bibliometric analysis based on journal articles indexed in the Web of Science platform from 1900-2022. We evaluated a) research areas and temporal evolution of keyword frequencies, b) temporal evolution and scientific mapping of the outputs over time, c) trends in the research topics analysis, d) marked journals and citation analysis, and e) competitive countries and dominant institutions to understand the temporal trends of root plasticity during both drought and recovery in the past 120 years. Results: Plant physiological factors, especially in the aboveground part (such as "photosynthesis", "gas-exchange", "abscisic-acid") in model plants Arabidopsis, crops such as wheat and maize, and trees were found to be the most popular study areas; they were also combined with other abiotic factors such as salinity, nitrogen, and climate change, while dynamic root growth and root system architecture responses received less attention. Co-occurrence network analysis showed that three clusters were classified for the keywords including 1) photosynthesis response; 2) physiological traits tolerance (e.g. abscisic acid); 3) root hydraulic transport. Thematically, themes evolved from classical agricultural and ecological research via molecular physiology to root plasticity during drought and recovery. The most productive (number of publications) and cited countries and institutions were situated on drylands in the USA, China, and Australia. In the past decades, scientists approached the topic mostly from a soil-plant hydraulic perspective and strongly focused on aboveground physiological regulation, whereas the actual belowground processes seemed to have been the elephant in the room. There is a strong need for better investigation into root and rhizosphere traits during drought and recovery using novel root phenotyping methods and mathematical modeling.

16.
Polymers (Basel) ; 15(2)2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36679266

RESUMEN

Polyetheretherketone (PEEK) is a thermoplastic material widely used in engineering applications due to its good biomechanical properties and high temperature stability. Compared to traditional metal and ceramic dental materials, PEEK dental implants exhibit less stress shielding, thus better matching the mechanical properties of bone. As a promising medical material, PEEK can be used as implant abutments, removable and fixed prostheses, and maxillofacial prostheses. It can be blended with materials such as fibers and ceramics to improve its mechanical strength for better clinical dental applications. Compared to conventional pressed and CAD/CAM milling fabrication, 3D-printed PEEK exhibits excellent flexural and tensile strength and parameters such as printing temperature and speed can affect its mechanical properties. However, the bioinert nature of PEEK can make adhesive bonding difficult. The bond strength can be improved by roughening or introducing functional groups on the PEEK surface by sandblasting, acid etching, plasma treatment, laser treatment, and adhesive systems. This paper provides a comprehensive overview of the research progress on the mechanical properties of PEEK for dental applications in the context of specific applications, composites, and their preparation processes. In addition, the research on the adhesive properties of PEEK over the past few years is highlighted. Thus, this review aims to build a conceptual and practical toolkit for the study of the mechanical and adhesive properties of PEEK materials. More importantly, it provides a rationale and a general new basis for the application of PEEK in the dental field.

17.
Plants (Basel) ; 11(15)2022 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-35956484

RESUMEN

Seed traits (ST) influence seedling establishment, population dynamics, community composition and ecosystem function and reflect the adaptability of plants and the environmental conditions they experienced. There has been a historical and global accumulation of studies on ST, but with few pertaining to visual and quantitative analyses. To understand the trends in the field of ST research in the past 30 years, we conducted a bibliometric analysis based on the Science Citation Index-Expanded (SCI-E) database. The analysis provided annual publications, time trends for keywords, the most productive journals, authors, institutions and countries, and a comprehensive overview of the ST field. Our results showed that in the past 30 years, the number of publications in ST research has increased at an average annual growth rate of 9.1%, while the average number of citations per paper per year showed a rapid increase-slow increase-decrease trend. Keyword analysis showed that "germination" was the most popular research section. Crop Science ranked first among the top journals and Theoretical and Applied Genetics had greater influence in this area and more citations than other journals. The 10 most productive institutions were mostly located in the United States, China and Australia. Furthermore, the three countries also had the largest number of publications and citations. Our analysis showed that the research interests in ST have evolved from genetics and agricultural science to ecological research over the last thirty years; as more fields embrace ST research, there are opportunities for international and interdisciplinary collaborations, cooperative institutions and new advances in the field.

18.
Acta Chim Slov ; 69(1): 133-146, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35298014

RESUMEN

Cerium carbonate crystal morphology is predicted using density functional theory (DFT) simulations in this paper. In the nucleation phase, the ketone group in polyvinylpyrrolidone (PVP) will preferentially bind to Ce3+ to form complexes and provide heterogeneous nucleation sites for the system, prompting the nucleation of cerium carbonate crystals. In the growth stage, due to the adsorption of PVP, the probability of (120) crystal plane appearing in the equilibrium state is the greatest, resulting in the formation of hexagonal flake cerium carbonate crystals with (120) crystal plane as the oblique edge. Experimentally, hexagonal sheet cerium carbonate crystals were successfully prepared using PVP as a template agent. Therefore, DFT can be used to predict the morphology of cerium carbonate crystals, which not only elucidates the growth mechanism of cerium carbonate crystals, but also greatly reduces the experimental cost.

19.
Front Plant Sci ; 13: 1062055, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36578349

RESUMEN

Ecologically vulnerable areas (EVAs) are regions with ecosystems that are fragile and vulnerable to degradation under external disturbances, e.g., environmental changes and human activities. A comprehensive understanding of the climate change characteristics of EVAs in China is of great guiding significance for ecological protection and economic development. The ecosystem carbon use efficiency (CUEe) can be defined as the ratio of the net ecosystem productivity (NEP) to gross primary productivity (GPP), one of the most important ecological indicators of ecosystems, representing the capacity for carbon transfer from the atmosphere to a potential ecosystem carbon sink. Understanding the variation in the CUEe and its controlling factors is paramount for regional carbon budget evaluation. Although many CUEe studies have been performed, the spatial variation characteristics and influencing factors of the CUEe are still unclear, especially in EVAs in China. In this study, we synthesized 55 field measurements (3 forestland sites, 37 grassland sites, 6 cropland sites, 9 wetland sites) of the CUEe to examine its variation and influencing factors in EVAs in China. The results showed that the CUEe in EVAs in China ranged from -0.39 to 0.67 with a mean value of 0.20. There were no significant differences in the CUEe among different vegetation types, but there were significant differences in CUEe among the different EVAs (agro-pastoral ecotones < Tibetan Plateau < arid and semiarid areas < Loess Plateau). The CUEe first decreased and then increased with increasing mean annual temperature (MAT), soil pH and soil organic carbon (SOC) and decreased with increasing mean annual precipitation (MAP). The most important factors affecting the CUEe were biotic factors (NEP, GPP, and leaf area index (LAI)). Biotic factors directly affected the CUEe, while climate (MAT and MAP) and soil factors (soil pH and SOC) exerted indirect effects. The results illustrated the comprehensive effect of environmental factors and ecosystem attributes on CUEe variation, which is of great value for the evaluation of regional ecosystem functions.

20.
Ying Yong Sheng Tai Xue Bao ; 33(8): 2077-2087, 2022 Aug.
Artículo en Zh | MEDLINE | ID: mdl-36043813

RESUMEN

Affected by the disturbance of forest fire and logging, the primary forest in Daxing'an Mountains gradually degenerates into secondary forest. In this study, we established 16 plots in each of three typical forests, including natural Betula platyphylla pure forest (pioneer stage), natural B. platyphylla and Larix gmelinii mixed forest (transition stage) and natural L. gmelinii pure forest (top stage). The methods of population age and tree height structure, static life table, survival analysis, dynamic index and time series prediction were used to quantitatively analyze the dynamics of dominant species (B. platyphylla and L. gmelinii) and all the arbors, aiming to provide scientific basis for the restoration and development of natural L. gmelinii forest. The results showed that the abundance of young co-dominant species and total arbors in each stage was large, and that all population had strong self-renewal potential. With the progress of succession, the abundance of B. platyphylla in each age class gradually decreased, whereas that of L. gmelinii gradually increased. The mortality and disappearance rates of total arbors and B. platyphylla in the transition stage and L. gmelinii in the pioneer stage gradually increased with the increases of age class, and the survival curve was Deevey-Ⅰ type. The survival analysis results showed that the population was stable in the early stage, increased in the middle stage, and declined in the later stage. In other stages, the mortality rates fluctuated slightly, the survival curves were Deevey-Ⅱ type, and the population increased in the early stage, declined in the middle stage, and stable in the later stage. The co-dominant species and total arbors were growing in the three succession stages, among which B. platyphylla in the pioneer stage, L. gmelinii and total arbors in the top stage showed the lowest sensitivity to the environment. The results of time series prediction showed that the co-dominant species and total arbors in each stage would increase in the future. During forest succession, it was necessary to strengthen the protection of seedlings and young trees, thin the forest with large coverage, and take appropriate measures to ensure population renewal.


Asunto(s)
Bosques , Larix , Betula , China , Árboles
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