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1.
Small ; : e2401116, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456370

RESUMO

In this study, the flexoelectric characteristics of 2D TiO2 nanosheets are examined. The theoretical calculations and experimental results reveal an excellent strain-induced flexoelectric potential (flexopotential) by an effective defect engineering strategy, which suppresses the recombination of electron-hole pairs, thus substantially improving the catalytic activity of the TiO2 nanosheets in the degradation of Rhodamine B dye and the hydrogen evolution reaction in a dark environment. The results indicate that strain-induced bandgap reduction enhances the catalytic activity of the TiO2 nanosheets. In addition, the TiO2 nanosheets degraded Rhodamine B, with kobs being ≈1.5 × 10-2 min-1 in dark, while TiO2 nanoparticles show only an adsorption effect. 2D TiO2 nanosheets achieve a hydrogen production rate of 137.9 µmol g-1 h-1 under a dark environment, 197% higher than those of TiO2 nanoparticles (70.1 µmol g-1 h-1 ). The flexopotential of the TiO2 nanosheets is enhanced by increasing the bending moment, with excellent flexopotential along the y-axis. Density functional theory is used to identify the stress-induced bandgap reduction and oxygen vacancy formation, which results in the self-dissociation of H2 O on the surface of the TiO in the dark. The present findings provide novel insights into the role of TiO2 flexocatalysis in electrochemical reactions.

2.
Small ; : e2401713, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693076

RESUMO

Aqueous zinc-based energy storage devices possess superior safety, cost-effectiveness, and high energy density; however, dendritic growth and side reactions on the zinc electrode curtail their widespread applications. In this study, these issues are mitigated by introducing a polyimide (PI) nanofabric interfacial layer onto the zinc substrate. Simulations reveal that the PI nanofabric promotes a pre-desolvation process, effectively desolvating hydrated zinc ions from Zn(H2O)6 2+ to Zn(H2O)4 2+ before approaching the zinc surface. The exposed zinc ion in Zn(H2O)4 2+ provides an accelerated charge transfer process and reduces the activation energy for zinc deposition from 40 to 21 kJ mol-1. The PI nanofabric also acts as a protective barrier, reducing side reactions at the electrode. As a result, the PI-Zn symmetric cell exhibits remarkable cycling stability over 1200 h, maintaining a dendrite-free morphology and minimal byproduct formation. Moreover, the cell exhibits high stability and low voltage hysteresis even under high current densities (20 mA cm-2, 10 mAh cm-2) thanks to the 3D porous structure of PI nanofabric. When integrated into full cells, the PI-Zn||AC hybrid zinc-ion capacitor and PI-Zn||MnVOH@SWCNT zinc-ion battery achieve impressive lifespans of 15000 and 600 cycles with outstanding capacitance retention. This approach paves a novel avenue for high-performance zinc metal electrodes.

3.
Korean J Physiol Pharmacol ; 28(1): 59-72, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38154965

RESUMO

To investigate the mechanism of Wenshen Xuanbi Decoction (WSXB) in treating osteoarthritis (OA) via network pharmacology, bioinformatics analysis, and experimental verification. The active components and prediction targets of WSXB were obtained from the TCMSP database and Swiss Target Prediction website, respectively. OA-related genes were retrieved from GeneCards and OMIM databases. Protein-protein interaction and functional enrichment analyses were performed, resulting in the construction of the Herb-Component-Target network. In addition, differential genes of OA were obtained from the GEO database to verify the potential mechanism of WSXB in OA treatment. Subsequently, potential active components were subjected to molecular verification with the hub targets. Finally, we selected the most crucial hub targets and pathways for experimental verification in vitro. The active components in the study included quercetin, linolenic acid, methyl linoleate, isobergapten, and beta-sitosterol. AKT1, tumor necrosis factor (TNF), interleukin (IL)-6, GAPDH, and CTNNB1 were identified as the most crucial hub targets. Molecular docking revealed that the active components and hub targets exhibited strong binding energy. Experimental verification demonstrated that the mRNA and protein expression levels of IL-6, IL-17, and TNF in the WSXB group were lower than those in the KOA group (p < 0.05). WSXB exhibits a chondroprotective effect on OA and delays disease progression. The mechanism is potentially related to the suppression of IL-17 and TNF signaling pathways and the down-regulation of IL-6.

4.
J Am Chem Soc ; 145(17): 9508-9519, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-36944079

RESUMO

With increasing regulations on per- and polyfluoroalkyl substances (PFAS) across the world, understanding the molecular level interactions that drive their binding by functional adsorbent materials is key to effective PFAS removal from water streams. With the phaseout of legacy long-chain PFAS, the emergence of short-chain PFAS has posed a significant challenge for material design due to their higher mobility and hydrophilicity and inefficient removal by conventional treatment methods. Here, we demonstrate how cooperative molecular interactions are essential to target short-chain PFAS (from C4 to C7) by tailoring structural units to enhance affinity while modulating the electrochemical control of capture and release of PFAS. We report a new class of fluorinated redox-active amine-functionalized copolymers to leverage both fluorophilic and electrostatic interactions for short-chain PFAS binding. We combine molecular dynamics (MD) simulations and electrosorption to elucidate the role of the designer functional groups in enabling affinity toward short-chain PFAS. Preferential interaction coefficients from MD simulations correlated closely with experimental trends: fluorination enhanced the overall PFAS uptake and promoted the capture of less hydrophobic short-chain PFAS (C ≤ 5), while electrostatic interactions provided by secondary amine groups were sufficient to capture PFAS with higher hydrophobicity (C ≥ 6). The addition of an induced electric field showed favorable kinetic enhancement for the shortest PFAS and increased the reversibility of release from the electrode. Integration of these copolymers with electrochemical separations showed potential for removing these contaminants at environmentally relevant conditions while eliminating the need for chemical regeneration.

5.
J Biochem Mol Toxicol ; 37(10): e23432, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37352222

RESUMO

Cumulative evidence indicates the important role of Nur77 in organ fibrogenesis. However, the role of Nur77 in hepatitis B virus (HBV)-related liver fibrosis (LF) remains unclear. Cells were transfected with the microRNA mimic miRNA-506-3p or inhibitor, and pcDNA3.1-Nur77 or Nur77 guide RNA. Exosomes were isolated from HBV-infected HepG2-sodium taurocholate cotransporting polypeptide cells. The levels of miR-506-3p, Nur77, and LF-related genes and proteins were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The pathology of the liver from HBV-infected patients was examined using hematoxylin-eosin and Masson's staining. The expression of Nur77 in liver tissue was determined by immunohistochemistry, and the LF score was assessed using the METAVIR system. The relationship between miR-506-3p/Nur77 and LF score was analyzed by correlation analysis. HBV infection downregulated miR-506-3p expression and upregulated Nur77 levels in hepatocytes. Exosomes from HBV-infected hepatocytes also displayed decreased gene expression of miR-506-3p and increased expressions of Nur77- and LF-related genes in stellate cells compared with exosomes from hepatocytes with mock infection. These changes were reversed by Nur77 guide RNA. Nur77 expression in liver tissue was strongly correlated with LF, whereas serum miR-506-3p was strongly negatively correlated with LF. Exosomes from HBV-infected hepatocytes activate stellate cells and aggravate LF through the miR-506-3p/Nur77 pathway. These exosomes may be the basis of a promising therapeutic strategy.

6.
Biochem Biophys Res Commun ; 569: 1-9, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34216991

RESUMO

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor without curable therapy. Surgical resection remains the first choice of patients with GBM but tumors relapse rapidly even combined with conventional chemoradiotherapy. The mechanism of GBM rapid recurrence is poorly understood, which is largely due to the lack of an appropriate animal model, thus heavily impedes the improvement of postoperative therapy. Here we established a highly reproducible mouse GBM surgical model by using the syngeneic G422TN-GBM cells, which faithfully recapitulates the features of rapid recurrence of human GBM after surgery. Implanting 2 × 103-5 × 104 of G422TN-GBM cells in mouse cerebral cortex caused death in all animal within 23 days, while surgery was an effective therapy but not curable. After complete removal of visible tumors on day 5-9 of tumor growth, the tumors recurred macroscopically within 5 days accompanied by increasing infiltrative cancer foci. Mechanistically, the rapid recurrence of resected tumors was positively correlated to early Akt activation, which subsequently upregulated PD-L1/Vimentin and promoted proliferation/migration of cancer cells. In addition, environmental astrocytic activation with strong PD-L1 signal was prominent. Taken together, we provided a novel GBM surgical recurrence model for preclinical studies and suggested complicated recurring mechanisms involving in strong oncogenic signaling as well as immune inhibitory signals from both GBM cells and their neighboring astrocytes.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Vimentina/metabolismo , Animais , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Terapia Combinada , Modelos Animais de Doenças , Glioblastoma/cirurgia , Glioblastoma/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Microscopia de Fluorescência/métodos , Recidiva Local de Neoplasia
7.
Phys Chem Chem Phys ; 22(30): 17106-17116, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32686809

RESUMO

The first-step hydrogenation of CO2 to methanol via a HCOO route, COOH route, and RWGS + CO-hydro route on NixW(111) (x = 0, 1, 3) has been studied using density functional theory (DFT) calculations. CO2 and H could be chemically adsorbed on Ni-doped W(111) surfaces with relatively high adsorption energy, due to the synergistic effect of W that helps anchoring CO2 and Ni that facilitates the adsorption of H. The HCOO route is the main path for the first-step hydrogenation of CO2 with lower barriers on all three surfaces. Besides, competition between the HCOO route and RWGS + CO-hydro route could be enhanced with the increase in doped Ni on the W(111) surface. Furthermore, the first-step hydrogenation of CO2 hardly undergoes the COOH pathway because of the higher barriers, although the doping of Ni has slightly reduced the barrier of COOH formation. Our calculated results indicate that the W(111) and Ni-doped W(111) surface are potential candidate surfaces for CO2 hydrogenation to methanol, and Ni doping could influence the selectivity of reduction pathways.

8.
Am J Ind Med ; 63(9): 741-754, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32474961

RESUMO

BACKGROUND: While international agreement supports a causal relationship of benzene exposure with acute myeloid leukemia, there is debate about benzene and lymphoid neoplasm risks. METHODS: In a case-cohort study with follow-up of 110 631 Chinese workers during 1972-1999, we evaluated benzene exposure-response for non-Hodgkin lymphoma (NHL), lymphoid leukemias (LL), acute lymphocytic leukemia (ALL), and total lymphoid neoplasms (LN). We estimated benzene exposures using state-of-the-art hierarchical modeling of occupational factors calibrated with historical routine measurements and evaluated cumulative exposure-response using Cox regression. RESULTS: NHL and other specified LN were increased in exposed vs unexposed workers. However, there was no evidence of exposure-response for NHL or other specified LN. Based on a linear exposure-response, relative risks at 100 parts per million-years (RR at 100 ppm-years) for cumulative benzene exposure using a 2-year lag (exposure at least 2 years before the time at risk) were 1.05 for NHL (95 percent confidence interval (CI) = 0.97, 1.27; 32 cases), 1.11 for LL (95% CI < 0, 1.66; 12 cases), 1.21 for ALL (95% CI < 0, 3.53; 10 cases), and 1.02 for total LN (95% CI < 0, 1.16; 49 cases). No statistically significant exposure-response trends were apparent for these LN for 2 to <10-year or ≥10-year lags. NHL risks were not significantly modified by sex, age, or year at first exposure, attained age, or time since exposure. CONCLUSION: Given the study strengths and limitations, we found little evidence of exposure-response for benzene and NHL, LL, ALL, or total LN, although NHL and other specified LN were increased in exposed vs unexposed individuals.


Assuntos
Benzeno/análise , Leucemia Linfoide/epidemiologia , Linfoma/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/análise , Adolescente , Adulto , Benzeno/toxicidade , China/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Leucemia Linfoide/induzido quimicamente , Linfoma/induzido quimicamente , Linfoma não Hodgkin/induzido quimicamente , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Modelos de Riscos Proporcionais , Análise de Regressão , Risco , Adulto Jovem
9.
BMC Cancer ; 19(1): 377, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31014273

RESUMO

BACKGROUND: Smoking is one of the well-established risk factors for gastric cancer incidence, yet whether men are more or equally susceptible to gastric cancer due to smoking compared with women is a matter of controversy. The aim of this study was to investigate and compare the effect of sex on gastric cancer risk associated with smoking. METHODS: We conducted a systemic literature search in MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify studies published from inception to December 2018. We included prospective observational studies which reported effect estimates with 95% confidence intervals (CIs) for associations of current or former smokers with the incidence of gastric cancer by sex. We calculated the ratio of relative risk (RRR) with corresponding 95% CI based on sex-specific effect estimates for current or former smokers versus non-smokers on the risk of gastric cancer. RESULTS: We included 10 prospective studies with 3,381,345 participants in our analysis. Overall, the summary RRR (male to female) for gastric cancer risk in current smokers was significantly increased compared with non-smokers (RRR: 1.30; 95% CI: 1.05-1.63; P = 0.019). Furthermore, there was no significant sex difference for the association between former smokers and gastric cancer risk (RRR: 1.20; 95% CI: 0.92-1.55; P = 0.178). However, the result of sensitivity analysis indicated the pooled result was not stable, which was altered by excluding a nested case-control study (RRR: 1.31; 95% CI: 1.10-1.57; P = 0.002). CONCLUSION: This systematic review showed a potential sex difference association between current smokers and the risk of gastric cancer. The sex differential in smokers can give important clues for the etiology of gastric cancers and should be examined in further studies.


Assuntos
Suscetibilidade a Doenças , Fumar/efeitos adversos , Neoplasias Gástricas/etiologia , Feminino , Humanos , Masculino , Estudos Observacionais como Assunto , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais
10.
BMC Cancer ; 19(1): 145, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760227

RESUMO

BACKGROUND: The brain is a common site for metastasis in non-small-cell lung cancer (NSCLC). This study was designed to evaluate the relationship between the mutational of the epidermal growth factor receptor (EGFR) and overall survival (OS) in NSCLC patients with brain metastases. METHODS: Searches were performed in PubMed, EmBase, and the Cochrane Library to identify studies evaluating the association of EGFR mutation with OS in NSCLC patients through September 2017. RESULTS: 4373 NSCLC patients with brain metastases in 18 studies were involved. Mutated EGFR associated with significantly improved OS compared with wild type. Subgroup analyses suggested that this relationship persisted in studies conducted in Eastern, with retrospective design, with sample size ≥500, mean age of patients ≥65.0 years, percentage male < 50.0%, percentage of patients receiving tyrosine kinase inhibitor ≥30.0%. Finally, although significant publication bias was observed using the Egger test, the results were not changed after adjustment using the trim and fill method. CONCLUSIONS: This meta-analysis suggests that EGFR mutation is an important predictive factor linked to improved OS for NSCLC patients with brain metastases. It can serve as a useful index in the prognostic assessment of NSCLC patients with brain metastases.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mutação/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/secundário , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Prognóstico
11.
Bioorg Med Chem ; 27(23): 115153, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31648877

RESUMO

In this study, a series of shikonin derivatives combined with benzoylacrylic had been designed and synthesized, which showed an inhibitory effect on both tubulin and the epidermal growth factor receptor (EGFR). In vitro EGFR and cell growth inhibition assay demonstrated that compound PMMB-317 exhibited the most potent anti-EGFR (IC50 = 22.7 nM) and anti-proliferation activity (IC50 = 4.37 µM) against A549 cell line, which was comparable to that of Afatinib (EGFR, IC50 = 15.4 nM; A549, IC50 = 6.32 µM). Our results on mechanism research suggested that, PMMB-317 could induce the apoptosis of A549 cells in a dose- and time-dependent manner, along with decrease in mitochondrial membrane potential (MMP), production of ROS and alterations in apoptosis-related protein levels. Also, PMMB-317 could arrest cell cycle at G2/M phase to induce cell apoptosis, and inhibit the EGFR activity through blocking the signal transduction downstream of the mitogen-activated protein MAPK pathway and the anti-apoptotic kinase AKT pathway; typically, such results were comparable to those of afatinib. In addition, PMMB-317 could suppress A549 cell migration through the Wnt/ß-catenin signaling pathway in a dose-dependent manner. Additionally, molecular docking simulation revealed that, PMMB-317 could simultaneously combine with EGFR protein (5HG8) and tubulin (1SA0) through various forces. Moreover, 3D-QSAR study was also carried out, which could optimize our compound through the structure-activity relationship analysis. Furthermore, the in vitro and in vivo results had collectively confirmed that PMMB-317 might serve as a promising lead compound to further develop the potential therapeutic anticancer agents.


Assuntos
Acrilatos/farmacologia , Antineoplásicos/farmacologia , Benzoatos/farmacologia , Naftoquinonas/farmacologia , Moduladores de Tubulina/farmacologia , Células A549 , Acrilatos/química , Acrilatos/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Benzoatos/química , Benzoatos/uso terapêutico , Desenho de Fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Camundongos Nus , Simulação de Acoplamento Molecular , Naftoquinonas/química , Naftoquinonas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/química , Moduladores de Tubulina/uso terapêutico
12.
Molecules ; 24(23)2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31779254

RESUMO

Foxtail millet is considered a 'smart food' because of nutrient richness and resilience to environments. A diversity panel of 92 foxtail millet landraces preserved by Taiwan indigenous peoples containing amylose content (AC) in the range of 0.7% to 16.9% exhibited diverse physiochemical properties revealed by a rapid viscosity analyzer (RVA). AC was significantly correlated with 5 RVA parameters, and some RVA parameters were also highly correlated with one another. In comparison to rice, foxtail millet contained less starch (65.9-73.1%) and no significant difference in totals of resistant starch (RS), slowly digestible starch (SDS), hydrolysis index (HI), and expected glycemic index (eGI) according to in vitro digestibility assays of raw flour with similar AC. RS was significantly positively correlated with AC and four RVA parameters, cold paste viscosity (CPV), setback viscosity (SBV), peak time (PeT), and pasting temperature (PaT), implying that suitable food processing to alter physicochemical properties of foxtail millet might mitigate hyperglycemia. This investigation of pasting properties and digestibility of diverse foxtail millet germplasm revealed much variation and showed potential for multi-dimensional utilizations in daily staple food and food industries.


Assuntos
Variação Genética/genética , Milhetes/genética , Setaria (Planta)/genética , Amilose/genética , Farinha , Genótipo , Oryza/genética , Amido/genética , Taiwan , Temperatura , Viscosidade
13.
Carcinogenesis ; 39(5): 661-668, 2018 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-29538615

RESUMO

Although benzene has long been recognized as a cause of human leukemia, the mechanism by which this simple molecule causes cancer has been problematic. A complicating factor is benzene metabolism, which produces many reactive intermediates, some specific to benzene and others derived from redox processes. Using archived serum from 20 nonsmoking Chinese workers, 10 with and 10 without occupational exposure to benzene (exposed: 3.2-88.9 ppm, controls: 0.002-0.020 ppm), we employed an adductomic pipeline to characterize protein modifications at Cys34 of human serum albumin, a nucleophilic hotspot in extracellular fluids. Of the 47 measured human serum albumin modifications, 39 were present at higher concentrations in benzene-exposed workers than in controls and many of the exposed-control differences were statistically significant. Correlation analysis identified three prominent clusters of adducts, namely putative modifications by benzene oxide and a benzene diolepoxide that grouped with other measures of benzene exposure, adducts of reactive oxygen and carbonyl species, and Cys34 disulfides of small thiols that are formed following oxidation of Cys34. Benzene diolepoxides are potent mutagens and carcinogens that have received little attention as potential causes of human leukemia. Reactive oxygen and carbonyl species-generated by redox processes involving polyphenolic benzene metabolites and by Cyp2E1 regulation following benzene exposure-can modify DNA and proteins in ways that contribute to cancer. The fact that these diverse human serum albumin modifications differed between benzene-exposed and control workers suggests that benzene can increase leukemia risks via multiple pathways involving a constellation of reactive molecules.


Assuntos
Benzeno/efeitos adversos , Carcinogênese/induzido quimicamente , Leucemia/induzido quimicamente , Adulto , Derivados de Benzeno/efeitos adversos , Carcinógenos/toxicidade , Cicloexanos/efeitos adversos , Compostos de Epóxi/efeitos adversos , Feminino , Humanos , Leucemia/sangue , Leucemia/metabolismo , Masculino , Mutagênicos/efeitos adversos , Exposição Ocupacional/efeitos adversos , Risco , Albumina Sérica/metabolismo
14.
Gastric Cancer ; 21(3): 361-371, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29455269

RESUMO

BACKGROUND: Advanced gastric cancer (AGC) is a severe malignant tumor associated with high mortality. Targeted therapy is an important approach for improving the therapeutic effects of AGC treatment. This study evaluates the efficacy and safety of targeted agents for AGC patients. METHODS: PubMed, EmBase, and the Cochrane Library were searched for double-blind randomized controlled trials (RCTs) of AGC treatments published prior to July 2017. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and severe adverse effects (AEs) were evaluated to determine the efficacy and safety of targeted agents. A network meta-analysis with a frequentist framework was performed to assess the effects of various targeted agents for AGC treatment. RESULTS: Our analysis included 16 articles involving 5371 patients and 11 types of agents. The network meta-analysis showed that apatinib (97.5%) was most likely to improve PFS, followed by regorafenib (86.3%) and rilotumumab (65.4%). Apatinib was similarly best for OS outcome, (95.5%) followed by rilotumumab (74.7%) and regorafenib (70%). Apatinib (89.6%) also had the best improvement on ORR, followed by rilotumumab (75.4%) and everolimus (68.4%). Bevacizumab (85.5%) was likely to get the lowest severe AEs, followed by sunitinib (63%). CONCLUSIONS: Apatinib, regorafenib, and rilotumumab improved patient PFS and OS. When combined with chemotherapy, ramucirumab and rilotumumab had high efficacy but low tolerability, and bevacizumab had moderate efficacy and tolerability for PFS. Without chemotherapy, ramucirumab and regorafenib had relatively high therapeutic efficacy tolerability for PFS.


Assuntos
Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular/métodos , Neoplasias Gástricas/tratamento farmacológico , Intervalo Livre de Doença , Humanos , Neoplasias Gástricas/mortalidade
15.
Int J Cancer ; 137(9): 2184-97, 2015 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25944549

RESUMO

Benzene exposure has been causally linked with acute myeloid leukemia (AML), but inconsistently associated with other hematopoietic, lymphoproliferative and related disorders (HLD) or solid tumors in humans. Many neoplasms have been described in experimental animals exposed to benzene. We used Poisson regression to estimate adjusted relative risks (RR) and the likelihood ratio statistic to derive confidence intervals for cause-specific mortality and HLD incidence in 73,789 benzene-exposed compared with 34,504 unexposed workers in a retrospective cohort study in 12 cities in China. Follow-up and outcome assessment was based on factory, medical and other records. Benzene-exposed workers experienced increased risks for all-cause mortality (RR = 1.1, 95% CI = 1.1, 1.2) due to excesses of all neoplasms (RR = 1.3, 95% CI = 1.2, 1.4), respiratory diseases (RR = 1.7, 95% CI = 1.2, 2.3) and diseases of blood forming organs (RR = ∞, 95% CI = 3.4, ∞). Lung cancer mortality was significantly elevated (RR = 1.5, 95% CI = 1.2, 1.9) with similar RRs for males and females, based on three-fold more cases than in our previous follow-up. Significantly elevated incidence of all myeloid disorders reflected excesses of myelodysplastic syndrome/acute myeloid leukemia (RR = 2.7, 95% CI = 1.2, 6.6) and chronic myeloid leukemia (RR = 2.5, 95% CI = 0.8, 11), and increases of all lymphoid disorders included excesses of non-Hodgkin lymphoma (RR = 3.9, 95%CI = 1.5, 13) and all lymphoid leukemia (RR = 5.4, 95%CI = 1.0, 99). The 28-year follow-up of Chinese benzene-exposed workers demonstrated increased risks of a broad range of myeloid and lymphoid neoplasms, lung cancer, and respiratory diseases and suggested possible associations with other malignant and non-malignant disorders.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Benzeno/toxicidade , Carcinógenos/toxicidade , Neoplasias Hematológicas/mortalidade , Neoplasias Pulmonares/mortalidade , Exposição Ocupacional , Adulto , Idoso , Feminino , Neoplasias Hematológicas/induzido quimicamente , Humanos , Incidência , Funções Verossimilhança , Neoplasias Pulmonares/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
16.
ArXiv ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-37961736

RESUMO

Peptides play a pivotal role in a wide range of biological activities through participating in up to 40% protein-protein interactions in cellular processes. They also demonstrate remarkable specificity and efficacy, making them promising candidates for drug development. However, predicting peptide-protein complexes by traditional computational approaches, such as Docking and Molecular Dynamics simulations, still remains a challenge due to high computational cost, flexible nature of peptides, and limited structural information of peptide-protein complexes. In recent years, the surge of available biological data has given rise to the development of an increasing number of machine learning models for predicting peptide-protein interactions. These models offer efficient solutions to address the challenges associated with traditional computational approaches. Furthermore, they offer enhanced accuracy, robustness, and interpretability in their predictive outcomes. This review presents a comprehensive overview of machine learning and deep learning models that have emerged in recent years for the prediction of peptide-protein interactions.

17.
RSC Chem Biol ; 5(5): 401-417, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38725911

RESUMO

Peptides play a pivotal role in a wide range of biological activities through participating in up to 40% protein-protein interactions in cellular processes. They also demonstrate remarkable specificity and efficacy, making them promising candidates for drug development. However, predicting peptide-protein complexes by traditional computational approaches, such as docking and molecular dynamics simulations, still remains a challenge due to high computational cost, flexible nature of peptides, and limited structural information of peptide-protein complexes. In recent years, the surge of available biological data has given rise to the development of an increasing number of machine learning models for predicting peptide-protein interactions. These models offer efficient solutions to address the challenges associated with traditional computational approaches. Furthermore, they offer enhanced accuracy, robustness, and interpretability in their predictive outcomes. This review presents a comprehensive overview of machine learning and deep learning models that have emerged in recent years for the prediction of peptide-protein interactions.

18.
Heliyon ; 10(6): e28155, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38545184

RESUMO

Background: In general, the identification of cholesterol-depleted lipid particles can be inferred from non-high-density lipoprotein cholesterol (non-HDL-C) concentration to apolipoprotein B (apoB) concentration ratio, which serves as a reliable indicator for assessing the risk of cardiovascular disease. However, the ability of non-HDL-C/apoB ratio to predict the risk of long-term mortality among the general population remains uncertain. The aim of this study is to explore the association of non-HDL-C/apoB ratio with long-term all-cause and cardiovascular mortality in adults of the United States. Methods: This retrospective cohort study was a further analysis of existing information from the National Health and Nutrition Examination Survey (NHANES). In the ultimate analysis, 12,697 participants from 2005 to 2014 were included. Kaplan-Meier (K-M) curves and the log-rank test were applied to visualize survival differences between groups. Multivariate Cox regression and restricted cubic spline (RCS) models were applied to evaluate the association of non-HDL-C/apoB ratio with all-cause and cardiovascular mortality. Subgroup analysis was conducted for the variables of age, sex, presence of coronary artery disease, diabetes and hypertriglyceridemia and usage of lipid-lowering drugs. Results: The average age of the cohort was 46.8 ± 18.6 years, with 6215 (48.9%) participants being male. During a median follow-up lasting 68.0 months, 891 (7.0%) deaths were documented and 156 (1.2%) patients died of cardiovascular disease. Individuals who experienced all-cause and cardiovascular deaths had a lower non-HDL-C/apoB ratio compared with those without events (1.45 ± 0.16 vs. 1.50 ± 0.17 and 1.43 ± 0.17 vs. 1.50 ± 0.17, both P values < 0.001). The results of adjusted Cox regression models revealed that non-HDL-C/apoB ratio exhibited independent significance as a risk factor for both long-term all-cause mortality [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.33-0.80] and cardiovascular mortality (HR = 0.33, 95% CI: 0.12-0.90). Additionally, a significant sex interaction was discovered (P for interaction <0.05), indicating a robust association between non-HDL-C/apoB ratio and long-term mortality among females. The RCS curve showed that non-HDL-C/apoB ratio had a negative linear association with long-term all-cause and cardiovascular mortality (P for non-linearity was 0.098 and 0.314). Conclusions: The non-HDL-C/apoB ratio may serve as a potential biomarker for predicting long-term mortality among the general population, independent of traditional risk factors.

19.
World J Gastrointest Surg ; 16(6): 1749-1755, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38983316

RESUMO

BACKGROUND: Intestinal colic is a common complication in patients who have undergone radical surgery for colorectal cancer. Traditional Chinese medicine has advantages, including safety and stability, for the treatment of intestinal colic. Lamp irradiation for abdominal ironing has been applied in the treatment of many gastrointestinal diseases. Purple gromwell oil has the effects of clearing heat, cooling blood, reducing swelling, and relieving pain. AIM: To investigate the impact of lamp irradiation combined with purple gromwell oil gauze on ameliorating intestinal colic in patients after radical surgery for colorectal cancer. METHODS: A total of 120 patients who experienced postoperative intestinal colic complications after radical surgery for colorectal cancer and who were admitted to Foshan Traditional Chinese Medicine Hospital between June 2019 and March 2023 were enrolled as study subjects. The patients were divided into a control group (60 patients) and an observation group (60 patients) based on treatment method. The control group was treated with lamp irradiation, while the observation group was treated with lamp irradiation and external application of purple gromwell oil gauze. The clinical efficacy, Numeric Rating Scale (NRS) score, duration of symptoms, and rate of adverse reaction occurrence were further compared between the two groups. RESULTS: The general effective rate in the observation group was 95.00%, which was significantly higher than that in the control group (86.67%, P < 0.05). Before treatment, there was no significant difference in the duration of symptoms between the groups (P > 0.05). After 1, 2, 3, and 4 d of treatment, the duration of symptoms in both groups were decreased, and the duration in the observation group was significantly lower than that in the control group (96.54 ± 9.57 vs 110.45 ± 11.23, 87.26 ± 12.07 vs 104.44 ± 11.68, 80.45 ± 16.21 vs 99.44 ± 14.95, 73.18 ± 15.58 vs 92.17 ± 14.20; P < 0.05). After 1, 3, 5, and 7 d of treatment, the NRS scores in both groups were decreased, and the NRS scores in the observation group were significantly lower than those in the control group (3.56 ± 0.41 vs 4.04 ± 0.58, 3.07 ± 0.67 vs 3.74 ± 1.02, 2.52 ± 0.76 vs 3.43 ± 0.85, 2.03 ± 0.58 vs 3.03 ± 0.82; P < 0.05). There was no significant difference in the rate of adverse reaction occurrence between the groups (P > 0.05). CONCLUSION: The use of lamp irradiation combined with purple gromwell oil gauze in patients with intestinal colic after radical surgery for colorectal cancer can reduce symptom duration, alleviate intestinal colic, and improve treatment efficacy, and this approach is safe. It is worth promoting the use of this treatment in clinical practice.

20.
J Genet Psychol ; : 1-11, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38014452

RESUMO

The study explored the relationship between teacher assessments of students' general language-cognitive and social-emotional abilities and Chinese children's reading development over an academic year. A series of reading measures (including reading vocabulary, reading comprehension, and lexical inferencing ability) were administered to Chinese-speaking second graders (N = 123) across time. Meanwhile, their six head teachers and assistant head teachers were asked to complete assessments of their language-cognitive and social-emotional abilities prior to the first data collection. By utilizing multivariate analyses, the results demonstrated that teacher-assessed linguistic and social abilities contributed to children's reading abilities within and across time after autoregressive effects were controlled for. More specifically, language and cognitive abilities made a more salient contribution to reading performance over time. The study suggests that teacher assessments could have diagnostic and preventive functions for enhancing sustainable reading development among Chinese elementary-age students.

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