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1.
Heliyon ; 10(7): e28312, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38571578

RESUMO

Hydropower stations that are part of the grid system frequently encounter challenges related to the uneven distribution of power generation and associated benefits, primarily stemming from delays in obtaining timely load data. This research addresses this issue by developing a scheduling model that combines power load prediction and dual-objective optimization. The practical application of this model is demonstrated in a real-case scenario, focusing on the Shatuo Hydropower Station in China. In contrast to current models, the suggested model can achieve optimal dispatch for grid-connected hydropower stations even when power load data is unavailable. Initially, the model assesses various prediction models for estimating power load and subsequently incorporates the predictions into the GA-NSGA-II algorithm, specifically an enhanced elite non-dominated sorting genetic algorithm. This integration is performed while considering the proposed objective functions to optimize the discharge flow of the hydropower station. The outcomes reveal that the CNN-GRU model, denoting Convolutional Neural Network-Gated Recursive Unit, exhibits the highest prediction accuracy, achieving R-squared and RMSE (i.e., Root Mean Square Error) values of 0.991 and 0.026, respectively. The variance between scheduling based on predicted load values and actual load values is minimal, staying within 5 (m3/s), showcasing practical effectiveness. The optimized scheduling outcomes in the real case study yield dual advantages, meeting both the demands of ship navigation and hydropower generation, thus achieving a harmonious balance between the two requirements. This approach addresses the real-world challenges associated with delayed load data collection and insufficient scheduling, offering an efficient solution for managing hydropower station scheduling to meet both power generation and navigation needs.

2.
World J Gastrointest Surg ; 16(3): 777-789, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38577068

RESUMO

BACKGROUND: Colorectal cancer is the third most common cancer and the second highest cause of cancer-related mortality worldwide. About 5%-10% of patients are diagnosed with locally advanced rectal cancer (LARC) on presentation. For LARC invading into other structures (i.e. T4b), multivisceral resection (MVR) and/or pelvic exenteration (PE) remains the only potential curative surgical treatment. MVR and/or PE is a major and complex surgery with high post-operative morbidity. Minimally invasive surgery (MIS) has been shown to improve short-term post-operative outcomes in other gastrointestinal malignancies, but there is little evidence on its use in MVR, especially so for robotic MVR. AIM: To assess the feasibility and safety of minimally invasive MVR (miMVR), and compare post-operative outcomes between robotic and laparoscopic MVR. METHODS: This is a single-center retrospective cohort study from 1st January 2015 to 31st March 2023. Inclusion criteria were patients diagnosed with cT4b rectal cancer and underwent MVR, or stage 4 disease with resectable systemic metastases. Patients who underwent curative MVR for locally recurrent rectal cancer, or metachronous rectal cancer were also included. Exclusion criteria were patients with systemic metastases with non-resectable disease. All patients planned for elective surgery were enrolled into the standard enhanced recovery after surgery pathway with standard peri-operative management for colorectal surgery. Complex surgery was defined based on technical difficulty of surgery (i.e. total PE, bladder-sparing prostatectomy, pelvic lymph node dissection or need for flap creation). Our primary outcomes were the margin status, and complication rates. Categorical values were described as percentages and analysed by the chi-square test. Continuous variables were expressed as median (range) and analysed by Mann-Whitney U test. Cumulative overall survival (OS) and recurrence-free survival (RFS) were analysed using Kaplan-Meier estimates with life table analysis. Log-rank test was performed to determine statistical significance between cumulative estimates. Statistical significance was defined as P < 0.05. RESULTS: A total of 46 patients were included in this study [open MVR (oMVR): 12 (26.1%), miMVR: 36 (73.9%)]. Patients' American Society of Anesthesiologists score, body mass index and co-morbidities were comparable between oMVR and miMVR. There is an increasing trend towards robotic MVR from 2015 to 2023. MiMVR was associated with lower estimated blood loss (EBL) (median 450 vs 1200 mL, P = 0.008), major morbidity (14.7% vs 50.0%, P = 0.014), post-operative intra-abdominal collections (11.8% vs 50.0%, P = 0.006), post-operative ileus (32.4% vs 66.7%, P = 0.04) and surgical site infection (11.8% vs 50.0%, P = 0.006) compared with oMVR. Length of stay was also shorter for miMVR compared with oMVR (median 10 vs 30 d, P = 0.001). Oncological outcomes-R0 resection, recurrence, OS and RFS were comparable between miMVR and oMVR. There was no 30-d mortality. More patients underwent robotic compared with laparoscopic MVR for complex cases (robotic 57.1% vs laparoscopic 7.7%, P = 0.004). The operating time was longer for robotic compared with laparoscopic MVR [robotic: 602 (400-900) min, laparoscopic: Median 455 (275-675) min, P < 0.001]. Incidence of R0 resection was similar (laparoscopic: 84.6% vs robotic: 76.2%, P = 0.555). Overall complication rates, major morbidity rates and 30-d readmission rates were similar between laparoscopic and robotic MVR. Interestingly, 3-year OS (robotic 83.1% vs 58.6%, P = 0.008) and RFS (robotic 72.9% vs 34.3%, P = 0.002) was superior for robotic compared with laparoscopic MVR. CONCLUSION: MiMVR had lower post-operative complications compared to oMVR. Robotic MVR was also safe, with acceptable post-operative complication rates. Prospective studies should be conducted to compare short-term and long-term outcomes between robotic vs laparoscopic MVR.

3.
Zootaxa ; 5415(1): 117-143, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38480212

RESUMO

Recent collection in Panti Forest Reserve in Johor, Peninsular Malaysia offered us the opportunity to better understand the species in southern Malay Peninsula. Two new species and one new genus of Meconematini are described here: Cercoteratura reflexa sp. n. and Platycercotura caricauda gen. et sp. n. We present new locality records for Peracca macritchiensis Tan & Ingrisch, 2014, Viriacca viridis Ingrisch, 1998; Lipotactes (Dialipotactes) maculatus Hebard, 1922; Asiophlugis rete Gorochov, 1998; and Arnobia pilipes tropica Gorochov, 1998, all of which were previously recorded in Pahang (Peninsular Malaysia) and Singapore, suggest that the distribution of these species is continuous between Pahang and Singapore. New locality record for Asiophlugis temasek temasek Gorochov & Tan, 2011, previously known only from Singapore, indicates that this subspecies is no longer endemic to Singapore.


Assuntos
Ortópteros , Animais , Malásia , Distribuição Animal
4.
Zootaxa ; 5410(2): 267-279, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480244

RESUMO

The taxonomy of the crickets from the genus Odontogryllodes Chopard, 1969 is reviewed. Two species new to science are described here, one from Peninsular Malaysia (part of Malay Peninsula) and another from East Malaysia (part of Borneo): Odontogryllodes undatus Tan, Muhammad & Abdullah sp. nov. from Panti Forest Reserve and Odontogryllodes magnus Tan, Japir & Chung sp. nov. from Tenompok Forest Reserve, respectively. We also present an updated key to the species of Odontogryllodes. In total, nine species are currently known.


Assuntos
Gryllidae , Animais , Distribuição Animal
5.
Zootaxa ; 5424(1): 61-79, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38480300

RESUMO

A new species of Itara (Phormincter) is described from Mindanao in the Philippines: Itara (Phormincter) mindanao Tan, Grumo, Gono & Bahoy, sp. nov. This represents the first record of this subgenus in the Philippines, having previously known only from Borneo, Java, Malay Peninsula and Sumatra; as well as only the second species of Itara known from the Philippines and the first from Mindanao Island. The male calling song of the holotype was also recorded and is described here. Additionally, the male calling song of another congener, Itara (Singitara) singularis Gorochov, 1997 from Sabah, is described here. A new species of Itara (Bornitara) is also described from Sabah in Borneo: Itara (Bornitara) tenompok Tan, Japir & Chung, sp. nov.


Assuntos
Ortópteros , Masculino , Animais , Malásia , Filipinas , Distribuição Animal
6.
Zootaxa ; 5419(4): 584-600, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38480307

RESUMO

Based on recent field sampling in the highlands of western Sabah, a new species of Depressacca Ingrisch, 1998 (Conocephalinae: Agraeciini) is described from Tenompok, Depressacca macrolima sp. nov., that can be easily distinguish from two other known congeners by the presence of numerous large and falcate spines on the legs numerous large and falcate spines on its legs. Based on the new material, we also document here the live images and/or new locality records for other katydids of the tribes Agraeciini and Meconematini: Bispinolakis longicauda Ingrisch, 1998, Palaeoagraecia philippina (Karny, 1926) and Salomona borneensis Willemse, 1959; Alloteratura (Meconemopsis) longa Gorochov, 2008, Borneratura kinabaluana (Bey-Bienko, 1971) and Rhinoteratura pulchra Gorochov, 2008.


Assuntos
Ortópteros , Animais , Malásia , Distribuição Animal
7.
Genes (Basel) ; 15(2)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38397203

RESUMO

Carotid intima-media thickness (CIMT) is a surrogate indicator for atherosclerosis and has been shown to predict cardiovascular risk in multiple large studies. Identification of molecular markers for carotid atheroma plaque formation can be critical for early intervention and prevention of atherosclerosis. This study performed transcription factor (TF) network analysis of global gene expression data focusing on two TF genes, ZNF385D and HAND2, whose polymorphisms have been recently reported to show association with CIMT. Genome-wide gene expression data were measured from pieces of carotid endarterectomy collected from 34 hypertensive patients (atheroma plaque of stages IV and above according to the Stary classification) each paired with one sample of distant macroscopically intact tissue (stages I and II). Transcriptional regulation networks or the regulons were reconstructed for ZNF385D (5644 target genes) and HAND2 (781 target genes) using network inference. Their association with the progression of carotid atheroma was examined using gene-set enrichment analysis with extremely high statistical significance for regulons of both ZNF385D and HAND2 (p < 6.95 × 10-7) suggesting the involvement of expression quantitative loci (eQTL). Functional annotation of the regulon genes found heavy involvement in the immune system's response to inflammation and infection in the development of atherosclerosis. Detailed examination of the regulation and correlation patterns suggests that activities of the two TF genes could have high clinical and interventional impacts on impairing carotid atheroma plaque formation and preventing carotid atherosclerosis.


Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/genética , Fatores de Transcrição/genética , Espessura Intima-Media Carotídea , Fatores de Risco , Doenças das Artérias Carótidas/genética , Regulação da Expressão Gênica
8.
ACS Nano ; 18(8): 6673-6689, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38353701

RESUMO

The current live rotavirus (RV) vaccines show reduced effectiveness in developing countries, calling for vaccine strategies with improved efficacy and safety. We generated pseudovirus nanoparticles (PVNPs) that display multiple ectodomains of RV viral protein 4 (VP4), named S-VP4e, as a nonreplicating RV vaccine candidate. The RV spike protein VP4s that bind host receptors and facilitate viral entry are excellent targets for vaccination. In this study, we developed scalable methods to produce three S-VP4e PVNPs, each displaying the VP4e antigens from one of the three predominant P[8], P[4], and P[6] human RVs (HRVs). These PVNPs were recognized by selected neutralizing VP4-specific monoclonal antibodies, bound glycan receptors, attached to permissive HT-29 cells, and underwent cleavage by trypsin between VP8* and VP5*. 3D PVNP models were constructed to understand their structural features. A trivalent PVNP vaccine containing the three S-VP4e PVNPs elicited high and well-balanced VP4e-specific antibody titers in mice directed against the three predominant HRV P types. The resulting antisera neutralized the three HRV prototypes at high titers; greater than 4-fold higher than the neutralizing responses induced by a trivalent vaccine consisting of the S60-VP8* PVNPs. Finally, the trivalent S-VP4e PVNP vaccine provided 90-100% protection against diarrhea caused by HRV challenge. Our data supports the trivalent S-VP4e PVNPs as a promising nonreplicating HRV vaccine candidate for parenteral delivery to circumvent the suboptimal immunization issues of all present live HRV vaccines. The established PVNP-permissive cell and PVNP-glycan binding assays will be instrumental for further investigating HRV-host cell interactions and neutralizing effects of VP4-specific antibodies and antivirals.


Assuntos
Rotavirus , Vacinas Virais , Animais , Camundongos , Humanos , 60547 , Proteínas Virais/metabolismo , Anticorpos Neutralizantes , Polissacarídeos , Imunidade , Anticorpos Antivirais
9.
Heliyon ; 10(3): e24746, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38318012

RESUMO

Objective: Half of the patients with acute large artery occlusion (LAO) have poor outcomes after endovascular treatment (EVT). Early complications such as cerebral edema and symptomatic intracranial hemorrhage (sICH) can lead to early neurological deterioration (END), which correlates with hemodynamics. This study aimed to identify the hemodynamic predictors of END and outcomes in LAO patients after EVT. Methods: A total of 76 patients with anterior circulation LAO who underwent EVT and received transcranial Doppler (TCD) monitoring were included. Bilateral middle cerebral artery (MCA) blood flow velocities (BFVs) were measured repeatedly within 1 week. Mean flow velocities (MFV) and MFV index (ipsilateral MFV/contralateral MFV) were calculated. The primary outcome was the incidence of END within 72 h. The secondary outcome was the functional outcome at 90 days-a good outcome was defined as a modified Rankin scale (mRS) score of 0-2, while a poor outcome was defined as an mRS score of 3-6. Results: A total of 13 patients (17.1 %) experienced END within 72 h, including 5 (38.5 %) with cerebral edema, 5 (38.5 %) with sICH, and 3 (23.0 %) with infarct progression. Multivariable logistic regression analysis showed that a higher 24 h MFV index was independently associated with END (aOR 10.5; 95 % CI 2.28-48.30, p = 0.003) and a poor 90-day outcome (aOR 5.10; 95 % CI 1.38-18.78, p = 0.014). The area under the receiver operating characteristic (ROC) curve (AUC) of the 24 h MFV index for predicting END was 0.807 (95 % CI 0.700-0.915, p = 0.0005), the sensitivity was 84.6 %, and the specificity was 66.7 %. At the 1-week TCD follow-up, patients who had poor 90-day outcomes showed significantly higher 1-week iMFV [73.5 (58.4-99.0) vs. 57.7 (45.3-76.3), p = 0.004] and MFV index [1.24 (0.98-1.57) vs.1.0 (0.87-1.15) p = 0.007]. A persistent high MFV index (PHMI) was independently associated with a poor outcome (aOR 7.77, 95 % CI 1.81-33.3, p = 0.006). Conclusion: TCD monitoring within 24 h after EVT in LAO patients can help predict END, while dynamic follow-up within 1 week is valuable in predicting clinical outcomes.

10.
Nat Prod Res ; : 1-6, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372270

RESUMO

A new isopimarane-type diterpene clinacanoid A (1) together with seven known terpenoids (2-8) were obtained from the Clinacanthus nutans. Their structures were elucidated based on extensive spectroscopic analysis (NMR, HR-ESI-MS), and the absolute configuration of 1 was established based on single crystal X-ray diffraction. The inhibitory activity of all the compounds on NO production in lipopolysaccharide-induced (LPS) mouse leukemic monocyte macrophage RAW264.7 cells was evaluated. Among them, compounds 1 and 3 showed potential anti-inflammatory activities, with IC50 values of 13.3 ± 0.3 and 12.4 ± 0.4 µM, respectively.

11.
Ultrasonics ; 138: 107234, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38171227

RESUMO

The development of alternative techniques to efficiently inactivate bacterial suspensions is crucial to prevent transmission of waterborne illness, particularly when commonly used techniques such as heating, filtration, chlorination, or ultraviolet treatment are not practical or feasible. We examine the effect of MHz-order acoustic wave irradiation in the form of surface acoustic waves (SAWs) on Gram-positive (Escherichia coli) and Gram-negative (Brevibacillus borstelensis and Staphylococcus aureus) bacteria suspended in water droplets. A significant increase in the relative bacterial load reduction of colony-forming units (up to 74%) can be achieved by either increasing (1) the excitation power, or, (2) the acoustic treatment duration, which we attributed to the effect of the acoustic radiation force exerted on the bacteria. Consequently, by increasing the maximum pressure amplitude via a hybrid modulation scheme involving a combination of amplitude and pulse-width modulation, we observe that the bacterial inactivation efficiency can be further increased by approximately 14%. By combining this scalable acoustic-based bacterial inactivation platform with plasma-activated water, a 100% reduction in E. coli is observed in less than 10 mins, therefore demonstrating the potential of the synergistic effects of MHz-order acoustic irradiation and plasma-activated water as an efficient strategy for water decontamination.


Assuntos
Bactérias , Escherichia coli , Bactérias/efeitos da radiação , Som , Acústica , Água
12.
Int J Biol Macromol ; 260(Pt 2): 129613, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38246440

RESUMO

The effects of pulsed electric field combined with ultrasound (PEF-US) on the recovery of polyphenols from litchi peels were investigated. In addition, the optimal purification parameters for polyphenol extracts and their biological activities were also explored in this study. Single-factor and orthogonal experiments were used to optimize the extraction conditions of polyphenols. After optimization, the total phenol content (TPC) of the sample extracted by PEF-US was 2.30 times higher than that of the sample extracted by traditional hot-water extraction. The mechanism of PEF-US enhancing polyphenol recovery was also revealed by morphological analysis of the powder surface. LX-7 was the best resin by comparing the purification effect of nine macroporous resins. The optimum conditions for purification of litchi peel polyphenols by LX-7 resin were also optimized through adsorption and desorption experiments. UHPLC-MS and HPLC results revealed that gentisic acid, catechin, procyanidin A2 and procyanidin B1 are four main substances in purified samples. The results of bioactivity experiments showed that the purified polyphenol samples had strong antioxidant and antibacterial activity. Overall, PEF-US is an efficient method for recovering polyphenols from litchi peels. Our study also provides a strategy for the comprehensive utilization of fruit processing waste.


Assuntos
Litchi , Polifenóis , Frutas/química , Extratos Vegetais , Antioxidantes/farmacologia
13.
Zootaxa ; 5397(2): 264-272, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38221205

RESUMO

Only one species of Pendleburyella Chopard, 1969 (Gryllidae, Pentacentrinae) was previously known to occur in Borneo: Pendleburyella eirmosa Tan, Muhammad & Wahab, 2023 from Brunei Darussalam. Here, two additional new species of crickets from the genus Pendleburyella are described from the highlands of Sabah, Borneo: Pendleburyella eremita sp. nov. from Bukit Hampuan and Pendleburyella nimba sp. nov. from Mount Trus Madi. In total, six species of Pendleburyella are currently known, three from Borneo and three from Malay Peninsula. It is likely that many more species are awaiting discovery owing to its cryptic morphology and elusive nature.


Assuntos
Críquete , Gryllidae , Animais , Malásia , Bornéu
14.
BMC Infect Dis ; 24(1): 20, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166673

RESUMO

BACKGROUND: Bacterial vaginosis (BV) is a widely occurring vaginal inflammation in women of childbearing age caused by dysbiosis of the vaginal flora. Few studies have investigated the effect of serum carotenoids on the development and pathogenesis of BV. This study thus aimed to explore the correlation between serum carotenoids and BV in American women. METHOD: The analysis included 1252 participants with BV from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2004. Multiple logistic regression was conducted to explore the correlation between BV and serum carotenoids, while smooth curve fitting was utilized to examine potential nonlinear correlations. Furthermore, stratified subgroup analyses and sensitivity analyses were conducted. ORs reflected the correlation between BV and serum carotenoids. RESULT: Results of multiple logistic regression indicated that total serum carotenoids and BV had an inverse correlation. In the fully adjusted model II, the quartile with the highest levels of α-carotene and ß-cryptoxanthin had a substantially lower incidence of BV. Smooth curve fitting revealed a significant negative linear correlation between serum carotenoids and the incidence of BV. The negative correlation between serum carotenoids and BV was relatively stable in stratified analyses. Moreover, in sensitivity analyses, the association between serum carotenoids and BV persisted, and ß-carotene became significantly negatively correlated with BV. CONCLUSION: This study found an inverse correlation between serum carotenoids and the prevalence of BV.


Assuntos
Vaginose Bacteriana , Humanos , Feminino , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Vaginose Bacteriana/epidemiologia , Carotenoides , beta Caroteno , Antioxidantes
15.
Virol J ; 21(1): 35, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297280

RESUMO

BACKGROUND: Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market are efficient in controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved in regulating the HBV life cycle will contribute to the development of new antiviral strategies. Zinc finger proteins have a significant function in HBV replication, according to earlier studies. Zinc finger protein 148 (ZNF148), a zinc finger transcription factor, regulates the expression of various genes by specifically binding to GC-rich sequences within promoter regions. The function of ZNF148 in HBV replication was investigated in this study. METHODS: HepG2-Na+/taurocholate cotransporting polypeptide (HepG2-NTCP) cells and Huh7 cells were used to evaluate the function of ZNF148 in vitro. Northern blotting and real-time PCR were used to quantify the amount of viral RNA. Southern blotting and real-time PCR were used to quantify the amount of viral DNA. Viral protein levels were elevated, according to the Western blot results. Dual-luciferase reporter assays were used to examine the transcriptional activity of viral promoters. ZNF148's impact on HBV in vivo was investigated using an established rcccDNA mouse model. RESULTS: ZNF148 overexpression significantly decreased the levels of HBV RNAs and HBV core DNA in HBV-infected HepG2-NTCP cells and Huh7 cells expressing prcccDNA. Silencing ZNF148 exhibited the opposite effects in both cell lines. Furthermore, ZNF148 inhibited the activity of HBV ENII/Cp and the transcriptional activity of cccDNA. Mechanistic studies revealed that ZNF148 attenuated retinoid X receptor alpha (RXRα) expression by binding to the RXRα promoter sequence. RXRα binding site mutation or RXRα overexpression abolished the suppressive effect of ZNF148 on HBV replication. The inhibitory effect of ZNF148 was also observed in the rcccDNA mouse model. CONCLUSIONS: ZNF148 inhibited HBV replication by downregulating RXRα transcription. Our findings reveal that ZNF148 may be a new target for anti-HBV strategies.


Assuntos
Vírus da Hepatite B , Hepatite B , Animais , Camundongos , Humanos , Vírus da Hepatite B/fisiologia , Replicação Viral , Células Hep G2 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , DNA Viral/genética
16.
Dalton Trans ; 53(5): 2143-2152, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38189098

RESUMO

Mitophagy, a selective autophagic process, has emerged as a pathway involved in degrading dysfunctional mitochondria. Herein, new platinum(II)-based chemotherapeutics with mitophagy-targeting properties are proposed. Four novel binuclear anticancer Pt(II) complexes with 4'-substituted-2,2':6',2''-terpyridine derivatives (tpy1-tpy4), i.e., [Pt2(tpy1)(DMSO)2Cl4]·CH3OH (tpy1Pt), [Pt(tpy2)Cl][Pt(DMSO)Cl3]·CH3COCH3 (tpy2Pt), [Pt(tpy3)Cl][Pt(DMSO)Cl3] (tpy3Pt), and [Pt(tpy4)Cl]Cl·CH3OH (tpy4Pt), were designed and prepared. Moreover, their potential antitumor mechanism was studied. Tpy1Pt-tpy4Pt exhibited more selective cytotoxicity against cisplatin-resistant SK-OV-3/DDP (SKO3cisR) cancer cells compared with those against ovarian SK-OV-3 (SKO3) cancer cells and normal HL-7702 liver (H702) cells. This selective cytotoxicity of Tpy1Pt-tpy4Pt was better than that of its ligands (i.e., tpy1-tpy4), the clinical drug cisplatin, and cis-Pt(DMSO)2Cl2. The results of various experiments indicated that tpy1Pt and tpy2Pt kill SKO3cisR cancer cells via a mitophagy pathway, which involves the disruption of the mitophagy-related protein expression, dissipation of the mitochondrial membrane potential, elevation of the [Ca2+] and reactive oxygen species levels, promotion of mitochondrial DNA damage, and reduction in the adenosine triphosphate and mitochondrial respiratory chain levels. Furthermore, in vivo experiments indicated that the dinuclear anticancer Pt(II) coordination compound (tpy1Pt) has remarkable therapeutic efficiency (ca. 52.4%) and almost no toxicity. Therefore, the new 4'-substituted-2,2':6',2''-terpyridine Pt(II) coordination compound (tpy1Pt) is a potential candidate for next-generation mitophagy-targeting dinuclear Pt(II)-based anticancer drugs.


Assuntos
Antineoplásicos , Cisplatino , Cisplatino/farmacologia , Platina/farmacologia , Dimetil Sulfóxido , Linhagem Celular Tumoral , Compostos Organoplatínicos/farmacologia , Antineoplásicos/farmacologia , Apoptose
17.
Eur J Cancer ; 196: 113439, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37980854

RESUMO

AIM: A bridging study of INTRIGUE study to assess the efficacy and safety of ripretinib versus sunitinib as second-line treatment in Chinese GIST patients. METHODS: This was a phase 2, multicenter, randomized, open-label study in China. GIST patients previously treated with imatinib were randomized (1:1) to receive ripretinib 150 mg once daily (QD) by continuous dosing in 42-day cycles or sunitinib 50 mg QD in 42-day cycles (four weeks on/two weeks off). Primary endpoint was progression-free survival (PFS) by independent radiological review (IRR). RESULTS: Between 6 December 2020 and 15 September 2021, 108 patients were randomized to receive ripretinib (n = 54) or sunitinib (n = 54) (all-patient [AP] intention-to-treat [ITT] population). Seventy patients had primary KIT exon 11 mutations (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT population). By data cut-off (20 July 2022), in AP ITT population, PFS by IRR was comparable between ripretinib and sunitinib arms (HR 0·99, 95 % CI 0·57, 1·69; nominal p = 0·92; median PFS [mPFS] 10·3 vs 8·3 months). In Ex11 ITT population, PFS by IRR was longer for ripretinib than sunitinib (HR 0·46, 95 % CI 0·23, 0·92; nominal p = 0·03; mPFS not reached in ripretinib arm and 4·9 months in sunitinib arm). Fewer patients experienced grade 3/4 treatment-related treatment-emergent adverse events with ripretinib (17%) versus sunitinib (56%). CONCLUSIONS: Ripretinib demonstrated similar efficacy and a favorable safety profile versus sunitinib as second-line treatment in Chinese GIST patients. Furthermore, ripretinib provided greater clinically meaningful benefit versus sunitinib in patients with KIT exon 11 mutation.


Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Sunitinibe , Humanos , Antineoplásicos/efeitos adversos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Mesilato de Imatinib/uso terapêutico , Sunitinibe/efeitos adversos
18.
J Prosthodont ; 33(1): 46-53, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36639956

RESUMO

PURPOSE: To study the effect of implant angulation on 3D linear and absolute angular distortions of implant analogs in printed resin models and conventional stone casts. MATERIALS AND METHODS: Three sectional master models with two implants with total inter-implant angulations of 0°, 10°, and 20° were fabricated. For each master model, five conventional stone casts (CS) and printed resin models (PM) were fabricated (n = 5). Test models were made with nonsplinted impression copings and open tray polyether impressions for the CS groups and scan bodies scanned using an intraoral scanner for the PM groups. The physical positions of the implants and implant analogs were measured with a coordinate measuring machine. 3D linear distortion (ΔR) and absolute angular distortion (Absdθ) defined the 3D positional accuracy of the analogs in the test models. Univariate ANOVA was used to analyze data followed by post hoc tests (Tukey HSD, α = 0.05). RESULTS: Mean ΔR was significantly greater for PM10 (73.5 ± 8.9 µm) and PM20 (65.5 ± 33.3 µm) compared to CS0 (16.8 ± 14.1 µm), CS10 (22.2 ± 13.0 µm), CS20 (15.6 ± 19.9 µm), and PM0 (23.9 ± 16.1 µm). For Absdθ, there were no significant differences between test groups. CONCLUSIONS: With conventional stone casts, implant angulation had no significant effect on 3D linear and absolute angular distortions. Amongst printed resin models test groups, angulated implants had significantly greater ΔR. Amongst angulated implants test groups, printed resin models had significantly greater ΔR than conventional stone casts. Compared to the master model, all test groups, regardless of inter-implant angulation, produced greater inter-analog distances.


Assuntos
Implantes Dentários , Materiais para Moldagem Odontológica , Técnica de Moldagem Odontológica , Modelos Dentários
19.
Food Chem ; 439: 138116, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38064830

RESUMO

The strong-fragrant rapeseed oil (SFRO) is a popular rapeseed oil in China with a low refining degree only degumming with hot water, which remarkably affects its storage stability. The present study compared the overall changes of physical/chemical/nutrient quality of FROs at various temperatures, light wavelengths and headspace volumes. Results showed that red light (680 nm) had a most significant adverse effect on the overall quality of SFRO with the higher correlation coefficients to PV and TOTOX of 0.71 and 0.70, and lower correlation coefficients to chlorophyll and tocopherol of -0.95 and -0.53, respectively. Further studies revealed that red light accelerated the oxidation of fragrant rapeseed oils by degrading chlorophyll to initiate the photo-oxidation process and synthesize high amount of secondary oxidation products including aliphatic and aromatic oxidized compounds from linolenic acid. These findings provided a reference to control the deterioration of FROs by preventing the transmittance of red light.


Assuntos
Brassica napus , Óleo de Brassica napus , Oxirredução , Tocoferóis , Clorofila , Óleos de Plantas
20.
J Inorg Biochem ; 251: 112443, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38100902

RESUMO

Fourteen novel tumor-targeting copper(II) and zinc(II) complexes, [Cu(ONQ)(QD1)(NO3)]·CH3OH (NQ3), [Cu(ONQ)(QD2)(NO3)] (NQ2), [Cu(NQ)(QD2)Cl] (NQ3), [Cu(ONQ)(QD1)Cl] (NQ4), [Cu(ONQ)(QD3)](NO3) (NQ5), [Cu(ONQ)(QD3)Cl] (NQ6), [Zn(ONQ)(QD4)Cl] (NQ7), [Zn(ONQ)(QD1)Cl] (NQ8), [Zn(ONQ)(QD5)Cl] (NQ9), [Zn(ONQ)(QD2)Cl] (NQ10), [Zn(ONQ)(QD6)Cl] (NQ11), [Zn(ONQ)(QD7)Cl] (NQ12), and [Zn(ONQ)(QD3)Cl] (NQ13) supported on 8-hydroxyquinoline-N-oxide (H-ONQ), 2,2'-dipyridyl (QD1), 5,5'-dimethyl-2,2'-bipyridyl (QD2), 1,10-phenanthroline (QD3), 4,4'-dimethoxy-2,2'-bipyridyl (QD4), 4,4'-dimethyl-2,2'-bipyridyl (QD5), 5-chloro-1,10-phenanthroline (QD6), and bathophenanthroline (QD7), were first synthesized and characterized using various spectroscopic techniques. Furthermore, NQ1-NQ13 exhibited higher antiproliferative activity and selectivity for cisplatin-resistant SK-OV-3/DDP tumor cells (CiSK3) compared to normal HL-7702 cells based on results obtained from the cell counting Kit-8 (CCK-8) assay. The complexation of copper(II) ion with QD2 and ONQ ligands resulted in an evident increase in the antiproliferation of NQ1-NQ6, with NQ6 exhibiting the highest antitumor potency against CiSK3 cells compared to NQ1-NQ5, H-ONQ, QD1-QD7, and NQ7-NQ13 as well as the reference cisplatin drug with an IC50 value of 0.17 ± 0.05 µM. Mechanistic studies revealed that NQ4 and NQ6 induced apoptosis of CiSK3 cells via mitophagy pathway regulation and adenosine triphosphate (ATP) depletion. Further, the differential induction of mitophagy decreased in the order of NQ6 > NQ4, which can be attributed to the major impact of the QD3 ligand with a large planar geometry and the Cl leaving group within the NQ6 complex. In summary, these results confirmed that the newly synthesized H-ONQ copper(II) and zinc(II) coordination metal compounds NQ1-NQ13 exhibit potential as anticancer drugs for cisplatin-resistant ovarian CiSK3 cancer treatment.


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias , Humanos , Cisplatino/farmacologia , Cobre/química , Complexos de Coordenação/química , Oxiquinolina , 2,2'-Dipiridil/química , Zinco/química , Fenantrolinas/farmacologia , Antineoplásicos/química , Ligantes
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