RESUMO
In a large-scale epidemic outbreak, there can be many high-risk individuals to be transferred for medical isolation in epidemic areas. Typically, the individuals are scattered across different locations, and available quarantine vehicles are limited. Therefore, it is challenging to efficiently schedule the vehicles to transfer the individuals to isolated regions to control the spread of the epidemic. In this paper, we formulate such a quarantine vehicle scheduling problem for high-risk individual transfer, which is more difficult than most well-known vehicle routing problems. To efficiently solve this problem, we propose a hybrid algorithm based on the water wave optimization (WWO) metaheuristic and neighborhood search. The metaheuristic uses a small population to rapidly explore the solution space, and the neighborhood search uses a gradual strategy to improve the solution accuracy. Computational results demonstrate that the proposed algorithm significantly outperforms several existing algorithms and obtains high-quality solutions on real-world problem instances for high-risk individual transfer in Hangzhou, China, during the peak period of the novel coronavirus pneumonia (COVID-19).
Assuntos
Infecções por Coronavirus/epidemiologia , Coronavirus , Veículos Automotores , Pneumonia Viral/epidemiologia , Quarentena , Transporte de Pacientes/organização & administração , Algoritmos , Agendamento de Consultas , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/terapia , Surtos de Doenças , Epidemias , Heurística , Humanos , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: Differentiation of cardiac fibroblasts (CFs) into myofibroblasts is a critical event in the initiation of myocardial fibrosis (MF). Previous studies have shown that arginine vasopressin (AVP) facilitates MF. However, the effects of AVP on CFs-myofibroblasts transformation, and its possible mechanisms are still unknown. METHODS: CFs obtained from neonatal Sprague-Dawley rats were stimulated with AVP in the absence or presence of AVP V1a receptor specific antagonist [d(CH2)5Tyr(Me)]AVP. CFs-myofibroblast transformation was detected by expression of alpha-smooth muscle actin (alpha-SMA) and collagen synthesis. Western bolt and immunofluorescent staining were used to detect expression of alpha-SMA, [H]Proline incorporation was used to detect collagen synthesis. AVP-induced transforming growth factor-beta1 (TGF-beta1) secretion was detected by enzyme-linked immunosorbent assay. CFs was also stimulated with exogenous TGF-beta1 to find out the required dose to induce CFs-myofibroblast transformation. RESULTS: 10 mol/L AVP increased alpha-SMA expression and collagen synthesis significantly, and this effect was blocked by [d(CH2)5Tyr(Me)]AVP at the concentration of 10 mol/L. Meanwhile, AVP significantly increased TGF-beta1 secretion of CFs in a dose-dependent manner, and this effect was also blocked by 10 mol/L [d(CH2)5Tyr(Me)]AVP. However, the maximum production of biologic active TGF-beta1 induced by AVP is far less than the dose of exogenous TGF-beta1 needed to induce CFs-myofibroblast transformation. CONCLUSIONS: AVP can induce CFs-myofibroblast transformation via its V1a receptor, AVP-induced increase of TGF-beta1 synthesis, which also is mediated by V1a receptor, may play a minor role in the transformation. Inducing differentiation of CFs into myofibroblasts may be a mechanism of AVP contributing to MF.
Assuntos
Arginina Vasopressina/fisiologia , Diferenciação Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Miocárdio/citologia , Receptores de Vasopressinas/fisiologia , Fator de Crescimento Transformador beta1/biossíntese , Actinas/biossíntese , Animais , Animais Recém-Nascidos , Antagonistas dos Receptores de Hormônios Antidiuréticos , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/antagonistas & inibidores , Arginina Vasopressina/farmacologia , Western Blotting , Células Cultivadas , Colágeno/biossíntese , Ensaio de Imunoadsorção Enzimática , Fibroblastos/patologia , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismoRESUMO
<p><b>AIM</b>To explore the effects of interleukin-1beta (IL-1beta) on inducible nitric oxide synthase (iNOS)-nitric oxide (NO) system activity in arginine vasopressin (AVP)-induced rat cardiac fibroblasts (CFs).</p><p><b>METHODS</b>CFs were isolated by trypsin digestion method. Nitric acid reductase method, spectrophotometry and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect NO contents, NOS activity and iNOS mRNA expression.</p><p><b>RESULTS</b>AVP significantly increased iNOS mRNA expressions, NOS activity and NO contents (P < 0.05) in CFs. IL-1beta enhanced the effects of AVP on iNOS-NO system activity in a concentration-dependent manner, moreover the iNOS mRNA expressions, NOS activity and NO contents of AVP + 3 ng/ml, AVP + 5 ng/ml IL-1beta group were both significantly higher than those of AVP group (P < 0.05). But when IL-1beta concentration increased to 5 ng/ml, the iNOS mRNA expressions, NOS activity and NO contents did not increase accordingly, slightly decreased instead.</p><p><b>CONCLUSION</b>Within certain range of concentrations IL-1beta cooperates with AVP to increase iNOS-NO system activity in CFs.</p>
Assuntos
Animais , Masculino , Ratos , Arginina Vasopressina , Farmacologia , Fibroblastos , Metabolismo , Interleucina-1beta , Farmacologia , Miócitos Cardíacos , Metabolismo , Óxido Nítrico , Metabolismo , Óxido Nítrico Sintase Tipo II , Metabolismo , Ratos Sprague-DawleyRESUMO
To investigate the changes in the nitric oxide (NO) contents, nitric oxide synthase (NOS) activity and inducible nitric oxide (iNOS) mRNA expression in arginine vasopressin (AVP)-induced cardiac fibroblasts (CFs) in vitro and its relation to nuclear factor-kappaB (NF-kappaB), CFs were isolated by trypsin digestion method. Nitric acid reductase method, spectrophotometry, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence-interactive laser cytometer techniques and Western blotting were used respectively to detect NO contents, NOS activity, iNOS mRNA expression and the activation of NF-kappaB in CFs. AVP increased NO contents, NOS activity and iNOS mRNA expressions in a concentration-dependent manner; NF-kappaB was activated and mobilized from cytoplasm to nucleus in AVP-induced CFs; PDTC, one of the inhibitors of NF-kappaB, could inhibit aforementioned increments. It is suggested that the increases in NO contents, elevation of NOS activity and increment of iNOS mRNA expression may be mediated through NF-kappaB activation pathway in cultured CFs induced by AVP, and that NF-kappaB is involved in the occurrence and development of myocardial fibrosis.