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1.
Small ; : e2402256, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38794863

RESUMEN

Sodium (Na)-metal batteries (SMBs) are considered one of the most promising candidates for the large-scale energy storage market owing to their high theoretical capacity (1,166 mAh g-1) and the abundance of Na raw material. However, the limited stability of electrolytes still hindered the application of SMBs. Herein, sulfolane (Sul) and vinylene carbonate (VC) are identified as effective dual additives that can largely stabilize propylene carbonate (PC)-based electrolytes, prevent dendrite growth, and extend the cycle life of SMBs. The cycling stability of the Na/NaNi0.68Mn0.22Co0.1O2 (NaNMC) cell with this dual-additive electrolyte is remarkably enhanced, with a capacity retention of 94% and a Coulombic efficiency (CE) of 99.9% over 600 cycles at a 5 C (750 mA g-1) rate. The superior cycling performance of the cells can be attributed to the homogenous, dense, and thin hybrid solid electrolyte interphase consisting of F- and S-containing species on the surface of both the Na metal anode and the NaNMC cathode by adding dual additives. Such unique interphases can effectively facilitate Na-ion transport kinetics and avoid electrolyte depletion during repeated cycling at a very high rate of 5 C. This electrolyte design is believed to result in further improvements in the performance of SMBs.

2.
Bioorg Med Chem Lett ; 98: 129574, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38052378

RESUMEN

Aurones are a minor subgroup of flavonoids. Unlike other subgroups such as chalcones, flavones, and isoflavones, aurones have not been extensively explored as pancreatic lipase inhibitors. In this work, we studied the pancreatic lipase inhibitory potency of synthetic aurone derivatives. Thirty-six compounds belonging to four series (4,6-dihydroxyaurone, 6-hydroxyaurone, 4,6-dialkoxyaurone, and 6-alkoxyaurone) were designed and synthesized. Their in vitro inhibitory activities were determined by spectrophotometric assay in comparison with quercetin and orlistat. Alkoxyaurone derivatives with long-chain (6-10 carbons) alkoxy substituents showed greater potency. Of them, 4,6-dialkoxyaurone 8 displayed the highest activity against pancreatic lipase (IC50 of 1.945 ± 0.520 µM) relative to quercetin (IC50 of 86.98 ± 3.859 µM) and orlistat (IC50 of 0.0334 ± 0.0015 µM). Fluorescence quenching measurement confirmed the affinity of alkoxyaurone derivatives to pancreatic lipase. Kinetic study showed that 8 inhibited lipase through a competitive mechanism (Ki of 1.288 ± 0.282 µM). Molecular docking results clarified the role of long-chain substituents on ring A in interacting with the hydrophobic pockets and pushing the inhibitor molecule closer to the catalytic triad. The findings in this study may contribute to the development of better pancreatic lipase inhibitors with aurone structure.


Asunto(s)
Lipasa , Quercetina , Inhibidores Enzimáticos/química , Flavonoides/química , Lipasa/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Orlistat/farmacología
3.
Pediatr Transplant ; 28(1): e14441, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37294691

RESUMEN

BACKGROUND: ND2 in Ho Chi Minh City is currently the only public center that performs PLT in Southern Vietnam. In 2005, the first PLT was successfully performed, with support from Belgian experts. This study reviews the implementation of PLT at our center and evaluates the results and challenges. METHODS: Implementation of PLT at ND2 required medico-surgical team building and extensive improvement of hospital facilities. Records of 13 transplant recipients from 2005 to 2020 were studied retrospectively. Short- and long-term complications, as well as the survival rates, were reported. RESULTS: The mean follow-up time was 8.3 ± 5.7 years. Surgical complications included one case of hepatic artery thrombosis that was successfully repaired, one case of colon perforation resulting in death from sepsis, and two cases of bile leak that were drained surgically. PTLD was observed in five patients, of whom three died. There were no cases of retransplantation. The 1-year, 5-year, and 10-year patient survival rates were 84.6%, 69.2%, and 69.2%, respectively. There were no cases of complication or death among the donors. CONCLUSION: Living-donor PLT was developed at ND2 for providing a life-saving treatment to children with end-stage liver disease. Early surgical complication rate was low, and the patient survival rate was satisfactory at 1 year. Long-term survival decreased considerably due to PTLD. Future challenges include surgical autonomy and improvement of long-term medical follow-up with a particular emphasis on prevention and management of Epstein-Barr virus-related disease.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Trasplante de Hígado , Niño , Humanos , Trasplante de Hígado/métodos , Donadores Vivos , Infecciones por Virus de Epstein-Barr/complicaciones , Estudios Retrospectivos , Vietnam , Herpesvirus Humano 4 , Complicaciones Posoperatorias/etiología
4.
BMC Biol ; 21(1): 69, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-37013580

RESUMEN

BACKGROUND: Pain is the primary reason people seek medical care, with chronic pain affecting ~ 20% of people in the USA. However, many existing analgesics are ineffective in treating chronic pain, while others (e.g., opioids) have undesirable side effects. Here, we describe the screening of a small molecule library using a thermal place aversion assay in larval zebrafish to identify compounds that alter aversion to noxious thermal stimuli and could thus serve as potential analgesics. RESULTS: From our behavioral screen, we discovered a small molecule, Analgesic Screen 1 (AS1), which surprisingly elicited attraction to noxious painful heat. When we further explored the effects of this compound using other behavioral place preference assays, we found that AS1 was similarly able to reverse the negative hedonic valence of other painful (chemical) and non-painful (dark) aversive stimuli without being inherently rewarding. Interestingly, targeting molecular pathways canonically associated with analgesia did not replicate the effects of AS1. A neuronal imaging assay revealed that clusters of dopaminergic neurons, as well as forebrain regions located in the teleost equivalent of the basal ganglia, were highly upregulated in the specific context of AS1 and aversive heat. Through a combination of behavioral assays and pharmacological manipulation of dopamine circuitry, we determined that AS1 acts via D1 dopamine receptor pathways to elicit this attraction to noxious stimuli. CONCLUSIONS: Together, our results suggest that AS1 relieves an aversion-imposed "brake" on dopamine release, and that this unique mechanism may provide valuable insight into the development of new valence-targeting analgesic drugs, as well as medications for other valence-related neurological conditions, such as anxiety and post-traumatic stress disorder (PTSD).


Asunto(s)
Dolor Crónico , Animales , Dopamina/metabolismo , Pez Cebra/metabolismo , Analgésicos/farmacología , Neuronas Dopaminérgicas/fisiología
5.
J Formos Med Assoc ; 123(3): 357-365, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37714767

RESUMEN

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is a potentially lethal infection commonly found in immunocompromised patients. It is considered the most aggressive subtype of fungal sinusitis and can lead to severe morbidity and mortality. There was a significant increase in the incidence of AIFR in post-COVID-19 patients compared to AIFR cases before the COVID-19 pandemic. This study aimed to describe the clinical presentation of AIFR associated with COVID-19 illness. METHODS: A retrospective study included 22 patients diagnosed with AIFR with a recent COVID-19 infection. RESULTS: The most frequent disease associated with AIFR was diabetes mellitus (95.5%). The mycological analysis identified infection caused by Aspergillus species in 72.7% of patients. Along with stabilizing hemodynamic parameters and controlling any comorbidities, all patients in the present study underwent combined surgical debridement followed by antifungal medications. The overall survival rate was 72.7%. The chance of developing a fatal outcome was significantly higher if meningitis presented initially (odds ratio 35.63, p < 0.05). CONCLUSION: The presence of meningitis upon initial diagnosis is related to a significantly higher chance of developing a fatal outcome and should be considered, especially in AIFR patients previously treated for COVID-19 infections. Early diagnosis, early use of antifungal agents, aggressive surgical debridement, and control of comorbid conditions remain crucial in managing AIFR.


Asunto(s)
COVID-19 , Meningitis , Rinitis , Rinosinusitis , Sinusitis , Humanos , Estudios Retrospectivos , Vietnam , Pandemias , Rinitis/epidemiología , Rinitis/terapia , COVID-19/complicaciones , Sinusitis/epidemiología , Sinusitis/microbiología , Enfermedad Aguda , Antifúngicos/uso terapéutico , Meningitis/tratamiento farmacológico
6.
Arch Environ Contam Toxicol ; 86(1): 48-57, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38063883

RESUMEN

The seeds of Annona glabra L., an invasive plant in Vietnam, were first employed as a new biosorbent for the adsorption of methylene blue (MB) from aqueous media. The characterizations of the material using FT-IR, SEM, nitrogen adsorption-desorption analysis, and point of zero charge reveals that it possesses a rough and irregular surface, various polar functional groups, and pHpzc of 5.5. Certain adsorption conditions including adsorbent dose, solution pH, contact time, and initial concentration of MB were found to affect adsorption efficiency. The kinetic data are well fitted with pseudo-second-order model with the adsorption rate of 0.002 g mg-1 min-1 and initial rate of 4.46 mg g-1 min-1. For the adsorption isotherm, three nonlinear models were used to analyze the experiment data, including Langmuir, Freundlich, and Temkin. The results indicate that the Langmuir model best describes the adsorption of Annona glabra L. seeds powder (AGSP) with a maximum adsorption capacity of 98.0 mg g-1. The investigation underpins the adsorption mechanism, whereby the electrostatic attraction between positively charged MB and negatively charged surface of AGSP is expected to be the predominant mechanism, together with hydrogen bonding and pi-pi interaction. These results make AGSP an interesting biosorbent concerning its environmental friendliness, cost-effectiveness, and relatively high dye adsorption capacity.


Asunto(s)
Annona , Contaminantes Químicos del Agua , Azul de Metileno/análisis , Azul de Metileno/química , Espectroscopía Infrarroja por Transformada de Fourier , Contaminantes Químicos del Agua/análisis , Concentración de Iones de Hidrógeno , Semillas/química , Adsorción , Cinética
7.
J Environ Manage ; 363: 121375, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38850926

RESUMEN

Evaluating the forthcoming impacts of climate change is important for formulating efficient and flexible approaches to water resource management. General Circulation Models (GCMs) are primary tools that enable scientists to study both past and potential future climate changes, as well as their impacts on policies and actions. In this work, we quantify the future projected impacts of hydroclimatic extremes on the coastal, risk-prone Tar-Pamlico River basin in North Carolina using GCMs from the Sixth International Coupled Model Intercomparison Project (CMIP6). These models incorporate projected future societal development scenarios (Shared Socioeconomic Pathways, SSPs) as defined in the Intergovernmental Panel on Climate Change (IPCC) Sixth Assessment Report (AR6). Specifically, we have utilized historical residential expansion data, the Soil and Water Assessment Tool Plus (SWAT+), the Standardized Precipitation Index (SPI), and the Interquartile Range (IQR) method for analyzing extremes from 2024 to 2100. Our findings include: (1) a trend toward wetter conditions is identified with an increase in flood events toward 2100; (2) projected increases in the severity of flood peaks are found, quantified by a rise of 21% compared to the 2000-2020 period; (3) downstream regions are forecast to experience severe droughts up to 2044; and (4) low-lying and coastal regions are found as particularly susceptible to higher flood peaks and more frequent drought events between 2045 and 2100. This work provides valuable insights into the anticipated shifts in natural disaster patterns and supports decision-makers and authorities in promoting adaptive strategies and sustainable policies to address challenges posed by future climate changes in the Tar-Pamlico region and throughout the state of North Carolina, United States.


Asunto(s)
Cambio Climático , Ríos , North Carolina , Inundaciones , Sequías
8.
Molecules ; 29(11)2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38893494

RESUMEN

Syzgium cumini (L.) Skeels powder (S. cumini powder), also known as Jamun, is well-known for its various medical and health benefits. It is especially recognized for its antidiabetic and antioxidant properties. Thus, S. cumini powder is used in various industries, such as the food and cosmetic industries. In this work, the fruit of S. cumini was utilized; its seeds were extracted, dried, and ground into powder. The ground powders were subjected to various techniques such as physicochemical tests, Fourier transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), particle size analysis, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and antioxidant analysis. From the physicochemical tests, it was revealed that the jamun seed filler contained cellulose (43.28%), hemicellulose (19.88%), lignin (23.28%), pectin (12.58%), and wax (0.98%). The FTIR analysis supported these results. For instance, a peak at 2889 cm-1 was observed and associated with CH stretching, typically found in methyl and methylene groups, characteristic of cellulose and hemicellulose structures. The XRD results demonstrated that the crystallinity index of the jamun seed filler was 42.63%. The particle analysis indicated that the mean (average) particle size was 25.34 µm. This observation was ensured with SEM results. The EDX spectrum results showed the elemental composition of the fillers. Regarding thermal degradation, the jamun seed filler had the ability to withstand temperatures of up to 316.5 °C. Furthermore, endothermic and exothermic peaks were observed at 305 °C and 400 °C, respectively. Furthermore, the antioxidant property of the powder displayed a peak scavenging activity of 91.4%. This comprehensive study not only underscores the viability of S. cumini powder as a sustainable and effective particulate filler in polymer composites but also demonstrates its potential to enhance the mechanical properties of composites, thereby offering significant implications for the development of eco-friendly materials in various industrial applications.

9.
Medicina (Kaunas) ; 60(6)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38929629

RESUMEN

Background and Objectives: Malaria continues to be a significant global health challenge. The efficacy of artemisinin-based combination therapies (ACTs) has declined in many parts of the Greater Mekong Subregion, including Vietnam, due to the spread of resistant malaria strains. This study was conducted to assess the efficacy of the Dihydroartemisinin (DHA)-Piperaquine (PPQ) regimen in treating uncomplicated falciparum malaria and to conduct molecular surveillance of antimalarial drug resistance in Binh Phuoc and Dak Nong provinces. Materials and Methods: The study included 63 uncomplicated malaria falciparum patients from therapeutic efficacy studies (TES) treated following the WHO treatment guidelines (2009). Molecular marker analysis was performed on all 63 patients. Methods encompassed Sanger sequencing for pfK13 mutations and quantitative real-time PCR for the pfpm2 gene. Results: This study found a marked decrease in the efficacy of the DHA-PPQ regimen, with an increased rate of treatment failures at two study sites. Genetic analysis revealed a significant presence of pfK13 mutations and pfpm2 amplifications, indicating emerging resistance to artemisinin and its partner drug. Conclusions: The effectiveness of the standard DHA-PPQ regimen has sharply declined, with rising treatment failure rates. This decline necessitates a review and possible revision of national malaria treatment guidelines. Importantly, molecular monitoring and clinical efficacy assessments together provide a robust framework for understanding and addressing detection drug resistance in malaria.


Asunto(s)
Antimaláricos , Artemisininas , Malaria Falciparum , Plasmodium falciparum , Quinolinas , Humanos , Artemisininas/uso terapéutico , Quinolinas/uso terapéutico , Vietnam , Antimaláricos/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Masculino , Femenino , Adulto , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Resistencia a Medicamentos/genética , Adolescente , Persona de Mediana Edad , Quimioterapia Combinada/métodos , Adulto Joven , Proteínas Protozoarias/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Mutación , Piperazinas
10.
Br J Cancer ; 128(10): 1964-1975, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36941406

RESUMEN

BACKGROUND: Patients with triple-negative breast cancer (TNBC) develop early recurrence. While PARP inhibitors (PARPi) have demonstrated potential in BRCA1/2-mutant (BRCAMUT) TNBC, durable responses will likely be achieved if PARPi are used in combination. It is plausible that sequential administration of a potent PARPi like talazoparib in combination with carboplatin can enhance primary tumour and metastasis inhibition in BRCAMUT and BRCA1/2 wild-type (BRCAWT) TNBCs, and decrease toxicity. METHODS: We evaluated the impact of the concurrent combination of talazoparib and carboplatin on cell survival in 13 TNBC cell lines. We compared the concurrent and sequential combination upon fork replication, migration and invasion. We also used three orthotopic xenograft models to evaluate primary tumour growth, distant metastasis, and toxicity. RESULTS: Concurrent talazoparib and carboplatin was synergistic in 92.3% of TNBC cell lines, independent of BRCA1/2-mutation status. The sequential combination decreased fork speed in normal cells, but not in TNBC cells. The talazoparib-first sequential combination resulted in a strong reduction in migration (70.4%, P < 0.0001), invasion (56.9%, P < 0.0001), lung micrometastasis (56.4%, P < 0.0001), and less toxicity in a BRCAWT model. CONCLUSION: The sequential combination of talazoparib and carboplatin is an effective approach to inhibit micrometastatic disease, providing rationale for the use of this combination in early TNBC patients.


Asunto(s)
Proteína BRCA1 , Neoplasias de la Mama Triple Negativas , Humanos , Carboplatino/farmacología , Proteína BRCA1/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína BRCA2/genética , Línea Celular Tumoral
11.
PLoS Pathog ; 17(4): e1009511, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33844702

RESUMEN

[This corrects the article DOI: 10.1371/journal.ppat.1009232.].

12.
PLoS Pathog ; 17(2): e1009232, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33600485

RESUMEN

Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans. During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration. In prion disorders, the diverse spectrum of illnesses exists because of the presence of different isoforms of PrPSc where they occupy distinct conformational states called strains. Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP). Characterization of the exact N-glycan structures attached on either PrPC or PrPSc is lacking. Here we report the characterization and comparison of N-glycans from two different sheep prion strains. PrPSc from both strains was isolated from brain tissue and enzymatically digested with trypsin. By using liquid chromatography coupled to electrospray mass spectrometry, a site-specific analysis was performed. A total of 100 structures were detected on both glycosylation sites. The N-glycan profile was shown to be similar to the one on mouse PrP, however, with additional 40 structures reported. The results presented here show no major differences in glycan composition, suggesting that glycans may not be responsible for the differences in the two analyzed prion strains.


Asunto(s)
Encéfalo/metabolismo , Glicopéptidos/análisis , Polisacáridos/análisis , Polisacáridos/química , Proteínas PrPSc/metabolismo , Priones/clasificación , Scrapie/metabolismo , Animales , Glicosilación , Proteínas PrPSc/genética , Priones/fisiología , Ovinos
13.
BMC Cancer ; 23(1): 233, 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36915069

RESUMEN

BACKGROUND: Late detection of hepatocellular carcinoma (HCC) results in an overall 5-year survival rate of less than 16%. Liquid biopsy (LB) assays based on detecting circulating tumor DNA (ctDNA) might provide an opportunity to detect HCC early noninvasively. Increasing evidence indicates that ctDNA detection using mutation-based assays is significantly challenged by the abundance of white blood cell-derived mutations, non-tumor tissue-derived somatic mutations in plasma, and the mutational tumor heterogeneity. METHODS: Here, we employed concurrent analysis of cancer-related mutations, and their fragment length profiles to differentiate mutations from different sources. To distinguish persons with HCC (PwHCC) from healthy participants, we built a classification model using three fragmentomic features of ctDNA through deep sequencing of thirteen genes associated with HCC. RESULTS: Our model achieved an area under the curve (AUC) of 0.88, a sensitivity of 89%, and a specificity of 82% in the discovery cohort consisting of 55 PwHCC and 55 healthy participants. In an independent validation cohort of 54 PwHCC and 53 healthy participants, the established model achieved comparable classification performance with an AUC of 0.86 and yielded a sensitivity and specificity of 81%. CONCLUSIONS: Our study provides a rationale for subsequent clinical evaluation of our assay performance in a large-scale prospective study.


Asunto(s)
Carcinoma Hepatocelular , ADN Tumoral Circulante , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Estudios Prospectivos , Biomarcadores de Tumor/genética , Mutación
14.
J Sleep Res ; 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37402610

RESUMEN

Obstructive sleep apnea (OSA) has a heavy health-related burden on patients and the healthcare system. Continuous positive airway pressure (CPAP) is effective in treating OSA, but adherence to it is often inadequate. A promising solution is to detect sleep apnea events in advance, and to adjust the pressure accordingly, which could improve the long-term use of CPAP treatment. The use of CPAP titration data may reflect a similar response of patients to therapy at home. Our study aimed to develop a machine-learning algorithm using retrospective electrocardiogram (ECG) data and CPAP titration to forecast sleep apnea events before they happen. We employed a support vector machine (SVM), k-nearest neighbour (KNN), decision tree (DT), and linear discriminative analysis (LDA) to detect sleep apnea events 30-90 s in advance. Preprocessed 30 s segments were time-frequency transformed to spectrograms using continuous wavelet transform, followed by feature generation using the bag-of-features technique. Specific frequency bands of 0.5-50 Hz, 0.8-10 Hz, and 8-50 Hz were also extracted to detect the most detected band. Our results indicated that SVM outperformed KNN, LDA, and DT across frequency bands and leading time segments. The 8-50 Hz frequency band gave the best accuracy of 98.2%, and a F1-score of 0.93. Segments 60 s before sleep events seemed to exhibit better performance than other pre-OSA segments. Our findings demonstrate the feasibility of detecting sleep apnea events in advance using only a single-lead ECG signal at CPAP titration, making our proposed framework a novel and promising approach to managing obstructive sleep apnea at home.

15.
Mol Divers ; 27(5): 2315-2330, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36319930

RESUMEN

IL(interleukin)-6 is a multifunctional cytokine crucial for immunological, hematopoiesis, inflammation, and bone metabolism. Strikingly, IL-6 has been shown to significantly contribute to the initiation of cytokine storm-an acute systemic inflammatory syndrome in Covid-19 patients. Recent study has showed that blocking the IL-6 signaling pathway with an anti-IL-6 receptor monoclonal antibody (mAb) can reduce the severity of COVID-19 symptoms and enhance patient survival. However, the mAb has several drawbacks, such as high cost, potential immunogenicity, and invasive administration due to the large-molecule protein product. Instead, these issues could be mitigated using small molecule IL-6 inhibitors, but none are currently available. This study aimed to discover IL-6 inhibitors based on the PPI with a novel camelid Fab fragment, namely 68F2, in a crystal protein complex structure (PDB ID: 4ZS7). The pharmacophore models and molecular docking were used to screen compounds from DrugBank databases. The oral bioavailability of the top 24 ligands from the screening was predicted by the SwissAMDE tool. Subsequently, the selected molecules from docking and MD simulation illustrated a promising binding affinity in the formation of stable complexes at the active binding pocket of IL-6. Binding energies using the MM-PBSA technique were applied to the top 4 hit compounds. The result indicated that DB08402 and DB12903 could form strong interactions and build stable protein-ligand complexes with IL-6. These potential compounds may serve as a basis for further developing small molecule IL-6 inhibitors in the future.


Asunto(s)
COVID-19 , Simulación de Dinámica Molecular , Humanos , Simulación del Acoplamiento Molecular , Interleucina-6 , Ligandos
16.
Mol Divers ; 2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37369956

RESUMEN

Diabetes mellitus is one of the top ten causes of death worldwide, accounting for 6.7 million deaths in 2021, and is one of the most rapidly growing global health emergencies of this century. Although several classes of therapeutic drugs have been invented and applied in clinical practice, diabetes continues to pose a serious and growing threat to public health and places a tremendous burden on those affected and their families. The strategy of reducing carbohydrate digestibility by inhibiting the activities of α-glucosidase and α-amylase is regarded as a promising preventative treatment for type 2 diabetes. In this study, we investigated the dual inhibitory effect against two polysaccharide hydrolytic enzymes of flavonoid derivatives from an in-house chemical database. By combining molecular docking and structure-activity relationship analysis, twelve compounds with docking energies less than or equal to - 8.0 kcal mol-1 and containing required structural features for dual inhibition of the two enzymes were identified and subjected to chemical synthesis and in vitro evaluation. The obtained results showed that five compounds exhibited dual inhibitory effects on the target enzymes with better IC50 values than the approved positive control acarbose. Molecular dynamics simulations were performed to elucidate the binding of these flavonoids to the enzymes. The predicted pharmacokinetic and toxicological properties suggest that these compounds are viable for further development as type 2 diabetes drugs.

17.
Public Health Nutr ; 26(8): 1644-1657, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37254445

RESUMEN

OBJECTIVE: The study's objective was to investigate multiple underlying social, economic and agricultural determinants of stunting among under-five children in three distinct ecological areas in rural Myanmar. DESIGN: Repeated cross-sectional surveys in three states of Myanmar. SETTING: Rural households in Chin (mountainous), Magway (plains) and Ayeyarwady (delta). PARTICIPANTS: From two purposively selected adjacent townships in each state, we randomly selected twenty villages and, in each village, thirty households with under-five children. Households in the first survey in 2016 were revisited in late 2017 to capture seasonal variations. RESULTS: Stunting increased from 40·4 % to 42·0 %, with the highest stunting prevalence in Chin state (62·4%). Univariate Poisson regression showed factors contributing to child stunting varied across the regions. Adjusted Poisson regression models showed that child's age and short maternal stature (aRR = 1·14 for Chin, aRR = 1·89 for Magway and aRR = 1·86 for Ayeyarwady) were consistently associated with child stunting across three areas. For Chin, village-level indicators such as crop consumption (aRR = 1·18), crop diversity (aRR = 0·82) and land ownership (aRR = 0·89) were significantly associated with stunting. In Magway, the number of household members (aRR = 1·92), wealth status (aRR = 0·46), food security status (aRR = 1·14), land ownership (aRR = 0·85) and in Ayeyarwady, women's decision-making (aRR = 0·67) and indicators related to hygiene (aRR = 1·13) and sanitation (aRR = 1·45) were associated with stunting. CONCLUSIONS: Area-specific factors were associated with stunting. Maternal short stature and child age were consistent determinants of stunting. A multi-sectoral local approach, including improvements in transport, is needed to address the intergenerational malnutrition problem.


Asunto(s)
Composición Familiar , Trastornos del Crecimiento , Humanos , Niño , Femenino , Lactante , Estudios Transversales , Mianmar/epidemiología , Encuestas y Cuestionarios , Trastornos del Crecimiento/epidemiología , Prevalencia , Factores Socioeconómicos
18.
Arch Environ Contam Toxicol ; 85(3): 324-331, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37249609

RESUMEN

Cassia fistula seed-derived coagulant has been reported to exhibit high coagulating-flocculating activity, environmental friendliness, and cost-effectiveness for the wastewater treatment, especially of textile wastewater. For heavy metal removal, however, research focusing on evaluating the feasibility of this material is still limited. Therefore, this study reports jar-test experiments in which the Zn2+ and Ni2+ removal efficiency of C. fistula coagulant was assessed. Moreover, a comparison of coagulation performance using a conventional chemical coagulant and the natural coagulant was performed. Characterization of the C. fistula seed-derived coagulant revealed the presence of important functional groups and fibrous networks with rough surfaces. A bench-scale study indicated that the coagulation performance of the two coagulants depends strongly on the initial concentration of metal ions, pH level, and coagulant dosage. The C. fistula seed-derived coagulant was found to possess higher removal efficiency than polyaluminum chloride. This natural coagulant removed over 80% of metal ions at the optimal conditions of pH 5.0, a metal ion concentration of 25 ppm, and a dosage of 0.8 and 1.6 g/L for Zn2+ and Ni2+, respectively. This study shows that C. fistula seed-derived coagulant is a potential alternative to chemical coagulants and could be developed to provide an environmentally friendly, economical, and efficient wastewater treatment.


Asunto(s)
Cassia , Fístula , Metales Pesados , Contaminantes Químicos del Agua , Purificación del Agua , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua/análisis , Metales Pesados/análisis , Semillas/química
19.
Pediatr Surg Int ; 39(1): 124, 2023 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-36786902

RESUMEN

PURPOSE: To evaluate outcomes of adopting the Swenson-like technique in transanal pull-through for Hirschsprung disease (HD) at a children's institution in Southeast Asia. METHODS: A retrospective chart review was performed over 42 months at a safety-net pediatric hospital in Vietnam. RESULTS: From January 2019 to June 2022, the Swenson-like technique was implemented and performed on 139 patients (115 male, 24 female, mean age 6.4 ± 11.96 months). There were 123 transanal-only resections, 5 transanal plus laparoscopic, and 11 transanal plus laparotomy. The mean operative time was 70.9 ± 43.6 min. The average length of the resected specimen was 18.8 ± 10.9 cm. No urethral or vaginal injuries occurred. Postoperative complications included 1 anastomotic leak (0.7%), 4 anastomotic stenoses (2.8%), and 2 perianal abscesses in the setting of recurrent enterocolitis (1.4%). With a mean follow-up of 26 ± 11.9 months (range 3-48 months), there were 25 enterocolitis cases (17.9%), 45 patients with constipation (32.3%), 1 episode of fecal incontinence lasting longer than 6 months (0.7%), and 1 rectal-vestibular fistula noted one year postoperatively (0.7%). There were no deaths. CONCLUSION: The Swenson-like technique in transanal pull-through for Hirschsprung's disease was safely adopted at our institution. The results show that applying this technique uniformly in a single institution led to excellent outcomes.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Enterocolitis , Enfermedad de Hirschsprung , Niño , Humanos , Masculino , Femenino , Lactante , Enfermedad de Hirschsprung/cirugía , Enfermedad de Hirschsprung/complicaciones , Vietnam/epidemiología , Estudios Retrospectivos , Recto/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Enterocolitis/etiología , Resultado del Tratamiento , Canal Anal/cirugía
20.
Sensors (Basel) ; 23(4)2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36850944

RESUMEN

We examine a general wireless sensor network (WSN) model which incorporates a large number of sensors distributed over a large and complex geographical area. The study proposes solutions for a flexible deployment, low cost and high reliability in a wireless sensor network. To achieve these aims, we propose the application of an unmanned aerial vehicle (UAV) as a flying relay to receive and forward signals that employ nonorthogonal multiple access (NOMA) for a high spectral sharing efficiency. To obtain an optimal number of subclusters and optimal UAV positioning, we apply a sensor clustering method based on K-means unsupervised machine learning in combination with the gap statistic method. The study proposes an algorithm to optimize the trajectory of the UAV, i.e., the centroid-to-next-nearest-centroid (CNNC) path. Because a subcluster containing multiple sensors produces cochannel interference which affects the signal decoding performance at the UAV, we propose a diagonal matrix as a phase-shift framework at the UAV to separate and decode the messages received from the sensors. The study examines the outage probability performance of an individual WSN and provides results based on Monte Carlo simulations and analyses. The investigated results verified the benefits of the K-means algorithm in deploying the WSN.

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