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This study applied an electro-Fenton process using chemically modified activated carbon derived from rubber seed shells loaded with α-FeOOH (RSCF) as catalyst to remove tetracycline residues from aquatic environment. Catalyst characteristics were evaluated using SEM, EDS, XRD, and XPS, showing successful insertion of iron onto the activated carbon. The effects of the parameters were investigated, and the highest treatment efficiency was achieved at pH of 3, Fe: H2O2 ratio (w/w) of 500:1, catalyst dose of 1 g/L, initial TCH concentration of 100 mg/L, and electric current of 150 mA, with more than 90% of TCH being eliminated within 30 min. Furthermore, even after five cycles of use, the treatment efficiency remains above 90%. The rate constant is calculated to be 0.218 min-1, with high regression coefficients (R 2 = 0.93). The activation energy (Ea) was found to be 32.2 kJ/mol, indicating that the degradation of TCH was a simple reaction with a low activation energy. These findings showed that the RSCF is a highly efficient and cost-effective catalyst for TCH degradation. Moreover, the use of e-Fenton process has the advantage of high efficiency, low cost thanks to the recyclability of the catalyst, and environmental friendliness thanks to less use of H2O2.
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The study investigated the effectiveness of Mg/Al LDH-zeolite (MALZ) in immobilizing exchangeable Cr (e-Cr) within the soil. The research systematically evaluated various variables affecting the immobilization of e-Cr in contaminated soil (CS), including soil pH levels (ranging from 5.0 to 9.0), different weight ratios of MALZ (1 %, 3 %, and 5 %), durations of differing incubation periods (15, 30 and 45 days), and different SM content levels (30 %, 50 %, and 70 %). The initial concentration of Cr in the CS was maintained at 50 mg/kg. The investigation findings revealed that the optimal conditions for immobilizing the e-Cr were a soil pH of 5.0, an MALZ weight ratio of 3 %, an incubation period of 30 days, and an SM level of 70 %. Under these ideal conditions, the percentage of e-Cr within the CS decreased significantly, from 87.49 % (45.64 mg/kg) in the control treatment (CT) to just 19.82 % (10.08 mg/kg) when incubated with MALZ. The primary mechanisms responsible for immobilizing the e-Cr onto MALZ included pore filling, reduction processes, co-precipitation, organic interactions and electrostatic attractions leading to the formation of carbonate-bound complexes such as Cr(VI)-carbonate, Cr(III)-carbonate, and organic complexes. Surface functional groups on MALZ, housing iron and aluminium oxyhydroxides and silicon and oxygen elements, expedited these procedures. This study provided a valuable understanding of the mitigation of soils contaminated with chromium and contributed to understanding the relations between MALZ and the e-Cr in the soil. The discoveries carry substantial consequences for the advancement of efficient remediation technologies.
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The phosphate lithium-ion conductor Li1.5Al0.5Ti1.5(PO4)3 (LATP) is an economically attractive solid electrolyte for the fabrication of safe and robust solid-state batteries, but high sintering temperatures pose a material engineering challenge for the fabrication of cell components. In particular, the high surface roughness of composite cathodes resulting from enhanced crystal growth is detrimental to their integration into cells with practical energy density. In this work, we demonstrate that efficient free-standing ceramic cathodes of LATP and LiFePO4 (LFP) can be produced by using a scalable tape casting process. This is achieved by adding 5 wt % of Li2WO4 (LWO) to the casting slurry and optimizing the fabrication process. LWO lowers the sintering temperature without affecting the phase composition of the materials, resulting in mechanically stable, electronically conductive, and free-standing cathodes with a smooth, homogeneous surface. The optimized cathode microstructure enables the deposition of a thin polymer separator attached to the Li metal anode to produce a cell with good volumetric and gravimetric energy densities of 289 Wh dm-3 and 180 Wh kg-1, respectively, on the cell level and Coulombic efficiency above 99% after 30 cycles at 30 °C.
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OBJECTIVE: This study aimed to assess the association of the neutrophil-to-lymphocyte ratio (NLR) with the occurrence of venous thromboembolism (VTE) and arterial thrombosis (AT). METHODS: This was a retrospective cross-sectional study including 585 medical records obtained from all consecutive patients who were suspected of having thrombosis. RESULTS: The AT group had a higher neutrophil count and NLR and a lower lymphocyte count than the non-thrombosis group. Receiver operating characteristic curve analysis showed the ability of the NLR to predict the presence of AT. The cut-off value for the NLR was 4.44. No distinction was found in the NLR between the VTE and non-thrombosis groups. Regression analysis showed that a high NLR was an independent factor related to the presence of AT. Patients with an NLR ≥ 4.44 had a higher risk of AT than those with an NLR < 4.44 (odds ratio = 2.015, 95% confidence interval: 1.180-3.443). CONCLUSION: A high NLR may be considered a predictive factor for the occurrence of AT, but an association with the presence of VTE was not found.
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Trombose , Tromboembolia Venosa , Humanos , Neutrófilos , Tromboembolia Venosa/diagnóstico , Estudos Retrospectivos , Estudos Transversais , Linfócitos , Curva ROC , PrognósticoRESUMO
Gallbladder volvulus (GV) is a medical emergency and a rare cause of acute abdominal pain among the pediatric population. GV is more prominent usually in boys in pediatric patients. If it is not diagnosed and surgically intervened promptly, GV will become a life-threating condition. Fortunately, a safe and effective laparoscopic cholecystectomy is now widely indicated. A 5 years old female patient with abdominal pain and heavy much vomiting was referred to the emergency room in our hospital. She was suspiciously diagnosed with acute inflammation of the gallbladder according to the results of abdominal ultrasound and computerized tomography (CT) scan already performed on admission. One day after the hospitalization, abdominal ultrasound, and CT scan were performed again because of intensification of her abdominal pain and revealed the clinical portrait of GV such as a "floating gallbladder" sign, an echogenic cone structure, an elongated axis displaced horizontally instead of vertically and a lack of intramural blood flow. The acute GV diagnosis was made and the patient was operated, using the laparoscopic cholecystectomy on time, the gallbladder was tightly twisted clockwise at approximately 720°. The operation and postoperative treatment went quite well and the patient was discharged from the hospital on postoperative Day 7. GV is very rare in children, easily omitted or misdiagnosed with cholecystitis. Imaging diagnosis such as ultrasound, CT with contrast helps make diagnosis promptly that avoids severe complications such as gallbladder perforation, necrosis, and biliary peritonitis.
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Drawing on the social practice theory, theory of planned behavior, social contagion theory, and social exchange theory, this study focused on tourist behaviors affecting tourism social sustainability and their drivers. Besides its unique contribution to distinguishing positive behaviors from negative ones, this study is the first exploring tourism social sustainability in remote communities in Vietnam, an emerging country and focusing on domestic tourists. The study reveals that tourists' knowledge about tourism social sustainability is not only the safeguard against conducting improper behaviors. Behaviors negatively impacting tourism social sustainability can be instigated by crowd, pampering of one's convenience, and superiority feeling. Furthermore, inappropriate behaviors can be nurtured by the community and service providers. This study also indicates a mixed finding regarding the role of tour operators and tour guides in enforcing the code of conduct and regulations; however, both leader and members of the community can play a critical role in promoting socially sustainable tourist behaviors.
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Background: Drugstores are preferred patients' channels of contact when getting minor ailments. Given the hike in both the prevalence and severity of influenza and acute childhood diarrhea, the role, and performances of pharmacy staff should be examined. Design and methods: A team of pharmacy students was voluntarily recruited and trained to play the role of simulated customer visiting 228 chosen community pharmacies in six districts in Can Tho city. This process is conducted from 2021 to 2022. Results: The study reveals detailed information about symptoms is the most common inquiry (99.2% in scenario 1). The consulting quality is poor, 85% of instances recorded to have no medical guidelines for influenza circumstances. Meanwhile, nearly four-fifths of pharmacists provide instructions on dosage intake. It is also found that length of services is statistically different between influenza and watery diarrhea (p < 0.05, CI = 95%). Conclusions: Clinical practices of community pharmacists, overall, are disappointing and far below expectations.
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The vacuolar H+-ATPase is a multisubunit enzyme which plays an essential role in the acidification and functions of lysosomes, endosomes, and synaptic vesicles. Many genes encoding subunits of V-ATPases, namely ATP6V0C, ATP6V1A, ATP6V0A1, and ATP6V1B2, have been associated with neurodevelopmental disorders and epilepsy. The autosomal dominant ATP6V1B2 p.Arg506* variant can cause both congenital deafness with onychodystrophy, autosomal dominant (DDOD) and deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndromes (DOORS). Some but not all individuals with this truncating variant have intellectual disability and/or epilepsy, suggesting incomplete penetrance and/or variable expressivity. To further explore the impact of the p.Arg506* variant in neurodevelopment and epilepsy, we generated Atp6v1b2emR506* mutant mice and performed standardized phenotyping using the International Mouse Phenotyping Consortium (IMPC) pipeline. In addition, we assessed the EEG profile and seizure susceptibility of Atp6v1b2emR506* mice. Behavioral tests revealed that the mice present locomotor hyperactivity and show less anxiety-associated behaviors. Moreover, EEG analyses indicate that Atp6v1b2emR506* mutant mice have interictal epileptic activity and that both heterozygous (like patients) and homozygous mice have reduced seizure thresholds to pentylenetetrazol. Our results confirm that variants in ATP6V1B2 can cause seizures and that the Atp6v1b2emR506* heterozygous mouse model is a valuable tool to further explore the pathophysiology and potential treatments for vacuolar ATPases-associated epilepsy and disorders.
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Artrogripose , Deficiência Intelectual , ATPases Vacuolares Próton-Translocadoras , Animais , Camundongos , Convulsões/genética , Causalidade , Adenosina Trifosfatases , Ansiedade , ATPases Vacuolares Próton-Translocadoras/genéticaRESUMO
Intestinal obstruction due to ligament (fibrous band) arising from the top of Meckel's diverticulum is a rare cause. To date, in the world, only a few cases have been reported and there are not enough statistics on the incidence of this disease. This case presentation will help doctors working in the field of pediatric surgery or of pediatric imaging diagnosis have more experiences on diagnosis and treatment, and enrich the medical literature on this rare disease. We report a case of an 8-year-old boy with intestinal obstruction due to ligament arising from Meckel's diverticulum with complete data set such as clinical manifestations, imaging diagnosis (ultrasound, unprepared abdominal x-ray, computerized tomography scanner with contrast injection), surgical information, and histopathological findings. Intestinal obstruction due to the ligament arising from the apex of Meckel's diverticulum is an extremely rare disease and has asymptomatic imaging features so the preoperative diagnosis is only based on the indirect findings of computerized tomography scanner. The early diagnosis of an intestinal obstruction due to fibrous band can be made by using imaging methods such as ultrasound, unprepared abdominal x-ray, computerized tomography scanner with contrast injection, contributing to the prompt diagnosis in order to avoid serious complications including bowel necrosis, intestinal perforation, and perforated diverticulum.
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Periodontitis is an inflammatory disease of gum that may predispose to serious systemic complications such as diabetes and cardiovascular diseases. Activation of macrophages and osteoclasts around periodontal tissue can accelerate gum inflammation. In addition, alteration of cyclic nucleotide levels is associated with the severity of periodontitis. Our previous study has shown that KMUP-1, a xanthine derivative exhibiting phosphodiesterase inhibition and soluble guanylyl cyclase activation, can inhibit lipopolysaccharide (LPS)-induced inflammation and receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclastogenesis. This study was aimed to investigate whether KMUP-1 could attenuate periodontitis both in vitro and in vivo. In vitro, the protective effect of KMUP-1 on inflammation and osteoclastogenesis was investigated in RANKL-primed RAW264.7 cells treated by Porphyromonas gingivalis LPS (PgLPS). The results showed that KMUP-1 attenuated PgLPS-induced osteoclast differentiation as demonstrated by decreased TRAP-positive multinuclear cells and TRAP activity. This reduction of osteoclast differentiation by KMUP-1 was reversed by KT5823, a protein kinase G inhibitor. Similarly, pro-inflammatory cytokine levels induced by PgLPS were inhibited by KMUP-1 in a dose-dependent manner whereas reversed by KT5823. Mechanistically, suppression of MAPKs, PI3K/Akt, and NF-κB signaling pathways and decrease of c-Fos and NFATc1 expression in osteoclast precursors by KMUP-1 may mediate its protective effect. In vivo, two models of periodontitis in rats were induced by gingival injections of PgLPS and ligature placement around molar teeth, respectively. Our results showed that KMUP-1 inhibited alveolar bone loss in both rat models, and this effect mediated at least partly by reduced osteoclastogenesis. In conclusion, our study demonstrated the therapeutic potential of KMUP-1 on periodontitis through suppression of inflammation and osteoclast differentiation.
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BACKGROUND: Inadequate attention has been given to ensuring ongoing training to improve knowledge, skills and capacity of primary health care providers in low- and middle-income countries. The Hanoi Medical University, Vietnam is providing training sessions for physicians working in commune health stations (CHSs) in three mountainous, remote northern provinces in 2019. This article aims to assess these physicians' knowledge of correct medical responses to emergencies in order to assess their training needs. METHODS: We conducted a cross-sectional study amongst doctors posted to CHSs located in 3 mountainous remote provinces of northern Vietnam. We used a self-administered questionnaire that comprised questions on common medical emergencies, maternal and child care, and non-communicable disease management. We performed Chi-square tests to assess the statistical significance of differences in the mean proportions of correct answers for each health care question category, and for differences in mean proportions of correct answers by doctor characteristics. RESULTS: In total 302 doctors were recruited to the study. More than half of the sample answered 30-50% of the questions correctly, followed by around a third who answered 50-70% correctly. Less than 2% of doctors answered more than 70% correct responses to the entire question set. There were statistically significant differences between question categories, with cardiovascular care questions answered correctly significantly less often than any of the categories (p < 0.00001). CONCLUSION: The findings reported here show that the doctors who participated in the study have relatively low knowledge on common emergencies, particularly to answer cardiovascular care questions. The results also support the need for continuing medical education to improve doctors' knowledge, who are mostly practicing in resource limited remote settings.
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Educação Médica Continuada , Médicos de Atenção Primária , Estudos Transversais , Emergências , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Avaliação das Necessidades , Inquéritos e Questionários , VietnãRESUMO
Colistin is widely used in agriculture and aquaculture as prophylaxis, particularly in Asia. Recently, mcr-1 and other mobilizable genes conferring colistin resistance have spread globally in community and hospital populations. Characterizing mcr-1 mobile genetic elements and host genetic background is important to understand the transmission of this resistance mechanism. We conducted whole-genome sequencing of 94 mcr-1-positive Escherichia coli isolates (Mcr1-Ec isolates) from human and animal feces, food, and water in a community cohort (N = 87) and from clinical specimens from a referral hospital (N = 7) in northern Vietnam. mcr-1 was plasmid-borne in 71 and chromosomally carried in 25 (2 isolates contain one copy on chromosome and one copy on a plasmid) of 94 E. coli isolates from the community and hospital settings. All seven clinical isolates carried mcr-1 on plasmids. Replicon types of mcr-1-carrying plasmids included IncI2, IncP, IncX4, and IncFIA single replicons and combinations of IncHI2, IncN, and IncX1 multireplicons. Alignment of a long-read sequence of an IncI2 plasmid from animal feces with short-read sequences of IncI2 plasmids from a healthy human, water, and hospitalized patients showed highly similar structures (query cover from 90% to 98%, overall identity of >81%). We detected the potential existence of multireplicon plasmids harboring mcr-1 regardless of sample setting, confirming 10/71 with long-read sequencing. An intact/conserved Tn6330 transposon sequence or its genetic context variants were found in 6/25 Mcr1-Ec isolates with chromosomally carried mcr-1. The dissemination of mcr-1 is facilitated by a high diversity of plasmid replicon types and a high prevalence of the chromosomal Tn6330 transposon. IMPORTANCE The article presented advances our understanding of genetic elements carrying mcr-1 in Escherichia coli in both community and hospital settings. We provide evidence to suggest that diverse plasmid types, including multireplicon plasmids, have facilitated the successful transmission of mcr-1 in different reservoirs. The widespread use of colistin in agriculture, where a high diversity of bacteria are exposed, has allowed the selection and evolution of various transmission mechanisms that will make it a challenge to get rid of. Colocalization of mcr-1 and other antibiotic resistance genes (ARGs) on multireplicon plasmids adds another layer of complexity to the rapid dissemination of mcr-1 genes among community and hospital bacterial populations and to the slow pandemic of antimicrobial resistance (AMR) in general.
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Infecções por Escherichia coli/microbiologia , Escherichia coli/genética , Sequências Repetitivas Dispersas , Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/classificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Fezes/microbiologia , Hospitais/estatística & dados numéricos , Humanos , Testes de Sensibilidade Microbiana , Filogenia , Plasmídeos/genética , Plasmídeos/metabolismo , VietnãRESUMO
OBJECTIVES: Mobile colistin resistance (mcr) genes are widely distributed around the world. To date, ten major variants of mcr genes are known (mcr-1 to mcr-10). However, only a few instances of Enterobacterales isolates harbouring mcr genes other than mcr-1 have been reported in Vietnam. The aim of this study was to investigate mcr-harbouring antimicrobial-resistant Enterobacterales isolates in Vietnam. METHODS: Two mcr-9-harbouring Enterobacter hormaechei clinical isolates (NIHE14-1904 and MH17-539M) were obtained from medical institutions in Hanoi, Vietnam, in 2014 and 2017, respectively. Their genomes and plasmid sequences were analysed by short-read and long-read sequencing. Subsequently, comparative sequence analysis of their mcr-9-carrying plasmids was performed. RESULTS: Strains NIHE14-1904 and MH17-539M belonged to sequence types ST916 and ST66, respectively, according to the Enterobacter cloacae multilocus sequence typing (MLST) scheme. NIHE14-1904 and MH17-539M harboured the mcr-9 gene on similar IncHI2 plasmids, namely pNIHE14-1904-mcr9 (373.1 kb) and pMH17-539M-mcr9 (289.3 kb), respectively. These plasmids were also highly identical to widespread IncHI2 plasmids that are often associated with mcr genes. CONCLUSION: For the first time, mcr-9-harbouring Enterobacterales isolates were detected in Vietnam, which carried mcr-9 on IncHI2 plasmids. The prevalence of such plasmids needs to be monitored in the future owing to their high dissemination.
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Antibacterianos , Colistina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Enterobacter , Enterobacter cloacae/genética , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Plasmídeos , VietnãRESUMO
BACKGROUND AND OBJECTIVES: To expand the clinical knowledge of GPAA1-related glycosylphosphatidylinositol (GPI) deficiency. METHODS: An international case series of 7 patients with biallelic GPAA1 variants were identified. Clinical, biochemical, and neuroimaging data were collected for comparison. Where possible, GPI-anchored proteins were assessed using flow cytometry. RESULTS: Ten novel variants were identified in 7 patients. Flow cytometry samples of 3 available patients confirmed deficiency of several GPI-anchored proteins on leukocytes. Extensive phenotypic information was available for each patient. The majority experienced developmental delay, seizures, and hypotonia. Neuroimaging revealed cerebellar anomalies in the majority of the patients. Alkaline phosphatase was within the normal range in 5 individuals and low in 1 individual, as has been noted in other transamidase defects. We notably describe individuals either less affected or older than the ones published previously. DISCUSSION: Clinical features of the cases reported broaden the spectrum of the known phenotype of GPAA1-related GPI deficiency, while outlining the importance of using functional studies such as flow cytometry to aid in variant classification.
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Aspergillus fumigatus is a ubiquitous mold that can cause invasive pulmonary infections in immunocompromised patients. Within the lung, A. fumigatus forms biofilms that can enhance resistance to antifungals and immune defenses. Aspergillus biofilm formation requires the production of a cationic matrix exopolysaccharide, galactosaminogalactan (GAG). In this study, recombinant glycoside hydrolases (GH)s that degrade GAG were evaluated as antifungal agents in a mouse model of invasive aspergillosis. Intratracheal GH administration was well tolerated by mice. Pharmacokinetic analysis revealed that although GHs have short half-lives, GH prophylaxis resulted in reduced fungal burden in leukopenic mice and improved survival in neutropenic mice, possibly through augmenting pulmonary neutrophil recruitment. Combining GH prophylaxis with posaconazole treatment resulted in a greater reduction in fungal burden than either agent alone. This study lays the foundation for further exploration of GH therapy in invasive fungal infections. IMPORTANCE The biofilm-forming mold Aspergillus fumigatus is a common causative agent of invasive fungal airway disease in patients with a compromised immune system or chronic airway disease. Treatment of A. fumigatus infection is limited by the few available antifungals to which fungal resistance is becoming increasingly common. The high mortality rate of A. fumigatus-related infection reflects a need for the development of novel therapeutic strategies. The fungal biofilm matrix is in part composed of the adhesive exopolysaccharide galactosaminogalactan, against which antifungals are less effective. Previously, we demonstrated antibiofilm activity with recombinant forms of the glycoside hydrolase enzymes that are involved in galactosaminogalactan biosynthesis. In this study, prophylaxis with glycoside hydrolases alone or in combination with the antifungal posaconazole in a mouse model of experimental aspergillosis improved outcomes. This study offers insight into the therapeutic potential of combining biofilm disruptive agents to leverage the activity of currently available antifungals.
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Antifúngicos/administração & dosagem , Aspergillus fumigatus/patogenicidade , Biofilmes/efeitos dos fármacos , Glicosídeo Hidrolases/administração & dosagem , Glicosídeo Hidrolases/genética , Aspergilose Pulmonar Invasiva/prevenção & controle , Animais , Antifúngicos/farmacocinética , Biofilmes/crescimento & desenvolvimento , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Glicosídeo Hidrolases/farmacocinética , Aspergilose Pulmonar Invasiva/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Neutropenia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , VirulênciaRESUMO
Millettia pulchra is traditionally used for treating diseases, including joint pain, fever, anemia, and allergies. It is also a potential resource of natural flavonoid derivatives, which represents major constituents of this plant. This study aimed to isolate the major compounds from M. pulchra radix, develop and validate the HPLC-PDA method to determine their contents, and optimize its extraction. Four major flavonoid derivatives (karanjin, lanceolatin B, 2",2"-dimethylpyrano-[5â³,6â³:7,8]-flavone, and pongamol) were isolated using silica gel column chromatography, crystallization techniques in large amounts with high purities (>95%). A simple, accurate high-performance liquid chromatography-photodiode array (HPLC-PDA) detection method has been developed and validated with significantly statistical impacts according to International Conference on Harmonization (ICH) guidelines. The Response Surface Methodology (RSM), Artificial Neural Network (ANN) models were employed to predictive performance and optimization of the extraction process. The optimized conditions for the extraction of major flavonoids were: extraction time (twice), solvent/material ratio (9.5), and ethanol concentration (72.5%). Our research suggests an effective method, which will be helpful for quality control in the pharmaceutical development of this species.
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Flavonoides/química , Flavonoides/isolamento & purificação , Millettia/química , Antioxidantes/química , China , Cromatografia Líquida de Alta Pressão/métodos , Etanol/química , Millettia/metabolismo , Extratos Vegetais/química , Raízes de Plantas/química , Solventes/químicaRESUMO
Early infantile epileptic encephalopathy 38 (EIEE38, MIM #617020) is caused by biallelic variants in ARV1, encoding a transmembrane protein of the endoplasmic reticulum with a pivotal role in glycosylphosphatidylinositol (GPI) biosynthesis. We ascertained seven new patients from six unrelated families harboring biallelic variants in ARV1, including five novel variants. Affected individuals showed psychomotor delay, hypotonia, early onset refractory seizures followed by regression and specific neuroimaging features. Flow cytometric analysis on patient fibroblasts showed a decrease in GPI-anchored proteins on the cell surface, supporting a lower residual activity of the mutant ARV1 as compared to the wildtype. A rescue assay through the transduction of lentivirus expressing wild type ARV1 cDNA effectively rescued these alterations. This study expands the clinical and molecular spectrum of the ARV1-related encephalopathy, confirming the essential role of ARV1 in GPI biosynthesis and brain function.
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Estudos de Associação Genética , Predisposição Genética para Doença , Proteínas de Membrana/deficiência , Fenótipo , Espasmos Infantis/diagnóstico , Espasmos Infantis/genética , Alelos , Substituição de Aminoácidos , Encéfalo/anormalidades , Proteínas de Transporte/genética , Análise Mutacional de DNA , Fácies , Feminino , Proteínas Ligadas por GPI/biossíntese , Estudos de Associação Genética/métodos , Glicosilfosfatidilinositóis/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Proteínas de Membrana/genética , Mutação , Linhagem , Gravidez , Diagnóstico Pré-Natal/métodos , Espasmos Infantis/metabolismoRESUMO
PURPOSE: Phosphatidylinositol Glycan Anchor Biosynthesis, class G (PIGG) is an ethanolamine phosphate transferase catalyzing the modification of glycosylphosphatidylinositol (GPI). GPI serves as an anchor on the cell membrane for surface proteins called GPI-anchored proteins (GPI-APs). Pathogenic variants in genes involved in the biosynthesis of GPI cause inherited GPI deficiency (IGD), which still needs to be further characterized. METHODS: We describe 22 individuals from 19 unrelated families with biallelic variants in PIGG. We analyzed GPI-AP surface levels on granulocytes and fibroblasts for three and two individuals, respectively. We demonstrated enzymatic activity defects for PIGG variants in vitro in a PIGG/PIGO double knockout system. RESULTS: Phenotypic analysis of reported individuals reveals shared PIGG deficiency-associated features. All tested GPI-APs were unchanged on granulocytes whereas CD73 level in fibroblasts was decreased. In addition to classic IGD symptoms such as hypotonia, intellectual disability/developmental delay (ID/DD), and seizures, individuals with PIGG variants of null or severely decreased activity showed cerebellar atrophy, various neurological manifestations, and mitochondrial dysfunction, a feature increasingly recognized in IGDs. Individuals with mildly decreased activity showed autism spectrum disorder. CONCLUSION: This in vitro system is a useful method to validate the pathogenicity of variants in PIGG and to study PIGG physiological functions.
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Transtorno do Espectro Autista , Deficiência Intelectual , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Humanos , Proteínas de Membrana , Linhagem , Convulsões , VirulênciaRESUMO
In-Situ composite materials of graphene (Gr) and ZnO microspindle with different Gr contents (1, 2 and 5 wt.%) were prepared via a facile one-step hydrothermal route with the assistance of hexamethylenetetramine. Graphene does not affect the hexagonal wurtzite crystal structure of composite materials but strongly affects the morphological, structural, optical and photocatalytic properties of composite materials. In detail, Gr causes a decrease in both the dimensions of ZnO microspindle and photoluminescence efficiency. The average crystalline size and microstrain first increase from 28.9 nm and 0.00394 to 49.5 nm and 0.00524 when Gr content increases from 0 to 1 wt.%, respectively; then decrease to 39.6 nm and 0.00404 when Gr content increase from 1 to 5 wt.%, respectively. Both pristine and composite materials show high photocatalytic activity with high methylene blue degradation efficiency?more than 90%-just after 40 min under UV irradiation. Composite material having a Gr content of 5 wt.% shows the highest degradation efficiency of 96.5% which confirms the role of Gr in enhancing the photocatalytic activity of ZnO.