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1.
PLoS One ; 19(5): e0298118, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38722833

RESUMEN

It is unclear how telomere-binding protein TPP1 interacts with human telomerase reverse transcriptase (hTERT) and influences cervical cancer development and progression. This study included all eligible 156 cervical cancers diagnosed during 2003-2008 and followed up through 2014, 102 cervical intraepithelial neoplasia (CIN) patients, and 16 participants with normal cervix identified at the same period. Correlation of expression of TPP1 and hTERT in these lesions was assessed using Kappa statistics. TPP1 was knocked down by siRNA in three cervical cancer cell lines. We assessed mRNA expression using quantitative real-time polymerase chain reaction and protein expression using tissue microarray-based immunohistochemical staining. We further analyzed the impact of TPP1 expression on the overall survival of cervical cancer patients by calculating the hazard ratio (HR) with 95% confidence intervals (CIs) using the multivariable-adjusted Cox regression model. Compared to the normal cervix, high TPP1expression was significantly associated with CIN 3 and cervical cancers (P<0.001 for both). Expressions of TPP1 and hTERT were highly correlated in CIN 3 (Kappa statistics = 0.50, P = 0.005), squamous cell carcinoma (Kappa statistics = 0.22, P = 0.011), and adenocarcinoma/adenosquamous carcinoma (Kappa statistics = 0.77, P = 0.001). Mechanistically, knockdown of TPP1 inhibited the expression of hTERT in both mRNA and protein levels. High expression of TPP1 (HR = 2.61, 95% CI 1.23-5.51) and co-high expression of TPP1 and hTERT (HR = 2.38, 95% CI 1.28-4.43) were independently associated with worse survival in cervical cancer patients. TPP1 and hTERT expression was correlated and high expression of TPP1 was associated with high risk of CIN 3 and cervical cancer and could predict a worse survival in cervical cancer.


Asunto(s)
Complejo Shelterina , Telomerasa , Proteínas de Unión a Telómeros , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/metabolismo , Proteínas de Unión a Telómeros/metabolismo , Proteínas de Unión a Telómeros/genética , Telomerasa/genética , Telomerasa/metabolismo , Persona de Mediana Edad , Displasia del Cuello del Útero/genética , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/metabolismo , Displasia del Cuello del Útero/mortalidad , Adulto , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Tripeptidil Peptidasa 1
2.
BMC Genomics ; 25(1): 471, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745153

RESUMEN

BACKGROUND: Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett's esophagus(BE) hasn't been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis. METHODS: Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N = 18,340) and Dutch Microbiome Project(N = 7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE. RESULTS: 11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR = 1.087, 95%CI = 1.01-1.17) and BE(OR = 1.388, 95%CI = 1.03-1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways. CONCLUSIONS: This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.


Asunto(s)
Esófago de Barrett , Reflujo Gastroesofágico , Microbioma Gastrointestinal , Análisis de la Aleatorización Mendeliana , Microbioma Gastrointestinal/genética , Reflujo Gastroesofágico/microbiología , Humanos , Esófago de Barrett/microbiología , Esófago de Barrett/genética , Factores de Riesgo , Polimorfismo de Nucleótido Simple
3.
Chemosphere ; 358: 142238, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38705413

RESUMEN

Predicting the metabolic activation mechanism and potential hazardous metabolites of environmental endocrine-disruptors is a challenging and significant task in risk assessment. Here the metabolic activation mechanism of benzophenone-3 catalyzed by P450 1A1 was investigated by using Molecular Dynamics, Quantum Mechanics/Molecular Mechanics and Density Functional Theory approaches. Two elementary reactions involved in the metabolic activation of BP-3 with P450 1A1: electrophilic addition and hydrogen abstraction reactions were both discussed. Further conversion reactions of epoxidation products, ketone products and the formaldehyde formation reaction were investigated in the non-enzymatic environment based on previous experimental reports. Binding affinities analysis of benzophenone-3 and its metabolites to sex hormone binding globulin indirectly demonstrates that they all exhibit endocrine-disrupting property. Toxic analysis shows that the eco-toxicity and bioaccumulation values of the benzophenone-3 metabolites are much lower than those of benzophenone-3. However, the metabolites are found to have skin-sensitization effects. The present study provides a deep insight into the biotransformation process of benzophenone-3 catalyzed by P450 1A1 and alerts us to pay attention to the adverse effects of benzophenone-3 and its metabolites in human livers.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38702170

RESUMEN

Objective: To investigate the impact of the restoration of non-bracket invisible orthodontic titanium alloy implant on individuals with dental malocclusion and arch deficiency accompanied by periodontitis and local periodontal Inflammation. Method: A cohort of 120 patients presenting with dental malocclusion and defects compounded by periodontitis, were treated at our institution between January 2021 and January 2022; these patients were enrolled in a randomized controlled trial.. These patients were allocated into two groups. The control group (comprising 60 cases) underwent titanium alloy implant restoration, while the research group (also with 60 cases) received titanium alloy implant restoration following invisible orthodontic treatment without brackets. A one-year post-treatment follow-up was conducted, during which various parameters, including pain levels, aesthetic improvement, inflammatory response, dental function, oral hygiene, and the incidence of adverse events, were evaluated and compared before and after treatment between the two groups. Results: After six months of treatment, the visual analog scale (VAS) in the study group was lower than that in the control group (P < .05). After 6 months of treatment, the research team observed the changes in gingival crevicular interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Interleuckin-1 (IL-1), plaque index (PLI), and soft dirt index (DI) were all lower than those in the control group (P < .05). After 6 months of treatment, the research group had higher scores for tooth functions such as chewing, swallowing, speech expression, and occlusion than the control group, as well as higher pink and white aesthetics indexes (P < .05). The difference in the incidence rate of adverse outcomes between the research and control group was not distinct (P > .05). Conclusion: In case of dental malocclusion accompanied by periodontal disease, the utilization of titanium implants for rectifying dental arch deformities without the use of orthodontic brackets, devoid of orthodontic brackets, has demonstrated notable efficacy in alleviating patients' periodontal discomfort, their oral hygiene, and dental functionality. This modality is conducive to augmenting dental aesthetics without incurring heightened rates of unfavorable consequences, thereby enhancing treatment outcomes.

5.
Small ; : e2402841, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693072

RESUMEN

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO2/EPM) is designed and fabricated with porous structures and 3D VO2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO2/EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO2. Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO2/EPM before and after the phase transition. Moreover, the application of VO2/EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices.

6.
JAMA ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656760
7.
Nat Prod Res ; : 1-7, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656927

RESUMEN

A new xanthone, allanxanthone F (1), and 10 known compounds were isolated from the ethanol extract of Garcinia bracteata. The structure of compound 1 was elucidated based on spectroscopic methods (UV, IR, HR-ESI-MS, and NMR). In addition, compounds 1-9 were assessed for their anti-inflammatory activities based on the expression of nitric oxide (NO) levels on lipopolysaccharide (LPS)-induced RAW264.7 macrophages, and compounds 1-3, 4 and 6-9 suggested potential anti-inflammatory activities.

8.
Environ Sci Technol ; 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38668375

RESUMEN

Pharmaceutically active compounds are an important category of emerging pollutants, and their biological transformation processes in the environment are crucial for understanding and evaluating the migration, transformation, and environmental fate of emerging pollutants. The cytochrome P450 105 enzyme family has been proven to play an important role in the degradation of exogenous environmental pollutants. However, its thermostability and catalytic activity still need to be improved to better adapt to complex environmental conditions. This work elucidates the key mechanisms and important residues of the degradation reaction through multiple computational strategies, establishes a mutation library, and obtains 21 single-point mutation designs. Experimental verification showed that 16 single mutants had enhanced thermostability, with the R89F and L197Y mutants showing the highest increases in thermostability at 135 and 119% relative to the wild-type enzyme, respectively. Additionally, as a result of the higher specific activity of D390Q, it was selected for combination mutagenesis, ultimately resulting in three combination mutants (R89F/L197Y, R89F/D390Q, and R89F/L197Y/D390Q) with enhanced thermostability and catalytic activity. This study provides a modification approach for constructing efficient enzyme variants through semirational design and can contribute to the development of control technologies for emerging pollutants.

9.
J Environ Manage ; 357: 120730, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38574705

RESUMEN

Volatile organic compounds (VOCs) significantly contribute to ozone pollution formation, and many VOCs are known to be harmful to human health. Plastic has become an indispensable material in various industries and daily use scenarios, yet the VOC emissions and associated health risks in the plastic manufacturing industry have received limited attention. In this study, we conducted sampling in three typical plastic manufacturing factories to analyze the emission characteristics of VOCs, ozone formation potential (OFP), and health risks for workers. Isopropanol was detected at relatively high concentrations in all three factories, with concentrations in organized emissions reaching 322.3 µg/m3, 344.8 µg/m3, and 22.6 µg/m3, respectively. Alkanes are the most emitted category of VOCs in plastic factories. However, alkenes and oxygenated volatile organic compounds (OVOCs) exhibit higher OFP. In organized emissions of different types of VOCs in the three factories, alkenes and OVOCs contributed 22.8%, 67%, and 37.8% to the OFP, respectively, highlighting the necessity of controlling them. The hazard index (HI) for all three factories was less than 1, indicating a low non-carcinogenic toxic risk; however, there is still a possibility of non-cancerous health risks in two of the factories, and a potential lifetime cancer risk in all of the three factories. For workers with job tenures exceeding 5 years, there may be potential health risks, hence wearing masks with protective capabilities is necessary. This study provides evidence for reducing VOC emissions and improving management measures to ensure the health protection of workers in the plastic manufacturing industry.


Asunto(s)
Contaminantes Atmosféricos , Ozono , Compuestos Orgánicos Volátiles , Humanos , Contaminantes Atmosféricos/análisis , Compuestos Orgánicos Volátiles/análisis , Monitoreo del Ambiente , Medición de Riesgo , Industria Manufacturera , Alquenos , China
10.
Orphanet J Rare Dis ; 19(1): 159, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38610036

RESUMEN

BACKGROUND: Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported. RESULTS: Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159_164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR. CONCLUSIONS: Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases.


Asunto(s)
Anomalías Múltiples , Errores Innatos del Metabolismo de los Aminoácidos , Síndrome de Angelman , Citrulinemia , Masculino , Femenino , Humanos , Niño , Proteínas de Transporte de Membrana Mitocondrial
11.
J Ethnopharmacol ; 330: 118232, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38670407

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Arbutin is a naturally occurring glucoside extracted from plants, known for its antioxidant and tyrosinase inhibiting properties. It is widely used in cosmetic and pharmaceutical industries. With in-depth study of arbutin, its application in disease treatment is expanding, presenting promising development prospects. However, reports on the metabolic stability, plasma protein binding rate, and pharmacokinetic properties of arbutin are scarce. AIM OF THE STUDY: The aim of this study is to enrich the data of metabolic stability and pharmacokinetics of arbutin through the early pre-clinical evaluation, thereby providing some experimental basis for advancing arbutin into clinical research. MATERIALS AND METHODS: We developed an efficient and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for determining arbutin in plasma. We investigated the metabolic and pharmacokinetic properties of arbutin through in vitro metabolism assay, cytochrome enzymes P450 (CYP450) inhibition studies, plasma protein binding rate analysis, Caco-2 cell permeability tests, and rat pharmacokinetics to understand its in vivo performance. RESULTS: In vitro studies show that arbutin is stable, albeit with some species differences. It exhibits low plasma protein binding (35.35 ± 11.03% âˆ¼ 40.25 ± 2.47%), low lipophilicity, low permeability, short half-life (0.42 ± 0.30 h) and high oral bioavailability (65 ± 11.6%). Arbutin is primarily found in the liver and kidneys and is eliminated in the urine. It does not significantly inhibit CYP450 up to 10 µM, suggesting a low potential for drug interactions. Futhermore, preliminary toxicological experiments indicate arbutin's safety, supporting its potential as a therapeutic agent. CONCLUSION: This study provides a comprehensive analysis the drug metabolism and pharmacokinetics (DMPK) of arbutin, enriching our understanding of its metabolism stability and pharmacokinetics properties, It establishes a foundation for further structural optimization, pharmacological studies, and the clinical development of arbutin.


Asunto(s)
Arbutina , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem , Arbutina/farmacocinética , Arbutina/farmacología , Espectrometría de Masas en Tándem/métodos , Animales , Humanos , Células CACO-2 , Masculino , Cromatografía Liquida/métodos , Ratas , Microsomas Hepáticos/metabolismo , Microsomas Hepáticos/efectos de los fármacos , Unión Proteica , Sistema Enzimático del Citocromo P-450/metabolismo , Productos Biológicos/farmacocinética , Productos Biológicos/farmacología , Productos Biológicos/química , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Inhibidores Enzimáticos del Citocromo P-450/farmacocinética , Cromatografía Líquida con Espectrometría de Masas
12.
Nature ; 629(8010): 193-200, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38600383

RESUMEN

Sex differences in mammalian complex traits are prevalent and are intimately associated with androgens1-7. However, a molecular and cellular profile of sex differences and their modulation by androgens is still lacking. Here we constructed a high-dimensional single-cell transcriptomic atlas comprising over 2.3 million cells from 17 tissues in Mus musculus and explored the effects of sex and androgens on the molecular programs and cellular populations. In particular, we found that sex-biased immune gene expression and immune cell populations, such as group 2 innate lymphoid cells, were modulated by androgens. Integration with the UK Biobank dataset revealed potential cellular targets and risk gene enrichment in antigen presentation for sex-biased diseases. This study lays the groundwork for understanding the sex differences orchestrated by androgens and provides important evidence for targeting the androgen pathway as a broad therapeutic strategy for sex-biased diseases.


Asunto(s)
Andrógenos , Células , Caracteres Sexuales , Análisis de la Célula Individual , Transcriptoma , Animales , Femenino , Humanos , Masculino , Ratones , Andrógenos/metabolismo , Andrógenos/farmacología , Presentación de Antígeno/efectos de los fármacos , Presentación de Antígeno/genética , Inmunidad Innata , Linfocitos/metabolismo , Linfocitos/citología , Linfocitos/inmunología , Linfocitos/efectos de los fármacos , Ratones Endogámicos C57BL , Transcriptoma/efectos de los fármacos , Transcriptoma/genética , Biobanco del Reino Unido , Células/efectos de los fármacos , Células/inmunología , Células/metabolismo
13.
J Environ Manage ; 358: 120866, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38663085

RESUMEN

Cu (II) is a toxic heavy metal commonly identified in groundwater contaminants. Bentonite-based cutoff wall is the most used method in isolating and adsorbing contaminants, while the bentonite in it easily to fail due to Cu(II) exchange. This study synthesized a novel material through the modification of calcium bentonite (CaB) utilizing sodium hexametaphosphate (SHMP) and nano zero-valent iron (NZVI). The characteristics, adsorption performance, and mechanism of the NZVI/SHMP-CaB were investigated comprehensively. The results showed that SHMP can disperse CaB and reduce flocculation, while NZVI can be further stabilized without agglomeration. The best adsorption performance of NZVI/SHMP-CaB could be obtained at the dosage of 2% SHMP and 4% NZVI. The NZVI/SHMP-CaB exhibited an outstanding removal efficiency of over 60% and 90% at a high Cu(II) concentration (pH = 6, Cu(II) = 300 mg/L) and acidic conditions (pH = 3-6, Cu(II) = 50 mg/L), respectively. The adsorption of Cu(II) by NZVI/SHMP-CaB followed a pseudo-second-order kinetic model, and fitting results from the Freundlich isothermal model suggested that the adsorption process occurred spontaneously. Besides the rapid surface adsorption on the NZVI/SHMP-CaB and ion exchange with interlayer ions in bentonite, the removal mechanism of Cu(II) also involved the chemical reduction to insoluble forms such as Cu0 and Cu2O. The generated FePO4 covered the surface of the homogenized NZVI particles, enhancing the resistance of NZVI/SHMP-CaB to acidic and oxidative environments. This study indicates that NZVI/SHMP-CaB is a promising alternative material which can be used for heavy metal removal from contaminated soil and water.


Asunto(s)
Bentonita , Cobre , Hierro , Fosfatos , Bentonita/química , Adsorción , Hierro/química , Cobre/química , Fosfatos/química , Cinética , Contaminantes Químicos del Agua/química , Concentración de Iones de Hidrógeno
14.
Talanta ; 274: 126108, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38640602

RESUMEN

Drug-induced liver injury (DILI) is a frequent adverse drug reaction. The current clinical diagnostic methods are inadequate for accurate and early detection of DILI due to the lack of effective diagnostic biomarkers. Hepatocyte-specific miR-122 is released from injured hepatocytes promptly and its efflux is significantly correlated with the progression of DILI. Therefore, achieving precise in situ detection of miR-122 with high sensitivity is vital for early visualization of DILI. Herein, a new nanoprobe, consisting of miR-122 aptamer, upconversion nanoparticles (UCNPs) and Prussian blue nanoparticles (PBNPs) was introduced for the early and sensitive detection of DILI in situ. As the nanoprobes reached in the liver, miR-122 aptamer-based entropy-driven strand displacement (ESDR) signal amplification reaction was triggered and luminescence resonance energy transfer (LRET) between UCNPs and PBNPs was responded to achieve the high-fidelity detection of DILI. A negative correlation was observed between the intensity of upconversion luminescence (UCL) and the concentration of miR-122. UCL imaging conducted both in vivo and ex vivo indicated that a reduction in miR-122 concentration led to an increase in UCL intensity, revealing a precise state of DILI. The detection technique demonstrated a positive correlation between signal intensity and severity, offering a more straightforward and intuitive method of visualizing DILI.


Asunto(s)
Biomarcadores , Enfermedad Hepática Inducida por Sustancias y Drogas , MicroARNs , Nanopartículas , MicroARNs/análisis , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico por imagen , Animales , Nanopartículas/química , Biomarcadores/análisis , Humanos , Ratones , Ferrocianuros/química , Aptámeros de Nucleótidos/química , Masculino
15.
Angew Chem Int Ed Engl ; 63(21): e202315802, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38453646

RESUMEN

The development of nonpyrolytic catalysts featuring precisely defined active sites represents an effective strategy for investigating the fundamental relationship between the catalytic activity of oxygen reduction reaction (ORR) catalysts and their local coordination environments. In this study, we have synthesized a series of model electrocatalysts with well-defined CoN4 centers and nonplanar symmetric coordination structures. These catalysts were prepared by a sequential process involving the chelation of cobalt salts and 1,10-phenanthroline-based ligands with various substituent groups (phen(X), where X=OH, CH3, H, Br, Cl) onto covalent triazine frameworks (CTFs). By modulating the electron-donating or electron-withdrawing properties of the substituent groups on the phen-based ligands, the electron density surrounding the CoN4 centers was effectively controlled. Our results demonstrated a direct correlation between the catalytic activity of the CoN4 centers and the electron-donating ability of the substituent group on the phenanthroline ligands. Notably, the catalyst denoted as BCTF-Co-phen(OH), featuring the electron-donating OH group, exhibited the highest ORR catalytic activity. This custom-crafted catalyst achieved a remarkable half-wave potential of up to 0.80 V vs. RHE and an impressive turnover frequency (TOF) value of 47.4×10-3 Hz at 0.80 V vs. RHE in an alkaline environment.

16.
Orphanet J Rare Dis ; 19(1): 126, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38504242

RESUMEN

OBJECTIVE: Idiopathic infantile hypercalcemia (IIH) is a rare disorder of PTH-independent hypercalcemia. CYP24A1 and SLC34A1 gene mutations cause two forms of hereditary IIH. In this study, the clinical manifestations and molecular aspects of six new Chinese patients were investigated. METHODS: The clinical manifestations and laboratory study of six patients with idiopathic infantile hypercalcemia were analyzed retrospectively. RESULTS: Five of the patients were diagnosed with hypercalcemia, hypercalciuria, and bilateral medullary nephrocalcinosis. Their clinical symptoms and biochemical abnormalities improved after treatment. One patient presented at age 11 years old with arterial hypertension, hypercalciuria and nephrocalcinosis, but normal serum calcium. Gene analysis showed that two patients had compound heterozygous mutations of CYP24A1, one patient had a monoallelic CYP24A1 variant, and three patients had a monoallelic SLC34A1 variant. Four novel CYP24A1 variants (c.116G > C, c.287T > A, c.476G > A and c.1349T > C) and three novel SLC34A1 variants (c.1322 A > G, c.1697_1698insT and c.1726T > C) were found in these patients. CONCLUSIONS: A monoallelic variant of CYP24A1 or SLC34A1 gene contributes to symptomatic hypercalcemia, hypercalciuria and nephrocalcinosis. Manifestations of IIH vary with onset age. Hypercalcemia may not necessarily present after infancy and IIH should be considered in patients with nephrolithiasis either in older children or adults.


Asunto(s)
Hipercalcemia , Enfermedades del Recién Nacido , Errores Innatos del Metabolismo , Nefrocalcinosis , Niño , Humanos , Hipercalcemia/genética , Hipercalciuria/genética , Mutación/genética , Nefrocalcinosis/genética , Estudios Retrospectivos , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIa/genética , Vitamina D3 24-Hidroxilasa/genética , Vitamina D3 24-Hidroxilasa/metabolismo
17.
Sensors (Basel) ; 24(6)2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38544252

RESUMEN

Lateral flow immunoassay (LFIA) is extensively utilized for point-of-care testing due to its ease of operation, cost-effectiveness, and swift results. This study investigates the flow dynamics and reaction mechanisms in LFIA by developing a three-dimensional model using the Richards equation and porous media transport, and employing numerical simulations through the finite element method. The study delves into the transport and diffusion behaviors of each reaction component in both sandwich LFIA and competitive LFIA under non-uniform flow conditions. Additionally, the impact of various parameters (such as reporter particle concentration, initial capture probe concentrations for the T-line and C-line, and reaction rate constants) on LFIA performance is analyzed. The findings reveal that, in sandwich LFIA, optimizing parameters like increasing reporter particle concentration and initial capture probe concentration for the T-line, as well as adjusting reaction rate constants, can effectively enhance detection sensitivity and broaden the working range. Conversely, in competitive LFIA, the effects are inverse. This model offers valuable insights for the design and enhancement of LFIA assays.


Asunto(s)
Nanopartículas del Metal , Inmunoensayo/métodos
18.
ACS Appl Mater Interfaces ; 16(12): 15121-15132, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38501443

RESUMEN

Acquiring the ideal blend morphology of the active layer to optimize charge separation and collection is a constant goal of polymer solar cells (PSCs). In this paper, the ternary strategy and the sequential deposition process were combined to make sufficient use of the solar spectrum, optimize the energy-level structure, regulate the vertical phase separation morphology, and ultimately enhance the power conversion efficiency (PCE) and stability of the PSCs. Specifically, the donor and acceptor illustrated a gradient-blended distribution in the sequential deposition-processed films, thus resulting in facilitated carrier characteristics in the gradient-blended devices. Consequently, the PSCs based on D18-Cl/Y6:ZY-4Cl have achieved a device efficiency of over 18% with the synergetic improvement of open-circuit voltage (VOC), short-circuit current density (JSC), and fill factor (FF). Therefore, this work reveals a facile approach to fabricating PSCs with improved performance and stability.

19.
Sci Total Environ ; 926: 171942, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38527553

RESUMEN

Wastewater reclaim in industrial parks can effectively reduce the dependence on external water resources, few literatures evaluated the reclaim system from perspectives of economy, technology, and environmental impact. It is very popular across China that a constructed wetland is linked with a wastewater plant and then discharged the tailwater into surface waters, based on current situation, pilot experiment, and other available techniques, six scenarios for wastewater reclaim system were designed for Shanghai Chemical Industrial Park. Using life cycle assessment, it was found that in scenario of pilot experiment, most environmental impact was derived from wastewater plant and ultra filtration - reverse osmosis, in which ultra filtration - reverse osmosis accounted >20 % for POCP, AP, and EP, Wastewater plant accounted >86 % for ADP, ODP. It was showed that electricity and sludge were most important parameters affecting LCA, when electricity consumption was reduced by 20 %, total standardized environmental impact would be changed in the range of 1.40 %-1.65 %, the most significant change was HTP (6.12 %-6.32 %) when 20 % up and downward change in sludge amount, followed by MAETP (5.27 %-5.36 %). A multi-criteria decision-making analysis was conducted on all the scenarios based on environmental impact, life cycle cost, technical efficiency, it was showed that the scenario designed for pilot experiment was the best available technique, which was consisted of wastewater plant, hybrid constructed wetland, ultra-filtration and reverse osmosis, and reused as desalted water. A wastewater reclaim plant is suggested from the result of this paper. It was believed that this study could provide references for construction of wastewater reclaim system in industrial parks of the world.

20.
Comput Biol Med ; 173: 108327, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552279

RESUMEN

Endometrial cancer (EC) is one of the most common malignant tumors in women, and the increasing incidence and mortality pose a serious threat to the public health. Early diagnosis of EC could prolong the survival period and optimize the survivorship, greatly alleviating patients' suffering and social medical pressure. In this study, we collected urine and serum samples from the recruited patients, analyzed the samples using LC-MS approach, and identified the differential metabolites through metabolomic analysis. Then, the differentially expressed genes were identified through the systematic transcriptomic analysis of EC-related dataset from Gene Expression Omnibus (GEO), followed by network profiling of metabolic-reaction-enzyme-gene. In this experiment, a total of 83 differential metabolites and 19 hub genes were discovered, of which 10 different metabolites and 3 hub genes were further evaluated as more potential biomarkers based on network analysis. According to the KEGG enrichment analysis, the potential biomarkers and gene-encoded proteins were found to be involved in the arginine and proline metabolism, histidine metabolism, and pyrimidine metabolism, which was of significance for the early diagnosis of EC. In particular, the combination of metabolites (histamine, 1-methylhistamine, and methylimidazole acetaldehyde) as well as the combination of RRM2, TYMS and TK1 exerted more accurate discrimination abilities between EC and healthy groups, providing more criteria for the early diagnosis of EC.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Endometriales , Humanos , Femenino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Detección Precoz del Cáncer , Biomarcadores , Metabolómica , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Perfilación de la Expresión Génica
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