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Progressive familial intrahepatic cholestasis (PFIC) is a rare childhood manifested disease associated with impaired bile secretion with severe pruritus yellow stool, and sometimes hepatosplenomegaly. PFIC is caused by mutations in ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, SLC51A, USP53, KIF12, ZFYVE19, and MYO5B genes depending on its type. ABCB11 mutations lead to PFIC2 that encodes the bile salt export pump (BSEP). Different mutations of ABCB11 have been reported in different population groups but no data available in Pakistani population being a consanguineous one. We sequenced coding exons of the ABCB11 gene along with its flanking regions in 66 unrelated Pakistani children along with parents with PFIC2 phenotype. We identified 20 variations of ABCB11: 12 in homozygous form, one compound heterozygous, and seven heterozygous. These variants include 11 missenses, two frameshifts, two nonsense mutations, and five splicing variants. Seven variants are novel candidate variants and are not detected in any of the 120 chromosomes from normal ethnically matched individuals. Insilico analysis revealed that four homozygous missense variations have high pathogenic scores. Minigene analysis of splicing variants showed exon skipping and the addition of exon. This data is a useful addition to the disease variants genomic database and would be used in the future to build a diagnostic algorithm.
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Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP , Colestasis Intrahepática , Humanos , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP/genética , Colestasis Intrahepática/genética , Pakistán , Masculino , Femenino , Niño , Preescolar , Lactante , Mutación , Exones/genética , Estudios de Cohortes , HomocigotoRESUMEN
Migratory birds play an important role in the cross-regional transmission of zoonotic pathogens. Assessing the presence of zoonotic pathogens carried by migratory birds is critical for disease control. However, information about Blastocystis infection in the migratory birds is very limited. Thus, we conducted this study with the aim to explore the occurrence, prevalence and subtyping of Blastocystis in four breeds of migratory birds in northeastern China. From October 2022 to April 2023, a total of 427 fresh fecal samples were obtained from four breeds of migratory birds in five nature reserves in northeastern China, and screened for Blastocystis by PCR amplification. Twenty-one (4.92 %) of the studied samples were confirmed Blastocystis-positive, and two known zoonotic subtypes ST6 and ST7 were founded, with ST7 being the major subtype. Until now, we firstly reported the infection status and subtyping of Blastocystis in the migratory Greater White-Fronted Goose, White Stork, Oriental White Stork and Bean Goose in China. More importantly, these findings present further data on the genetic diversity and transmission routes of Blastocystis and further arouse public health concerns about this organism.
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Liver fibrosis is a severe global health problem. However, no effective antifibrotic drugs have been approved. Surf4 is primarily located in the endoplasmic reticulum (ER) and mediates the transport of secreted proteins from the ER to the Golgi apparatus. Knockout of hepatic Surf4 (Surf4 LKO) in mice impairs very-low-density lipoprotein secretion without causing overt liver damage. Here, we found that collagen levels are significantly reduced in the liver of Surf4 LKO mice compared with control Surf4 flox mice, as demonstrated by proteomics, Western blot, and quantitative reverse transcription polymerase chain reaction. Therefore, this study aims to investigate whether and how hepatic Surf4 affects liver fibrosis. We observed that CCl4-induced liver fibrosis is significantly lower in Surf4 LKO mice than in Surf4 flox mice. Mechanistically, hepatic Surf4 deficiency reduces serum amyloid A1 (SAA1) secretion and hepatic stellate cell (HSC) activation. Surf4 coimmunoprecipitates and colocalizes with SAA1. Lack of hepatic Surf4 significantly reduces SAA1 secretion from hepatocytes, and SAA1 activates cultured human HSCs (LX-2 cells). Conditioned medium (CM) from Surf4-deficient primary hepatocytes activates LX-2 cells to a much lesser extent than CM from Surf4 flox primary hepatocytes, and this reduced effect is restored by the addition of recombinant SAA1 to CM from Surf4-deficient hepatocytes. Knockdown of SAA1 in primary hepatocytes or TLR2 in LX-2 cells significantly reduces LX-2 activation induced by CM from Surf4 flox hepatocytes but not from Surf4 LKO hepatocytes. Furthermore, knockdown of SAA1 significantly ameliorates liver fibrosis in Surf4 flox mice but does not further reduce liver fibrosis in Surf4 LKO mice. We also observe substantial expression of Surf4 and SAA1 in human fibrotic livers. Therefore, hepatic Surf4 facilitates SAA1 secretion, activates HSCs, and aggravates liver fibrosis, suggesting that hepatic Surf4 and SAA1 may serve as treatment targets for liver fibrosis.
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Cognition is crucial to brain function, and accurately classifying cognitive load is essential for understanding the psychological processes across tasks. This paper innovatively combines functional near-infrared spectroscopy (fNIRS) with eye tracking technology to delve into the classification of cognitive load at the neurocognitive level. This integration overcomes the limitations of a single modality, addressing challenges such as feature selection, high dimensionality, and insufficient sample capacity. We employ fNIRS-eye tracking technology to collect neural activity and eye tracking data during various cognitive tasks, followed by preprocessing. Using the maximum relevance minimum redundancy algorithm, we extract the most relevant features and evaluate their impact on the classification task. We evaluate the classification performance by building models (naive Bayes, support vector machine, K-nearest neighbors, and random forest) and employing cross-validation. The results demonstrate the effectiveness of fNIRS-eye tracking, the maximum relevance minimum redundancy algorithm, and machine learning techniques in discriminating cognitive load levels. This study emphasizes the impact of the number of features on performance, highlighting the need for an optimal feature set to improve accuracy. These findings advance our understanding of neuroscientific features related to cognitive load, propelling neural psychology research to deeper levels and holding significant implications for future cognitive science.
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INTRODUCTION: Abnormal placental cord insertions (APCIs) are significant risk factors for pregnancy complications, encompassing marginal cord insertion (MCI), velamentous cord insertion (VCI), and vasa previa (VP). While ultrasound is the primary imaging modality, its accuracy can be limited by factors such as maternal obesity and fetal positioning. Complementary to ultrasound, magnetic resonance imaging (MRI) offers a more precise visualization of the fetus, placenta, and umbilical cord relationships. This study aims to investigate the diagnostic value of prenatal magnetic resonance imaging (MRI) for APCIs compared with prenatal ultrasound. METHODS: We retrospectively collected data from 613 patients who underwent prenatal placental ultrasound and MRI. Of those who were confirmed as APCIs through surgery or pathology, the prenatal MRI features were compared with prenatal ultrasound. The diagnostic efficacy of prenatal MRI and ultrasound for APCIs was assessed based on the clinicopathological findings. RESULTS: Fifty-six patients were confirmed as APCIs by surgery or pathology, comprising 31 marginal cord insertions (MCIs), 18 velamentous cord insertions (VCIs), 5 vasa previa (VP) cases, and 2 VCI cases combined with VP. Ultrasound examination showed 55.36 % sensitivity (31/56) and 98.38 % specificity (486/494) in diagnosing APCIs, whereas MRI demonstrated 87.50 % sensitivity (49/56) and 98.88 % specificity (531/537). CONCLUSION: For APCIs complicated by placental location or morphological abnormalities, MRI demonstrates superior diagnostic efficacy compared to ultrasound in late pregnancy.
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Alpinia oxyphylla is famous for its neuroprotective and memory-improving effects. A crude polysaccharide AO70 from A. oxyphylla remarkably ameliorated neuroinflammation and cognitive dysfunction in Alzheimer's disease mice. This study aimed to explore the bioactive component of AO70 and its mechanism of action. A homogeneous polysaccharide (AOP70-1) rich in arabinose and xylose was purified from AO70, which was consisted of α-L-Araf-(1â, â5)-α-L-Araf-(1â, ß-D-Xylp-(1â,â2,4)-ß-D-Xylp-(1â, â2,3,4)-ß-D-Xylp-(1â, α-L-Rhap-(1â, α-D-Manp-(1â, â4)-α-D-Glcp-(1â, â4)-α-D-GlcpA-(1â, ß-D-Galp-(1â, â2)-α-D-Galp-(1â, â6)-α-D-Galp-(1 â and â3,6)-α-D-Manp-(1 â. AOP70-1 (2.5, 5, 10 µM) significantly suppressed NO, IL-1ß, and TNF-α production in a concentration-dependent manner and inhibited the migration of BV2 microglia. AOP70-1 inhibited LPS-mediated activation of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein (MyD88), and nuclear factor kappa B (NF-κB). Moreover, AOP70-1 exerted neuroprotection on SH-SY5Y cells and primary neurons by reducing neuronal apoptosis (72 %, 44 %), alleviating ROS accumulation (63 %, 55 %), and improving mitochondrial membrane potential (63 %, 77 %). Overall, AOP70-1 is one of the major bioactive components in AO70 from A. oxyphylla, which has great potential in the prevention and treatment of neuroinflammation.
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Vitamins, as indispensable organic compounds in life activities, demonstrate a complex and refined metabolic network in organisms. This network involves the coordination of multiple enzymes and the integration of various metabolic pathways. Despite the achievements in metabolic engineering and catalytic mechanism research, the lack of studies regarding detailed enzymatic properties for a large number of key enzymes limits the enhancement of vitamin production efficiency and hinders the in-depth understanding and optimization of vitamin synthesis mechanisms. Such limitations not only restrict the industrial application of vitamins but also impede the development of related bio-technologies. This study comprehensively reviews the research progress in the enzymes involved in vitamin biosynthesis and details the current status of research on the enzymes of 13 vitamin synthesis pathways, including their catalytic mechanisms, kinetic properties, and applications in biology. In addition, this study compares the properties of enzymes involved in vitamin metabolic pathways and the glycolysis pathway, and reveals the characteristics of catalytic efficiency and substrate affinity of enzymes in vitamin synthesis pathways. Furthermore, this study discusses the potential and prospects of applying deep learning methods to the research on properties of enzymes associated with vitamin biosynthesis, giving new insights into the production and optimization of vitamins.
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Redes y Vías Metabólicas , Vitaminas , Vitaminas/biosíntesis , Vitaminas/metabolismo , Vías Biosintéticas , Enzimas/metabolismo , Ingeniería Metabólica/métodos , GlucólisisRESUMEN
Transcription factor ELONGATED HYPOCOTYL5 (HY5) is the central hub for seedling photomorphogenesis. E3 ubiquitin (Ub) ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) inhibits HY5 protein accumulation through ubiquitination. However, the process of HY5 deubiquitination, which antagonizes E3 ligase-mediated ubiquitination to maintain HY5 homeostasis has never been studied. Here, we identified that Arabidopsis thaliana deubiquitinating enzyme, Ub-SPECIFIC PROTEASE 14 (UBP14) physically interacts with HY5 and enhances its protein stability by deubiquitination. The da3-1 mutant lacking UBP14 function exhibited a long hypocotyl phenotype, and UBP14 deficiency led to the failure of rapid accumulation of HY5 during dark to light. In addition, UBP14 preferred to stabilize nonphosphorylated form of HY5 which is more readily bound to downstream target genes. HY5 promoted the expression and protein accumulation of UBP14 for positive feedback to facilitate photomorphogenesis. Our findings thus established a mechanism by which UBP14 stabilizes HY5 protein by deubiquitination to promote photomorphogenesis in A. thaliana.
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Proteínas de Arabidopsis , Arabidopsis , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Regulación de la Expresión Génica de las Plantas , Ubiquitinación , Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Proteasas Ubiquitina-Específicas/metabolismo , Proteasas Ubiquitina-Específicas/genética , Estabilidad Proteica/efectos de la radiación , Luz , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Hipocótilo/crecimiento & desarrollo , Hipocótilo/metabolismo , Hipocótilo/genéticaRESUMEN
With the development of artificial intelligence systems, it is necessary to develop optoelectronic devices with photoresponse and storage capacity to simulate human visual perception systems. The key to an artificial visual perception system is to integrate components with both sensing and storage capabilities of illumination information. Although module integration components have made useful progress, they still face challenges such as multispectral response and high energy consumption. Here, we developed a light-adapted optoelectronic-memristive device integrated by an organic photodetector and ferroelectric-based memristor to simulate human visual perception. ITO/P3HT:PC71BM/Au as the light sensor unit shows a high on/off ratio (Iph/Id) reaching â¼5 × 104 at 0 V. The memristor unit, consisting of ITO/CBI@P(VDF-TrFE)/Cu, has a RON/ROFF ratio window of â¼106 under 0.05 V read voltage and ultralow power consumption of â¼1 pW. Moreover, the artificial visual perception unit shows stable light-adapted memory windows under different wavelengths of irradiation light (400, 500, and 600 nm; they meet the spectral range of human visual recognition) and can clearly identify the target image ("T" shape) because of the apparent contrast, which results from the high ROFF/RON ratio values. These results provide a potential design strategy for the development of intelligent artificial vision systems.
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Fluorescence flow cytometry is a powerful instrument to distinguish cells or particles labelled with high-specificity fluorophores. However, traditional flow cytometry is complex, bulky, and inconvenient for users to adjust fluorescence channels. In this paper, we present a modular fluorescence flow cytometry (M-FCM) system in which fluorescence channels can be flexibly arranged. Modules for particle focusing and fluorescence detection were developed. After hydrodynamical focusing, the cells were measured in the detection modules, which were integrated with in situ illumination and fluorescence detection. The signal-to-noise ratio of the detection reached to 33.2 dB. The crosstalk among the fluorescence channels was eliminated. The M-FCM system was applied to evaluate cell viability in drug screening, agreeing well with the commercial cytometry. The modular cytometry presents several outstanding features: flexibility in setting fluorescence channels, cost efficiency, compact construction, ease of operation, and the potential to upgrade for multifunctional measurements. The modular cytometry provides a multifunctional platform for various biophysical measurements, e.g., electrical impedance and refractive-index detection. The proposed work paves an innovative avenue for the multivariate analysis of cellular characteristics.
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Citometría de Flujo , Citometría de Flujo/métodos , Fluorescencia , Humanos , Colorantes Fluorescentes , Supervivencia Celular , Relación Señal-Ruido , Técnicas BiosensiblesRESUMEN
Scanning probe microscopy (SPM) has enabled significant new insights into the nanoscale and microscale properties of solar cell materials and underlying working principles of photovoltaic and optoelectronic technology. Various SPM modes, including atomic force microscopy, Kelvin probe force microscopy, conductive atomic force microscopy, piezoresponse force microscopy, and scanning near-field optical microscopy, can be used for the investigation of electrical, optical and chemical properties of associated functional materials. A large body of work has improved the understanding of solar cell device processing and synthesis in close synergy with SPM investigations in recent years. This review provides an overview of SPM measurement capabilities and attainable insight with a focus on recently widely investigated halide perovskite materials.
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The purple leaves of Brassica napus are abundant in anthocyanins, which are renowned for their role in conferring distinct colors, stress tolerance, and health benefits, however the genetic basis of this trait in B. napus remains largely unelucidated. Herein, the purple leaf B. napus (PL) exhibited purple pigments in the upper epidermis and a substantial increase in anthocyanin accumulation, particularly of cyanidin, compared to green leaf B. napus (GL). The genetic control of the purple leaf trait was attributed to a semi-dominant gene, pl, which was mapped to the end of chromosome A03. However, sequencing of the fragments amplified by the markers linked to pl indicated that they were all mapped to chromosome B05 from B. juncea. Within this B05 chromosomal segment, the BjMYB113 gene-specific marker showed perfect co-segregation with the purple leaf trait in the F2 population, suggesting that the BjMYB113 introgression from B. juncea was the candidate gene for the purple leaf trait in B. napus. To further verify the function of candidate gene, CRISPR/Cas9 was performed to knock out the BjMYB113 gene in PL. The three myb113 mutants exhibited evident green leaf phenotype, absence of purple pigments in the adaxial epidermis, and a significantly reduced accumulation of anthocyanin compared to PL. Additionally, the genes involved in positive regulatory (TT8), late anthocyanin biosynthesis (DFR, ANS, UFGT), as well as transport genes (TT19) were significantly suppressed in the myb113 mutants, further confirming that BjMYB113 was response for the anthocyanin accumulation in purple leaf B. napus. This study contributes to an advanced understanding of the regulation mechanism of anthocyanin accumulation in B. napus.
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Antocianinas , Brassica napus , Planta de la Mostaza , Pigmentación , Hojas de la Planta , Brassica napus/genética , Brassica napus/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Antocianinas/metabolismo , Planta de la Mostaza/genética , Planta de la Mostaza/metabolismo , Pigmentación/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fenotipo , Introgresión Genética , Genes de Plantas , Mapeo Cromosómico , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Investigating the self-sorting behaviour of assemblies with subtle structural differences is a captivating yet challenging endeavour. Herein, we elucidate the unusual self-sorting behaviour of metallacages with subtle structural differences in batch reactors and microdroplets. Narcissistic self-sorting of metallacages has been observed for two ligands with identical sizes, shapes, and symmetries, with only minor differences in the substituted groups. In particular, the self-sorting process in microdroplets occurs within 1 min at room temperature, in stark contrast to batch reactors, which require equilibration for 30 min. To reveal the mechanism of self-sorting and the role of microdroplets, we conducted a series of experiments and theoretical calculations, including competitive self-assembly, cage-to-cage transformation, control experiments involving model metallacages with larger cavities, noncovalent interaction analysis, and root mean square deviation (RMSD) analysis. This research demonstrates an unusual case of self-sorting of very similar assemblies and provides a new strategy for facilitating the self-sorting efficiency of supramolecular systems.
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The control of a molecule's geometry, chirality, and physical properties has long been a challenging pursuit. Our study introduces a dependable method for assembling D3-symmetric trigonal bipyramidal coordination cages. Specifically, D2h-symmetric anions, like oxalate and chloranilic anions, self-organize around a metal ion to form chiral-at-metal anionic complexes, which template the formation of D3-symmetric trigonal bipyramidal coordination cages. The chirality of the trigonal bipyramid is determined by the point chirality of chiral amines used in forming the ligands. Additionally, these cages exhibit chiral selectivity for the included chiral-at-metal anionic template. Our method is broadly applicable to various ligand systems, enabling the construction of larger cages when larger D2h-symmetric anions, like chloranilic anions, are employed. Furthermore, we successfully produce enantiopure trigonal bipyramidal cages with anthracene-containing backbones using this approach, which would be otherwise infeasible. These cages exhibit circularly polarized luminescence, which is modulable through the reversible photo-oxygenation of the anthracenes.
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Lipophilic compounds have a variety of positive effects on human physiological functions and exhibit good effects in the prevention and treatment of clinical diseases. This has led to significant interest in the technical applications of synthetic biology for the production of lipophilic compounds. However, the strict selective permeability of the cell membrane and the hydrophobic nature of lipophilic compounds pose significant challenges to their production. During fermentation, lipophilic compounds tend to accumulate within cell membrane compartments rather than being secreted extracellularly. The toxic effects of excessive lipophilic compound accumulation can threaten cell viability, while the limited space within the cell membrane restricts further increases in production yield. Consequently, to achieve efficient production of lipophilic compounds, research is increasingly focused on constructing robust and multifunctional microbial cell factories. Utilizing membrane engineering techniques to construct highly flexible cell membranes is considered an effective strategy to break through the upper limit of lipophilic compound production. Currently, there are two main approaches to cell membrane modification: constructing artificial storage compartments for lipophilic compounds and engineering the cell membrane structure to facilitate product outflow. This review summarizes recent cell membrane engineering strategies applied in microbial cell factories for the production of liposoluble compounds, discussing the challenges and future prospects. These strategies enhance membrane flexibility and effectively promote the production of liposoluble compounds.
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The coarctation of the aorta (CoA) combined with heart defects or cerebral artery aneurysms is more prevalent in clinical practice. However, cases of concurrent bilateral iliac artery dissection (IAD) are extremely rare and have not been reported. Here, we described a case with CoA combined with bilateral IAD. The patient, a 62-year-old male, presented with acute intermittent claudication accompanied by pain and aching in both lower limbs after walking. Following a thorough medical history inquiry and examination, the patient was diagnosed with acute bilateral IAD combined with CoA. The patient underwent endovascular treatment. Postoperatively, the aortic diameter recovered, and the bilateral IAD disappeared, yielding satisfactory therapeutic results. Conclusively, endovascular treatment of aortic coarctation combined with IAD is an effective therapeutic approach, enhancing patient survival and improving their quality of life.
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Coartación Aórtica , Disección Aórtica , Procedimientos Endovasculares , Humanos , Masculino , Persona de Mediana Edad , Disección Aórtica/complicaciones , Disección Aórtica/diagnóstico , Disección Aórtica/cirugía , Procedimientos Endovasculares/métodos , Coartación Aórtica/complicaciones , Coartación Aórtica/cirugía , Coartación Aórtica/diagnóstico , Arteria Ilíaca , Aneurisma Ilíaco/complicaciones , Aneurisma Ilíaco/cirugía , Aneurisma Ilíaco/diagnóstico , Claudicación Intermitente/etiología , Claudicación Intermitente/diagnóstico , Resultado del Tratamiento , Calidad de VidaRESUMEN
Home testing technology strategy is critical for early screening of disease. However, current home testing technologies often require complex processes, which limits their application. In this study, a time-resolved cascade logic gate microfluidic chip (TCLMC) was revealed to enable capillary force-based one-step operation without manual intervention or professional equipment. By analogy with logic gates in the circuit, TCLMC could automatically control the fluid flow and regulate the incubation time to optimize the immunoassay. The limit of detection of TCLMC for SARS-CoV-2 and influenza B virus (Flu B) was 134.94 and 79.17 pg mL-1 within 10 min. Additionally, this study tested saliva samples from 12 Flu B patients and 24 healthy controls to verify its clinical application. The results showed that TCLMC had high sensitivity (100%), specificity (100%), and accuracy (100%). This study provides a new one-step strategy for home testing and demonstrates its great potential in the diagnosis field.
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Técnicas Biosensibles , COVID-19 , Virus de la Influenza B , Gripe Humana , Dispositivos Laboratorio en un Chip , SARS-CoV-2 , Humanos , SARS-CoV-2/aislamiento & purificación , COVID-19/diagnóstico , COVID-19/virología , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Gripe Humana/diagnóstico , Gripe Humana/virología , Virus de la Influenza B/aislamiento & purificación , Saliva/virología , Saliva/química , Diseño de Equipo , Inmunoensayo/instrumentación , Inmunoensayo/métodos , Límite de Detección , Técnicas Analíticas Microfluídicas/instrumentaciónRESUMEN
While the empathizing-systemizing (E-S) theory provides a valuable framework for explaining gender differences in STEM majors, previous studies suffer from methodological issues (i.e., the arbitrary cut-off criteria and WEIRD sampling) as well as discrepancies in the behavioral correlates of E-S types. To address the gaps, this study utilized a 3-step latent profile analysis to identify naturally occurring E-S profiles in a Chinese sample and explored the predictors and distal outcomes of the identified profiles. The study recruited 785 (aged 18-25 years, 60% female) Chinese undergraduates. Results revealed five E-S profiles: Disengaged, Empathizers, Navigating systemizers, Technological systemizers, and Self-declared allrounders. Controlling for socioeconomic status, being male predicted a higher likelihood of membership into the Technological systemizers. Besides, membership to the Navigating systemizers and Technological systemizers was associated with better intuitive physics performance. However, no significant variation was observed for social sensitivity performance across E-S profiles. Overall, our results partially conformed to previous findings, highlighting the importance of cultural adaptation and methodological considerations when classifying students' cognitive types.
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Although rapid progression and a poor prognosis in influenza A virus (IAV) infection-induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are frequently associated with metabolic energy disorders, the underlying mechanisms and rescue strategies remain unknown. We herein demonstrated that the level of resting energy expenditure increased significantly in IAV-induced AECOPD patients and that cellular energy exhaustion emerged earlier and more significantly in IAV-infected primary COPD bronchial epithelial (pDHBE) cells. The differentially expressed genes were enriched in the oxidative phosphorylation (OXPHOS) pathway; additionally, we consistently uncovered much earlier ATP exhaustion, more severe mitochondrial structural destruction and dysfunction, and OXPHOS impairment in IAV-inoculated pDHBE cells, and these changes were rescued by melatonin. The level of OMA1-dependent cleavage of OPA1 in the mitochondrial inner membrane and the shift in energy metabolism from OXPHOS to glycolysis were significantly increased in IAV-infected pDHBE cells; however, these changes were rescued by OMA1-siRNA or melatonin further treatment. Collectively, our data revealed that melatonin rescued IAV-induced cellular energy exhaustion via OMA1-OPA1-S to improve the clinical prognosis in COPD. This treatment may serve as a potential therapeutic agent for patients in which AECOPD is induced by IAV.
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Metabolismo Energético , GTP Fosfohidrolasas , Virus de la Influenza A , Melatonina , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Metabolismo Energético/efectos de los fármacos , GTP Fosfohidrolasas/metabolismo , GTP Fosfohidrolasas/genética , Virus de la Influenza A/efectos de los fármacos , Gripe Humana/metabolismo , Gripe Humana/tratamiento farmacológico , Melatonina/farmacología , Metaloendopeptidasas , Fosforilación Oxidativa/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológicoRESUMEN
Pathogenic microorganisms play a crucial role in the global disease burden due to their ability to cause various diseases and spread through multiple transmission routes. Immunity tests identify antigens related to these pathogens, thereby confirming past infections and monitoring the host's immune response. Traditional pathogen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and chemiluminescent immunoassays (CLIAs), are often labor-intensive, slow, and reliant on sophisticated equipment and skilled personnel, which can be limiting in resource-poor settings. In contrast, the development of microfluidic technologies presents a promising alternative, offering automation, miniaturization, and cost efficiency. These advanced methods are poised to replace traditional assays by streamlining processes and enabling rapid, high-throughput immunity testing for pathogens. This review highlights the latest advancements in microfluidic systems designed for rapid and high-throughput immunity testing, incorporating immunosensors, single molecule arrays (Simoas), a lateral flow assay (LFA), and smartphone integration. It focuses on key pathogenic microorganisms such as SARS-CoV-2, influenza, and the ZIKA virus (ZIKV). Additionally, the review discusses the challenges, commercialization prospects, and future directions to advance microfluidic systems for infectious disease detection.