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1.
Nat Immunol ; 24(9): 1443-1457, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37563309

RESUMEN

Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages. Whether TRMs and monocyte-derived macrophages have district roles under differing pathologies is not understood. Here, we showed that a substantial portion of the macrophages that accumulated during pancreatitis and pancreatic cancer in mice had expanded from TRMs. Pancreas TRMs had an extracellular matrix remodeling phenotype that was important for maintaining tissue homeostasis during inflammation. Loss of TRMs led to exacerbation of severe pancreatitis and death, due to impaired acinar cell survival and recovery. During pancreatitis, TRMs elicited protective effects by triggering the accumulation and activation of fibroblasts, which was necessary for initiating fibrosis as a wound healing response. The same TRM-driven fibrosis, however, drove pancreas cancer pathogenesis and progression. Together, these findings indicate that TRMs play divergent roles in the pathogenesis of pancreatitis and cancer through regulation of stromagenesis.


Asunto(s)
Páncreas , Pancreatitis , Ratones , Animales , Páncreas/patología , Macrófagos , Pancreatitis/genética , Pancreatitis/patología , Fibrosis , Neoplasias Pancreáticas
2.
Nature ; 619(7971): 743-748, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37495879

RESUMEN

Machine perception uses advanced sensors to collect information about the surrounding scene for situational awareness1-7. State-of-the-art machine perception8 using active sonar, radar and LiDAR to enhance camera vision9 faces difficulties when the number of intelligent agents scales up10,11. Exploiting omnipresent heat signal could be a new frontier for scalable perception. However, objects and their environment constantly emit and scatter thermal radiation, leading to textureless images famously known as the 'ghosting effect'12. Thermal vision thus has no specificity limited by information loss, whereas thermal ranging-crucial for navigation-has been elusive even when combined with artificial intelligence (AI)13. Here we propose and experimentally demonstrate heat-assisted detection and ranging (HADAR) overcoming this open challenge of ghosting and benchmark it against AI-enhanced thermal sensing. HADAR not only sees texture and depth through the darkness as if it were day but also perceives decluttered physical attributes beyond RGB or thermal vision, paving the way to fully passive and physics-aware machine perception. We develop HADAR estimation theory and address its photonic shot-noise limits depicting information-theoretic bounds to HADAR-based AI performance. HADAR ranging at night beats thermal ranging and shows an accuracy comparable with RGB stereovision in daylight. Our automated HADAR thermography reaches the Cramér-Rao bound on temperature accuracy, beating existing thermography techniques. Our work leads to a disruptive technology that can accelerate the Fourth Industrial Revolution (Industry 4.0)14 with HADAR-based autonomous navigation and human-robot social interactions.

3.
Nat Immunol ; 16(11): 1124-33, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26414766

RESUMEN

Subsets of innate lymphoid cells (ILCs) reside in the mucosa and regulate immune responses to external pathogens. While ILCs can be phenotypically classified into ILC1, ILC2 and ILC3 subsets, the transcriptional control of commitment to each ILC lineage is incompletely understood. Here we report that the transcription factor Runx3 was essential for the normal development of ILC1 and ILC3 cells but not of ILC2 cells. Runx3 controlled the survival of ILC1 cells but not of ILC3 cells. Runx3 was required for expression of the transcription factor RORγt and its downstream target, the transcription factor AHR, in ILC3 cells. The absence of Runx3 in ILCs exacerbated infection with Citrobacter rodentium. Therefore, our data establish Runx3 as a key transcription factor in the lineage-specific differentiation of ILC1 and ILC3 cells.


Asunto(s)
Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Inmunidad Innata , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Animales , Antígenos Ly/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Diferenciación Celular/inmunología , Linaje de la Célula/inmunología , Citrobacter rodentium/inmunología , Citrobacter rodentium/patogenicidad , Subunidad alfa 3 del Factor de Unión al Sitio Principal/deficiencia , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Subunidad beta del Factor de Unión al Sitio Principal/deficiencia , Subunidad beta del Factor de Unión al Sitio Principal/genética , Subunidad beta del Factor de Unión al Sitio Principal/metabolismo , Infecciones por Enterobacteriaceae/etiología , Infecciones por Enterobacteriaceae/inmunología , Subunidad alfa del Receptor de Interleucina-7/metabolismo , Mucosa Intestinal/citología , Mucosa Intestinal/inmunología , Subgrupos Linfocitarios/citología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor 1 Gatillante de la Citotoxidad Natural/metabolismo , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/deficiencia , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo
4.
Hum Mol Genet ; 32(1): 122-138, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35925866

RESUMEN

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive retinal degenerative disease characterized by yellow-white crystal deposits in the posterior pole, degeneration of the retinal pigment epithelium (RPE), and sclerosis of the choroid. Mutations in the cytochrome P450 4V2 gene (CYP4V2) cause BCD, which is associated with lipid metabolic disruption. The use of gene-replacement therapy in BCD has been hampered by the lack of disease models. To advance CYP4V2 gene-replacement therapy, we generated BCD patient-specific induced pluripotent stem cell (iPSC)-RPE cells and Cyp4v3 knockout (KO) mice as disease models and AAV2/8-CAG-CYP4V2 as treatment vectors. We demonstrated that after adeno-associated virus (AAV)-mediated CYP4V2 gene-replacement therapy BCD-iPSC-RPE cells presented restored cell survival and reduced lipid droplets accumulation; restoration of vision in Cyp4v3 KO mice was revealed by elevated electroretinogram amplitude and ameliorated RPE degeneration. These results suggest that AAV-mediated gene-replacement therapy in BCD patients is a promising strategy.


Asunto(s)
Distrofias Hereditarias de la Córnea , Células Madre Pluripotentes Inducidas , Degeneración Retiniana , Enfermedades de la Retina , Animales , Ratones , Distrofias Hereditarias de la Córnea/genética , Sistema Enzimático del Citocromo P-450/genética , Familia 4 del Citocromo P450/genética , Familia 4 del Citocromo P450/metabolismo , Dependovirus/genética , Dependovirus/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Mutación , Degeneración Retiniana/genética , Degeneración Retiniana/terapia , Enfermedades de la Retina/genética , Humanos
5.
Hum Genet ; 143(2): 197-210, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38282009

RESUMEN

The purpose of this study was to screen Copy Number Variations (CNVs) in 35 unsolved Inherited Retinal Dystrophy (IRD) families. Initially, next generation sequencing, including a specific Hereditary Eye Disease Enrichment Panel or Whole exome sequencing, was employed to screen (likely) pathogenic Single-nucleotide Variants (SNVs) and small Insertions and Deletions (indels) for these cases. All available SNVs and indels were further validated and co-segregation analyses were performed in available family members by Sanger sequencing. If not, after excluding deep intronic variants, Multiplex ligation-dependent probe amplification (MLPA), quantitative fluorescence PCR (QF-PCR) and Sanger sequencing were employed to screen CNVs. We determined that 18 probands who had heterozygous SNVs/indels or whose parents were not consanguineous but had homozygous SNVs/indels in autosomal recessive IRDs genes had CNVs in another allele of these genes, 11 families had disease-causing hemizygous CNVs in X-linked IRD genes, 6 families had (likely) pathogenic heterozygous CNVs in PRPF31 gene. Of 35 families, 33 different CNVs in 16 IRD-associated genes were detected, with PRPF31, EYS and USH2A the most common disease-causing gene in CNVs. Twenty-six and 7 of them were deletion and duplication CNVs, respectively. Among them, 14 CNVs were first reported in this study. Our research indicates that CNVs contribute a lot to IRDs, and screening of CNVs substantially increases the diagnostic rate of IRD. Our results emphasize that MLPA and QF-PCR are ideal methods to validate CNVs, and the novel CNVs reported herein expand the mutational spectrums of IRDs.


Asunto(s)
Distrofias Retinianas , Síndromes de Usher , Humanos , Variaciones en el Número de Copia de ADN , Mutación , Heterocigoto , Proteínas del Ojo/genética
6.
Biochem Biophys Res Commun ; 708: 149810, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38531222

RESUMEN

At present, the physiological roles of various hormones in fish glucose metabolism have been elucidated. Spexin, a 14-amino acids polypeptide, is highly conserved in many species and has functions such as reducing body weight and improving insulin resistance. In this paper, the open reading frame (ORF) of spx21 in grass carp (Ctenopharyngodon idella) was cloned, and the tissue distribution of spx1 and spx2, their direct and indirect regulatory effects on glucose metabolism of grass carp were investigated. The ORF of spx2 gene in grass carp was 279 bp in length. Moreover, spx1 was highly expressed in the adipose tissue, while spx2 was highly expressed in the brain. In vitro, SPX1 and SPX2 showed opposite effects on the glycolytic pathway in the primary hepatocytes. In vivo, intraperitoneal injection of SPX1 and SPX2 significantly reduced serum glucose levels and increased hepatopancreas glycogen contents. Meanwhile, SPX1 and SPX2 promoted the expression of key genes of glycolysis (pk) and glycogen synthesis (gys) in the hepatopancreas at 3 h post injection. As for indirect effects, 1000 nM SPX1 and SPX2 significantly increased insulin-mediated liver type phosphofructokinase (pfkla) mRNA expression and enhanced the inhibitory effects of insulin on glucose-6-phosphatase (g6pase), phosphoenolpyruvate carboxykinase (pepck), glycogen phosphorylase L (pygl) mRNA expression. Our results show that SPX1 and SPX2 have similar indirect effects on the regulation of glucose metabolism that enhance insulin activity, but they exhibit opposite roles in terms of direct effects.


Asunto(s)
Carpas , Glucosa , Animales , Glucosa/metabolismo , Carpas/metabolismo , Insulina , ARN Mensajero/genética , Glucógeno , Proteínas de Peces/genética , Proteínas de Peces/metabolismo
7.
J Virol ; 97(5): e0165822, 2023 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-37071015

RESUMEN

Japanese encephalitis virus (JEV), with neurotoxic and neuroinvasive properties, is the major cause of human viral encephalitis in Asia. Although Guillain-Barré syndrome caused by JEV infections is not frequent, a few cases have been reported in recent years. To date, no existing animal model for JEV-induced peripheral nerve injury (PNI) has been established, and thus the pathogenic mechanism is not clarified. Therefore, an animal model is urgently required to clarify the correlation between JEV infection and PNI. In the present study, we used JEV GIb strain of NX1889 to establish a mouse model of JEV infection. The general neurological signs emerged on day 3 of modeling. The motor function continued to deteriorate, reaching a maximum at 8 to 13 days postinfection (dpi) and gradually recovered after 16 dpi. The injuries of 105 PFU and 106 PFU groups were the most severe. Transmission electron microscopy and immunofluorescence staining showed varying degrees of demyelination and axonal degeneration in the sciatic nerves. The electrophysiological recordings demonstrated the presence of demyelinating peripheral neuropathy with reduced nerve conduction velocity. The decreased amplitudes and the prolonged end latency revealed axonal-type motor neuropathy. Demyelination is predominant in the early stage, followed by axonal injury. The expression level of JEV-E protein and viral RNA was elevated in the injured sciatic nerves, suggesting that it may cause PNI at the early stage. Inflammatory cell infiltration and increased inflammatory cytokines indicated that neuroinflammation is involved in JEV-induced PNI. IMPORTANCE JEV is a neurotropic flavivirus belonging to the Flaviviridae family and causes high mortality and disability rates. It invades the central nervous system and induces acute inflammatory injury and neuronal death. Thus, JEV infection is a major global public health concern. Previously, motor dysfunction was mainly attributed to central nervous system damage. Our knowledge regarding JEV-induced PNI is vague and neglected. Therefore, a laboratory animal model is essential. Herein, we showed that C57BL/6 mice can be used to study JEV-induced PNI through multiple approaches. We also demonstrated that viral loads might be positively correlated with lesion severity. Therefore, inflammation and direct virus infection may be the putative mechanisms underlying JEV-induced PNI. The results of this study laid the foundation for further elucidation of the pathogenesis mechanisms of PNI caused by JEV.


Asunto(s)
Modelos Animales de Enfermedad , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Traumatismos de los Nervios Periféricos , Animales , Humanos , Ratones , Enfermedades Desmielinizantes , Virus de la Encefalitis Japonesa (Especie)/fisiología , Ratones Endogámicos C57BL
8.
Bioconjug Chem ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023912

RESUMEN

Photoredox is a powerful synthetic tool in organic chemistry and has been widely used in various fields, including nuclear medicine and molecular imaging. In particular, acridinium-based organophotoredox radiolabeling has significantly impacted the production and discovery of positron emission tomography (PET) agents. Despite their extensive use in preclinical research, no PET agents synthesized by acridinium photoredox labeling have been tested in humans. [18F]FDOPA is clinically used for tumor diagnosis and the evaluation of neuropsychiatric disorders, but its application is limited by complex synthesis methods, the need for expensive modules, and/or the high cost of consumable materials/cassettes. In this report, we integrated a photoredox labeling unit with an automated module and produced [18F]FDOPA for human study. This research not only represents the first human study of a PET agent generated by acridinium-based organophotoredox reactions but also demonstrates the safety of this novel labeling method, serving as a milestone/reference for the clinical translation of other PET agents generated by this technique in the future.

9.
BMC Cancer ; 24(1): 670, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824514

RESUMEN

BACKGROUND: An accurate and non-invasive approach is urgently needed to distinguish tuberculosis granulomas from lung adenocarcinomas. This study aimed to develop and validate a nomogram based on contrast enhanced-compute tomography (CE-CT) to preoperatively differentiate tuberculosis granuloma from lung adenocarcinoma appearing as solitary pulmonary solid nodules (SPSN). METHODS: This retrospective study analyzed 143 patients with lung adenocarcinoma (mean age: 62.4 ± 6.5 years; 54.5% female) and 137 patients with tuberculosis granulomas (mean age: 54.7 ± 8.2 years; 29.2% female) from two centers between March 2015 and June 2020. The training and internal validation cohorts included 161 and 69 patients (7:3 ratio) from center No.1, respectively. The external testing cohort included 50 patients from center No.2. Clinical factors and conventional radiological characteristics were analyzed to build independent predictors. Radiomics features were extracted from each CT-volume of interest (VOI). Feature selection was performed using univariate and multivariate logistic regression analysis, as well as the least absolute shrinkage and selection operator (LASSO) method. A clinical model was constructed with clinical factors and radiological findings. Individualized radiomics nomograms incorporating clinical data and radiomics signature were established to validate the clinical usefulness. The diagnostic performance was assessed using the receiver operating characteristic (ROC) curve analysis with the area under the receiver operating characteristic curve (AUC). RESULTS: One clinical factor (CA125), one radiological characteristic (enhanced-CT value) and nine radiomics features were found to be independent predictors, which were used to establish the radiomics nomogram. The nomogram demonstrated better diagnostic efficacy than any single model, with respective AUC, accuracy, sensitivity, and specificity of 0.903, 0.857, 0.901, and 0.807 in the training cohort; 0.933, 0.884, 0.893, and 0.892 in the internal validation cohort; 0.914, 0.800, 0.937, and 0.735 in the external test cohort. The calibration curve showed a good agreement between prediction probability and actual clinical findings. CONCLUSION: The nomogram incorporating clinical factors, radiological characteristics and radiomics signature provides additional value in distinguishing tuberculosis granuloma from lung adenocarcinoma in patients with a SPSN, potentially serving as a robust diagnostic strategy in clinical practice.


Asunto(s)
Adenocarcinoma del Pulmón , Granuloma , Neoplasias Pulmonares , Nomogramas , Tomografía Computarizada por Rayos X , Humanos , Femenino , Persona de Mediana Edad , Masculino , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Diagnóstico Diferencial , Granuloma/diagnóstico por imagen , Granuloma/patología , Anciano , Tuberculosis Pulmonar/diagnóstico por imagen , Periodo Preoperatorio , Radiómica
10.
Hematol Oncol ; 42(1): e3224, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37712442

RESUMEN

Myelodysplastic syndromes (MDS) patients often experience CD8+ T lymphocytes exhaustion, which plays a crucial role in the development of MDS. However, the specific role of thymocyte selection-associated high mobility box protein (TOX) in the CD8+ T lymphocytes exhaustion in MDS patients remains unclear. In this study, we investigated the role of TOX in CD8+ T lymphocytes exhaustion in patients with MDS. The expression of TOX, inhibitory receptors (IRs), and functional molecules in peripheral blood T lymphocytes of MDS patients and normal controls were detected using flow cytometry. Lentiviral transduction was used to create stable TOX-knockdown CD8+ T lymphocytes, and small interfering RNA (si-RNA) was used to knock down TOX in Jurkat cells. The expression of TOX was found to be significantly higher in CD8+ T lymphocytes of MDS patients compared to normal controls. This was associated with upregulated IRs and reduced expression of functional molecules such as Granzyme and Perforin. Myelodysplastic syndromes patients with higher TOX expression had poor clinical indicators and shorter survival. Knockdown of TOX using sh-RNA partially reverses the exhausted phenotype and enhances the lethality of CD8+ T lymphocytes. Moreover, the knockdown of TOX using si-RNA in Jurkat cells improved cell proliferation activity, down-regulated IRs and activated PI3K/AKT/mTOR signaling pathway. TOX promotes the exhaustion of CD8+ T lymphocytes by inhibiting PI3K/AKT/mTOR pathway, and targeted inhibition of TOX could partially restore the effector functions and activity of CD8+ T lymphocytes.


Asunto(s)
Síndromes Mielodisplásicos , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Linfocitos T CD8-positivos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Timocitos/metabolismo , Serina-Treonina Quinasas TOR , ARN/metabolismo
11.
Cell Commun Signal ; 22(1): 114, 2024 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347622

RESUMEN

Sirtuins, which are NAD+-dependent class III histone deacetylases, are involved in various biological processes, including DNA damage repair, immune inflammation, oxidative stress, mitochondrial homeostasis, autophagy, and apoptosis. Sirtuins are essential regulators of cellular function and organismal health. Increasing evidence suggests that the development of age-related diseases, including kidney diseases, is associated with aberrant expression of sirtuins, and that regulation of sirtuins expression and activity can effectively improve kidney function and delay the progression of kidney disease. In this review, we summarise current studies highlighting the role of sirtuins in renal diseases. First, we discuss sirtuin family members and their main mechanisms of action. We then outline the possible roles of sirtuins in various cell types in kidney diseases. Finally, we summarise the compounds that activate or inhibit sirtuin activity and that consequently ameliorate renal diseases. In conclusion, targeted modulation of sirtuins is a potential therapeutic strategy for kidney diseases. Video Abstract.


Asunto(s)
Enfermedades Renales , Sirtuinas , Humanos , Sirtuinas/metabolismo , Enfermedades Renales/tratamiento farmacológico , Estrés Oxidativo , Reparación del ADN
12.
Am J Hematol ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980207

RESUMEN

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

13.
Fish Shellfish Immunol ; 144: 109289, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38104699

RESUMEN

High-carbohydrate (HC) diets may lead to the deterioration of the antioxidant and immune properties of Yellow River carp and the healthy development of the industry. Studies in mammals have found that sea buckthorn flavonoids (SF) improve antioxidant and immune performance. Therefore, this study comprehensively evaluated the effects of SF on Yellow River carp using in vitro and feeding trials with an HC diet. Control (C, 27.23 %), high-carbohydrate (HC, 42.99 %), and HC + SF (0.1 %, 0.2 %, and 0.4 %) groups were studied in a 10-week aquaculture experiment. The main findings were as follows: (1) SF scavenged O2·-, ·OH, and DPPH free radicals in vitro, which gradually increased with the SF concentration. (2) The antioxidant and immune performance of Yellow River carp was enhanced by dietary supplementation with SF, which involved the regulation of activities of antioxidant and immune enzymes, as well as their changes at the transcription and protein levels. In terms of antioxidant properties, compared to the HC group, HC + SF significantly decreased the activities of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase and the contents of H2O2 and malondialdehyde in the serum and hepatopancreas. The activities of glutathione, glutathione-Px, superoxide dismutase, catalase, and total antioxidant activity in the HC-diet group. In contrast, the addition of SF increased antioxidant enzyme activity. In the hepatopancreas and muscles, SF regulated and activated Nrf2-Keap1, a key signaling pathway for oxidative stress. SF significantly increased the mRNA expression levels of downstream genes (gr, ho-1, cat, and sod) regulated by nrf2. In terms of immune performance, 0.4 % SF markedly increased the activity of immune-related enzymes. SF inhibited the gene expression of pro-inflammatory factors induced by the HC diet and promoted the gene expression of anti-inflammatory factors. In addition, the resistance of Yellow River carp to Aeromonas hydrophila was enhanced by SF. In summary, SF supplementation can reduce oxidative stress and inflammatory harm caused by the HC diet and improve the antioxidant and immune performance of Yellow River carp to varying degrees.


Asunto(s)
Carpas , Hippophae , Animales , Antioxidantes/metabolismo , Carpas/metabolismo , Suplementos Dietéticos , Hippophae/metabolismo , Dieta/veterinaria , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Peróxido de Hidrógeno/metabolismo , Glutatión/metabolismo , Carbohidratos , Alimentación Animal/análisis , Mamíferos/metabolismo
14.
J Fluoresc ; 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38520620

RESUMEN

We designed and synthesized a new Schiff base probe, which incorporated the salicylaldehyde-analogue α-cyanostilbene and benzophenone hydrazone by the imine linkage. Its chemical structure was verified by FT-IR, MALDI-TOF-MS, HR-MS and 1H/13C NMR technologies. It could exhibit a red fluorescence based on the synergistical effects of aggregation-induce emission (AIE), excited-state intramolecular proton transfer (ESIPT) and twisted intramolecular charge-transfer (TICT) in the aggregation or solid states. Interestingly, the TLC-based test strip loaded with the target compound showed the reversible fluorescence response to amine/acid vapor and on-site visual fluorescence quenching response to Fe3+. In THF/water mixtures (fw = 90%, 10 µM, pH = 7.4), the detection limit (DL) and the binding constant (Ka) of the developed probe towards Fe3+ were evaluated as 5.50 × 10- 8 M and 1.69 × 105, respectively. The developed probe was successfully applied for the detection of Fe3+ with practical, reliable, and satisfying results.

15.
Macromol Rapid Commun ; 45(12): e2300715, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38539063

RESUMEN

The raw materials of Poly(ethylene terephthalate) (PET) are derived from petroleum-based resources, which are no sustainable. Therefore, previous researchers introduced biomass-derived 2,5-tetrahydrofurfuryl dimethanol (THFDM) into PET. However, its heat resistance has decreased compared to PET. In this paper, a novel bio-based copolyester, poly(ethylene glycol-co-2,5-tetrahydrofuran dimethanol-co-isosorbide terephthalate) (PEIFT), is prepared by introducing biomass-derived isosorbide (ISB) and THFDM into the PET chains through melting copolymerization process. With the introduction of ISB content, copolyesters' hydrophilicity and rigidity improve. Compared to PET, glass transition temperature (Tg) increases by over 5 °C. In addition, the toughness and spinning performance of PEIFT have also been improved as a result of the addition of THFDM components. The hydrophobicity of PEIFTs electrospinning is greatly improved, with a contact angle exceeding 135°. Finally, due to the good hydrophobicity of PEIFTs nanofibers, they have potential application value in the manufacture of hydrophobic nanofiber and filter films. Given its biomass source and excellent performance, they make it easier to replace materials derived from petroleum.


Asunto(s)
Interacciones Hidrofóbicas e Hidrofílicas , Nanofibras , Poliésteres , Nanofibras/química , Poliésteres/química , Poliésteres/síntesis química , Isosorbida/química , Biomasa , Tereftalatos Polietilenos/química , Furanos/química
16.
J Med Genet ; 60(7): 655-661, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36446583

RESUMEN

BACKGROUND: Diagnosis of a genetic disease and determination of the causative molecular lesion rely on the availability of the disease-associated pedigrees. Microphthalmia is a congenital eye defect due to an insufficiently developed visual system; its prevalence is 1-3 in 10 000 live births. OBJECTIVE: We analysed a pedigree exhibiting autosomal dominant inheritance of microphthalmia to determine the genetic lesion; used AlphaFold2 to predict the changes in the protein's 3-Dimensional structure; and compared wild-type and variant proteins in cultured cells or Drosophila model was used to explore the cellular or developmental function of the encoded product. RESULTS: We identified a novel missense variation, F52L, in MAB21L1 that is absent in population databases and present exclusively in the individuals diagnosed with microphthalmia in this pedigree. Common structural changes were predicted for the disease-associated variants clustered at amino acids 49-52, and these variant products were also predominantly trapped in the cytoplasm of cultured human lens epithelia. To recapitulate its dominant effect in development, we expressed the Drosophila homologue corresponding to MAB21L1F52L and caused malformation of sensory organs. CONCLUSION: Mutations at the residues 49-52 of MAB21L1 compromise eye development. We recommend including MAB21L1 in the genetic testing panel for congenital eye disorders.


Asunto(s)
Anomalías del Ojo , Microftalmía , Humanos , Microftalmía/genética , Aminoácidos/genética , Pruebas Genéticas , Anomalías del Ojo/genética , Mutación , Linaje , Proteínas de Homeodominio/genética
17.
BMC Med Imaging ; 24(1): 197, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090610

RESUMEN

BACKGROUND: This study was designed to develop a combined radiomics nomogram to preoperatively predict the risk categorization of thymomas based on contrast-enhanced computed tomography (CE-CT) images. MATERIALS: The clinical and CT data of 178 patients with thymoma (100 patients with low-risk thymomas and 78 patients with high-risk thymomas) collected in our hospital from March 2018 to July 2023 were retrospectively analyzed. The patients were randomly divided into a training set (n = 125) and a validation set (n = 53) in a 7:3 ratio. Qualitative radiological features were recorded, including (a) tumor diameter, (b) location, (c) shape, (d) capsule integrity, (e) calcification, (f) necrosis, (g) fatty infiltration, (h) lymphadenopathy, and (i) enhanced CT value. Radiomics features were extracted from each CE-CT volume of interest (VOI), and the least absolute shrinkage and selection operator (LASSO) algorithm was performed to select the optimal discriminative ones. A combined radiomics nomogram was further established based on the clinical factors and radiomics scores. The differentiating efficacy was determined using receiver operating characteristic (ROC) analysis. RESULTS: Only one clinical factor (incomplete capsule) and seven radiomics features were found to be independent predictors and were used to establish the radiomics nomogram. In differentiating low-risk thymomas (types A, AB, and B1) from high-risk ones (types B2 and B3), the nomogram demonstrated better diagnostic efficacy than any single model, with the respective area under the curve (AUC), accuracy, sensitivity, and specificity of 0.974, 0.921, 0.962 and 0.900 in the training cohort, 0.960, 0.892, 0923 and 0.897 in the validation cohort, respectively. The calibration curve showed good agreement between the prediction probability and actual clinical findings. CONCLUSIONS: The nomogram incorporating clinical factors and radiomics features provides additional value in differentiating the risk categorization of thymomas, which could potentially be useful in clinical practice for planning personalized treatment strategies.


Asunto(s)
Nomogramas , Radiómica , Timoma , Neoplasias del Timo , Tomografía Computarizada por Rayos X , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medios de Contraste , Diagnóstico Diferencial , Estudios Retrospectivos , Medición de Riesgo , Curva ROC , Toracotomía , Timoma/diagnóstico por imagen , Timoma/cirugía , Neoplasias del Timo/diagnóstico por imagen , Neoplasias del Timo/cirugía , Tomografía Computarizada por Rayos X/métodos
18.
BMC Med Imaging ; 24(1): 56, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443817

RESUMEN

BACKGROUND: This study aimed to establish a dedicated deep-learning model (DLM) on routine magnetic resonance imaging (MRI) data to investigate DLM performance in automated detection and segmentation of meningiomas in comparison to manual segmentations. Another purpose of our work was to develop a radiomics model based on the radiomics features extracted from automatic segmentation to differentiate low- and high-grade meningiomas before surgery. MATERIALS: A total of 326 patients with pathologically confirmed meningiomas were enrolled. Samples were randomly split with a 6:2:2 ratio to the training set, validation set, and test set. Volumetric regions of interest (VOIs) were manually drawn on each slice using the ITK-SNAP software. An automatic segmentation model based on SegResNet was developed for the meningioma segmentation. Segmentation performance was evaluated by dice coefficient and 95% Hausdorff distance. Intra class correlation (ICC) analysis was applied to assess the agreement between radiomic features from manual and automatic segmentations. Radiomics features derived from automatic segmentation were extracted by pyradiomics. After feature selection, a model for meningiomas grading was built. RESULTS: The DLM detected meningiomas in all cases. For automatic segmentation, the mean dice coefficient and 95% Hausdorff distance were 0.881 (95% CI: 0.851-0.981) and 2.016 (95% CI:1.439-3.158) in the test set, respectively. Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). For meningioma classification, the radiomics model based on automatic segmentation performed well in grading meningiomas, yielding a sensitivity, specificity, accuracy, and area under the curve (AUC) of 0.778 (95% CI: 0.701-0.856), 0.860 (95% CI: 0.722-0.908), 0.848 (95% CI: 0.715-0.903) and 0.842 (95% CI: 0.807-0.895) in the test set, respectively. CONCLUSIONS: The DLM yielded favorable automated detection and segmentation of meningioma and can help deploy radiomics for preoperative meningioma differentiation in clinical practice.


Asunto(s)
Aprendizaje Profundo , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Radiómica , Imagen por Resonancia Magnética , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía
19.
BMC Public Health ; 24(1): 1289, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734652

RESUMEN

BACKGROUND: Under a changing climate, the joint effects of temperature and relative humidity on tuberculosis (TB) are poorly understood. To address this research gap, we conducted a time-series study to explore the joint effects of temperature and relative humidity on TB incidence in China, considering potential modifiers. METHODS: Weekly data on TB cases and meteorological factors in 22 cities across mainland China between 2011 and 2020 were collected. The proxy indicator for the combined exposure levels of temperature and relative humidity, Humidex, was calculated. First, a quasi-Poisson regression with the distributed lag non-linear model (DLNM) was constructed to examine the city-specific associations between humidex and TB incidence. Second, a multivariate meta-regression model was used to pool the city-specific effect estimates, and to explore the potential effect modifiers. RESULTS: A total of 849,676 TB cases occurred in the 22 cities between 2011 and 2020. Overall, a conspicuous J-shaped relationship between humidex and TB incidence was discerned. Specifically, a decrease in humidex was positively correlated with an increased risk of TB incidence, with a maximum relative risk (RR) of 1.40 (95% CI: 1.11-1.76). The elevated RR of TB incidence associated with low humidex (5th humidex) appeared on week 3 and could persist until week 13, with a peak at approximately week 5 (RR: 1.03, 95% CI: 1.01-1.05). The effects of low humidex on TB incidence vary by Natural Growth Rate (NGR) levels. CONCLUSION: A J-shaped exposure-response association existed between humidex and TB incidence in China. Humidex may act as a better predictor to forecast TB incidence compared to temperature and relative humidity alone, especially in regions with higher NGRs.


Asunto(s)
Humedad , Tuberculosis , China/epidemiología , Humanos , Tuberculosis/epidemiología , Incidencia , Temperatura , Ciudades/epidemiología , Cambio Climático
20.
Biotechnol Lett ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39083114

RESUMEN

OBJECTIVE: To introduce the Cre-loxP system for constructing marker-less multiple-gene deletion mutants in Pectobacterium, overcoming limitations of antibiotic markers and enhancing the understanding of pathogenic mechanisms. RESULTS: Firstly, a plasmid named pEX18-Cre, containing a sacB sucrose suicide gene, was constructed to express Cre recombinase in Pectobacterium. Secondly, a mutant in which the loxP-Km fragment replaced the target gene was obtained through homologous recombination double-crossover with the chromosome. Finally, pEX18-Cre was introduced into the mutant to excise the DNA between the loxP sites, thereby removing the markers and achieving multiple gene deletions. By utilizing the Cre-loxP system, we successfully constructed multiple marker-less gene deletion mutants in Pectobacterium strains. CONCLUSIONS: The Cre-loxP system efficiently creates marker-less multiple-gene deletion mutants, enhancing the study of Pectobacterium pathogenic mechanisms by overcoming antibiotic marker limitations.

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