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1.
Comput Biol Med ; 179: 108793, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38955126

RESUMEN

Skin tumors are the most common tumors in humans and the clinical characteristics of three common non-melanoma tumors (IDN, SK, BCC) are similar, resulting in a high misdiagnosis rate. The accurate differential diagnosis of these tumors needs to be judged based on pathological images. However, a shortage of experienced dermatological pathologists leads to bias in the diagnostic accuracy of these skin tumors in China. In this paper, we establish a skin pathological image dataset, SPMLD, for three non-melanoma to achieve automatic and accurate intelligent identification for them. Meanwhile, we propose a lesion-area-based enhanced classification network with the KLS module and an attention module. Specifically, we first collect thousands of H&E-stained tissue sections from patients with clinically and pathologically confirmed IDN, SK, and BCC from a single-center hospital. Then, we scan them to construct a pathological image dataset of these three skin tumors. Furthermore, we mark the complete lesion area of the entire pathology image to better learn the pathologist's diagnosis process. In addition, we applied the proposed network for lesion classification prediction on the SPMLD dataset. Finally, we conduct a series of experiments to demonstrate that this annotation and our network can effectively improve the classification results of various networks. The source dataset and code are available at https://github.com/efss24/SPMLD.git.

2.
J Biol Chem ; : 107526, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960041

RESUMEN

The human ether-g-go-go-related gene (hERG) encodes the Kv11.1 (or hERG) channel that conducts the rapidly activating delayed rectifier potassium current (IKr). Naturally occurring mutations in hERG impair the channel function and cause long QT syndrome type 2 (LQT2). Many missense hERG mutations lead to a lack of channel expression on the cell surface, representing a major mechanism for the loss-of-function of mutant channels. While it is generally thought that a trafficking defect underlies the lack of channel expression on the cell surface, in the present study, we demonstrate that the trafficking defective mutant hERG G601S can reach the plasma membrane but is unstable and quickly degrades, which is akin to Wild Type (WT) hERG channels under low K+ conditions. We previously showed that Serine (S) residue at 624 in the innermost position of the selectivity filter of hERG is involved in hERG membrane stability such that substitution of Serine 624 with Threonine (S624T) enhances hERG stability and renders hERG insensitive to low K+ culture. Here, we report that the intragenic addition of S624T substitution to trafficking defective hERG mutants G601S, N470D and P596R led to a complete rescue of the function of these otherwise loss-of-function mutant channels to a level similar to the WT channel, representing the most effective rescue means for the function of mutant hERG channels. These findings not only provide novel insights into hERG mutation-mediated channel dysfunction, but also point to the critical role of S624 in hERG stability on the plasma membrane.

3.
Aging Med (Milton) ; 7(3): 384-392, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38975318

RESUMEN

Objectives: This study aims to describe the differences in body composition among different body parts of the elderly in the community and its relationship with sarcopenia. Methods: Elderly people aged ≥65 underwent bioelectric impedance analysis testing and were categorized into a sarcopenia group, possible sarcopenia group, and control group. The characteristics of body composition indicators in different parts and their relationship with different stages of sarcopenia were analyzed. Results: The sarcopenia group illustrated the lowest values of FFM, FFM%, BFM, BFM%, ICW, and limb PhA, along with higher ECW/TBW in the trunk and left leg compared to the control group. The possible sarcopenia group showed lower FFM% in limbs and trunk, and higher BFM% compared to the control group. Gender differences in elderly body composition were observed, with an increase in BFM% in various body parts posing a risk factor for possible sarcopenia in elderly males, whereas an increase in BFM% except in the left arm was a protective factor for sarcopenia in elderly females. Conclusion: The body composition of the elderly in the community varied significantly in different stages of sarcopenia and genders, which correlated with sarcopenia.

4.
Adv Sci (Weinh) ; : e2402025, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38976572

RESUMEN

As a significant infectious disease in livestock, porcine reproductive and respiratory syndrome (PRRS) imposes substantial economic losses on the swine industry. Identification of diagnostic markers and therapeutic targets has been a focal challenge in PPRS prevention and control. By integrating metabolomic and lipidomic serum analyses of clinical pig cohorts through a machine learning approach with in vivo and in vitro infection models, lysophosphatidic acid (LPA) is discovered as a serum metabolic biomarker for PRRS virus (PRRSV) clinical diagnosis. PRRSV promoted LPA synthesis by upregulating the autotaxin expression, which causes innate immunosuppression by dampening the retinoic acid-inducible gene I (RIG-I) and type I interferon responses, leading to enhanced virus replication. Targeting LPA demonstrated protection against virus infection and associated disease outcomes in infected pigs, indicating that LPA is a novel antiviral target against PRRSV. This study lays a foundation for clinical prevention and control of PRRSV infections.

5.
Sheng Wu Gong Cheng Xue Bao ; 40(7): 1981-1996, 2024 Jul 25.
Artículo en Chino | MEDLINE | ID: mdl-39044570

RESUMEN

Proteins serve as the primary executors of cellular activities in organisms, and thus investigating the subcellular localization and interactions of proteins is crucial for understanding protein functions and elucidating the molecular mechanisms in organisms. Proximity labeling is a recently developed effective method for detecting protein-protein interactions in live cells. Compared with the conventional methods for studying protein-protein interactions, proximity labeling demonstrates high sensitivity, strong specificity, and low background and is widely employed in the research of protein-protein interactions between pathogens and hosts. This article reviews the recent progress in the development and applications of the biotin ligase BirA and its mutants and elucidates the functioning principles of several classical biotin ligases. This review aims to clarify the role of proximity labeling based on BirA and its mutants in identifying protein-protein interactions between pathogens and hosts.


Asunto(s)
Ligasas de Carbono-Nitrógeno , Interacciones Huésped-Patógeno , Mutación , Ligasas de Carbono-Nitrógeno/metabolismo , Ligasas de Carbono-Nitrógeno/genética , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Biotina/metabolismo , Humanos , Mapeo de Interacción de Proteínas , Escherichia coli/genética , Escherichia coli/metabolismo
6.
Biomed Pharmacother ; 177: 117146, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39013219

RESUMEN

Folliculin interacting protein 1 (FNIP1), a novel folliculin interacting protein 1, is a key regulatory factor for mitochondrial function. FNIP1 mainly responds to energy signal transduction through physical interactions with 5'-AMP activated protein kinase (AMPK). Simultaneously, it affects the transcription of mitochondria-associated genes by regulating the lysosomal localization of mechanistic target of rapamycin kinase (mTORC1). This article takes FNIP1 as the core and first introduces its involvement in the development of B cells and invariant natural killer T (iNKT) cells, muscle fiber type conversion, and the thermogenic remodeling of adipocytes by regulating mitochondrial function. In addition we discuss the detailed impact of upstream regulatory factors of FNIP1 on its function. Finally, the impact of FNIP1 on the prognosis and treatment of clinically related metabolic diseases is summarized, aiming to provide a new theoretical basis and treatment plans for the diagnosis and treatment of such diseases.

8.
Org Lett ; 26(26): 5506-5510, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38900141

RESUMEN

A palladium(II)-catalyzed norbornene-mediated remote selective meta-C-H silylation of primary benzamides was developed for the synthesis of arylsilanes. Such a conversion provides access to a range of arylsilanes with exclusive selectivity using norbornene (NBE) as the meta-C-H activator. The amide directing group can be detached simultaneously through C-C bond cleavage or undergo a dehydration reaction pathway to form nitriles.

9.
Int J Biol Macromol ; 274(Pt 1): 133278, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38906342

RESUMEN

Removing free hemoglobin generated during extracorporeal circulation remains a challenge. Currently, there is no adsorbent with specificity and good biosafety for removing hemoglobin. In this study, a new chitosan/sodium alginate/carbon nitride (CS/SA/C3N4) hydrogel adsorbent was prepared by blending SA with C3N4 to drop into CS/CaCl2 solution. The physicochemical properties of CS/SA/C3N4 hydrogel were evaluated using some techniques, including scanning electron microscope, Zeta potential measurement, and thermogravimetric analysis. Hemoglobin adsorption in vitro, stability, hemocompatibility, cell compatibility, inflammatory reaction and blood extracorporeal circulation in vivo were also evaluated. The findings revealed that the CS/SA/C3N4-0.4 % hydrogel exhibited an impressive adsorption capacity of 142.35 mg/g for hemoglobin. The kinetic data of hemoglobin adsorption were well-described by pseudo second-order model, while the isothermal model data conformed to the Langmuir model. The hardness and modulus of CS/SA/C3N4-0.4 % was 11.7 KPa and 94.66 KPa respectively, which indicated robust resistance to breakage. CS/SA/C3N4 demonstrated excellent hemocompatibility, biocompatibility and anti-inflammatory properties. In addition, the results of in vivo rabbit extracorporeal blood circulation experiment demonstrated that CS/SA/C3N4 could adsorb free hemoglobin from blood while maintaining high biosafety standard. Consequently, CS/SA/C3N4 hydrogel emerges as a promising candidate for use as a hemoglobin adsorbent in extracorporeal blood circulation system.

10.
Int Ophthalmol ; 44(1): 255, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909160

RESUMEN

PURPOSE: To explore ocular characteristics of patients with cataracts after renal transplantation and analyze the results of phacoemulsification combined with intraocular lens (IOL) implantation. METHODS: Patients with cataracts after renal transplantation and control patients who underwent phacoemulsification combined with IOL implantation were enrolled. All patients underwent phacoemulsification combined with IOL implantation. Visual acuity, intraocular pressure, type of lens opacity, corneal endothelial cell density, and ocular biological parameters were evaluated before surgery. Visual prognosis, dry eye, and postoperative complications were monitored for 6 months after phacoemulsification. RESULTS: We analyzed 25 eyes of 16 patients after renal transplantation and 30 eyes of 21 control patients. The most common type of cataract of renal transplantation group was posterior subcapsular, while the most common type of cataract of control group was cortical. Significant differences in corneal astigmatism, white-to-white ratio, and keratometry values were observed between the groups. The postoperative visual acuity of both groups significantly improved following surgery. Postoperative complications, such as the degree of anterior and posterior capsule opacification and the incidence of a requirement of neodymium-doped yttrium aluminum garnet laser capsulotomy, were significantly lower in the renal transplantation group. Moreover, secondary glaucoma occurred in two eyes in the renal transplantation group. CONCLUSION: This study showed that cataracts after renal transplantation were mostly posterior subcapsular. Postoperative visual acuity recovered well in most patients, with reduced incidence of postoperative complications. This study suggested that phacoemulsification combined with IOL implantation was safe and effective, providing a reference for multi-focal IOL implantation in kidney transplant recipients.


Asunto(s)
Catarata , Trasplante de Riñón , Facoemulsificación , Agudeza Visual , Humanos , Facoemulsificación/efectos adversos , Facoemulsificación/métodos , Masculino , Femenino , Catarata/complicaciones , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Adulto , Presión Intraocular/fisiología , Implantación de Lentes Intraoculares/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Estudios de Seguimiento , Anciano
11.
Virology ; 597: 110129, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38908046

RESUMEN

Group A rotaviruses (RVAs) are major causes of severe gastroenteritis in infants and young animals. To enhance our understanding of the relationship between human and animals RVAs, complete genome data are necessary. We screened 92 intestinal and stool samples from diarrheic piglets by RT‒PCR targeting the VP6 gene, revealing a prevalence of 10.9%. RVA was confirmed in two out of 5 calf samples. We successfully isolated two porcine samples using MA104 cell line. The full-length genetic constellation of the two isolates were determined to be G9-P[23]-I5-R1-C1-M1-A8-N1-T7-E1-H1, with close similarity to human Wa-like and porcine strains. Sequence analysis revealed the majority of genes were closely related to porcine and human RVAs. Phylogenetic analysis revealed that these isolates might have their ancestral origin from pigs, although some of their gene segments were related to human strains. This study reveals evidence of reassortment and possible interspecies transmission between pigs and humans in China.


Asunto(s)
Genoma Viral , Filogenia , Infecciones por Rotavirus , Rotavirus , Enfermedades de los Porcinos , Animales , Rotavirus/genética , Rotavirus/aislamiento & purificación , Rotavirus/clasificación , Porcinos , Infecciones por Rotavirus/virología , Infecciones por Rotavirus/veterinaria , Infecciones por Rotavirus/transmisión , Infecciones por Rotavirus/epidemiología , Humanos , China/epidemiología , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/transmisión , Enfermedades de los Porcinos/epidemiología , Bovinos , Heces/virología , Secuenciación Completa del Genoma , Genotipo , Diarrea/virología , Diarrea/veterinaria , Diarrea/epidemiología , Línea Celular , Virus Reordenados/genética , Virus Reordenados/aislamiento & purificación , Virus Reordenados/clasificación
12.
Cancer Immunol Immunother ; 73(8): 152, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38833153

RESUMEN

BACKGROUND: Patients treated with immune checkpoint inhibitors (ICIs) are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Lymphocyte subsets play a pivotal role in the antitumor response, this study attempted to combine the absolute counts of lymphocyte subsets (ACLS) with the clinicopathological parameters to construct nomograms to accurately predict the prognosis of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1 inhibitors. METHODS: This retrospective study included a training cohort (n = 200) and validation cohort (n = 100) with aNSCLC patients treated with anti-PD-1 inhibitors. Logistic and Cox regression were conducted to identify factors associated with efficacy and progression-free survival (PFS) respectively. Nomograms were built based on independent influencing factors, and assessed by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. RESULT: In training cohort, lower baseline absolute counts of CD3+ (P < 0.001) and CD4+ (P < 0.001) were associated with for poorer efficacy. Hepatic metastases (P = 0.019) and lower baseline absolute counts of CD3+ (P < 0.001), CD4+ (P < 0.001), CD8+ (P < 0.001), and B cells (P = 0.042) were associated with shorter PFS. Two nomograms to predict efficacy at 6-week after treatment and PFS at 4-, 8- and 12-months were constructed, and validated in validation cohort. The area under the ROC curve (AUC-ROC) of nomogram to predict response was 0.908 in training cohort and 0.984 in validation cohort. The C-index of nomogram to predict PFS was 0.825 in training cohort and 0.832 in validation cohort. AUC-ROC illustrated the nomograms had excellent discriminative ability. Calibration curves showed a superior consistence between the nomogram predicted probability and actual observation. CONCLUSION: We constructed two nomogram based on ACLS to help clinicians screen of patients with possible benefit and make individualized treatment decisions by accurately predicting efficacy and PFS for advanced NSCLC patient treated with anti-PD-1 inhibitors.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Nomogramas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Pronóstico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Subgrupos Linfocitarios/inmunología , Adulto , Recuento de Linfocitos
13.
J Biol Chem ; 300(7): 107453, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38852886

RESUMEN

Identification of a conserved G-quadruplex in E165R of ASFVAfrican swine fever virus (ASFV) is a double-stranded DNA arbovirus with high transmissibility and mortality rates. It has caused immense economic losses to the global pig industry. Currently, no effective vaccines or medications are to combat ASFV infection. G-quadruplex (G4) structures have attracted increasing interest because of their regulatory role in vital biological processes. In this study, we identified a conserved G-rich sequence within the E165R gene of ASFV. Subsequently, using various methods, we verified that this sequence could fold into a parallel G4. In addition, the G4-stabilizers pyridostatin and 5,10,15,20-tetrakis-(N-methyl-4-pyridyl) porphin (TMPyP4) can bind and stabilize this G4 structure, thereby inhibiting E165R gene expression, and the inhibitory effect is associated with G4 formation. Moreover, the G4 ligand pyridostatin substantially impeded ASFV proliferation in Vero cells by reducing gene copy number and viral protein expression. These compelling findings suggest that G4 structures may represent a promising and novel antiviral target against ASFV.

14.
J Biol Chem ; 300(7): 107483, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38897569

RESUMEN

The voltage-gated Kv1.5 potassium channel, conducting the ultra-rapid delayed rectifier K+ current (IKur) in human cells, plays important roles in the repolarization of atrial action potentials and regulation of the vascular tone. We previously reported that activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) induces endocytic degradation of cell-surface Kv1.5 channels, and a point mutation removing the phosphorylation site, T15A, in the N terminus of Kv1.5 abolished the PMA-effect. In the present study, using mutagenesis, patch clamp recording, Western blot analysis, and immunocytochemical staining, we demonstrate that ubiquitination is involved in the PMA-mediated degradation of mature Kv1.5 channels. Since the expression of the Kv1.4 channel is unaffected by PMA treatment, we swapped the N- and/or C-termini between Kv1.5 and Kv1.4. We found that the N-terminus alone did not but both N- and C-termini of Kv1.5 did confer PMA sensitivity to mature Kv1.4 channels, suggesting the involvement of Kv1.5 C-terminus in the channel ubiquitination. Removal of each of the potential ubiquitination residue Lysine at position 536, 565, and 591 by Arginine substitution (K536R, K565R, and K591R) had little effect, but removal of all three Lysine residues with Arginine substitution (3K-R) partially reduced PMA-mediated Kv1.5 degradation. Furthermore, removing the cysteine residue at position 604 by Serine substitution (C604S) drastically reduced PMA-induced channel degradation. Removal of the three Lysines and Cys604 with a quadruple mutation (3K-R/C604S) or a truncation mutation (Δ536) completely abolished the PKC activation-mediated degradation of Kv1.5 channels. These results provide mechanistic insight into PKC activation-mediated Kv1.5 degradation.

15.
Mayo Clin Proc ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38935019

RESUMEN

OBJECTIVE: To evaluate the performance of Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers in a tertiary neurology clinic setting with high frequency of non-AD cases, including normal pressure hydrocephalus (NPH). METHODS: There were 534 patients who underwent AD CSF biomarkers (Roche Elecsys Aß42, p-Tau181, total-Tau) from April 1, 2020, through April 23, 2021. A behavioral neurologist blinded to CSF results assigned a clinical diagnosis retrospectively on the basis of consensus criteria, and a neuroradiologist blinded to the diagnosis and CSF studies graded brain magnetic resonance images for indicators of CSF dynamics disorders. Associations between biomarkers, diagnoses, and imaging were assessed by χ2, analysis of covariance, and linear regression methods. RESULTS: Median age at time of testing was 67 years (range, 19 to 96 years), median symptom duration was 2 years (range, 0.4 to 28 years), and median Short Test of Mental Status score was 30 (range, 0 to 38). Clinical diagnoses significantly correlated with different CSF biomarker values (χ2=208.3; P=10e-4). p-Tau181/Aß42 ratios above 0.023 positively correlated with Alzheimer dementia (more than individual measures). This ratio also had the best performance for differentiating Alzheimer dementia from NPH (area under the curve, 0.869). Imaging markers supportive of CSF dynamics disorders correlated with low Aß42, p-Tau181, and total-Tau. CONCLUSION: In a heterogeneous clinical population, abnormal p-Tau181/Aß42 ratios (>0.023) have the strongest association with Alzheimer dementia and probably represent a comorbid AD pathologic component in persons clearly matching non-AD neurodegenerative syndromes. Altered CSF dynamics were associated with lower concentrations of AD CSF biomarkers regardless of clinical diagnosis, but the ratio compensates for these changes. In the appropriate clinical setting, an isolated abnormal Aß42 should prompt consideration of NPH.

16.
Int J Nanomedicine ; 19: 5157-5172, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855731

RESUMEN

Background: Poly-L-lactic acid (PLLA) stents have broad application prospects in the treatment of cardiovascular diseases due to their excellent mechanical properties and biodegradability. However, foreign body reactions caused by stent implantation remain a bottleneck that limits the clinical application of PLLA stents. To solve this problem, the biocompatibility of PLLA stents must be urgently improved. Albumin, the most abundant inert protein in the blood, possesses the ability to modify the surface of biomaterials, mitigating foreign body reactions-a phenomenon described as the "stealth effect". In recent years, a strategy based on albumin camouflage has become a focal point in nanomedicine delivery and tissue engineering research. Therefore, albumin surface modification is anticipated to enhance the surface biological characteristics required for vascular stents. However, the therapeutic applicability of this modification has not been fully explored. Methods: Herein, a bionic albumin (PDA-BSA) coating was constructed on the surface of PLLA by a mussel-inspired surface modification technique using polydopamine (PDA) to enhance the immobilization of bovine serum albumin (BSA). Results: Surface characterization revealed that the PDA-BSA coating was successfully constructed on the surface of PLLA materials, significantly improving their hydrophilicity. Furthermore, in vivo and in vitro studies demonstrated that this PDA-BSA coating enhanced the anticoagulant properties and pro-endothelialization effects of the PLLA material surface while inhibiting the inflammatory response and neointimal hyperplasia at the implantation site. Conclusion: These findings suggest that the PDA-BSA coating provides a multifunctional biointerface for PLLA stent materials, markedly improving their biocompatibility. Further research into the diverse applications of this coating in vascular implants is warranted.


Asunto(s)
Materiales Biocompatibles Revestidos , Poliésteres , Polímeros , Albúmina Sérica Bovina , Stents , Poliésteres/química , Animales , Albúmina Sérica Bovina/química , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Polímeros/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Indoles/química , Indoles/farmacología , Propiedades de Superficie , Humanos , Ensayo de Materiales , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos
17.
Front Oncol ; 14: 1382154, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38894864

RESUMEN

The incidence of multiple primary tumors(MPTs) is on the rise in recent years, but patients having four or more primary tumors is still rare. Lynch syndrome (LS) patients have a high risk of developing MPTs. NGS sequencing could identify the genetic alterations in different tumors to make a definite diagnosis of uncommon cases in clinical practice. Here, we report the case of a 66-year-old female patient who develops four MPTS between the ages of 41 and 66, that is sigmoid colon cancer, acute non-lymphocytic leukemia, urothelial carcinoma and ascending colon cancer. She has survived for more than 26 years since the first discovery of tumor. Targeted sequencing indicates that she has a pathogenic germline mutation in the exon 13 of MSH2, and her 2020 ureteral cancer sample and 2023 colon cancer sample have completely different mutation profiles. To the best of our knowledge, this is the first case of multiple primary tumors with an acute non-lymphocytic leukemia in LS patients.

18.
J Nanobiotechnology ; 22(1): 239, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735951

RESUMEN

Widespread distribution of porcine epidemic diarrhea virus (PEDV) has led to catastrophic losses to the global pig farming industry. As a result, there is an urgent need for rapid, sensitive and accurate tests for PEDV to enable timely and effective interventions. In the present study, we develop and validate a floating gate carbon nanotubes field-effect transistor (FG CNT-FET)-based portable immunosensor for rapid identification of PEDV in a sensitive and accurate manner. To improve the affinity, a unique PEDV spike protein-specific monoclonal antibody is prepared by purification, and subsequently modified on FG CNT-FET sensor to recognize PEDV. The developed FET biosensor enables highly sensitive detection (LoD: 8.1 fg/mL and 100.14 TCID50/mL for recombinant spike proteins and PEDV, respectively), as well as satisfactory specificity. Notably, an integrated portable platform consisting of a pluggable FG CNT-FET chip and a portable device can discriminate PEDV positive from negative samples and even identify PEDV and porcine deltacoronavirus within 1 min with 100% accuracy. The portable sensing platform offers the capability to quickly, sensitively and accurately identify PEDV, which further points to a possibility of point of care (POC) applications of large-scale surveillance in pig breeding facilities.


Asunto(s)
Técnicas Biosensibles , Nanotubos de Carbono , Virus de la Diarrea Epidémica Porcina , Virus de la Diarrea Epidémica Porcina/aislamiento & purificación , Animales , Porcinos , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Nanotubos de Carbono/química , Límite de Detección , Inmunoensayo/métodos , Inmunoensayo/instrumentación , Anticuerpos Monoclonales/inmunología , Transistores Electrónicos , Enfermedades de los Porcinos/diagnóstico , Enfermedades de los Porcinos/virología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/análisis , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Anticuerpos Antivirales/inmunología , Diseño de Equipo
19.
J Mol Cell Cardiol ; 192: 79-93, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38761990

RESUMEN

Ferroptosis is an iron-dependent programmed cell death form resulting from lipid peroxidation damage, it plays a key role in organ damage and tumor development from various causes. Sepsis leads to severe host response after infection with high mortality. The long non-coding RNAs (LncRNAs) are involved in different pathophysiological mechanisms of multiple diseases. Here, we used cecal ligation and puncture (CLP) operation to mimic sepsis induced myocardial injury (SIMI) in mouse model, and LncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Based on the microarray results, 552 LncRNAs and 520 mRNAs were differentially expressed in the sham and CLP groups, among them, LncRNA Lcn2-204 was the highest differentially expressed up-regulated LncRNA. Iron metabolism disorder was involved in SIMI by bioinformatics analysis, meanwhile, myocardial iron content and lipocalin-2 (Lcn2) protein expressions were increased. The CNC network comprised 137 positive interactions and 138 negative interactions. Bioinformatics analysis showed several iron-related terms were enriched and six genes (Scara5, Tfrc, Lcn2, Cp, Clic5, Ank1) were closely associated with iron metabolism. Then, we constructed knockdown LncRNA Lcn2-204 targeting myocardium and found that it ameliorated cardiac injury in mouse sepsis model through modulating iron overload and ferroptosis. In addition, we found that LncRNA Lcn2-204 was involved in the regulation of Lcn2 expression in septic myocardial injury. Based on these findings, we conclude that iron overload and ferroptosis are the key mechanisms leading to myocardial injury in sepsis, knockdown of LncRNA Lcn2-204 plays the cardioprotective effect through inhibition of iron overload, ferroptosis and Lcn2 expression. It may provide a novel therapeutic approach to ameliorate sepsis-induced myocardial injury.


Asunto(s)
Ferroptosis , Técnicas de Silenciamiento del Gen , Sobrecarga de Hierro , Lipocalina 2 , Miocardio , ARN Largo no Codificante , Sepsis , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ferroptosis/genética , Sepsis/complicaciones , Sepsis/genética , Sepsis/metabolismo , Ratones , Lipocalina 2/metabolismo , Lipocalina 2/genética , Masculino , Sobrecarga de Hierro/genética , Sobrecarga de Hierro/metabolismo , Sobrecarga de Hierro/complicaciones , Miocardio/metabolismo , Miocardio/patología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Hierro/metabolismo , Lesiones Cardíacas/etiología , Lesiones Cardíacas/metabolismo , Lesiones Cardíacas/genética , Perfilación de la Expresión Génica
20.
Sci Total Environ ; 939: 173610, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38815821

RESUMEN

During the process of cleaning aquaculture ponds, the drainage contributes significantly to antibiotic pollution in the surrounding water environment. Therefore, we conducted a study on the distribution of 26 antibiotics in 57 ponds within the Taihu Lake basin. The results revealed that the detection frequency of antibiotics ranged from 1.75 % to 80.7 %, with the overall detection concentrations ranging from 3.27 to 708.72 ng/L. Among them, the detection rate of 8 antibiotics exceeded 50 %. Regarding the spatial distribution, the concentration of antibiotics was relatively high in aquaculture ponds located in the Changzhou area, with the highest concentration reaching 708.72 ng/L. This observation is likely due to the large size and intensive breeding practices in Changzhou. Fish ponds exhibited a significantly higher total antibiotic concentration of 3.27 to 445.57 ng/L compared to crab ponds (13.01 to 206.30 ng/L) and shrimp ponds (23.17 to 107.40 ng/L). Quinolones and sulfonamides were the predominant antibiotic classes found in fish ponds, accounting for 51.49 % of the total antibiotic concentration. Notably, sulfamethoxazole (SMX) and enrofloxacin (ENR) exhibited the highest antibiotic concentrations. Risk assessments demonstrated that SMX, ENR, and ofloxacin (OFX) contributed significantly to ecological risks. Furthermore, the study found that the tertiary constructed wetland treatment process achieved a remarkable removal rate of 92.44 % for antibiotics in aquaculture wastewater, while other treatment processes displayed limited effectiveness in removing antibiotics. This study addresses the knowledge gap concerning antibiotic pollution during the cleaning process of aquaculture ponds within the Taihu Lake basin.


Asunto(s)
Antibacterianos , Acuicultura , Monitoreo del Ambiente , Lagos , Estanques , Contaminantes Químicos del Agua , China , Contaminantes Químicos del Agua/análisis , Estanques/química , Lagos/química , Antibacterianos/análisis , Medición de Riesgo
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