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1.
Br J Haematol ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267281

RESUMEN

The efficacy and safety of recombinant human thrombopoietin (rhTPO) in children and adolescent patients with chronic primary immune thrombocytopenia (ITP) remains unclear. A multicentre, randomized, double-blind, placebo-controlled phase III trial was performed. Patients aged 6-17 years, diagnosed with ITP and resistant or relapsed to corticosteroid treatment were included. For the trial, part 1 was exploratory and part 2 was the main analysis, with part 1 determining whether part 2 was stratified by age. Patients in part 1 were treated with rhTPO (the 6- to 11-/12- to 17-year-old groups; 1:1). Patients in part 2 were randomized (3:1) to receive either rhTPO treatment or placebo. Patients received rhTPO or placebo at a dose of 300 U/kg once daily for up to 14 days. A total of 68 patients were included [part 1 (12 patients), part 2 (56 patients)]. The total response rate (TRR) in part 1 was 50.0% (95% CI: 21.09%-78.91%). For part 2, the TRR was 58.5% (95% CI: 42.11%-73.68%) and 13.3% (95% CI: 1.66%-40.46%) in the rhTPO and placebo groups (FAS) respectively. The difference in TRR between the rhTPO group and placebo group was 45.2% (95% CI: 22.33%-68.08%) and 44.6% (95% CI: 21.27%-67.85%) on the FAS and per-protocol set (PPS), respectively, which indicates the superiority of rhTPO treatment.

2.
Int J Mol Sci ; 25(17)2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39273530

RESUMEN

Activating FLT3 mutations plays a crucial role in leukemogenesis, but identifying the optimal candidates for FLT3 inhibitor therapy remains controversial. This study aims to explore the impacts of FLT3 mutations in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) and to compare the mutation profiles between the two types to inspire the targeted application of FLT3 inhibitors. We retrospectively analyzed 243 ALL and 62 AML cases, grouping them into FLT3-mutant and wild-type categories, respectively. We then assessed the associations between FLT3 mutations and the clinical manifestations, genetic characteristics, and prognosis in ALL and AML. Additionally, we compared the distinct features of FLT3 mutations between ALL and AML. In ALL patients, those with FLT3 mutations predominantly exhibited hyperdiploidy (48.6% vs. 14.9%, p < 0.001) and higher FLT3 expression (108.02 [85.11, 142.06] FPKM vs. 23.11 [9.16, 59.14] FPKM, p < 0.001), but lower expression of signaling pathway-related genes such as HRAS, PIK3R3, BAD, MAP2K2, MAPK3, and STAT5A compared to FLT3 wild-type patients. There was no significant difference in prognosis between the two groups. In contrast, AML patients with FLT3 mutations were primarily associated with leucocytosis (82.90 [47.05, 189.76] G/L vs. 20.36 [8.90, 55.39] G/L, p = 0.001), NUP98 rearrangements (30% vs. 4.8%, p = 0.018), elevated FLT3 expression (74.77 [54.31, 109.46] FPKM vs. 34.56 [20.98, 48.28] FPKM, p < 0.001), and upregulated signaling pathway genes including PIK3CB, AKT1, MTOR, BRAF, and MAPK1 relative to FLT3 wild-type, correlating with poor prognosis. Notably, internal tandem duplications were the predominant type of FLT3 mutation in AML (66.7%) with higher inserted base counts, whereas they were almost absent in ALL (6.3%, p < 0.001). In summary, our study demonstrated that the forms and impacts of FLT3 mutations in ALL differed significantly from those in AML. The gene expression profiles of FLT3-related pathways may provide a rationale for using FLT3 inhibitors in AML rather than ALL when FLT3 mutations are present.


Asunto(s)
Leucemia Mieloide Aguda , Mutación , Leucemia-Linfoma Linfoblástico de Células Precursoras , Tirosina Quinasa 3 Similar a fms , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Niño , Masculino , Femenino , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Preescolar , Pronóstico , Transcriptoma , Lactante , Adolescente , Estudios Retrospectivos , Transducción de Señal/genética , Terapia Molecular Dirigida , Regulación Leucémica de la Expresión Génica/efectos de los fármacos
3.
Ecotoxicol Environ Saf ; 285: 117037, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39270477

RESUMEN

BACKGROUND: The associations between prenatal antibiotics exposure and attention-deficit/hyperactivity disorder (ADHD) in preschoolers, and the role of maternal vitamin D in these associations, remain to be explored. OBJECTIVES: To evaluate the relationships between multiple maternal urinary antibiotics levels and preschoolers' ADHD symptoms, and to identify the potential modifying effects of maternal vitamin D. METHODS: Based on a prospective birth cohort, the present study included 2033 motherchild pairs. Maternal urine and serum samples were collected during all three trimesters to measure the urinary concentrations of 43 antibiotics (including two metabolites) and the serum vitamin D levels. The ADHD symptoms of preschoolers were assessed using the Diagnostic and Statistical Manual-oriented ADHD problems scale in the Achenbach Child Behavior Checklist. Multiple informant models in the form of logistic regression were conducted to investigate the associations between prenatal antibiotics exposure and preschooler ADHD symptoms, and these associations were stratified by child sex and maternal vitamin D status. RESULTS: Compared with the lowest tertile concentrations, maternal exposure to the middle tertile concentrations of doxycycline and human antibiotics/preferred as human antibiotics (HAs/PHAs), and the highest tertile concentrations of doxycycline during the first trimester were associated with an increased risk of ADHD symptoms in children. An increased risk of ADHD symptoms was observed in girls exposed to the highest tertile levels of sulfamethazine during the second trimester. Furthermore, pregnant women with vitamin D deficiency have a greater risk of ADHD symptoms in their offspring after exposure to doxycycline in the first trimester. CONCLUSIONS: Maternal exposure to doxycycline and HAs/PHAs during the first trimester increases the risk of ADHD symptoms in preschoolers. Mid-pregnancy sulfamethazine exposure increases the risk of ADHD symptoms in girls. Maternal vitamin D deficiency during pregnancy may exacerbate the adverse effects of doxycycline exposure on ADHD symptoms.

4.
Nat Comput Sci ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266669

RESUMEN

Prosocial motives such as social equality and efficiency are key to altruistic behaviors. However, predicting the range of altruistic behaviors in varying contexts and individuals proves challenging if we limit ourselves to one or two motives. Here we demonstrate the numerous, interdependent motives in altruistic behaviors and the possibility to disentangle them through behavioral experimental data and computational modeling. In one laboratory experiment (N = 157) and one preregistered online replication (N = 1,258), across 100 different situations, we found that both third-party punishment and third-party helping behaviors (that is, an unaffected individual punishes the transgressor or helps the victim) aligned best with a model of seven socioeconomic motives, referred to as a motive cocktail. For instance, the inequality discounting motives imply that individuals, when confronted with costly interventions, behave as if the inequality between others barely exists. The motive cocktail model also provides a unified explanation for the differences in intervention willingness between second parties (victims) and third parties, and between punishment and helping.

5.
J Multidiscip Healthc ; 17: 3637-3648, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100899

RESUMEN

The central nervous system (CNS) is less prone to infection owing to protection from the brain-blood barrier. However, craniotomy destroys this protection and increases the risk of infection in the brain of patients who have undergone craniotomy. CNS infection after craniotomy significantly increases the patient's mortality rate and disability. Controlling the occurrence of intracranial infection is very important for post-craniotomy patients. CNS infection after craniotomy is caused by several factors such as preoperative, intraoperative, and post-operative factors. Craniotomy may lead to postsurgical intracranial infection, which is mainly associated with surgery duration, infratentorial (posterior fossa) surgery, cerebrospinal fluid leakage, drainage tube placement, unregulated use of antibiotics, glucocorticoid use, age, diabetes, and other systemic infections. Understanding the risk factors of CNS infection after craniotomy can benefit reducing the incidence of intracranial infectious diseases. This will also provide the necessary guidance and evidence in clinical practice for planning to control intracranial infection in patients with craniotomy.

6.
Front Pharmacol ; 15: 1406454, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39108745

RESUMEN

Objective: To analyze the clinical and laboratory characteristics and to identify predictors of moderate to severe anti-tuberculosis drug-induced liver injury (ATB-DILI) in patients with tuberculosis. Methods: This prospective study enrolled Tuberculosis (TB) patients treated with first-line anti-tuberculosis drugs at the Affiliated Hospital of Zunyi Medical University between May 2022 and June 2023. The occurrence of ATB-DILI was monitored, and demographic and clinical data were gathered. We analyzed risk factors for the development of moderate to severe ATB-DILI. Results: ATB-DILI was detected in 120 (10.7%) of the patients, with moderate to severe ATB-DILI occurring in 23 (2.0%) of the 1,124 patients treated with anti-tuberculosis treatment. Multivariate cox regression analysis identified malnutrition (HR = 4.564, 95% CI: 1.029-20.251, p = 0.046) and hemoglobin levels <120 g/L (HR = 2.825, 95% CI: 1.268-11.540, p = 0.017) as independent risk factors for moderate to severe ATB-DILI. Conclusion: The incidence of moderate to severe ATB-DILI was found to be 2.0%. Malnutrition and hemoglobin levels below 120 g/L emerged as significant independent risk factors for the occurrence of moderate to severe ATB-DILI in this patient population.

7.
Small ; : e2400671, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101624

RESUMEN

Brain lipidic peroxidation is closely associated with the pathophysiology of various psychiatric diseases including depression. Malondialdehyde (MDA), a reactive aldehyde produced in lipid region, serves as a crucial biomarker for lipid peroxidation. However, techniques enabling real-time detection of MDA are still lacking due to the inherent trade-off between recognition dynamics and robustness. Inspired by the structure of phospholipid bilayers, amphiphilic carbon dots named as CG-CDs targeted to cell membrane are designed for real-time monitoring of MDA fluctuations. The design principle relies on the synergy of dynamic hydrogen bonding recognition and cell membrane targetability. The latter facilitates the insertion of CG-CDs into lipid regions and provides a hydrophobic environment to stabilize the labile hydrogen bonding between CG-CDs and MDA. As a result, recognition robustness and dynamics are simultaneously achieved for CG-CDs/MDA, allowing for in situ visualization of MDA kinetics in cell membrane due to the instant response (<5 s), high sensitivity (9-fold fluorescence enhancement), intrinsic reversibility (fluorescence on/off), and superior selectivity. Subsequently, CG-CDs are explored to visualize nerve cell membrane impairment in depression models of living cells and zebrafish, unveiling the extensive heterogeneity of the lipid peroxidation process and indicating a positive correlation between MDA levels and depression.

9.
Materials (Basel) ; 17(15)2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39124413

RESUMEN

In this study, the crystal plasticity finite element method was established by coupling the crystal plasticity and finite element method (FEM). The effect of rolling deformation and slip system of polycrystalline Al-Mg-Si aluminum alloy was investigated. The results showed that there was a pronounced heterogeneity in the stress and strain distribution of the material during cold rolling. The maximum strain and shear strain occurred at surface of the material. The smaller the grain size, the lower the strain concentration at the grain boundary. Meanwhile, a smaller strain difference existed between the grain interior and near the boundary. The rotation of grains leads to significant differences in deformation and rotation depending on their initial orientations during the rolling process. The slip system of (11-1)<-110> had a large effect on the plastic deformation, (111)<10-1> is second, and the effect of (1-11)<011> slip system on the plastic deformation is the smallest. After deformation, the grain orientation concentration was increased with deformation. Therefore, both the strength and volume fraction of texture were increased with the increase in rolling deformation. The experimental results of EBSD indicated that the large rolling reduction resulted in severe grain twisting, so the texture strength was increased. The simulation results were in close agreement with the experimental results. This study provides a theoretical basis for the rolling process, microstructure, and performance control of aluminum alloys.

10.
J Hazard Mater ; 478: 135445, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39116743

RESUMEN

Graphitic carbon nitride (CN) as an adsorbent exhibit promising potential for the removal of uranium in water. However, the lack of active sites seriously restricts its practical application. In contrast to the traditional method of introducing new ligands, we propose a strategy to activate original ligands on CN by injecting π electrons, which can be realized by grafting 4-phenoxyphenol (PP) on CN (PCN). Compared with CN, the maximum adsorption capacity of PCN for uranium increased from 150.9 mg/g to 380.6 mg/g. Furthermore, PCN maintains good adsorption properties over a wide range of uranium concentrations (1 ∼ 60 mg/L) and pH (4 ∼ 8). After 5 consecutive cycles, PCN exhibited sustained uranium removal performance with a little of losses. The experimental and theoretical results show that the enhancement of adsorption performance is mainly due to the ligands activation of CN by delocalization of π electrons from PP. Furthermore, this activation can be enhanced by irradiation, as the CN can be photoexcited to provide additional photoelectrons for PP. As a result, dormant ligands such as N-CN, C-O-C, C-N-H and N-(C)3 can be activated to participate in coordination with uranium. This work provides theoretical guidance for the design and preparation of high efficiency uranium adsorbent.

11.
Bioresour Technol ; 412: 131396, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39216706

RESUMEN

Microbial cell factories provide an efficient approach for the green manufacturing of chemicals. However, the excessive use of sugars increases the potential risk of food crisis. Methanol, an abundant feedstock, holds promise in facilitating low-carbon production processes. However, the current methanol bioconversion is hindered by limited regulatory strategies and relatively low conversion efficiency. Here, a yeast biocatalyst was extensively engineered for efficient biosynthesis of fatty alcohols through reinforcement of precursor supply and methanol assimilation in Pichia pastoris. Furthermore, the dual cytoplasmic and peroxisomal biosynthetic pathways were constructed by mating and exhibited robust production of 5.6 g/L fatty alcohols by using methanol as the sole carbon source. This study provides a heterozygous diploid P. pastoris strain with dual cytoplasmic and peroxisomal biosynthetic pathways, which achieved the highest fatty alcohol production from one-carbon feedstocks to date.


Asunto(s)
Vías Biosintéticas , Alcoholes Grasos , Ingeniería Metabólica , Metanol , Metanol/metabolismo , Alcoholes Grasos/metabolismo , Ingeniería Metabólica/métodos , Saccharomycetales
12.
ACS Infect Dis ; 10(9): 3138-3157, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39141008

RESUMEN

Antimicrobial peptides (AMPs) possess strong antibacterial activity and low drug resistance, making them ideal candidates for bactericidal drugs for addressing the issue of traditional antibiotic resistance. In this study, a template (G(XXKK)nI, G = Gly; X = Leu, Ile, Phe, or Trp; n = 2, 3, or 4; K = Lys; I = Ile.) was employed for the devised of a variety of novel α-helical AMPs with a high therapeutic index. The AMP with the highest therapeutic index, WK2, was ultimately chosen following a thorough screening process. It demonstrates broad-spectrum and potent activity against both standard and multidrug-resistant bacteria, while also showing low hemolysis and rapid and efficient time-kill kinetics. Additionally, WK2 exhibits excellent efficacy in treating mouse models of Klebsiella pneumonia-induced lung infections and methicillin-resistant Staphylococcus aureus (MRSA)-induced skin wound infections while demonstrating good safety profiles in vivo. In conclusion, the template-based design methodology for novel AMPs with high therapeutic indices offers new insights into addressing antibiotic resistance problems. WK2 represents a promising antimicrobial agent.


Asunto(s)
Antibacterianos , Péptidos Antimicrobianos , Klebsiella pneumoniae , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Infección de Heridas , Animales , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Klebsiella pneumoniae/efectos de los fármacos , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Femenino , Modelos Animales de Enfermedad , Humanos , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/microbiología
13.
Acta Psychol (Amst) ; 249: 104430, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39178496

RESUMEN

BACKGROUND: No single risk factor is decisive in shaping an individual's healthy development. This study aimed to analyze the relationship between depressive symptoms and a cumulative risk index comprising individual, family, and social variables among nursing students. METHODS: We enrolled 1716 Chinese nursing students from three universities in a paperless survey that assessed a range of individual, family, and social risk factors associated with depressive symptoms. Multiple risk analysis was conducted to create a composite risk score for each individual. A test for trend was employed to assess the relationship between the multiple risk classification and depressive symptoms individually. Additionally, a 2-step cluster analysis and χ2 tests were used to examine the relationship between the different clusters and the level of depressive symptoms. RESULTS: The mean scores of depressive symptoms increased significantly as the number of risk factors increased, regardless of their combination. As the number of risk factors increased, the proportion of nursing students in the normal group decreased, while the proportion in the group with depressive symptoms of varying severity tended to increase (P < 0.001). A high-risk cluster characterized by poor sleep quality combined with problematic smartphone use was associated with higher levels of depressive symptoms (P < 0.001). CONCLUSION: Based on these findings that cumulative exposure to multiple risk factors is more harmful than cumulative exposure to fewer risk factors, then interventions that isolate only one risk factor are less likely to be effective than those that are multifaceted.


Asunto(s)
Depresión , Teléfono Inteligente , Estudiantes de Enfermería , Humanos , Femenino , Estudiantes de Enfermería/estadística & datos numéricos , Masculino , Depresión/epidemiología , Factores de Riesgo , Estudios Transversales , Adulto Joven , Adulto , Teléfono Inteligente/estadística & datos numéricos , China/epidemiología , Adolescente , Trastorno de Adicción a Internet/epidemiología , Encuestas y Cuestionarios
14.
Ecotoxicol Environ Saf ; 284: 116949, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39208579

RESUMEN

BACKGROUND: Maternal exposure to multiple antibiotics exposure during pregnancy has attracted extensive attention, but biomonitoring studies linking prenatal antibiotic exposure to emotional and behavioural problems in children are limited. METHODS: A total of 2475 pregnant women from the Ma'anshan Birth Cohort were included, and the Strengths and Difficulties Questionnaire was completed when their children turned four years of age. The levels of 41 maternal urinary antibiotics and two metabolites were measured during the first, second and third trimesters. Generalized estimating equations and binary logistic regression models were applied to analyse the associations between maternal antibiotic exposure and emotional and behavioural problems in children and to determine the sensitive period, respectively. A quantile-based g-computation (QGC) approach was employed to examine the combined effects of multiple antibiotics on emotional and behavioural problems in children. RESULTS: Overall, florfenicol and preferred-as-veterinary antibiotic (PVA) exposure during pregnancy increased the risk of emotional problems in children, and ofloxacin exposure increased the risk of hyperactivity-inattention. Maternal exposure to trimethoprime, ciprofloxacin, florfenicol, other antibiotics and PVA exposure during the first trimester was positively associated with emotional problems in children. Second-trimester trimethoprime concentrations and third-trimester ciprofloxacin concentrations were positively associated with hyperactivity-inattention. Third-trimester veterinary antibiotic (VA) exposure was negatively associated with hyperactivity-inattention, and second-trimester VA and PVA exposure was negatively associated with peer problems. The QGC model revealed that mixed antibiotic exposure in the first trimester exacerbated the risk of childhood emotional problems (the contribution of ciprofloxacin is prominent), and mixed antibiotic exposure in the second trimester increased the risk of hyperactivity-inattention (the contribution of trimethoprime is prominent). CONCLUSION: Maternal mixed antibiotic exposure during the first and second trimesters increases the risk of emotional problems and hyperactivity-inattention in children at four years of age.

15.
Free Radic Biol Med ; 224: 190-203, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39197599

RESUMEN

Cisplatin-induced acute kidney injury (AKI) is characterized by mitochondrial damage and apoptosis, and safe and effective therapeutic agents are urgently needed. Renal tubular epithelial cells, the main site of AKI, are enriched with a large number of mitochondria, which are crucial for the progression of AKI with an impaired energy supply. Vincamine has anti-inflammatory and antioxidant effects in mouse AKI models. As a natural compound derived from Tabernaemontana pandacaqui, (+)-14, 15-Dehydrovincamine and Vincamine differ in structure by only one double bond, and the role and exact mechanism of (+)-14, 15-Dehydrovincamine remains to be elucidated in AKI. The present study demonstrated that (+)-14,15-Dehydrovincamine significantly ameliorated mitochondrial dysfunction and maintained mitochondrial homeostasis in a cisplatin-induced AKI model. Furthermore, (+)-14,15-Dehydrovincamine ameliorates cytochrome C-dependent apoptosis in renal tubular epithelial cells. c-Jun NH2-terminal kinase (JNK) was identified as a potential target protein of (+)-14,15-Dehydrovincamine attenuating AKI by network pharmacological analysis. (+)-14,15-Dehydrovincamine inhibited cisplatin-induced JNK activation, mitochondrial fission factor (Mff) phosphorylation, and dynamin-related protein 1 (Drp1) translocation to the mitochondria in renal tubular epithelial cells. Meanwhile, the JNK activator anisomycin restored Mff phosphorylation and Drp1 translocation, counteracting the protective effect of (+)-14,15-Dehydrovincamine on mitochondrial dysfunction in cisplatin-induced TECs injury. In conclusion, (+)-14,15-Dehydrovincamine reduced mitochondrial fission, maintained mitochondrial homeostasis, and attenuated apoptosis by inhibiting the JNK/Mff/Drp1 pathway, which in turn ameliorated cisplatin-induced AKI.

18.
Ital J Pediatr ; 50(1): 139, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080799

RESUMEN

BACKGROUND: Epstein-Barr virus DNA (EBV-DNA) is closely related to the pathogenesis and prognosis of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). The quantitative measurement of blood EBV-DNA is widely used in EBV-HLH, but there remains a lack of evidence to guide clinicians. METHODS: A retrospective analysis was conducted on clinical manifestations, laboratory tests, 310 blood EBV-DNA loads, and prognosis of 51 pediatric patients diagnosed with EBV-HLH. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cutoff values of EBV-DNA for predicting mortality and evaluating the active status of EBV-HLH. RESULTS: EBV-positive- lymphoma-HLH had higher initial plasma EBV-DNA load(1.10 × 106copies/ml) compared to the EBV-HLH group (1.98 × 104 copies/ml) (P = 0.006), and experienced recurrently elevated plasma EBV-DNA levels during treatment. The optimal cut-off value of initial plasma EBV-DNA load in predicting mortality was 2.68 × 105 copies/ml, with a sensitivity of 88.57% and a specificity of 56.25%. For determining the active status of HLH, the optimal cutoff value of PBMC EBV-DNA load during treatment was 2.95 × 105 copies/ml, with a sensitivity of 69.14% and a specificity of 64.71%. The cut-off value of plasma EBV-DNA for determining active status was 1.32 × 103 copies/ml, with a sensitivity of 84.34%, and a specificity of 87.67%. Patients with higher PBMC and plasma EBV-DNA at initial and those with repeated elevated plasma EBV-DNA during treatment had worse prognoses (P < 0.05). CONCLUSION: Dynamic monitoring of EBV-DNA is a valuable tool for assessing disease status and predicting the prognosis of EBV-HLH, with plasma EBV-DNA being more effective than PBMC EBV-DNA. Patients with high levels of PBMC and plasma EBV-DNA at initial and those with repeated elevated plasma EBV-DNA during treatment had worse prognoses.


Asunto(s)
ADN Viral , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Linfohistiocitosis Hemofagocítica , Humanos , Linfohistiocitosis Hemofagocítica/sangre , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/virología , Estudios Retrospectivos , Masculino , Femenino , ADN Viral/sangre , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/genética , China , Pronóstico , Lactante , Carga Viral , Adolescente , Pueblos del Este de Asia
19.
Mol Divers ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39020133

RESUMEN

Helicobacter pylori is the main causative agent of gastric cancer, especially non-cardiac gastric cancers. This bacterium relies on urease producing much ammonia to colonize the host. Herein, the study provides valuable insights into structural patterns driving urease inhibition for high-activity molecules designed via exploring known inhibitors. Firstly, an ensemble model was devised to predict the inhibitory activity of novel compounds in an automated workflow (R2 = 0.761) that combines four machine learning approaches. The dataset was characterized in terms of chemical space, including molecular scaffolds, clustering analysis, distribution for physicochemical properties, and activity cliffs. Through these analyses, the hydroxamic acid group and the benzene ring responsible for distinct activity were highlighted. Activity cliff pairs uncovered substituents of the benzene ring on hydroxamic acid derivatives are key structures for substantial activity enhancement. Moreover, 11 hydroxamic acid derivatives were designed, named mol1-11. Results of molecular dynamic simulations showed that the mol9 exhibited stabilization of the active site flap's closed conformation and are expected to be promising drug candidates for Helicobacter pylori infection and further in vitro, in vivo, and clinical trials to demonstrate in future.

20.
Sci Rep ; 14(1): 15649, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977748

RESUMEN

In order to enhance the hyperspectral camouflage efficacy of stealth coatings against a natural vegetative backdrop, LiCl, known for its significant hygroscopic properties, was incorporated into green Mg-Al layered double hydroxide (Mg-Al LDHs) material. Micron-sized composite microspheres were subsequently synthesized via the spray-drying granulation technique. The structure, morphology, and chemical composition of these microspheres were thoroughly characterized by X-ray diffraction, scanning electron microscopy, laser particle size analysis, nitrogen adsorption-desorption isotherms, and Fourier-transform infrared spectroscopy. The effect of LiCl content on the moisture absorption capacity and near-infrared reflectance spectra of the microspheres was systematically evaluated. We found that incorporating an optimal amount of LiCl into the internal pores of the Mg-Al LDHs microspheres did not compromise their smooth surface morphology and uniform particulate distribution. Notably, when the LiCl content was 10%, the maximum saturation moisture uptake ratio of the coating increased to 0.75 g/g. This hygroscopicity significantly enhanced the absorption and scattering of near-infrared radiation by the coating while concurrently improving its ability to modulate the shape and reflectance of both the visible and near-infrared spectral curves. Spectral congruence between the synthetic coating and natural green foliage was quantified at 97.41%. Moreover, this performance was maintained over 10 cycles of programmed drying and re-humidification, and the coating consistently demonstrated stable hygroscopic properties and sustained over 95% spectral congruence. These optimized artificial coatings were found to effectively confuse hyperspectral classification algorithms, thus blending seamlessly into a natural foliage backdrop. This study provides a new method for regulating VIS and NIR spectral (visible-near infrared spectrum) features, which will be critical for applications in advanced hyperspectral camouflage materials.

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