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1.
Int J Ophthalmol ; 17(5): 838-844, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38766334

RESUMEN

AIM: To report a technique used with intermittent sliding-lock-knot (ISLK) fixation for limbal conjunctival autografts in pterygium surgery and compared with those of routine intermittent (RI) fixation. METHODS: Consecutive patients with primary pterygium who had undergone pterygium excision combined with limbal conjunctival autograft transplantation between March 2021 and March 2022 at our institute were retrospectively analyzed. Primary outcome measures were mean duration of surgery and suture removal, degree of conjunctival hyperemia on postoperative day 1, pain score at suture removal, postoperative symptoms at 6mo, including conjunctival hyperemia, foreign body sensation, and graft stability. RESULTS: Ninety-eight patients underwent monocular surgery and were divided into ISLK (51 eyes) and RI (47 eyes) groups according to the type of conjunctiva autograft fixation method planned. There was no significant difference in mean duration of surgery between the two groups (18.59±2.39min vs 18.15±2.20min, P=0.417); however, compared to the RI group, shorter suture removal times were observed in the ISLK group [0.58min (0.42-0.87) vs 3.00min (2.21-4.15), P<0.001]. The degree of conjunctival hyperemia on postoperative day 1 was milder in the ISLK group (P<0.001). Pain scores at suture removal were lower in the ISLK group than in RI group [1 (0-3) vs 2 (1-4), P<0.001]. Postoperative symptoms at 6mo were comparable between the groups (P=0.487), with no recurrence. CONCLUSION: ISLK is an innovative method for limbal conjunctival autograft fixation after pterygium excision. Compared to RI fixation, ISLK facilitates suture removal and reduces discomfort, with comparable surgery duration and less conjunctival hyperemia.

2.
Front Med (Lausanne) ; 11: 1386161, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38784232

RESUMEN

Background: Fungal infections are associated with high morbidity and mortality in the intensive care unit (ICU), but their diagnosis is difficult. In this study, machine learning was applied to design and define the predictive model of ICU-acquired fungi (ICU-AF) in the early stage of fungal infections using Random Forest. Objectives: This study aimed to provide evidence for the early warning and management of fungal infections. Methods: We analyzed the data of patients with culture-positive fungi during their admission to seven ICUs of the First Affiliated Hospital of Chongqing Medical University from January 1, 2015, to December 31, 2019. Patients whose first culture was positive for fungi longer than 48 h after ICU admission were included in the ICU-AF cohort. A predictive model of ICU-AF was obtained using the Least Absolute Shrinkage and Selection Operator and machine learning, and the relationship between the features within the model and the disease severity and mortality of patients was analyzed. Finally, the relationships between the ICU-AF model, antifungal therapy and empirical antifungal therapy were analyzed. Results: A total of 1,434 cases were included finally. We used lasso dimensionality reduction for all features and selected six features with importance ≥0.05 in the optimal model, namely, times of arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation. The area under the curve of the model for predicting ICU-AF was 0.981 in the test set, with a sensitivity of 0.960 and specificity of 0.990. The times of arterial catheter (p = 0.011, OR = 1.057, 95% CI = 1.053-1.104) and invasive mechanical ventilation (p = 0.007, OR = 1.056, 95%CI = 1.015-1.098) were independent risk factors for antifungal therapy in ICU-AF. The times of arterial catheter (p = 0.004, OR = 1.098, 95%CI = 0.855-0.970) were an independent risk factor for empirical antifungal therapy. Conclusion: The most important risk factors for ICU-AF are the six time-related features of clinical parameters (arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation), which provide early warning for the occurrence of fungal infection. Furthermore, this model can help ICU physicians to assess whether empiric antifungal therapy should be administered to ICU patients who are susceptible to fungal infections.

3.
Angew Chem Int Ed Engl ; : e202406060, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789390

RESUMEN

The hydroxylation of remote C(sp3)-H bonds in aliphatic amino acids yields crucial precursors for the synthesis of high-value compounds. However, accurate regulation of the regioselectivity of remote C(sp3)-H bonds hydroxylation in aliphatic amino acids continues to be a common challenge in chemosynthesis and biosynthesis. In this study, the Fe(II)/α-ketoglutarate-dependent dioxygenase from Bacillus subtilis (BlAH) was mined and found to catalyze hydroxylation at the γ and δ sites of aliphatic amino acids. Through crystal structure analysis, molecular dynamic simulation and quantum chemical calculations revealed that regioselectivity was regulated by the spatial effect of BlAH. Based on this result, the spatial effect of BlAH was reconstructed to stabilize the transition state at the δ site of aliphatic amino acids, thereby successfully reversing the γ site regioselectivity to the δ site. For example, the regioselectivity of L-Homoleucine (5a) was reversed from the γ site (1:12) to the δ site (>99:1). The present study not only expands the toolbox of biocatalysts for the regioselective functionalization of remote C(sp3)-H bonds, but also provides a theoretical guidance for the precision-driven modification of similarly remote C(sp3)-H bonds in complex molecules.

4.
Insects ; 15(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38786878

RESUMEN

Predators are dependent on the capture of prey to meet their energetic and nutritive requirements, which brings the risk of predation to prey. The predation risk is divided into consumptive and non-consumptive effects. Non-consumptive effects may manifest through altered growth and ontogenetic trajectories in prey species, a dynamic modulated by olfactory or other sensory cues from predators. Bactrocera dorsalis Hendel represents a major invasive threat to global horticulture. While earlier research was primarily centered on the consumptive interactions between B. dorsalis and its natural enemies, the potential consequences of non-consumptive interactions on the development of B. dorsalis have been overlooked. In this study, we investigated the impact of predation risk effects, induced by both visual exposure to the predatory mantis Hierodula patellifera Serville and its associated odor, on the life history traits of B. dorsalis. Female B. dorsalis demonstrated a reduced developmental time in the presence of a caged predator (H. patellifera) or predator odors, but showed significantly increased fecundity. Conversely, males displayed no significant change in developmental time. Additionally, neither the female nor male body weight at death was significantly influenced by the predation risk from the caged predator or predator odors. This study investigated the effects of predation risk on the development and reproduction of B. dorsalis, emphasizing the potential importance of odor risk in biological and pest control.

5.
J Agric Food Chem ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602702

RESUMEN

Pyridoxal 5'-phosphate (PLP) is highly valuable in food and medicine. However, achieving the efficient biosynthesis of PLP remains challenging. Here, a salvage pathway using acid phosphatase from Salmonella typhi (StAPase) and pyridoxine oxidase from Escherichia coli (EcPNPO) as pathway enzymes was established for the first time to synthesize PLP from pyridoxine (PN) and pyrophosphate (PPi). StAPase was identified as a rate-limiting enzyme. Two protein modification strategies were developed based on the PN phosphorylation mechanism: (1) improving the binding of PN into StAPase and (2) enhancing the hydrophobicity of StAPase's substrate binding pocket. The kcat/Km of optimal mutant M7 was 4.9 times higher than that of the wild type. The detailed mechanism of performance improvement was analyzed. Under the catalysis of M7 and EcPNPO, a PLP high-yielding strain of 14.5 ± 0.55 g/L was engineered with a productivity of 1.0 ± 0.02 g/(L h) (the highest to date). The study suggests a promising method for industrial-scale PLP production.

6.
Proc Natl Acad Sci U S A ; 121(16): e2318935121, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38588421

RESUMEN

Glucose is required for generating heat during cold-induced nonshivering thermogenesis in adipose tissue, but the regulatory mechanism is largely unknown. CREBZF has emerged as a critical mechanism for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). We investigated the roles of CREBZF in the control of thermogenesis and energy metabolism. Glucose induces CREBZF in human white adipose tissue (WAT) and inguinal WAT (iWAT) in mice. Lys208 acetylation modulated by transacetylase CREB-binding protein/p300 and deacetylase HDAC3 is required for glucose-induced reduction of proteasomal degradation and augmentation of protein stability of CREBZF. Glucose induces rectal temperature and thermogenesis in white adipose of control mice, which is further potentiated in adipose-specific CREBZF knockout (CREBZF FKO) mice. During cold exposure, CREBZF FKO mice display enhanced thermogenic gene expression, browning of iWAT, and adaptive thermogenesis. CREBZF associates with PGC-1α to repress thermogenic gene expression. Expression levels of CREBZF are negatively correlated with UCP1 in human adipose tissues and increased in WAT of obese ob/ob mice, which may underscore the potential role of CREBZF in the development of compromised thermogenic capability under hyperglycemic conditions. Our results reveal an important mechanism of glucose sensing and thermogenic inactivation through reversible acetylation.


Asunto(s)
Tejido Adiposo Pardo , Glucosa , Ratones , Humanos , Animales , Glucosa/metabolismo , Tejido Adiposo Pardo/metabolismo , Acetilación , Tejido Adiposo Blanco/metabolismo , Metabolismo Energético , Obesidad/genética , Obesidad/metabolismo , Termogénesis/genética , Ratones Endogámicos C57BL , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo
7.
Int J Lab Hematol ; 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38679027

RESUMEN

INTRODUCTION: Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic stem cell disorders. DNA hypermethylation is considered to be the key mechanism of pathogenesis for MDS. Studies have demonstrated that DNA methylation can be regulated by the co-effect between long non-coding RNAs (lncRNAs) and DNA methyltransferases (DNMTs). The aim of this study was to identify DNMTs-associated differentially expressed (DE) lncRNAs, which may be a novel diagnostic and therapeutic target for MDS. METHODS: Two gene expression profile datasets (GSE4619 and GSE19429) were downloaded from the Gene Expression Omnibus (GEO) database. Systematic bioinformatics analysis was conducted. Then we verified the expression of PRKCQ-AS1 in MDS patients and features in SKM-1 cells. RESULTS: Bioinformatics analysis revealed that the DNMT-associated DE-lncRNA PRKCQ-AS1 was functionally related to DNA methylation. The target genes of PRKCQ-AS1 associated with DNA methylation are mainly methionine synthetase (MTR) and ten-eleven-translocation 1 (TET1). Moreover, the high expression of PRKCQ-AS1 was verified in real MDS cases. Further cellular analysis in SKM-1 cells revealed that overexpressed PRKCQ-AS1 promoted methylation levels of long interspersed nuclear element 1 (LINE-1) and cell proliferation, and apparently elevated both mRNA and protein levels of MTR and TET1, while knockdown of PRKCQ-AS1 showed opposite trend in SKM-1 cells. CONCLUSION: DNMT-associated DE-lncRNA PRKCQ-AS1 may affects DNA methylation levels by regulating MTR and TET1.

8.
Animals (Basel) ; 14(8)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38672351

RESUMEN

Decapterus maruadsi is a typical representative of small pelagic fish characterized by fast growth rate, small body size, and high fecundity. It is a high-quality marine commercial fish with high nutritional value. However, the underlying genetics and genomics research focused on D. maruadsi is not comprehensive. Herein, a high-quality chromosome-level genome of a male D. maruadsi was assembled. The assembled genome length was 716.13 Mb with contig N50 of 19.70 Mb. Notably, we successfully anchored 95.73% contig sequences into 23 chromosomes with a total length of 685.54 Mb and a scaffold N50 of 30.77 Mb. A total of 22,716 protein-coding genes, 274.90 Mb repeat sequences, and 10,060 ncRNAs were predicted, among which 22,037 (97%) genes were successfully functionally annotated. The comparative genome analysis identified 459 unique, 73 expanded, and 52 contracted gene families. Moreover, 2804 genes were identified as candidates for positive selection, of which some that were related to the growth and development of bone, muscle, cardioid, and ovaries, such as some members of the TGF-ß superfamily, were likely involved in the evolution of typical biological features in D. maruadsi. The study provides an accurate and complete chromosome-level reference genome for further genetic conservation, genomic-assisted breeding, and adaptive evolution research for D. maruadsi.

9.
Cytokine ; 179: 156618, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38663252

RESUMEN

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.


Asunto(s)
Quimiocina CXCL11 , Quimiocina CXCL9 , Derrame Pleural , Receptores CXCR3 , Tuberculosis Pleural , Humanos , Quimiocina CXCL9/metabolismo , Quimiocina CXCL11/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Derrame Pleural/metabolismo , Derrame Pleural/diagnóstico , Receptores CXCR3/metabolismo , Tuberculosis Pleural/diagnóstico , Tuberculosis Pleural/metabolismo , Adulto , Ligandos , Método Doble Ciego , Células THP-1 , Biomarcadores/metabolismo , Macrófagos/metabolismo , Estudios Prospectivos , Anciano , Curva ROC
10.
Enzyme Microb Technol ; 178: 110448, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38657401

RESUMEN

D-allulose is a naturally occurring rare sugar and beneficial to human health. However, the efficient biosynthesis of D-allulose remains a challenge. Here, we mined a new D-tagatose 3-epimerase from Kroppenstedtia eburnean (KeDt3e) with high catalytic efficiency. Initially, crucial factors contributing to the low conversion of KeDt3e were identified through crystal structure analysis, density functional theory calculations (DFT), and molecular dynamics (MD) simulations. Subsequently, based on the mechanism, combining restructuring the flexible region, proline substitution based onconsensus sequence analysis, introducing disulfide bonds, and grafting properties, and reshaping the active center, the optimal mutant M5 of KeDt3e was obtained with enhanced thermostability and activity. The optimal mutant M5 exhibited an enzyme activity of 130.8 U/mg, representing a 1.2-fold increase; Tm value increased from 52.7 °C to 71.2 °C; and half-life at 55 °C extended to 273.7 min, representing a 58.2-fold improvement, and the detailed mechanism of performance improvement was analyzed. Finally, by screening the ribosome-binding site (RBS) of the optimal mutant M5 recombinant bacterium (G01), the engineered strain G08 with higher expression levels was obtained. The engineered strain G08 catalyzed 500 g/L D-fructose to produce 172.4 g/L D-allulose, with a conversion of 34.4% in 0.5 h and productivity of 344.8 g/L/h on a 1 L scale. This study presents a promising approach for industrial-scale production of D-allulose.


Asunto(s)
Carbohidrato Epimerasas , Estabilidad de Enzimas , Hexosas , Hexosas/metabolismo , Carbohidrato Epimerasas/genética , Carbohidrato Epimerasas/metabolismo , Carbohidrato Epimerasas/química , Simulación de Dinámica Molecular , Fructosa/metabolismo , Cinética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Especificidad por Sustrato , Ingeniería de Proteínas , Racemasas y Epimerasas/metabolismo , Racemasas y Epimerasas/genética , Racemasas y Epimerasas/química
11.
Fitoterapia ; 175: 105967, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38631597

RESUMEN

Sulfur-containing natural products possess a variety of biological functions including antitumor, antibacterial, anti-inflammatory and antiviral activities. In this study, four previously undescribed sulfur-containing compounds asperteretals L and M, terreins A and B, together with 17 known compounds were obtained from a culture of marine fungus A. terreus supplemented with inorganic sulfur source Na2SO4. Their planar structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD experiments. The in vitro cytotoxicities of compounds 1-21 against HCT-116 and Caco-2 were evaluated by SRB assay. Asperteretal M (2) exhibited activity against HCT-116 with the IC50 value at 30µM. The antiproliferative effect of asperteretal M was confirmed by colony formation assay and cell death staining. Furthermore, the preliminary study on the anti-colon cancer mechanism of asperteretal M was performed by RNA-seq analysis. Western blotting validated that asperteretal M significantly decreased the expression of cell-cycle regulatory proteins CDK1, CDK4, and PCNA in a concentration-dependent manner.


Asunto(s)
Antineoplásicos , Aspergillus , Compuestos de Azufre , Humanos , Aspergillus/química , Estructura Molecular , Células HCT116 , Compuestos de Azufre/farmacología , Compuestos de Azufre/aislamiento & purificación , Antineoplásicos/farmacología , Antineoplásicos/aislamiento & purificación , Células CACO-2 , Neoplasias del Colon/tratamiento farmacológico
12.
J Org Chem ; 89(7): 4395-4405, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38501298

RESUMEN

A visible-light-induced chemodivergent synthesis of tetracyclic quinazolinones and 3-iminoisoindoliones has been developed. This chemodivergent reaction afforded two kinds of different products by substrate control. A detailed investigation of the reaction mechanism revealed that this consecutive photoinduced electron transfer (ConPET) cascade cyclization involved a radical process, and the aryl radical was the crucial intermediate. This method employed 4-DPAIPN as a photocatalyst and i-Pr2NEt as a sacrificial electron donor leading to metal-free conditions.

13.
Org Biomol Chem ; 22(15): 2968-2973, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38529682

RESUMEN

An Fe-catalyzed visible-light induced condensation of alkylbenzenes with anthranilamides has been developed. Upon irradiation, the trivalent iron complex could generate chlorine radicals, which successfully abstracted the hydrogen of benzylic C-H bonds to form benzyl radicals. And these benzyl radicals were converted into oxygenated products under air conditions, which subsequently reacted with anthranilamides for the synthesis of quinazolinones.

14.
Org Biomol Chem ; 22(15): 2953-2957, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38546108

RESUMEN

An efficient method for the synthesis of alkynyl sulfides via a C(sp3)-S bond cleavage of α-bromostyrene sulfonium salts has been developed. This base-promoted nucleophilic ring-opening pathway allows the preparation of diverse alkynyl sulfide compounds using tetramethylene sulfoxide as the sulfur source. The reaction proceeds with good functional group tolerance and could be applied to the late-stage functionalization of bioactive molecules and drugs. Furthermore, the synthetic utility of this method was demonstrated by a one-pot synthesis, scale-up reaction and further modification of various alkynyl sulfide products.

15.
Diabetes Metab Syndr Obes ; 17: 1025-1037, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476349

RESUMEN

Purpose: Migraine is a complex neurovascular disorder with obesity as a notable risk factor. This study aimed to investigate an under-researched area of the association between migraine duration and body composition. Patients and Methods: Patients with migraine from a neurology outpatient department were enrolled and were categorized into four groups based on illness duration: 1 year, 1-5 years, 5-10 years, and >10 years. Patient demographics, blood biochemistry, and body composition data were collected and analyzed statistically. Results: Patients with migraine were predominantly female, with lower education levels, significant work stress, poor sleep, and limited exercise. Longer migraine duration corresponded to increased obesity metrics. Notably, those patients with under 1 year of illness showed elevated blood lipid and liver function levels, whereas those with >10 years showed increased weight, waist circumference, body mass index, and fat content, despite higher physical activity. Significant positive correlation between obesity metrics and migraine duration was seen in patients who had migraine for >1 year. Conclusion: Our findings indicate that protracted episodes of migraine could amplify obesity tendencies, underscoring the imperative of weight regulation in migraine intervention to diminish ensuing adiposity-associated hazards.

16.
Aging Clin Exp Res ; 36(1): 69, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38483650

RESUMEN

Individuals with chronic obstructive pulmonary disease (COPD) are prone to malnutrition and sarcopenia as a result of nutritional deficiencies and increased energy metabolism. However, the effects of nutrient supplements (NS) on treating sarcopenia in patients with COPD are not well established from systematic evidence. This meta-analysis examined the effect of NS on sarcopenia in patients with COPD. A systematic search of multiple databases was conducted, and 29 randomized controlled trials involving 1625 participants (age, mean [SD] = 67.9 [7.8] years) were analyzed. NS demonstrated significant improvements in body weight (MD,1.33 kg; 95% CI, 0.60, 2.05 kg; P = 0.0003; I2 = 87%), fat-free mass index (MD, 0.74 kg/m2; 95% CI, 0.21, 1.27 kg/m2; P = 0.007; I2 = 75%), and 6-min walk test (MD, 19.43 m; 95% CI, 4.91, 33.94 m; P = 0.009; I2 = 81%) compared with control. However, NS had nonsignificant effects on handgrip strength (SMD, 0.36; 95% CI, - 0.15, 0.88; P = 0.16; I2 = 87%) and quadriceps muscle strength (SMD, 0.11; 95% CI, -  0.06, 0.27; P = 0.20; I2 = 25%) compared with the control. In conclusion, NS may be an effective treatment for improving body composition and physical performance in COPD. Future studies should explore the effects of intervention durations, specific NS types, or combined training in patients with COPD and sarcopenia.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Sarcopenia , Humanos , Sarcopenia/terapia , Fuerza de la Mano , Calidad de Vida , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/terapia , Fuerza Muscular
17.
Virus Evol ; 10(1): vead084, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38516655

RESUMEN

In secondary lymphoid tissues, human immunodeficiency virus (HIV) can replicate in both the follicular and extrafollicular compartments. Yet, virus is concentrated in the follicular compartment in the absence of antiretroviral therapy, in part due to the lack of cytotoxic T lymphocyte (CTL)-mediated activity there. CTLs home to the extrafollicular compartment, where they can suppress virus load to relatively low levels. We use mathematical models to show that this compartmentalization can explain seemingly counter-intuitive observations. First, it can explain the observed constancy of the viral decline slope during antiviral therapy in the peripheral blood, irrespective of the presence of CTL in Simian Immunodeficiency Virus (SIV)-infected macaques, under the assumption that CTL-mediated lysis significantly contributes to virus suppression. Second, it can account for the relatively long times it takes for CTL escape mutants to emerge during chronic infection even if CTL-mediated lysis is responsible for virus suppression. The reason is the heterogeneity in CTL activity and the consequent heterogeneity in selection pressure between the follicular and extrafollicular compartments. Hence, to understand HIV dynamics more thoroughly, this analysis highlights the importance of measuring virus populations separately in the extrafollicular and follicular compartments rather than using virus load in peripheral blood as an observable; this hides the heterogeneity between compartments that might be responsible for the particular patterns seen in the dynamics and evolution of the HIV in vivo.

18.
World J Clin Cases ; 12(6): 1144-1149, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38464923

RESUMEN

BACKGROUND: This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome (AS) following coronavirus disease 2019 (COVID-19) in a 33-year-old man diagnosed with Klinefelter syndrome (KS). CASE SUMMARY: A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19. Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs, accompanied by signs of partial bronchial inflation. Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen. A biopsy specimen revealed organizing pneumonia with alveolar septal thickening. Additionally, extensive auto-antibody tests showed strong positivity for anti-SSA, anti-SSB, anti-Jo-1, and anti-Ro-52. Following multidisciplinary discussions, the patient received a final diagnosis of AS, leading to rapidly progressing respiratory failure. CONCLUSION: This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

19.
PLoS One ; 19(3): e0299720, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38427643

RESUMEN

Ewing's sarcoma (ES) is the second most common bone and soft tissue malignancy in children and adolescents with a poor prognosis. The identification of genes with prognostic value may contribute to the prediction and treatment of this disease. The GSE17679, GSE68776, GSE63155, and GSE63156 datasets were downloaded from the Gene Expression Omnibus database and qualified. Prognostic value of differentially expressed genes (DEGs) between the normal and tumor groups and immune cell infiltration were explored by several algorithms. A prognostic model was established and validated. Finally, functional analyses of the DEGs were performed. Proline rich 11 (PRR11) and mast cell infiltration were noted as the key indicators for the prognosis of ES. Kaplan-Meier and scatter plots for the training and two validation sets showed that patients in the low-PRR11 expression group were associated with better outcomes than those in the high-PRR11 expression group. The concordance indices and calibration analyses of the prognostic model indicated good predictive accuracy in the training and validation sets. The area under the curve values obtained through the receiver operating characteristic analysis for 1-, 3-, 5-year prediction were ≥ 0.75 in the three cohorts, suggesting satisfactory sensitivity and specificity of the model. Decision curve analyses suggested that patients could benefit more from the model than the other strategies. Functional analyses suggested that DEGs were mainly clustered in the cell cycle pathway. PRR11 and mast cell infiltration are potential prognostic indicators in ES. PRR11 possibly affects the prognosis of patients with ES through the cell cycle pathway.


Asunto(s)
Sarcoma de Ewing , Sarcoma , Adolescente , Niño , Humanos , Algoritmos , Calibración , Pronóstico , Sarcoma de Ewing/genética
20.
Appl Neuropsychol Child ; : 1-11, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38316010

RESUMEN

This study examines functional brain network changes in children with frontal lobe tumors (FLT). Ten pediatric FLT patients from Beijing Tiantan Hospital and 20 healthy children were compared in terms of cognitive performance and resting-state functional magnetic resonance imaging (rs-fMRI) connectivity. The FLT group showed lower cognitive performance, particularly in visual and working memory domains, but had comparable attention abilities to the healthy controls. There were notable differences in connectivity between the default mode network (DMN) and sensorimotor network (SMN) in both groups. The FLT group also displayed a significant reduction in local efficiency in the left lateral parietal area within the DMN. Importantly, reduced DMN-SMN connections and increased DMN-lateral prefrontal cortex connectivity may facilitate maintaining attention and memory tasks in FLT children. This study sheds light on how the brains of children with FLT adapt, preserving "normal" attention functions despite frontal lobe damage.

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