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1.
bioRxiv ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38586019

RESUMO

Background: Identifying biomarkers that predict substance use disorder (SUD) propensity may better strategize anti-addiction treatment. The melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) critically mediates interactions between sleep and substance use; however, their activities are largely obscured in surface electroencephalogram (EEG) measures, hindering the development of biomarkers. Methods: Surface EEG signals and real-time Ca2+ activities of LH MCH neurons (Ca2+MCH) were simultaneously recorded in male and female adult rats. Mathematical modeling and machine learning were then applied to predict Ca2+MCH using EEG derivatives. The robustness of the predictions was tested across sex and treatment conditions. Finally, features extracted from the EEG-predicted Ca2+MCH either before or after cocaine experience were used to predict future drug-seeking behaviors. Results: An EEG waveform derivative - a modified theta-to-delta ratio (EEG Ratio) - accurately tracks real-time Ca2+MCH in rats. The prediction was robust during rapid eye movement sleep (REMS), persisted through REMS manipulations, wakefulness, circadian phases, and was consistent across sex. Moreover, cocaine self-administration and long-term withdrawal altered EEG Ratio suggesting shortening and circadian redistribution of synchronous MCH neuron activities. In addition, features of EEG Ratio indicative of prolonged synchronous MCH neuron activities predicted lower subsequent cocaine seeking. EEG Ratio also exhibited advantages over conventional REMS measures for the predictions. Conclusions: The identified EEG Ratio may serve as a non-invasive measure for assessing MCH neuron activities in vivo and evaluating REMS; it may also serve as a potential biomarker predicting drug use propensity.

2.
AMB Express ; 14(1): 34, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600342

RESUMO

Heat stress is one of the major abiotic stresses affecting the growth, sporulation, colonization and survival of Trichoderma viride. This study aimed to gain a better insight into the underlying mechanism governing the heat stress response of T. viride Tv-1511. We analysed the transcriptomic changes of Tv-1511 under normal and heat stress conditions using RNA sequencing. We observed that Tv-1511 regulates the biosynthesis of secondary metabolites through a complex network of signalling pathways. Additionally, it significantly activates the anti-oxidant defence system, heat shock proteins and stress-response-related transcription factors in response to heat stress. TvHSP70 was identified as a key gene, and transgenic Tv-1511 overexpressing TvHSP70 (TvHSP70-OE) was generated. We conducted an integrated morphological, physiological and molecular analyses of the TvHSP70-OE and wild-type strains. We observed that TvHSP70 over-expression significantly triggered the growth, anti-oxidant capacity, anti-fungal activity and growth-promoting ability of Tv-1511. Regarding anti-oxidant capacity, TvHSP70 primarily up-regulated genes involved in enzymatic and non-enzymatic anti-oxidant systems. In terms of anti-fungal activity, TvHSP70 primarily activated genes involved in the synthesis of enediyne, anti-fungal and aminoglycoside antibiotics. This study provides a comparative analysis of the functional significance and molecular mechanisms of HSP70 in Trichoderma. These findings provide a valuable foundation for further analyses.

3.
Am J Reprod Immunol ; 91(3): e13831, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444103

RESUMO

BACKGROUND: The COVID-19 pandemic is an unprecedented health crisis that has affected in vitro fertilization practices globally. Previous studies have shown that SARS-CoV-2 impacts the quality of embryos by inducing an immunological response in infertile patients. In this study, the early embryonic development of SARS-CoV-2-infected infertile patients was investigated. METHODS: Sixty-five SARS-CoV-2 infected infertile patients and 258 controls were involved in this study. The major outcome parameters for the cycle were analyzed, including the number of oocytes, maturation oocytes, available embryos per cycle, and embryo morpho kinetic characteristics. RESULTS: From SARS-CoV-2 infection until oocyte retrieval, it took an average of 6.63 days. The results revealed that the number of oocytes and high-quality embryos on day 3 dramatically reduced in SARS-CoV-2-infected infertile patients. SARS-CoV-2 was detected in the follicular fluid of three infertile patients. SARS-CoV-2 infection had negatively impacted the number of oocytes in multivariate linear regression models. The early embryonic development in the SARS-CoV-2 infection group had a noticeable delay from the six-cell stage to blastocyst stage. CONCLUSIONS: SARS-CoV-2 infection reduced the number of oocytes and high-quality embryos on day 3. It delays the early embryonic development from the six-cell stage to blastocyst stage and has a negative impact on the quality of embryos.


Assuntos
COVID-19 , Infertilidade , Feminino , Gravidez , Humanos , SARS-CoV-2 , Pandemias , Oócitos , Desenvolvimento Embrionário
4.
Front Plant Sci ; 15: 1308553, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38516663

RESUMO

Lettuce (Lactuca sativa) germination is sensitive to environmental conditions. Recently, hydrogel has received increased attention as an alternative media to soil for seed germination. Compared to soil seeding, hydrogel-aided germination provides more controlled seeding environments. However, there are still challenges preventing hydrogel-aided seed germination from being widely used in industry production or academic studies, such as hydrogel formulation variations, seeding operation standardization, and germination evaluation. In this study, we tested how the combination of multiple environmental conditions affect lettuce seed germination time, which is measured as the time needed for the first pair of leaves to appear (leaf emergence) or, alternatively, the third leaf to appear (leaf development). We found that germination time and success rate of two lettuce varieties (Iceberg A and Butter Crunch) showed different sensitivities to pH, Hoagland formulations and concentrations, light intensity, and hydrogel content. We have conducted statistical analysis on the correlation between germination time and these environmental conditions.

5.
Med Ultrason ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38537183

RESUMO

AIM: Prostate cancer (PCa) is one of the most common neoplasms in men. However, the value of ultrasound-based radiomics for diagnosing PCa remains uncertain. MATERIAL AND METHODS: We retrospectively analyzed ultrasonic and clinical data from 373 patients. Patients were divided into two groups according to the pathological results. Radiomics features wereextracted from TRUS, and we screened the optimal features to construct radiomics models. Relationships between clinical characteristics and prostate lesions were identified by univariate and multivariate logistic regression analysis. Finally, a clinical-radiomics model was developed, and then visualized in the form of a nomogram. RESULTS: Of the 373 patients, 178 had benign disease and 195 had malignant disease. The support vector machine (SVM) classification model showed the best performance, while the diagnostic performance of the clinical model was poorer than that of the radiomics model (p<0.05) or the combined (clinical-radiomics) model (p<0.05). In general, the combined model demonstrated the highest AUC and proved to be more advantageous. CONCLUSION: The prediction model we constructed based on TRUS predicted PCa preoperatively with high efficiency. In addition, combining radiomics with clinical factors improved diagnostic accuracy.

6.
J Imaging ; 10(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38535139

RESUMO

Personal privacy protection has been extensively investigated. The privacy protection of face recognition applications combines face privacy protection with face recognition. Traditional face privacy-protection methods encrypt or perturb facial images for protection. However, the original facial images or parameters need to be restored during recognition. In this paper, it is found that faces can still be recognized correctly when only some of the high-order and local feature information from faces is retained, while the rest of the information is fuzzed. Based on this, a privacy-preserving face recognition method combining random convolution and self-learning batch normalization is proposed. This method generates a privacy-preserved scrambled facial image and an image fuzzy degree that is close to an encryption of the image. The server directly recognizes the scrambled facial image, and the recognition accuracy is equivalent to that of the normal facial image. The method ensures the revocability and irreversibility of the privacy preserving of faces at the same time. In this experiment, the proposed method is tested on the LFW, Celeba, and self-collected face datasets. On the three datasets, the proposed method outperforms the existing face privacy-preserving recognition methods in terms of face visual information elimination and recognition accuracy. The recognition accuracy is >99%, and the visual information elimination is close to an encryption effect.

7.
Discov Oncol ; 15(1): 37, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363409

RESUMO

BACKGROUND: Endoplasmic reticulum stress (ERS) acts critical roles on cell growth, proliferation, and metastasis in various cancers. However, the relationship between ERs and lung squamous cell carcinoma (LUSC) prognoses still remains unclear. METHODS: The consensus clustering analysis of ERS-related genes and the differential expression analysis between clusters were investigated in LUSC based on TCGA database. Furthermore, ERS-related prognostic risk models were constructed by LASSO regression and Cox regression analyses. Then, the predictive effect of the risk model was evaluated by Kaplan-Meier, Cox regression, and ROC Curve analyses, as well as validated in the GEO cohort. According to the optimal threshold, patients with LUSC were divided into high- and low- risk groups, and somatic mutations, immune cell infiltration, chemotherapy response and immunotherapy effect were systematically analyzed. RESULTS: Two ERS-related clusters were identified in patients with LUSC that had distinct patterns of immune cell infiltration. A 5-genes ERS-related prognostic risk model and nomogram were constructed and validated. Kaplan-Meier curves and Cox regression analysis showed that ERS risk score was an independent prognostic factor (p < 0.001, HR = 1.317, 95% CI = 1.159-1.496). Patients with low-risk scores presented significantly lower TIDE scores and significantly lower IC50 values for common chemotherapy drugs such as cisplatin and gemcitabine. CONCLUSION: ERS-related risk signature has certain prognostic value and may be a potential therapeutic target and prognostic biomarker for LUSC patients.

8.
J Fish Dis ; 47(4): e13922, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38204197

RESUMO

The purpose of this study was to investigate whether a defensin-like antimicrobial peptide (C-13326 peptide) identified in Hermetia illucens could possess protective effect against multidrug-resistant Aeromonas schubertii in hybrid snakehead (Channa maculate ♀ × Channa argus ♂). The cDNA of C-13326 peptide comprised 243 nucleotides encoding 80 amino acids, with six conserved cysteine residues and the classical CSαß structure. The recombinant expression plasmid pPIC9K-C-13326 was constructed and transformed into GS115 Pichia pastoris, and the C-13326 peptide was expressed by induction with 1% methanol. The crude extract of C-13326 peptide was precipitated by ammonium sulfate, assayed by Braford method, detected by tricine-SDS-PAGE, evaluated by BandScan software and identified by liquid chromatography-mass spectrometry. The C-13326 peptide was shown to have inhibitory activity against the growth of multidrug-resistant A. schubertii DM210910 by using the minimum growth inhibitory concentration and Oxford cup method. In addition, scanning electron microscopy analysis suggested that C-13326 peptide inhibited the growth of A. schubertii DM210910 by damaging the bacterial cell membrane. To explore the role of peptide C-13326 in vivo, hybrid snakehead was fed with peptide C-13326 as feed additives for 7 days. The results revealed that C-13326 peptide could significantly down-regulate the expression levels of IL-1ß, IL-8, IL-12 and TNF-α (p < .05), and significantly improved the survival rate of hybrid snakehead after challenging with A. schubertii DM210910. Therefore, the C-13326 peptide is a promising antimicrobial agent for A. schubertii treatment in aquaculture.


Assuntos
Aeromonas , Doenças dos Peixes , Animais , Doenças dos Peixes/prevenção & controle , Doenças dos Peixes/microbiologia , Peixes/genética , Aeromonas/genética , Peptídeos , Defensinas/genética , Defensinas/farmacologia
9.
Clin Cancer Res ; 30(7): 1248-1255, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38190117

RESUMO

PURPOSE: Patients with peripheral T-cell lymphomas (PTCL) in the relapsed or refractory (r/r) setting have only a limited number of therapies available, and the prognosis is extremely poor. SHR2554 is an oral inhibitor against EZH2, a rational therapeutic target for lymphomas. PATIENTS AND METHODS: This was a multicenter, two-part, phase I study of SHR2554 in r/r mature lymphoid neoplasms. In part I, 350 mg twice daily was established as the recommended phase II dose (RP2D) based on the findings during dose escalation and expansion; subsequently, selected lymphoma subtypes were recruited in clinical expansion cohorts to receive SHR2554 at RP2D. Here, we provide an in-depth assessment of SHR2554 at RP2D in subpopulation with r/r PTCL. RESULTS: Twenty-eight patients were included for analysis (17 angioimmunoblastic T-cell lymphoma and 11 not otherwise specified). Eighteen (64%) patients had received ≥2 lines of previous anticancer therapies. The objective response rate was 61% [95% confidence interval (CI), 41-78]. Responses were still ongoing in 59% (10/17) of the responders; estimated median duration of response was 12.3 months (95% CI, 7.4-not reached). Median progression-free survival was 11.1 months (95% CI, 5.3-22.0), and 12-month overall survival rate was 92% (95% CI, 72-98). The most common grade 3 or 4 treatment-related adverse events were decreased platelet count [nine (32%)] as well as decreased white blood cell count, decreased neutrophil count, and anemia [four (14%) for each]. No treatment-related deaths were reported. CONCLUSIONS: This extended follow-up analysis further supports SHR2554 as a therapeutic opportunity for patients with r/r PTCL.


Assuntos
Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/patologia , Resultado do Tratamento , Proteína Potenciadora do Homólogo 2 de Zeste , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Inibidores Enzimáticos/uso terapêutico
10.
Eur J Clin Pharmacol ; 80(1): 115-125, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37932381

RESUMO

PURPOSE: To investigate the association between proton pump inhibitors (PPIs) administration during hospitalization and mortality and length of stay in critically ill pediatric patients. MATERIALS AND METHODS: This is a retrospective observational cohort study on pediatric ICU patients (0 to 18 years). Propensity score matching (PSM), Kaplan-Meier curves, Cox proportional hazards model and Linear regression model was applied for assessing the effects of PPIs on mortality and other outcomes during hospitalization. RESULTS: A total of 2269 pediatric ICU patients were included, involving 1378 omeprazole (OME) users and 891 non-OME users. The results showed significant association between OME exposure and decreased ICU stay (ß -0.042; 95% CI -0.073--0.011; P = 0.008) but prolonged non-ICU hospital stay (ß 0.121; 95% CI 0.097-0.155; P = 0.040). No statistical significance was observed between OME exposure and reduced mortality, but the OME group had a slightly decreased tendency in 28-day mortality (HR 0.701; 95% CI 0.418-1.176) and in-hospital mortality (HR 0.726; 95% CI 0.419-1.257). Furthermore, subgroup analyses revealed that the decreased tendency of mortality were more obvious in patients less than 1 year old compared with older pediatric patients, although not statistically significant. In addition, we also observed that OME exposure was significantly associated with reduced mortality of general ICU subgroup. CONCLUSIONS: This study provided a sign that PPIs used only in the ICU, rather than throughout hospital stay, might provide more benefit for critically ill pediatric patients. Additionally, younger pediatric patients might gain relatively more benefit than older children when receiving PPIs.


Assuntos
Estado Terminal , Omeprazol , Humanos , Criança , Adolescente , Lactente , Tempo de Internação , Estudos de Coortes , Omeprazol/uso terapêutico , Estado Terminal/terapia , Mortalidade Hospitalar , Inibidores da Bomba de Prótons/uso terapêutico , Unidades de Terapia Intensiva , Estudos Retrospectivos
11.
J Anim Physiol Anim Nutr (Berl) ; 108(1): 148-162, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37609936

RESUMO

Breeding pigeons is a fundamental source of profit in various enterprises but little is known on the metabolic laws governing their lactation. In this study, we analysed the metabolic profile of different sex of breeding pigeons (Columba livia, European pigeons, Mimas) during lactation. We found that male pigeons exhibited catabolism during lactation. Extension of lactation resulted in increased weight loss, then slow recovery of body weight. Conversely, the weight loss in female pigeons peaked on the seventh day of lactation. They then gradually recovered their body weight. Male pigeons showed more duration of combing, while female pigeons showed more duration of resting. In male pigeons, except for triglyceride (TG), which increased, blood lipid indexes barely changed during lactation. Conversely, in females, both TG and total cholesterol increased in middle and late lactation. The level of oxidative stress in female pigeons during lactation was higher than in males, lipid peroxide malondialdehyde, hydrogen peroxide (H2 O2 ), plasma calcium (Ca) and phosphorus (P) levels increased in late lactation. Levels of estradiol and progesterone in female pigeons increased during lactation, whereas those of luteotropic hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL) and testosterone gradually decreased. As per LC-MS spectra analysis, the differential metabolites in the plasma on the day of hatching and before laying in female pigeons in lactation were enriched in retrograde endocannabinoid signalling, α-linolenic acid, arachidonic acid, choline, glycerophospholipid metabolisms, and valine, leucine, and isoleucine degradations. Levels of fatty acids, amino acids, sphingomyelin and phosphatidylinositol related to the secretion of pigeon milk had reduced, whereas the levels of phosphatidylcholine, phosphatidylethanolamine, and TG, which are all related to egg production, had increased. In conclusion, our study systematically revealed the different metabolic characteristics of male and female breeding pigeons during lactation. This is useful for precision feeding of pigeons and applicable in nutritional interventions for improved production.


Assuntos
Columbidae , Lactação , Feminino , Masculino , Animais , Estresse Oxidativo , Peso Corporal , Redução de Peso
12.
J Infect Dev Ctries ; 17(11): 1566-1573, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38064390

RESUMO

INTRODUCTION: Accurate identification of pathogens that cause pulmonary infections is essential for effective treatment and hastening recovery in adults diagnosed with pneumonia. At present, despite metagenomic next-generation sequencing (mNGS) technology has been widely used in clinical practice for pathogen identification, the clinical significance and necessity of detecting pathogen in bronchoalveolar lavage fluid (BALF) for pneumonia-stricken adults remain ambiguous. METHODOLOGY: In this study, 80 patients suffering from pulmonary infection were enrolled, who were admitted to the Affiliated Changzhou Second People's Hospital of Nanjing Medical University between January 2020 and September 2022. The diagnostic performances of mNGS and conventional methods (CM) were systematically analyzed based on BALF samples, and we further investigated the influence of mNGS and CM in diagnosis modification and treatment. RESULTS: We found a significantly higher positive rate for the mNGS method in contrast to CM. Bacteria were the most common pathogens, and Streptococcus pneumoniae was the most commonly identified pathogen. Candida albicans and Epstein-Barr virus were the most frequently identified fungus and virus. Atypical pathogens such as Mycobacterium tuberculosis, virus Nontuberculous mycobacteria, and Chlamydia psittaci were also identified. A total of 77 patients were identified with mixed infections by mNGS. As the disease progressed and recurrent antibiotic treatment persisted, significant dynamic changes in the clinical manifestation from the BALF samples could be found by mNGS. CONCLUSIONS: This study underscores the efficacy of mNGS in detecting pathogens in BALF samples from patients suffering pulmonary infections. Compared with the CM, mNGS significantly enhanced the positive diagnosis ratio, particularly in diagnosing Mycobacterium tuberculosis, atypical pathogens, and viral or fungal infections.


Assuntos
Infecções por Vírus Epstein-Barr , Mycobacterium tuberculosis , Pneumonia , Adulto , Humanos , Herpesvirus Humano 4 , Pneumonia/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Streptococcus pneumoniae , Sensibilidade e Especificidade
13.
Oral Dis ; 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129744

RESUMO

OBJECTIVES: This study aimed to assess the epidemiological and three-dimensional (3D) radiological characterizations of odontomas, as well as the spatial relationship between odontomas and gubernaculum tracts (GT). MATERIALS AND METHODS: We retrieved the cone-beam computed tomography (CBCT) data of 87,590 patients. Dentition, location, type, diameter of the odontomas, width of the dental follicle (DF), the spatial relationship between the odontoma and GT, and the influence on adjacent teeth were evaluated. RESULTS: Significant differences were found in age, dentition, location, Max/Min diameter, width of DF, impaction, retention, and root bending of adjacent teeth among different spatial relationships between the odontoma and GT (all p < 0.05), as well as in age, type and size, absence, impaction, malposition, and retention of adjacent teeth among different locations of odontomas (all p < 0.05). Compared to the odontomas without impaction, those with impaction had larger diameter (p < 0.05 in all directions). This statistically significant association was consistent for odontomas with malposition, while no similar result was observed in the maximum diameter. CONCLUSION: Our findings provide the preliminary data for clinicians to comprehensively understand the incidence, radiographic characterizations and symptoms of odontoma in Chinese population.

14.
Elife ; 122023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37963179

RESUMO

In substance use disorders, drug use as unconditioned stimulus (US) reinforces drug taking. Meanwhile, drug-associated cues (conditioned stimulus [CS]) also gain incentive salience to promote drug seeking. The basolateral amygdala (BLA) is implicated in both US- and CS-mediated responses. Here, we show that two genetically distinct BLA neuronal types, expressing Rspo2 versus Ppp1r1b, respectively, project to the nucleus accumbens (NAc) and form monosynaptic connections with both dopamine D1 and D2 receptor-expressing neurons. While intra-NAc stimulation of Rspo2 or Ppp1r1b presynaptic terminals establishes intracranial self-stimulation (ICSS), only Ppp1r1b-stimulated mice exhibit cue-induced ICSS seeking. Furthermore, increasing versus decreasing the Ppp1r1b-to-NAc, but not Rspo2-to-NAc, subprojection increases versus decreases cue-induced cocaine seeking after cocaine withdrawal. Thus, while both BLA-to-NAc subprojections contribute to US-mediated responses, the Ppp1r1b subprojection selectively encodes CS-mediated reward and drug reinforcement. Such differential circuit representations may provide insights into precise understanding and manipulation of drug- versus cue-induced drug seeking and relapse.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Cocaína , Ratos , Camundongos , Animais , Sinais (Psicologia) , Núcleo Accumbens , Ratos Sprague-Dawley , Recompensa , Cocaína/farmacologia
15.
Front Pharmacol ; 14: 1273640, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38035020

RESUMO

Background: Our previous study reported that histamine H2 receptor antagonists (H2RAs) exposure was associated with decreased mortality in critically ill patients with heart failure (HF) through the same pharmacological mechanism as ß-blockers. However, population-based clinical study directly comparing the efficacy of H2RAs and ß-blockers on mortality of HF patients are still lacking. This study aims to compare the association difference of H2RAs and ß-blockers on mortality in critically ill patients with HF using the Medical Information Mart for Intensive Care III database (MIMIC-III). Methods: Study population was divided into 4 groups: ß-blockers + H2RAs group, ß-blockers group, H2RAs group, and Non-ß-blockers + Non-H2RAs group. Kaplan-Meier curves and multivariable Cox regression models were employed to evaluate the differences of all-cause mortalities among the 4 groups. Propensity score matching (PSM) was used to increase comparability of four groups. Results: A total of 5593 patients were included. After PSM, multivariate analyses showed that patients in H2RAs group had close all-cause mortality with patients in ß-blockers group. Furthermore, 30-day, 1-year, 5-year and 10-year all-mortality of patients in ß-blockers + H2RAs group were significantly lower than those of patients in ß-blockers group, respectively (HR: 0.64, 95%CI: 0.50-0.82 for 30-day; HR: 0.80, 95%CI: 0.69-0.93 for 1-year mortality; HR: 0.83, 95%CI: 0.74-0.93 for 5-year mortality; and HR: 0.85, 95%CI: 0.76-0.94 for 10-year mortality, respectively). Conclusion: H2RAs exposure exhibited comparable all-cause mortality-decreasing effect as ß-blockers; and, furthermore, H2RAs and ß-blockers had additive or synergistic interactions to improve survival in critically ill patients with HF.

16.
Nat Commun ; 14(1): 6547, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848409

RESUMO

PACS1 syndrome is a neurodevelopmental disorder (NDD) caused by a recurrent de novo missense mutation in PACS1 (p.Arg203Trp (PACS1R203W)). The mechanism by which PACS1R203W causes PACS1 syndrome is unknown, and no curative treatment is available. Here, we use patient cells and PACS1 syndrome mice to show that PACS1 (or PACS-1) is an HDAC6 effector and that the R203W substitution increases the PACS1/HDAC6 interaction, aberrantly potentiating deacetylase activity. Consequently, PACS1R203W reduces acetylation of α-tubulin and cortactin, causing the Golgi ribbon in hippocampal neurons and patient-derived neural progenitor cells (NPCs) to fragment and overpopulate dendrites, increasing their arborization. The dendrites, however, are beset with varicosities, diminished spine density, and fewer functional synapses, characteristic of NDDs. Treatment of PACS1 syndrome mice or patient NPCs with PACS1- or HDAC6-targeting antisense oligonucleotides, or HDAC6 inhibitors, restores neuronal structure and synaptic transmission in prefrontal cortex, suggesting that targeting PACS1R203W/HDAC6 may be an effective therapy for PACS1 syndrome.


Assuntos
Histona Desacetilases , Tubulina (Proteína) , Humanos , Camundongos , Animais , Desacetilase 6 de Histona/genética , Desacetilase 6 de Histona/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Tubulina (Proteína)/metabolismo , Neurônios/metabolismo , Processamento de Proteína Pós-Traducional , Síndrome , Acetilação , Inibidores de Histona Desacetilases/farmacologia , Proteínas de Transporte Vesicular/genética
17.
Res Vet Sci ; 165: 105051, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37856946

RESUMO

Pigeons like to eat raw grains, but meat pigeon enterprises often use compound feeds instead of raw grains to feed breeding pigeons to increase economic efficiency, which may change the pigeon's dietary behavior, and consequently lead to health and welfare problems. The purpose of this study was to investigate the effect of granular feeds on the health of high-yielding breeding pigeons and squabs in lactation. The results showed that, compared with raw grain group, the provision of granular feed resulted in lower total feed intake without affecting the weight of lactating breeding pigeons. Meanwhile, reproductive metabolism was improved and no oxidative stress was observed, which indicated that granular feeds had a positive effect on breeding pigeon's health. However, granular feed adversely affected jejunum development in squabs, compare wtih raw grain group, the growth rate of squab was reduced. Sequencing of the 16 s rRNA gene revealed that granular feed induced intestinal microbiota dysbiosis in the squabs. The use of granular feed reduced the relative abundance of gut microorganisms in functional categories related to lipid and energy metabolism, resulting in a decrease in the relative abundance of beneficial bacteria such as Bifidobacterium, Ligilactobacillus, Atopobium, and an increase in that of inflammation-related Limosilactobacillus, which likely inhibited squab intestinal development and growth. Although the use of granular feed can improve breeder metabolism, it affect the composition of the microbial community and gut development of squabs. Therefore, the use of granular feed in production should be more careful to avoid causing growth obstruction of squab.


Assuntos
Columbidae , Microbiota , Feminino , Animais , Lactação , Melhoramento Vegetal , Reprodução , Ração Animal
18.
Front Oncol ; 13: 1209111, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711208

RESUMO

Background: Hepatocellular cancer (HCC) is one of the most common tumors worldwide, and Ki-67 is highly important in the assessment of HCC. Our study aimed to evaluate the value of ultrasound radiomics based on intratumoral and peritumoral tissues in predicting Ki-67 expression levels in patients with HCC. Methods: We conducted a retrospective analysis of ultrasonic and clinical data from 118 patients diagnosed with HCC through histopathological examination of surgical specimens in our hospital between September 2019 and January 2023. Radiomics features were extracted from ultrasound images of both intratumoral and peritumoral regions. To select the optimal features, we utilized the t-test and the least absolute shrinkage and selection operator (LASSO). We compared the area under the curve (AUC) values to determine the most effective modeling method. Subsequently, we developed four models: the intratumoral model, the peritumoral model, combined model #1, and combined model #2. Results: Of the 118 patients, 64 were confirmed to have high Ki-67 expression while 54 were confirmed to have low Ki-67 expression. The AUC of the intratumoral model was 0.796 (0.649-0.942), and the AUC of the peritumoral model was 0.772 (0.619-0.926). Furthermore, combined model#1 yielded an AUC of 0.870 (0.751-0.989), and the AUC of combined model#2 was 0.762 (0.605-0.918). Among these models, combined model#1 showed the best performance in terms of AUC, accuracy, F1-score, and decision curve analysis (DCA). Conclusion: We presented an ultrasound radiomics model that utilizes both intratumoral and peritumoral tissue information to accurately predict Ki-67 expression in HCC patients. We believe that incorporating both regions in a proper manner can enhance the diagnostic performance of the prediction model. Nevertheless, it is not sufficient to include both regions in the region of interest (ROI) without careful consideration.

19.
Poult Sci ; 102(10): 102964, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37573846

RESUMO

The nutritional requirements of breeding pigeons depend on their physiological period, breeding pattern, and environmental conditions. Despite works on reduced litter size in winter production to combat high mortality and the poor welfare of squabs, there are few studies on the related nutritional requirements of these pigeons. A total of 432 pairs of European Mimas pigeons were randomly divided into 9 groups in which 3 crude protein (CP) levels (15, 16.5, and 18%) and 3 metabolizable energy (ME) levels (12.2 MJ/kg, 12.4 MJ/kg, and 12.6 MJ/kg) were tested to determine the optimal energy and protein requirements of breeding pigeons in the winter "2 + 3" breeding pattern. The results showed that ME and CP levels had little effect on the body weight, feed intake, and egg quality of breeding pigeons during the lactation period. An 18% CP diet significantly increased the laying rate and hatchability (P < 0.05), but there was no difference in the laying rate with 18% CP and 16.5% CP during the whole reproductive cycle (P > 0.05). There was a significant interaction between ME and CP levels, and the laying interval of breeding pigeons in group 9 (18% CP; 12.6 MJ/kg) was significantly shortened (P < 0.05). For squabs, the ME level had no effect on growth performance, slaughter performance, or meat quality. The body weight of 21-day-old squabs in the 18% CP group increased by 3.16% compared with that of the 15% CP group, but there was no difference between the 18% CP and 16.5% CP groups. Compared with other experimental groups, group 7 (18% CP; 12.2 MJ/kg) had the fastest growth rate in squabs (P < 0.05), and the corresponding slaughter weight was also the heaviest (P < 0.05). We further found that the height of the squab intestinal epithelium was significantly increased in both the 16.5% CP and 18% CP groups of squabs (P < 0.01), but male breeding pigeons showed a certain degree of oxidative stress with an increase in CP level. In conclusion, the effects of 15 to 18% CP levels and 12.2 to 12.6 MJ/kg ME levels on the reproductive metabolism of breeding pigeons and the growth and development of squabs in the "2 + 3" breeding pattern during winter are small. For economic efficiency, we suggest that the CP level can be reduced to 16.5% while the ME level should not be less than 12.2 MJ/kg in practical production.


Assuntos
Columbidae , Ingestão de Energia , Feminino , Masculino , Animais , Galinhas , Dieta/veterinária , Lactação , Peso Corporal , Metabolismo Energético , Ração Animal/análise , Proteínas na Dieta
20.
Cytokine ; 170: 156312, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37542945

RESUMO

BACKGROUND: Recently, increasing evidence has demonstrated that IL-10 single nucleotide polymorphisms (SNPs) are associated with the risk of acute leukemia (AL), but the findings of different articles remain controversial. Thus, we performed a meta-analysis to further investigate the exact roles of IL-10 SNPs in AL susceptibility. METHODS: Six common Chinese and English databases were utilized to retrieve eligible studies. The strength of the association was assessed by calculating odds ratios and 95 % confidence intervals. All analyses were carried out using Review Manager (version 5.3) and STATA (version 15.1). The registered number of this research is CRD42022373362. RESULTS: A total of 6391 participants were enrolled in this research. The results showed that the AG genotype of rs1800896 increased AL risk in the heterozygous codominant model (AG vs. AA, OR = 1.41, 95 % CI = 1.04-1.92, P = 0.03) and overdominant model (AG vs. AA + GG, OR = 1.32, 95 % CI = 1.04-1.70, P = 0.03). In the subgroup analysis, associations between the G allele, GG genotype, AG genotype, AG + GG genotype of rs1800896 and increased AL risk were also observed in the mixed population based on allelic, homozygote codominant, heterozygous codominant, dominant, and overdominant models. Furthermore, an association between the AC genotype of rs1800872 and increased AL risk was observed in the Caucasian population in the overdominant model. However, the rs1800871, rs3024489 and rs3024493 polymorphisms did not affect AL risk. CONCLUSION: IL-10 rs1800896 and rs1800872 affected the susceptibility of AL and therefore may be biomarkers for early screening and risk prediction of AL.


Assuntos
Interleucina-10 , Leucemia Mieloide Aguda , Humanos , Estudos de Casos e Controles , Predisposição Genética para Doença/genética , Genótipo , Interleucina-10/genética , Leucemia Mieloide Aguda/genética , Polimorfismo de Nucleotídeo Único/genética
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