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1.
BMC Infect Dis ; 24(1): 485, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730327

RESUMEN

BACKGROUND: Neurobrucellosis (NB) is a rare and serious complication of brucellosis. Its clinical manifestations vary, with no obvious specificity. At present, there is no clear clinical diagnosis or treatment for reference. In this study, we retrospectively analyzed the clinical data for 21 patients with NB to provide reference data for its further study. METHODS: We analyzed the epidemiological and clinical manifestations, laboratory tests, imaging examinations, cerebrospinal fluid, and treatment plans of 21 patients diagnosed with NB in the Department of Neurology, Xuanwu Hospital, Capital Medical University Beijing, China. RESULTS: The ages of the patients ranged from 15 to 60 years old (mean age 40.1 ± 13.33 years), the male: female ratio was 4.25:1. Thirteen patients had a history of animal (sheep, cattle) contact, three had no history of animal contact, and the contact status of four was unknown. Brucella can invade various systems of the body and show multi-system symptoms, the main general manifestations were fever (66.67%), fatigue (57.14%) and functional urination or defecation disturbance (42.86%). The main nervous system manifestations were limb weakness (52.38%) and hearing loss (47.62%).The main positive signs of the nervous system included positive pathological signs (71.43%), sensory abnormalities (52.38%), limb paralysis (42.86%). Nervous system lesions mainly included spinal cord damage (66.67%), cranial nerve involvement (61.90%), central demyelination (28.57%) and meningitis (28.57%). In patients with cranial nerve involvement, 69.23% of auditory nerve, 15.38% of optic nerve and 15.38% of oculomotor nerve were involved. The blood of eight patients was cultured for Brucella, and three (37.5%) cultures were positive and five (63.5%) negative. The cerebrospinal fluid (CSF) of eight patients was cultured for Brucella, and two (25.00%) cultures were positive and six (75.00%) negative. Nineteen of the patients underwent a serum agglutination test (SAT), 18 (94.74%) of whom were positive and one (5.26%) of whom were negative. A biochemical analysis of the CSF was performed in 21 patients, and the results were all abnormal. Nineteen patients underwent magnetic resonance imaging (MRI). Twenty-one patients were treated with doxycycline and/or rifampicin, combined with ceftriaxone, quinolone, aminoglycoside, or minocycline. After hospitalization, 15 patients improved (71.43%), two patients did not recover, and the status of four patients was unknown. CONCLUSIONS: The clinical manifestations, CSF parameters, and neurological imaging data for patients with NB show no significant specificity or correlations. When patients with unexplained neurological symptoms accompanied by fever, fatigue, and other systemic manifestations in a brucellosis epidemic area or with a history of contact with cattle, sheep, animals, or raw food are encountered in clinical practice, the possibility of NB should be considered. Treatment is based on the principles of an early, combined, and long course of treatment, and the general prognosis is good.


Asunto(s)
Antibacterianos , Brucelosis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Brucelosis/tratamiento farmacológico , Brucelosis/microbiología , Brucelosis/líquido cefalorraquídeo , Brucelosis/diagnóstico , Brucelosis/epidemiología , Adulto , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Adolescente , Adulto Joven , China/epidemiología , Resultado del Tratamiento , Brucella/aislamiento & purificación , Animales
2.
J Clin Anesth ; 95: 111467, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38593491

RESUMEN

STUDY OBJECTIVE: To assess the impact of preoperative infection with the contemporary strain of severe acute respiratory coronavirus 2 (SARS-CoV-2) on postoperative mortality, respiratory morbidity and extrapulmonary complications after elective, noncardiac surgery. DESIGN: An ambidirectional observational cohort study. SETTING: A tertiary and teaching hospital in Shanghai, China. PATIENTS: All adult patients (≥ 18 years of age) who underwent elective, noncardiac surgery under general anesthesia at Huashan Hospital of Fudan University from January until March 2023 were screened for eligibility. A total of 2907 patients were included. EXPOSURE: Preoperative coronavirus disease 2019 (COVID-19) positivity. MEASUREMENTS: The primary outcome was 30-day postoperative mortality. The secondary outcomes included postoperative pulmonary complications (PPCs), myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), postoperative delirium (POD) and postoperative sleep quality. Multivariable logistic regression was used to assess the risk of postoperative mortality and morbidity imposed by preoperative COVID-19. MAIN RESULTS: The risk of 30-day postoperative mortality was not associated with preoperative COVID-19 [adjusted odds ratio (aOR), 95% confidence interval (CI): 0.40, 0.13-1.28, P = 0.123] or operation timing relative to diagnosis. Preoperative COVID-19 did not increase the risk of PPCs (aOR, 95% CI: 0.99, 0.71-1.38, P = 0.944), MINS (aOR, 95% CI: 0.54, 0.22-1.30; P = 0.168), or AKI (aOR, 95% CI: 0.34, 0.10-1.09; P = 0.070) or affect postoperative sleep quality. Patients who underwent surgery within 7 weeks after COVID-19 had increased odds of developing delirium (aOR, 95% CI: 2.26, 1.05-4.86, P = 0.036). CONCLUSIONS: Preoperative COVID-19 or timing of surgery relative to diagnosis did not confer any added risk of 30-day postoperative mortality, PPCs, MINS or AKI. However, recent COVID-19 increased the risk of POD. Perioperative brain health should be considered during preoperative risk assessment for COVID-19 survivors.


Asunto(s)
COVID-19 , Procedimientos Quirúrgicos Electivos , Complicaciones Posoperatorias , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , COVID-19/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Procedimientos Quirúrgicos Electivos/efectos adversos , Anciano , China/epidemiología , Estudios de Cohortes , Adulto , Factores de Riesgo , Periodo Preoperatorio
3.
J Am Chem Soc ; 146(19): 12969-12975, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38625041

RESUMEN

Separation of methanol/benzene azeotrope mixtures is very challenging not only by the conventional distillation technique but also by adsorbents. In this work, we design and synthesize a flexible Ca-based metal-organic framework MAF-58 consisting of cheap raw materials. MAF-58 shows selective methanol-induced pore-opening flexibility. Although the opened pores are large enough to accommodate benzene molecules, MAF-58 shows methanol/benzene molecular sieving with ultrahigh experimental selectivity, giving 5.1 mmol g-1 high-purity (99.99%+) methanol and 2.0 mmol g-1 high-purity (99.97%+) benzene in a single adsorption/desorption cycle. Computational simulations reveal that the preferentially adsorbed, coordinated methanol molecules act as the gating component to selectively block the diffusion of benzene, offering a new gating adsorption mechanism.

4.
Front Psychiatry ; 15: 1354999, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38563028

RESUMEN

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

5.
Nat Commun ; 15(1): 3267, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627361

RESUMEN

In vitro biotransformation (ivBT) facilitated by in vitro synthetic enzymatic biosystems (ivSEBs) has emerged as a highly promising biosynthetic platform. Several ivSEBs have been constructed to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA). However, some systems are hindered by their reliance on costly ATP, limiting their practicality. This study presents the design of an ATP-free ivSEB for one-pot PHB biosynthesis via acetyl-CoA utilizing starch-derived maltodextrin as the sole substrate. Stoichiometric analysis indicates this ivSEB can self-maintain NADP+/NADPH balance and achieve a theoretical molar yield of 133.3%. Leveraging simple one-pot reactions, our ivSEBs achieved a near-theoretical molar yield of 125.5%, the highest PHB titer (208.3 mM, approximately 17.9 g/L) and the fastest PHB production rate (9.4 mM/h, approximately 0.8 g/L/h) among all the reported ivSEBs to date, and demonstrated easy scalability. This study unveils the promising potential of ivBT for the industrial-scale production of PHB and other acetyl-CoA-derived chemicals from starch.


Asunto(s)
Hidroxibutiratos , Polihidroxibutiratos , Polisacáridos , Almidón , Acetilcoenzima A/metabolismo , Almidón/metabolismo , Hidroxibutiratos/metabolismo , Poliésteres/metabolismo , NADP/metabolismo , Biotransformación
6.
Sci Data ; 11(1): 387, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627416

RESUMEN

Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated with 43 proteins in brain, 150 regions associated with 247 proteins in cerebrospinal fluid, and 95 regions associated with 145 proteins in plasma. Compared to our previous study, this study newly identified 12 loci in brain, 30 loci in cerebrospinal fluid, and 22 loci in plasma. Our improved genomic atlas uncovers the genetic control of protein regulation across multiple tissues. These resources are accessible through the Online Neurodegenerative Trait Integrative Multi-Omics Explorer for use by the scientific community.


Asunto(s)
Regulación de la Expresión Génica , Proteoma , Sitios de Carácter Cuantitativo , Humanos , Encéfalo , Estudio de Asociación del Genoma Completo , Genómica , Fenotipo , Proteoma/genética , Plasma , Líquido Cefalorraquídeo
7.
Int J Ophthalmol ; 17(4): 729-735, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38638245

RESUMEN

AIM: To evaluate the effectiveness and safety of intravitreal ranibizumab (IVR) for diabetic macular edema (DME) in vitrectomized versus non-vitrectomized eyes. METHODS: The PubMed, EMBASE, Web of Science, Cochrane, EBSCO were comprehensively searched for studies comparing vitrectomized and non-vitrectomized eyes with DME. Clinical outcomes of best-corrected visual acuity (BCVA), central macular thickness (CMT), the mean number of intravitreal injection and adverse events were extracted and analyzed. RESULTS: Six studies involving 641 eyes were included. Final visual gain significantly improved and CMT significantly reduced in vitrectomized eyes at 6mo and 12mo visits (P<0.05). Although the mean reduction in CMT among non-vitrectomized eyes was significantly greater than in vitrectomized eyes at the 6mo [mean difference (MD)=53.57, 95% confidence interval (CI): 28.03 to 78.72, P<0.0001] and 12mo (MD=49.65, 95%CI: 19.58 to 79.72, P=0.01), no significant difference was detected in improvement in BCVA at either 6mo (MD=0.05, 95%CI: -0.02 to 0.13, P=0.14) or 12mo (MD=0.03, 95%CI: -0.04 to 0.09, P=0.43). Injection number of ranibizumab in non-vitrectomized eyes was significantly less than that in vitrectomized eyes during 6-month period (MD=0.60, 95%CI: 0.16 to 1.04, P=0.008), while there was no statistically significant difference between the two groups during 12mo of follow-up. CONCLUSION: Evidence from current study suggests that IVR was useful for both vitrectomized group and non-vitrectomized group with DME. Although less reduction in macular thickness is found in vitrectomized group, visual improvement between two groups is similar.

8.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1506-1516, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-38621934

RESUMEN

Rubus chingii and R. chingii var. suavissimus are unique dual-purpose plant resources, with significant nutraceutical, pharmaceutical, and economic value, as well as promising prospects for further development. To investigate the genetic structure and evolutionary characteristics of these two varieties, this study conducted plastome sequencing using the Illumina HiSeq XTen sequencing platform. Subsequently, the study performed assembly, annotation, and characterization of the genomes, followed by a comparative plastome and phylogenetic analysis using bioinformatics techniques. The results revealed that the plastomes of R. chingii and R. chingii var. suavissimus exhibited a tetrad structure, comprising a large single-copy region(LSC), a small single-copy region(SSC), and two inverted repeat regions(IRs). The study identified a total of 56 simple sequence repeats(SSRs) after comparative analysis, predominantly consisting of A and T. Furthermore, the structure of the IR boundary genes in both varieties was found to be highly conserved, with only minor nucleotide variations. Additionally, the study identified three highly variable regions: rps16-trnQ-psbK, trnR-atpA, and trnT-trnL, which held promise as potential identification marks for further development and utilization. Phylogenetic analysis results obtained by the maximum likelihood and Bayesian inference methods demonstrated a close clustering of R. chingii and R. chingii var. suavissimus(100% support), with their closest relatives being R. trianthus. This study, focusing on plastome-level genetic distinctions between these two varieties, lays a foundation for future species protection, development, and utilization.


Asunto(s)
Rubus , Filogenia , Teorema de Bayes , Evolución Biológica , Repeticiones de Microsatélite
10.
Prog Neurobiol ; 236: 102614, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38641040

RESUMEN

Complement activation and prefrontal cortical dysfunction both contribute to the pathogenesis of major depressive disorder (MDD), but their interplay in MDD is unclear. We here studied the role of complement C3a receptor (C3aR) in the medial prefrontal cortex (mPFC) and its influence on depressive-like behaviors induced by systematic lipopolysaccharides (LPS) administration. C3aR knockout (KO) or intra-mPFC C3aR antagonism confers resilience, whereas C3aR expression in mPFC neurons makes KO mice susceptible to LPS-induced depressive-like behaviors. Importantly, the excitation and inhibition of mPFC neurons have opposing effects on depressive-like behaviors, aligning with increased and decreased excitability by C3aR deletion and activation in cortical neurons. In particular, inhibiting mPFC glutamatergic (mPFCGlu) neurons, the main neuronal subpopulation expresses C3aR, induces depressive-like behaviors in saline-treated WT and KO mice, but not in LPS-treated KO mice. Compared to hypoexcitable mPFCGlu neurons in LPS-treated WT mice, C3aR-null mPFCGlu neurons display hyperexcitability upon LPS treatment, and enhanced excitation of mPFCGlu neurons is anti-depressant, suggesting a protective role of C3aR deficiency in these circumstances. In conclusion, C3aR modulates susceptibility to LPS-induced depressive-like behaviors through mPFCGlu neuronal excitability. This study identifies C3aR as a pivotal intersection of complement activation, mPFC dysfunction, and depression and a promising therapeutic target for MDD.


Asunto(s)
Depresión , Lipopolisacáridos , Ratones Noqueados , Neuronas , Corteza Prefrontal , Animales , Corteza Prefrontal/metabolismo , Corteza Prefrontal/efectos de los fármacos , Lipopolisacáridos/farmacología , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Ratones , Depresión/metabolismo , Depresión/inducido químicamente , Receptores de Complemento/metabolismo , Ratones Endogámicos C57BL , Masculino , Ácido Glutámico/metabolismo
11.
bioRxiv ; 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38659961

RESUMEN

A salient neuroanatomical feature of the human brain is its pronounced cortical folding, and there is mounting evidence that sulcal morphology is relevant to functional brain architecture and cognition. Recent studies have emphasized putative tertiary sulci (pTS): small, shallow, late-developing, and evolutionarily new sulci that have been posited to serve as functional landmarks in association cortices. A fruitful approach to characterizing brain architecture has been to delineate regions based on transitions in fMRI-based functional connectivity profiles; however, exact regional boundaries can change depending on the data used to generate the parcellation. As sulci are fixed neuroanatomical structures, here, we propose to anchor functional connectivity to individual-level sulcal anatomy. We characterized fine-grained patterns of functional connectivity across 42 sulci in lateral prefrontal (LPFC) and lateral parietal cortices (LPC) in a pediatric sample (N = 43; 20 female; ages 7-18). Further, we test for relationships between pTS morphology and functional network architecture, focusing on depth as a defining characteristic of these shallow sulci, and one that has been linked to variability in cognition. We find that 1) individual sulci have distinct patterns of connectivity, but nonetheless cluster together into groups with similar patterns - in some cases with distant rather than neighboring sulci, 2) there is moderate agreement in cluster assignments at the group and individual levels, underscoring the need for individual-level analyses, and 3) across individuals, greater depth was associated with higher network centrality for several pTS. These results highlight the importance of considering individual sulcal morphology for understanding functional brain organization. Significance Statement: A salient, and functionally relevant, feature of the human brain is its pronounced cortical folding. However, the links between sulcal anatomy and brain function are still poorly understood - particularly for small, shallow, individually variable sulci in association cortices. Here, we explore functional connectivity among individually defined sulci in lateral prefrontal and parietal regions. We find that individual sulci have distinct patterns of connectivity but nonetheless cluster together into groups with similar connectivity - in some cases spanning lateral prefrontal and parietal sulci. We further show that the network centrality of specific sulci is positively associated with their depth, thereby helping to bridge the gap between individual differences in brain anatomy and functional networks leveraging the sulcal anatomy of the individual.

13.
Trials ; 25(1): 200, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38509589

RESUMEN

BACKGROUND: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory. METHODS: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. DISCUSSION: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.


Asunto(s)
Enfermedad de Parkinson , Estimulación Transcraneal de Corriente Directa , Humanos , Persona de Mediana Edad , Anciano , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/complicaciones , Estimulación Transcraneal de Corriente Directa/efectos adversos , Estimulación Transcraneal de Corriente Directa/métodos , Calidad de Vida , Terapia por Ejercicio/métodos , Método Doble Ciego , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
J Phys Chem A ; 128(12): 2323-2329, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38483325

RESUMEN

Studying the cleavage of the C═O bond during CO2 activation at room temperature is highly significant for comprehending the CO2 conversion processes. Herein, mass spectrometry experiments and density functional theory calculations indicate that the niobium carbide anions Nb3C4- can continuously convert five CO2 molecules to CO under thermal collision conditions, while the other clusters with less carbon ligands Nb3C1-3- reduce fewer CO2 molecules. Size-dependent reactivity of Nb3C1-4- cluster anions toward CO2 is observed. Interestingly, the carbon atoms in Nb3C4- not only act as highly active adsorption sites for CO2 but also serve as electron donors to reduce CO2. The stored electrons are released through a carbon-carbon coupling process. Our findings on the role of carbon ligands in enhancing transition metal carbide reactivity can offer new insights for designing active sites on catalysts with both high activity and selectivity.

15.
Acta Cardiol Sin ; 40(2): 147, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38532814
16.
Acta Cardiol Sin ; 40(2): 148-171, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38532817

RESUMEN

Heart failure with preserved ejection fraction (HFpEF) is a multi-organ systemic syndrome that involves cardiac and extra-cardiac pathophysiological abnormalities. Its growing prevalence causes a major public concern worldwide. HFpEF is usually associated with multiple comorbidities, and non-cardiovascular death is common in patients with HFpEF. In Asia, patients with HFpEF has a younger age, higher prevalence of diabetes and chronic kidney disease than Western countries. A 2-step diagnostic algorithm is recommended in this guideline. In the first step, the diagnosis of HFpEF can be made if patients have symptoms and/or signs of heart failure, left ventricular ejection fraction ≥ 50%, increased natriuretic peptide, and objective evidence of left atrial or left ventricular abnormalities or raised left ventricular filling pressure. If diagnosis is still uncertain, invasive or noninvasive stress test can be performed in the second step. Comorbidities need to be controlled in HFpEF. Weight reduction for obesity and supervised exercise training are recommended for HFpEF. For pharmacological therapy, diuretic is used to relieve congestion and sodium-glucose cotransporter 2 inhibitor, empagliflozin or dapagliflozin, is recommended to improve prognosis of HFpEF. The research on HFpEF is advancing at a rapid pace. It is expected that newer modalities for diagnosis and management of HFpEF could appear in the near future.

17.
Brief Bioinform ; 25(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38349057

RESUMEN

Efficient and accurate recognition of protein-DNA interactions is vital for understanding the molecular mechanisms of related biological processes and further guiding drug discovery. Although the current experimental protocols are the most precise way to determine protein-DNA binding sites, they tend to be labor-intensive and time-consuming. There is an immediate need to design efficient computational approaches for predicting DNA-binding sites. Here, we proposed ULDNA, a new deep-learning model, to deduce DNA-binding sites from protein sequences. This model leverages an LSTM-attention architecture, embedded with three unsupervised language models that are pre-trained on large-scale sequences from multiple database sources. To prove its effectiveness, ULDNA was tested on 229 protein chains with experimental annotation of DNA-binding sites. Results from computational experiments revealed that ULDNA significantly improves the accuracy of DNA-binding site prediction in comparison with 17 state-of-the-art methods. In-depth data analyses showed that the major strength of ULDNA stems from employing three transformer language models. Specifically, these language models capture complementary feature embeddings with evolution diversity, in which the complex DNA-binding patterns are buried. Meanwhile, the specially crafted LSTM-attention network effectively decodes evolution diversity-based embeddings as DNA-binding results at the residue level. Our findings demonstrated a new pipeline for predicting DNA-binding sites on a large scale with high accuracy from protein sequence alone.


Asunto(s)
Análisis de Datos , Lenguaje , Sitios de Unión , Secuencia de Aminoácidos , Bases de Datos Factuales
18.
J Biol Chem ; 300(3): 105773, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38382671

RESUMEN

The nucleolus, a membrane-less organelle, is responsible for ribosomal RNA transcription, ribosomal RNA processing, and ribosome assembly. Nucleolar size and number are indicative of a cell's protein synthesis rate and proliferative capacity, and abnormalities in the nucleolus have been linked to neurodegenerative diseases and cancer. In this study, we demonstrated that the nucleolar protein ZNF692 directly interacts with nucleophosmin 1 (NPM1). Knocking down ZNF692 resulted in the nucleolar redistribution of NPM1 in ring-like structures and reduced protein synthesis. Purified NPM1 forms spherical condensates in vitro but mixing it with ZNF692 produces irregular condensates more closely resembling living cell nucleoli. Our findings indicate that ZNF692, by interacting with NPM1, plays a critical role in regulating nucleolar architecture and function in living cells.


Asunto(s)
Nucléolo Celular , Proteínas de Unión al ADN , Nucleofosmina , Factores de Transcripción , Nucléolo Celular/genética , Nucléolo Celular/metabolismo , Proteínas Nucleares/metabolismo , Unión Proteica , ARN Ribosómico/metabolismo , Humanos , Factores de Transcripción/metabolismo , Proteínas de Unión al ADN/metabolismo
19.
Nat Commun ; 15(1): 1108, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38321000

RESUMEN

The next generation of high-capacity, multi-task optical informatics requires sophisticated manipulation of multiple degrees of freedom (DoFs) of light, especially when they are coupled in a non-separable way. Vector beam, as a typical non-separable state between the spin and orbital angular momentum DoFs, mathematically akin to entangled qubits, has inspired multifarious theories and applications in both quantum and classical regimes. Although qubit rotation is a vital and ubiquitous operation in quantum informatics, its classical analogue is rarely studied. Here, we demonstrate the logical rotation of vectorial non-separable states via the uniform self-assembled chiral superstructures, with favorable controllability, high compactness and exemption from formidable alignment. Photonic band engineering of such 1D chiral photonic crystal renders the incident-angle-dependent evolution of the spatially-variant polarizations. The logical rotation angle of a non-separable state can be tuned in a wide range over 4π by this single homogeneous device, flexibly providing a set of distinguished logic gates. Potential applications, including angular motion tracking and proof-of-principle logic network, are demonstrated by specific configuration. This work brings important insight into soft matter photonics and present an elegant strategy to harness high-dimensional photonic states.

20.
Clin Oral Implants Res ; 35(4): 427-442, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38314615

RESUMEN

OBJECTIVE: This study aimed to synthesize zinc-incorporated nanowires structure modified titanium implant surface (Zn-NW-Ti) and explore its superior osteogenic and antibacterial properties in vitro and in vivo. MATERIALS AND METHODS: Zn-NW-Ti was synthesized via displacement reactions between zinc sulfate solutions and the titanium (Ti) surface, which was pretreated by hydrofluoric acid etching and hyperthermal alkalinization. The physicochemical properties of the Zn-NW-Ti surface were examined. Moreover, the biological effects of Zn-NW-Ti on MC3T3-E1 cells and its antibacterial property against oral pathogenic bacteria (Staphylococcus aureus, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans) compared with sandblasted and acid-etched Ti (SLA-Ti) and nanowires modified Ti (NW-Ti) surface were assessed. Zn-NW-Ti and SLA-Ti modified implants were inserted into the anterior extraction socket of the rabbit mandible with or without exposure to the mixed bacterial solution (S. aureus, P. gingivalis, and A. actinomycetemcomitans) to investigate the osteointegration and antibacterial performance via radiographic and histomorphometric analysis. RESULTS: The Zn-NW-Ti surface was successfully prepared. The resultant titanium surface appeared as a nanowires structure with hydrophilicity, from which zinc ions were released in an effective concentration range. The Zn-NW-Ti surface performed better in facilitating the adhesion, proliferation, and differentiation of MC3T3-E1 cells while inhibiting the colonization of bacteria compared with SLA-Ti and NW-Ti surface. The Zn-NW-Ti implant exhibited enhanced osseointegration in vivo, which was attributed to increased osteogenic activity and reduced bacterial-induced inflammation compared with the SLA-Ti implant. CONCLUSIONS: The Zn-incorporated nanowires structure modified titanium implant surface exhibited improvements in osteogenic and antibacterial properties, which optimized osteointegration in comparison with SLA titanium implant surface.


Asunto(s)
Implantes Dentales , Nanocables , Animales , Conejos , Titanio/farmacología , Titanio/química , Staphylococcus aureus , Antibacterianos/farmacología , Oseointegración , Bacterias , Zinc/química , Zinc/farmacología , Propiedades de Superficie , Osteogénesis
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