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1.
Nat Commun ; 15(1): 2868, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570478

RESUMO

Signal communication mechanisms within the human body rely on the transmission and modulation of action potentials. Replicating the interdependent functions of receptors, neurons and synapses with organic artificial neurons and biohybrid synapses is an essential first step towards merging neuromorphic circuits and biological systems, crucial for computing at the biological interface. However, most organic neuromorphic systems are based on simple circuits which exhibit limited adaptability to both external and internal biological cues, and are restricted to emulate only specific the functions of an individual neuron/synapse. Here, we present a modular neuromorphic system which combines organic spiking neurons and biohybrid synapses to replicate a neural pathway. The spiking neuron mimics the sensory coding function of afferent neurons from light stimuli, while the neuromodulatory activity of interneurons is emulated by neurotransmitters-mediated biohybrid synapses. Combining these functions, we create a modular connection between multiple neurons to establish a pre-processing retinal pathway primitive.


Assuntos
Interneurônios , Neurônios , Humanos , Neurônios/fisiologia , Potenciais de Ação/fisiologia , Neurônios Aferentes , Sinapses/fisiologia , Neurotransmissores
2.
Int J Infect Dis ; : 107023, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38555060

RESUMO

OBJECTIVES: To evaluate the clinical and economic outcomes in adults hospitalized with invasive pneumococcal disease (IPD) and non-invasive all-cause pneumonia (ACP) overall and by antimicrobial resistance (AMR) status. METHODS: Hospitalized adults from the BD Insights Research Database with an ICD10 code for IPD, non-invasive ACP or a positive Streptococcus pneumoniae culture/urine antigen test were included. Descriptive statistics and multivariable analyses were used to evaluate outcomes (in-hospital mortality, length of stay [LOS], cost per admission, and hospital margin [costs - payments]). RESULTS: The study included 88,182 adult patients at 90 US hospitals (October 2015-February 2020). Most (98.6%) had non-invasive ACP and 40.2% were <65 years old. Of 1,450 culture-positive patients, 37.7% had an isolate resistant to ≥1 antibiotic class. Observed mortality, median LOS, cost per admission, and hospital margins were 8.3%, 6 days, $9,791, and $11, respectively. Risk factors for mortality included ≥50 years of age, higher risk of pneumococcal disease (based on chronic or immunocompromising conditions), and intensive care unit admission. Patients with IPD had similar mortality rates and hospital margins compared with non-invasive ACP, but greater costs per admission and LOS. CONCLUSION: IPD and non-invasive ACP are associated with substantial clinical and economic burden across all adult age groups. Expanded pneumococcal vaccination programs may help reduce disease burden and decrease hospital costs.

4.
Nat Commun ; 15(1): 2782, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555300

RESUMO

Developing supramolecular porous crystalline frameworks with tailor-made architectures from advanced secondary building units (SBUs) remains a pivotal challenge in reticular chemistry. Particularly for hydrogen-bonded organic frameworks (HOFs), construction of geometrical cavities through secondary units has been rarely achieved. Herein, a body-centered cubic HOF (TCA_NH4) with octahedral cages was constructed by a C3-symmetric building block and NH4+ node-assembled cluster (NH4)4(COOH)8(H2O)2 that served as supramolecular secondary building units (SSBUs), akin to the polynuclear SBUs in reticular chemistry. Specifically, the octahedral cages could encapsulate four homogenous haloforms including CHCl3, CHBr3, and CHI3 with truncated octahedron configuration. Crystallographic evidence revealed the cages served as spatially-confined nanoreactors, enabling fast, broadband photochromic effect associated with the reversible photo/thermal transformation between encapsulated CHI3 and I2. Overall, this work provides a strategy by shaping SSBUs to expand the framework topology of HOFs and a prototype of hydrogen-bonded nanoreactors to accommodate reversible photochromic reactions.

5.
Clin Infect Dis ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483935

RESUMO

BACKGROUND: Growing evidence indicates antimicrobial resistance disproportionately affects individuals living in socially vulnerable areas. This study evaluated the association between Streptococcus pneumoniae (SP) antimicrobial resistance (AMR) and the CDC/ATSDR Social Vulnerability Index (SVI) in the United States. METHODS: Adult patients ≥ 18 years with 30-day nonduplicate SP isolates from ambulatory/hospital settings from January 2011-December 2022 with zip codes of residence were evaluated across 177 facilities in the BD Insights Research Database. Isolates were identified as SP AMR if they were non-susceptible to ≥ 1 antibiotic class (macrolide, tetracycline, extended-spectrum cephalosporins, or penicillin). Associations between SP AMR and SVI score (overall and themes) were evaluated using generalized estimating equations with repeated measurements within county to account for within-cluster correlations. RESULTS: Of 8,008 unique SP isolates from 574 US counties across 39 states, the overall proportion of AMR was 49.9%. A significant association between socioeconomic status (SES) theme and SP AMR was detected with higher SES theme SVI score (indicating greater social vulnerability) associated with greater risk of AMR. On average, a decile increase of SES, indicating greater vulnerability, was associated with a 1.28% increased risk of AMR (95% confidence interval [CI], 0.61%, 1.95%; P=0.0002). A decile increase of household characteristic score was associated with a 0.81% increased risk in SP AMR (95% CI,0.13%, 1.49%; P=0.0197). There was no association between racial/ethnic minority status, housing type and transportation theme, or overall SVI score and SP AMR. CONCLUSIONS: SES and household characteristics were the SVI themes most associated with SP AMR.

6.
Antimicrob Resist Infect Control ; 13(1): 21, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355621

RESUMO

BACKGROUND: Antimicrobial resistance research in uncomplicated urinary tract infection typically focuses on the main causative pathogen, Escherichia coli; however, little is known about the antimicrobial resistance burden of Klebsiella species, which can also cause uncomplicated urinary tract infections. This retrospective cohort study assessed the prevalence and geographic distribution of antimicrobial resistance among Klebsiella species and antimicrobial resistance trends for K. pneumoniae in the United States (2011-2019). METHODS: K. pneumoniae and K. oxytoca urine isolates (30-day, non-duplicate) among female outpatients (aged ≥ 12 years) with presumed uUTI at 304 centers in the United States were classified by resistance phenotype(s): not susceptible to nitrofurantoin, trimethoprim/sulfamethoxazole, or fluoroquinolone, extended-spectrum ß-lactamase-positive/not susceptible; and multidrug-resistant based on ≥ 2 and ≥ 3 resistance phenotypes. Antimicrobial resistance prevalence by census division and age, as well as antimicrobial resistance trends over time for Klebsiella species, were assessed using generalized estimating equations. RESULTS: 270,552 Klebsiella species isolates were evaluated (250,719 K. pneumoniae; 19,833 K. oxytoca). The most frequent resistance phenotypes in 2019 were nitrofurantoin not susceptible (Klebsiella species: 54.0%; K. pneumoniae: 57.3%; K. oxytoca: 15.1%) and trimethoprim/sulfamethoxazole not susceptible (Klebsiella species: 10.4%; K. pneumoniae: 10.6%; K. oxytoca: 8.6%). Extended-spectrum ß-lactamase-positive/not susceptible prevalence was 5.4%, 5.3%, and 6.8%, respectively. K. pneumoniae resistance phenotype prevalence varied (p < 0.0001) geographically and by age, and increased over time (except for the nitrofurantoin not susceptible phenotype, which was stable and > 50% throughout). CONCLUSIONS: There is a high antimicrobial resistance prevalence and increasing antimicrobial resistance trends among K. pneumoniae isolates from female outpatients in the United States with presumed uncomplicated urinary tract infection. Awareness of K. pneumoniae antimicrobial resistance helps to optimize empiric uncomplicated urinary tract infection treatment.


Assuntos
Klebsiella , Infecções Urinárias , Feminino , Humanos , Antibacterianos/farmacologia , beta-Lactamases/genética , Farmacorresistência Bacteriana , Escherichia coli , Klebsiella pneumoniae , Nitrofurantoína/farmacologia , Pacientes Ambulatoriais , Prevalência , Estudos Retrospectivos , Combinação Trimetoprima e Sulfametoxazol , Estados Unidos/epidemiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/tratamento farmacológico
7.
Proc Natl Acad Sci U S A ; 121(8): e2309465121, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38354262

RESUMO

Phagocytes promptly resolve ingested targets to replenish lysosomes and maintain their responsiveness. The resolution process requires that degradative hydrolases, solute transporters, and proteins involved in lipid traffic are delivered and made active in phagolysosomes. It also involves extensive membrane remodeling. We report that cation channels that localize to phagolysosomes were essential for resolution. Specifically, the conductance of Na+ by two-pore channels (TPCs) and the presence of a Na+ gradient between the phagolysosome lumen and the cytosol were critical for the controlled release of membrane tension that permits deformation of the limiting phagolysosome membrane. In turn, membrane deformation was a necessary step to efficiently transport the cholesterol extracted from cellular targets, permeabilizing them to hydrolases. These results place TPCs as regulators of endomembrane remodeling events that precede target degradation in cases when the target is bound by a cholesterol-containing membrane. The findings may help to explain lipid metabolism dysfunction and autophagic flux impairment reported in TPC KO mice and establish stepwise regulation to the resolution process that begins with lysis of the target.


Assuntos
Fagossomos , 60694 , Camundongos , Animais , Fagossomos/metabolismo , Lisossomos/metabolismo , Hidrolases/metabolismo , Colesterol/metabolismo
8.
Water Sci Technol ; 89(3): 811-822, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38358504

RESUMO

Advanced oxidation technologies based on hydroxyl radical (•OH) and sulfate radical (SO4-•) are two common types of advanced oxidation technologies, but there are not many reports on the application of advanced oxidation methods in actual wastewater pretreatment. This article compares the pre-treatment performance of Fe2+/H2O2 and Fe2+/Persulfate systems in actual pharmaceutical wastewater, and combines EEM, GC-MS, and toxicity testing results to explore the differences in TOC, COD, and NH3-N removal rates, optimal catalyst dosage, applicable pH range, toxicity of effluent after reaction, and pollutant structure between the two systems. The results indicate that the Fe2+/H2O2 system has a higher pollutant removal rate (TOC: 71.9%, COD: 66.9%, NH3-N: 34.1%), but also requires a higher catalyst (Fe2+) concentration (6.0 g/L), and its effluent exhibits characteristic peaks of aromatic proteins. The Fe2+/Persulfate system has a wider pH range (pH ≈ 3-7) and is more advantageous in treating wastewater containing more cyclic organic compounds, but the effluent contains some sulfur-containing compounds. In addition, toxicity tests have shown that the toxicity reduction effect of the Fe2+/Persulfate system is stronger than that of the Fe2+/H2O2 system.


Assuntos
Poluentes Ambientais , Peróxido de Hidrogênio , Águas Residuárias , Cromatografia Gasosa-Espectrometria de Massas , Compostos de Enxofre , Preparações Farmacêuticas
9.
Bioresour Technol ; 395: 130361, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286171

RESUMO

The control of effluent total nitrogen (TN) and total energy consumption (TEC) is a key issue in managing wastewater treatment plants. In this study, effluent TN and TEC predictive models were established by selecting influent water quality and process control indicators as input features. The prediction performance of machine learning methods under different random seeds was explored, the moving average method was used for data amplification, and the Bayesian algorithm was used for hyperparameter optimization. The results showed that compared with the traditional hyperparameter optimization method for effluent TN prediction, the coefficient of determination (R2) increased by 0.092 and 0.067, reaching 0.725, and the root mean square error (RMSE) decreased by 0.262 and 0.215 mg/L, reaching 1.673 mg/L, respectively, after Bayesian optimization and data amplification. During TEC prediction, R2 increased by 0.068 and 0.042, reaching 0.884, and the RMSE decreased by 232.444 and 197.065 kWh, reaching 1305.829 kWh, respectively.


Assuntos
Águas Residuárias , Purificação da Água , Nitrogênio/análise , Teorema de Bayes , Purificação da Água/métodos , Qualidade da Água
11.
Water Res ; 249: 120950, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38056201

RESUMO

The efficient removal of emerging pollutant from water is the ultimate frontiers of advanced oxidation processes (AOPs), yet it is challenging to obtain higher catalytic activity and oxidation rate. Herein, a sustainable solution was proposed by optimizing the curvature of confined structure to modulate the electronic state of the active sites in nanochannels for improving the catalytic activity. In addition, the confined effect can enhance the oxidation rate by shorting the mass transfer of active species and pollutants. A void-nanoconfined nanoreactor was prepared by loading Fe2O3 into the nanochannels (<5 nm) of the hollow carbon sphere. An enhancement of 3 orders of magnitude was obtained in the degradation rate constant of void-nanoconfined catalytic system toward sulfamethoxazole (SMX) (6.25 min-1) compared with the non-confined system. The kinetics enhancement was attributed to the larger electron potential difference between the outer and inner nanochannel caused by the curvature increase of carbon sphere, accelerating the electron transfer, so that the energy barrier of SMX degradation reaction was reduced by 31 kcal/mol with the assistance of confinement energy. Importantly, the NC-IN/PDS system exhibited outstanding removal efficiency for the actual river water using a continuous flow reactor. This work provides a new insight into designing an efficient and stable catalytic nanoreactor, enriching the domain of advanced wastewater treatment strategies.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Domínio Catalítico , Oxirredução , Sulfametoxazol/química , Carbono , Água , Eletrônica , Poluentes Químicos da Água/química
12.
Biomaterials ; 304: 122384, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38016334

RESUMO

siRNA has demonstrated a promising paradigm for therapy of acute lung injury(ALI). However, the pulmonary mucus layer barrier powerfully hinders the therapeutic efficacy. Herein, we proposed to use dual drive power to enhance the mucus permeation of siRNA by constructing the neutral and targeted selenium nanozymes therapeutic system. The multifunctional selenium nanozymes (CWP-Se@Man) were synthesized by modifying with cationic water-soluble pillar arene (CWP) and mannose (Man). After loading CCR2-siRNA, the CWP-Se@Man reached electroneutrality that co-driven by electroneutrality and targeting, the mucus permeation capacity of CWP-Se@Man enhanced by ∼15 fold, thus effectively penetrate pulmonary mucus layer and deliver CCR2-siRNA into macrophages. Moreover, with optimizing the composition of CWP-Se@Man made of CWP (Slutsky, 2013) [5] or CWP (Ichikado et al., 2012) [6], the therapeutic system CWP (Ichikado et al., 2012) [6]-Se@Man showed better biological activities due to smaller size. In inflamed modes, the CWP-Se@Man nanotherapeutic systems loading CCR2-siRNA not only exerted pronounced anti-inflammatory effect through combining inhibit the chemotactic effect and ROS, but also effectively against ALI after blocking the circulatory effect of ROS and inflammatory cytokines. Therefore, this strategy of dual-driving force penetration mucus renders a unique approach for mediating trans-mucus nucleic acid delivery in lungs, and provide a promising treatment for the acute lung injury therapy.


Assuntos
Lesão Pulmonar Aguda , Nanopartículas , Selênio , Humanos , Espécies Reativas de Oxigênio , RNA Interferente Pequeno , Lesão Pulmonar Aguda/tratamento farmacológico , Muco , Pulmão
13.
Infect Control Hosp Epidemiol ; 45(1): 48-56, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37449415

RESUMO

OBJECTIVES: To evaluate the incidence of a candidate definition of healthcare facility-onset, treated Clostridioides difficile (CD) infection (cHT-CDI) and to identify variables and best model fit of a risk-adjusted cHT-CDI metric using extractable electronic heath data. METHODS: We analyzed 9,134,276 admissions from 265 hospitals during 2015-2020. The cHT-CDI events were defined based on the first positive laboratory final identification of CD after day 3 of hospitalization, accompanied by use of a CD drug. The generalized linear model method via negative binomial regression was used to identify predictors. Standardized infection ratios (SIRs) were calculated based on 2 risk-adjusted models: a simple model using descriptive variables and a complex model using descriptive variables and CD testing practices. The performance of each model was compared against cHT-CDI unadjusted rates. RESULTS: The median rate of cHT-CDI events per 100 admissions was 0.134 (interquartile range, 0.023-0.243). Hospital variables associated with cHT-CDI included the following: higher community-onset CDI (CO-CDI) prevalence; highest-quartile length of stay; bed size; percentage of male patients; teaching hospitals; increased CD testing intensity; and CD testing prevalence. The complex model demonstrated better model performance and identified the most influential predictors: hospital-onset testing intensity and prevalence, CO-CDI rate, and community-onset testing intensity (negative correlation). Moreover, 78% of the hospitals ranked in the highest quartile based on raw rate shifted to lower percentiles when we applied the SIR from the complex model. CONCLUSIONS: Hospital descriptors, aggregate patient characteristics, CO-CDI burden, and clinical testing practices significantly influence incidence of cHT-CDI. Benchmarking a cHT-CDI metric is feasible and should include facility and clinical variables.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Humanos , Masculino , Benchmarking , Estudos de Viabilidade , Infecção Hospitalar/epidemiologia , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Hospitais de Ensino
14.
J Am Chem Soc ; 145(51): 28096-28110, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38088827

RESUMO

Bottom-up fabrication protocols for uniform 3D hierarchical structures in solution are rare. We report two different approaches to fabricate uniform 3D spherulites and their precursors using mixtures of poly(ferrocenyldimethylsilane) (PFS) block copolymer (BCP) and PFS homopolymer (HP). Both protocols are designed to promote defects in 2D assemblies that serve as intermediate structures. In a multistep seeded growth protocol, we add the BCP/HP mixture to (1D) rod-like PFS micelles in a selective solvent as first-generation seeds. This leads to 2D platelet structures. If this step is conducted at a high supersaturation, secondary crystals form on the basal surface of these platelets. Co-crystallization and rapid crystallization of BCP/HP promote the formation of defects that act as nucleation sites for secondary crystals, resulting in multilayer platelets. This is the key step. The multilayer platelets serve as second-generation seeds upon subsequent addition of BCP/HP blends and, with increasing supersaturation, lead to the sequential formation of uniform (3D) hedrites, sheaves, and spherulites. Similar structures can also be obtained by a simple one-pot direct self-assembly (heating-cooling-aging) protocol of PFS BCP/HP blends. In this case, for a carefully chosen but narrow temperature range, PFS HPs nucleate formation of uniform structures, and the annealing temperature regulates the supersaturation level. In both protocols, the competitive crystallization kinetics of HP/BCP affects the morphology. Both protocols exhibit broad generality. We believe the morphological transformation from 2D to 3D structures, regulated by defect formation, co-crystallization, and supersaturation levels, could apply to various semicrystalline polymers. Moreover, the 3D structures are sufficiently robust to serve as recoverable carriers for nanoparticle catalysts, exhibiting valuable catalytic activity and opening new possibilities for applications requiring exquisite 3D structures.

15.
Elife ; 122023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37991488

RESUMO

SARS-CoV-2 spike protein plays a key role in mediating viral entry and inducing host immune responses. It can adopt either an open or closed conformation based on the position of its receptor-binding domain (RBD). It is yet unclear what causes these conformational changes or how they influence the spike's functions. Here, we show that Lys417 in the RBD plays dual roles in the spike's structure: it stabilizes the closed conformation of the trimeric spike by mediating inter-spike-subunit interactions; it also directly interacts with ACE2 receptor. Hence, a K417V mutation has opposing effects on the spike's function: it opens up the spike for better ACE2 binding while weakening the RBD's direct binding to ACE2. The net outcomes of this mutation are to allow the spike to bind ACE2 with higher probability and mediate viral entry more efficiently, but become more exposed to neutralizing antibodies. Given that residue 417 has been a viral mutational hotspot, SARS-CoV-2 may have been evolving to strike a balance between infection potency and immune evasion, contributing to its pandemic spread.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Ligação Proteica
16.
J Virol ; 97(11): e0144823, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37855638

RESUMO

IMPORTANCE: The COVID-19 pandemic exposed limitations of conventional antibodies as therapeutics, including high cost, limited potency, ineffectiveness against new viral variants, and primary reliance on injection-only delivery. Nanobodies are single-domain antibodies with therapeutic potentials. We discovered three anti-SARS-CoV-2 nanobodies, named Nanosota-2, -3, and -4, from an immunized alpaca. Nanosota-2 is super potent against prototypic SARS-CoV-2, Nanosota-3 is highly potent against the omicron variant, and Nanosota-4 is effective against both SARS-CoV-1 and SARS-CoV-2. In addition to their super potency and combined broad antiviral spectrum, these nanobodies are cost-effective, can be easily adapted to new viral variants through phage display, and can potentially be administered as inhalers. The Nanosota series are powerful therapeutic candidates to combat circulating SARS-CoV-2 and prepare for possible future coronavirus pandemics.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos de Domínio Único , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais/uso terapêutico , COVID-19/terapia , Pandemias , Anticorpos de Domínio Único/farmacologia , Glicoproteína da Espícula de Coronavírus
17.
Hum Brain Mapp ; 44(17): 6245-6257, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37837649

RESUMO

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.


Assuntos
Transtorno Depressivo Maior , Humanos , Encéfalo/diagnóstico por imagem , Córtex Pré-Frontal , Função Executiva , Lobo Frontal , Imageamento por Ressonância Magnética , Mapeamento Encefálico
18.
Nutrients ; 15(20)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37892424

RESUMO

Eriodictyol occurs naturally in a variety of fruits and vegetables, and has drawn significant attention for its potential health benefits. This study aims to look into the effects of eriodictyol on acute liver injury (ALI) induced by LPS/D-GalN and elucidate its potential molecular biological mechanisms. A total of 47 targets were predicted for the treatment of ALI with eriodictyol, and the PI3K/AKT signaling pathway played a key role in the anti-ALI processing of this drug. The in vivo experiment showed that eriodictyol can effectively reduce liver function-related biochemical indicators such as ALT, AST, and AKP. Eriodictyol can also up-regulate the levels of SOD and GSH, and inhibit the release of IL-1ß, IL-6, and TNF-α. Additionally, TUNEL staining, immunohistochemistry, and RT-PCR experiments showed that eriodictyol activated the PI3K/AKT pathway and decreased the expression of Bax, caspase3, and caspase8 while increasing the expression of Bcl-2 m-RNA. Finally, molecular docking experiments and molecular dynamics simulations confirmed the stable binding between eriodictyol and PI3K, AKT molecules. This study showed that eriodictyol can activate the PI3K/AKT signaling pathway to alleviate ALI-related oxidative stress and apoptosis.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Lipopolissacarídeos/farmacologia , Simulação de Acoplamento Molecular , Transdução de Sinais , Fígado/metabolismo , Estresse Oxidativo , Apoptose
19.
Angew Chem Int Ed Engl ; 62(49): e202313951, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37877955

RESUMO

Hybrid hydrogen-bonded (H-bonded) frameworks built from charged components or metallotectons offer diverse guest-framework interactions for target-specific separations. We present here a study to systematically explore the coordination chemistry of monovalent halide anions, i.e., F- , Cl- , Br- , and I- , with the aim to develop hybrid H-bond synthons that enable the controllable construction of microporous H-bonded frameworks exhibiting fine-tunable surface polarity within the adaptive cavities for realistic xenon/krypton (Xe/Kr) separation. The spherical halide anions, especially Cl- , Br- , and I- , are found to readily participate in the charge-assisted H-bonding assembly with well-defined coordination behaviors, resulting in robust frameworks bearing open halide anions within the distinctive 1D pore channels. The activated frameworks show preferential binding towards Xe (IAST Xe/Kr selectivity ca. 10.5) because of the enhanced polarizability and the pore confinement effect. Specifically, dynamic column Xe/Kr separation with a record-high separation factor (SF=7.0) among H-bonded frameworks was achieved, facilitating an efficient Xe/Kr separation in dilute, CO2 -containing gas streams exactly mimicking the off-gas of spent nuclear fuel (SNF) reprocessing.

20.
BMC Gastroenterol ; 23(1): 335, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37770848

RESUMO

INTRODUCE: The purpose of this study was to establish a comprehensive prognosis nomogram for patients with liver cirrhosis complicated with hepatic encephalopathy (HE) in the intensive care unit (ICU) and to evaluate the predictive value of the nomogram. METHOD: This study analyzed 620 patients with liver cirrhosis complicated with HE from the Medical Information Mart for Intensive Care III(MIMIC-III) database. The patients were randomly divided into two groups in a 7-to-3 ratio to form a training cohort (n = 434) and a validation cohort (n = 176). Cox regression analyses were used to identify associated risk variables. Based on the multivariate Cox regression model results, a nomogram was established using associated risk predictor variables to predict the 90-day survival rate of patients with cirrhosis complicated with HE. The new model was compared with the Sequential organ failure assessment (SOFA) scoring model in terms of the concordance index (C-index), the area under the curve (AUC) of receiver operating characteristic (ROC) analysis, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration curve, and decision curve analysis (DCA). RESULTS: This study showed that older age, higher mean heart rate, lower mean arterial pressure, lower mean temperature, higher SOFA score, higher RDW, and the use of albumin were risk factors for the prognosis of patients with liver cirrhosis complicated with HE. The use of proton pump inhibitors (PPI) was a protective factor. The performance of the nomogram was evaluated using the C-index, AUC, IDI value, NRI value, and DCA curve, showing that the nomogram was superior to that of the SOFA model alone. Calibration curve results showed that the nomogram had excellent calibration capability. The decision curve analysis confirmed the good clinical application ability of the nomogram. CONCLUSION: This study is the first study of the 90-day survival rate prediction of cirrhotic patients with HE in ICU through the data of the MIMIC-III database. It is confirmed that the eight-factor nomogram has good efficiency in predicting the 90-day survival rate of patients.


Assuntos
Encefalopatia Hepática , Nomogramas , Humanos , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Prognóstico , Cirrose Hepática/complicações , Fatores de Risco
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