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1.
Sensors (Basel) ; 24(13)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39000889

RESUMEN

Emotions in speech are expressed in various ways, and the speech emotion recognition (SER) model may perform poorly on unseen corpora that contain different emotional factors from those expressed in training databases. To construct an SER model robust to unseen corpora, regularization approaches or metric losses have been studied. In this paper, we propose an SER method that incorporates relative difficulty and labeling reliability of each training sample. Inspired by the Proxy-Anchor loss, we propose a novel loss function which gives higher gradients to the samples for which the emotion labels are more difficult to estimate among those in the given minibatch. Since the annotators may label the emotion based on the emotional expression which resides in the conversational context or other modality but is not apparent in the given speech utterance, some of the emotional labels may not be reliable and these unreliable labels may affect the proposed loss function more severely. In this regard, we propose to apply label smoothing for the samples misclassified by a pre-trained SER model. Experimental results showed that the performance of the SER on unseen corpora was improved by adopting the proposed loss function with label smoothing on the misclassified data.


Asunto(s)
Emociones , Habla , Humanos , Emociones/fisiología , Habla/fisiología , Algoritmos , Reproducibilidad de los Resultados , Reconocimiento de Normas Patrones Automatizadas/métodos , Bases de Datos Factuales
2.
Ann Clin Microbiol Antimicrob ; 23(1): 62, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978096

RESUMEN

BACKGROUND: This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn1546-type transposons harboring the vanA operon. METHODS: All E. faecium blood isolates were collected from eight general hospitals in South Korea during one-year study period. Antimicrobial susceptibility testing and vanA and vanB PCR were performed. Growth rates of E. faecium isolates were determined. The vanA-positive isolates were subjected to whole genome sequencing and conjugation experiments. RESULTS: Among 308 E. faecium isolates, 132 (42.9%) were positive for vanA. All Tn1546-type transposons harboring the vanA operon located on the plasmids, but on the chromosome in seven isolates. The plasmids harboring the vanA operon were grouped into four types; two types of circular, nonconjugative plasmids (Type A, n = 50; Type B, n = 46), and two types of putative linear, conjugative plasmids (Type C, n = 16; Type D, n = 5). Growth rates of vanA-positive E. faecium isolates were significantly lower than those of vanA-negative isolates (P < 0.001), and reduction in growth rate under vancomycin pressure was significantly larger in isolates harboring putative linear plasmids than in those harboring circular plasmids (P = 0.020). CONCLUSIONS: The possession of vanA operon was costly to bacterial hosts in antimicrobial-free environment, which provide evidence for the importance of reducing vancomycin pressure for prevention of VREfm dissemination. Fitness burden to bacterial hosts was varied by type and size of the vanA operon-harboring plasmid.


Asunto(s)
Antibacterianos , Proteínas Bacterianas , Ligasas de Carbono-Oxígeno , Elementos Transponibles de ADN , Enterococcus faecium , Pruebas de Sensibilidad Microbiana , Operón , Plásmidos , Plásmidos/genética , Enterococcus faecium/genética , Humanos , Proteínas Bacterianas/genética , República de Corea , Ligasas de Carbono-Oxígeno/genética , Antibacterianos/farmacología , Secuenciación Completa del Genoma , Infecciones por Bacterias Grampositivas/microbiología , Enterococos Resistentes a la Vancomicina/genética , Resistencia a la Vancomicina/genética , Aptitud Genética , Vancomicina/farmacología , Conjugación Genética
3.
Animals (Basel) ; 14(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38929439

RESUMEN

This study investigated the effects of rumen-protected L-tryptophan or L-ascorbic acid supplementation on the productivity of lactating Holstein cows during a high-temperature period. Thirty cows were assigned to three dietary groups: control (CON), treatment 1 (TRT 1; rumen-protected L-tryptophan, 20 g/cow/d), and treatment 2 (TRT 2; rumen-protected L-ascorbic acid, 20 g/cow/d). As the high-temperature period progressed, the decrease in milk yield and dry matter intake (DMI) in the TRT 1 and TRT 2 groups was lower than that in the CON group. The total protein level in the plasma of the TRT 1 group was higher than that in the CON group (p < 0.05). Milk melatonin concentration was higher in the TRT 1 group than in the CON and TRT 2 groups (p < 0.05). Thus, the present results indicate that rumen-protected L-tryptophan or L-ascorbic acid has positive effects in preventing declines in DMI and milk yield by reducing heat stress in Holstein cows. In particular, rumen-protected L-tryptophan is considered effective in increasing the melatonin concentration in milk.

4.
Med Mycol ; 62(6)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935910

RESUMEN

This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%. Risk factors for disease principally include immunosuppression from HIV, but other types of immunosuppression are increasingly recognised, including solid organ and haematopoietic stem cell transplantation, autoimmune and inflammatory disease, and chemotherapy for cancer. Although prophylaxis is available and generally effective, burdensome side effects may lead to discontinuation. After a period of decline associated with improvement in access to HIV treatment, new risk groups of immunosuppressed patients with PJP are increasingly identified, including solid organ transplant patients.


Asunto(s)
Huésped Inmunocomprometido , Infecciones Fúngicas Invasoras , Pneumocystis carinii , Organización Mundial de la Salud , Humanos , Infecciones Fúngicas Invasoras/epidemiología , Infecciones Fúngicas Invasoras/prevención & control , Infecciones Fúngicas Invasoras/mortalidad , Infecciones Fúngicas Invasoras/microbiología , Factores de Riesgo , Salud Global , Neumonía por Pneumocystis/microbiología , Neumonía por Pneumocystis/epidemiología , Neumonía por Pneumocystis/mortalidad , Antifúngicos/uso terapéutico , Incidencia
5.
Sensors (Basel) ; 24(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38931762

RESUMEN

A multichannel speech enhancement system usually consists of spatial filters such as adaptive beamformers followed by postfilters, which suppress remaining noise. Accurate estimation of the power spectral density (PSD) of the residual noise is crucial for successful noise reduction in the postfilters. In this paper, we propose a postfilter utilizing proposed a posteriori speech presence probability (SPP) and noise PSD estimators, which are based on both the coherence and the statistical models. We model the coherence-based a posteriori SPP as a simple function of the magnitude of coherence between two microphone signals and combine it with a single-channel SPP based on statistical models. The coherence-based estimator for the PSD of the noise remaining in the beamformer output in the presence of speech is derived using the pseudo-coherence considering the effect of the beamformers, which is used to construct the coherence-based noise PSD estimator. Then, the final noise PSD estimator is obtained by combining the coherence-based and statistical model-based noise PSD estimators with the proposed SPP. The spectral gain function is also modified, incorporating the proposed SPP. Experimental results demonstrate that the proposed method led to more accurate noise PSD estimation and perceptual evaluation of speech quality scores in various diffuse noise environments, and did not degrade the speech quality under the presence of directional interference, although the proposed method utilizes the coherence information.

6.
Med Mycol ; 62(6)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935900

RESUMEN

The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and Web of Science were used to find studies published from 1 January 2011 to 18 February 2021, reporting on predefined criteria including: mortality, morbidity (i.e., hospitalization and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. Thirty-seven studies were included in the final analysis. The overall and 30-day mortality rates associated with C. auris candidaemia ranged from 29% to 62% and 23% to 67%, respectively. The median length of hospital stay was 46-68 days, ranging up to 140 days. Late-onset complications of C. auris candidaemia included metastatic septic complications. Resistance rates to fluconazole were as high as 87%-100%. Susceptibility to isavuconazole, itraconazole, and posaconazole varied with MIC90 values of 0.06-1.0 mg/l. Resistance rates to voriconazole ranged widely from 28% to 98%. Resistance rates ranged between 8% and 35% for amphotericin B and 0%-8% for echinocandins. Over the last ten years, outbreaks due to C. auris have been reported in in all WHO regions. Given the outbreak potential of C. auris, the emergence and spread of MDR strains, and the challenges associated with its identification, and eradication of its environmental sources in healthcare settings, prevention and control measures based on the identified risk factors should be evaluated for their effectiveness and feasibility. Global surveillance studies could better inform the incidence rates and distribution patterns to evaluate the global burden of C. auris infections.


Asunto(s)
Antifúngicos , Candida auris , Candidiasis , Farmacorresistencia Fúngica , Organización Mundial de la Salud , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candidiasis/microbiología , Candidiasis/epidemiología , Candidiasis/tratamiento farmacológico , Candida auris/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Candidemia/epidemiología , Candidemia/microbiología , Candidemia/tratamiento farmacológico , Brotes de Enfermedades , Candida/efectos de los fármacos , Candida/clasificación , Candida/aislamiento & purificación , Incidencia
7.
Med Mycol ; 62(6)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935903

RESUMEN

Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges, particularly in immunocompromised individuals such as people living with HIV/AIDS and organ transplant recipients. This systematic review, aimed at informing the World Health Organization's Fungal Priority Pathogens List, critically examines literature from 2011 to 2021 using PubMed and Web of Science, focusing on the incidence, mortality, morbidity, antifungal resistance, preventability, and distribution of Histoplasma. We also found a high prevalence (22%-44%) in people living with HIV, with mortality rates ranging from 21% to 53%. Despite limited data, the prevalence of histoplasmosis seems stable, with lower estimates in Europe. Complications such as central nervous system disease, pulmonary issues, and lymphoedema due to granuloma or sclerosis are noted, though their burden remains uncertain. Antifungal susceptibility varies, particularly against fluconazole (MIC: ≥32 mg/l) and caspofungin (MICs: 4-32 mg/l), while resistance to amphotericin B (MIC: 0.125-0.16 mg/l), itraconazole (MICs: 0.004-0.125 mg/l), and voriconazole (MICs: 0.004-0.125 mg/l) remains low. This review identifies critical knowledge gaps, underlining the need for robust, globally representative surveillance systems to better understand and combat this fungal threat.


Asunto(s)
Antifúngicos , Farmacorresistencia Fúngica , Histoplasma , Histoplasmosis , Organización Mundial de la Salud , Humanos , Histoplasmosis/epidemiología , Histoplasmosis/microbiología , Histoplasmosis/tratamiento farmacológico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Histoplasma/efectos de los fármacos , Histoplasma/aislamiento & purificación , Prevalencia , Huésped Inmunocomprometido
8.
Med Mycol ; 62(6)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935912

RESUMEN

Candida parapsilosis is globally distributed and recognised for causing an increasing proportion of invasive Candida infections. It is associated with high crude mortality in all age groups. It has been particularly associated with nosocomial outbreaks, particularly in association with the use of invasive medical devices such as central venous catheters. Candida parapsilosis is one of the pathogens considered in the WHO priority pathogens list, and this review was conducted to inform the ranking of the pathogen in the list. In this systematic review, we searched PubMed and Web of Science to find studies between 2011 and 2021 reporting on the following criteria for C. parapsilosis infections: mortality, morbidity (hospitalisation and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. We identified 336 potentially relevant papers, of which 51 were included in the analyses. The included studies confirmed high mortality rates, ranging from 17.5% to 46.8%. Data on disability and sequelae were sparse. Many reports highlighted concerns with azole resistance, with resistance rates of >10% described in some regions. Annual incidence rates were relatively poorly described, although there was clear evidence that the proportion of candidaemia cases caused by C. parapsilosis increased over time. While this review summarises current data on C.parapsilosis, there remains an urgent need for ongoing research and surveillance to fully understand and manage this increasingly important pathogen.


Asunto(s)
Antifúngicos , Candida parapsilosis , Farmacorresistencia Fúngica , Organización Mundial de la Salud , Humanos , Candida parapsilosis/efectos de los fármacos , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Incidencia , Candidiasis/epidemiología , Candidiasis/microbiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología
9.
J Hosp Infect ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38740300

RESUMEN

BACKGROUND: The healthcare water environment is a potential reservoir of carbapenem-resistant organisms (CROs). Here, we report the role of the water environment as a reservoir and the infection control measures applied to suppress a prolonged outbreak of Klebsiella pneumoniae carbapenemase-producing Serratia marcescens (KPC-SM) in two intensive care units (ICUs). METHODS: The outbreak occurred in the ICUs of a tertiary hospital from October 2020 to July 2021. Comprehensive patient contact tracing and environmental assessments were conducted, and a case-control study was performed to identify factors associated with the acquisition of KPC-SM. Associations among isolates were assessed via pulsed-field gel electrophoresis (PFGE). Antibiotic usage was analyzed. . RESULTS: The outbreak consisted of two waves involving a total of 30 patients with KPC-SM. Multiple environmental cultures identified KPC-SM in a sink, a dirty utility room, and a communal bathroom shared by the ICUs, together with the waste bucket of a continuous renal replacement therapy (CRRT) system. The genetic similarity of the KPC-SM isolates from patients and the environment was confirmed by PFGE. A retrospective review of 30 cases identified that the use of CRRT and antibiotics were associated with acquisition of KPC-SM (p < 0.05). There was a continuous increase in the use of carbapenems; notably, the use of colistin has increased since 2019. CONCLUSION: Our study demonstrates that CRRT systems, along with other hospital water environments, are significant potential sources of resistant microorganisms, underscoring the necessity of enhancing infection control practices in these areas.

10.
Adv Mater ; : e2400614, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38689548

RESUMEN

Neuromorphic olfactory systems have been actively studied in recent years owing to their considerable potential in electronic noses, robotics, and neuromorphic data processing systems. However, conventional gas sensors typically have the ability to detect hazardous gas levels but lack synaptic functions such as memory and recognition of gas accumulation, which are essential for realizing human-like neuromorphic sensory system. In this study, a seamless architecture for a neuromorphic olfactory system capable of detecting and memorizing the present level and accumulation status of nitrogen dioxide (NO2) during continuous gas exposure, regulating a self-alarm implementation triggered after 147 and 85 s at a continuous gas exposure of 20 and 40 ppm, respectively. Thin-film-transistor type gas sensors utilizing carbon nanotube semiconductors detect NO2 gas molecules through carrier trapping and exhibit long-term retention properties, which are compatible with neuromorphic excitatory applications. Additionally, the neuromorphic inhibitory performance is also characterized via gas desorption with programmable ultraviolet light exposure, demonstrating homeostasis recovery. These results provide a promising strategy for developing a facile artificial olfactory system that demonstrates complicated biological synaptic functions with a seamless and simplified system architecture.

11.
Sci Rep ; 14(1): 11522, 2024 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-38769102

RESUMEN

Digital PCR (dPCR) is a technique for absolute quantification of nucleic acid molecules. To develop a dPCR technique that enables more accurate nucleic acid detection and quantification, we established a novel dPCR apparatus known as centrifugal force real-time dPCR (crdPCR). This system is efficient than other systems with only 2.14% liquid loss by dispensing samples using centrifugal force. Moreover, we applied a technique for analyzing the real-time graph of the each micro-wells and distinguishing true/false positives using artificial intelligence to mitigate the rain, a persistent issue with dPCR. The limits of detection and quantification were 1.38 and 4.19 copies/µL, respectively, showing a two-fold higher sensitivity than that of other comparable devices. With the integration of this new technology, crdPCR will significantly contribute to research on next-generation PCR targeting absolute micro-analysis.


Asunto(s)
ADN , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , ADN/análisis , ADN/genética , Centrifugación/métodos , Límite de Detección
13.
Dalton Trans ; 53(15): 6809-6817, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38545959

RESUMEN

Three Fe(III)-based coordination complexes [Fe(dqmp)2](NO3)·H2O (1), [Fe(dqmp)2](BF4)·2CH3COCH3 (2), and [Fe(dqmp)2](ClO4) (3) were synthesized from Fe(NO3)3·9H2O/Fe(ClO4)3·xH2O, NaBF4, and 2,4-dichloro-6-((quinoline-8-ylimino)methyl)phenol (Hdqmp) in methanol/acetone and characterized. The structures of complexes 1-3 were determined via single-crystal X-ray crystallography at 100 K and room temperature, and their magnetic properties in the solid and solution forms were investigated. All complexes showed meridional structures with two tridentate dqmp- ligands coordinated with Fe(III) cations. In the solid state, complex 1 showed an abrupt and complete spin crossover at 225 K, whereas complexes 2 and 3 exhibited an incomplete spin crossover at 135 and 150 K, respectively. In a dimethylformamide solution, the complexes showed counterion-dependent spin transitions. In contrast to the solid state, in solution, complex 1 did not exhibit complete spin crossover. However, complexes 2 and 3 showed more complete spin transitions in solutions than in the solid state. The relaxation times, T1 and T2, for 1 and 2 were determined and both increased with temperature from 220 to 380 K. The T1 of 1 was larger than that of 2 at 380 K, and the T1 values were larger than the T2 values.

14.
PLoS One ; 19(3): e0300295, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38466692

RESUMEN

BACKGROUND: Handgrip strength (HGS) is acknowledged as a key indicator of overall physical fitness and is associated with various health outcomes. OBJECTIVES: This research investigates the correlation between HGS and quality of life (QoL), focusing on its relation to pulmonary function in the general adult population. METHOD: The study involved 19,402 participants aged 40 and above, spanning from 2014 to 2019, who underwent pulmonary function and HGS tests. Participants were categorized based on lung function, and regression analyses were employed to examine the relationship between HGS and QoL, with adjustments made for lung function. RESULTS: The average age of the cohort was 58.2 years, comprising 44.6% males and 41.2% smokers. Out of the 18,708 participants who completed the European Quality of Life Scale-Five Dimensions (EQ-5D-3L) assessment, higher severity levels in mobility, self-care, usual activities, pain or discomfort, and anxiety or depression were linked to lower HGS in both sexes. Additionally, among the 3,723 participants who completed the Health-related Quality of Life Instrument with 8 Items (HINT-8) assessment, higher severity levels in pain, work, and depression were associated with lower HGS in men. In women, higher severity levels in climbing stairs, pain, vitality, and work correlated with lower HGS. CONCLUSIONS: As problems indicated by EQ-5D worsened, there was a consistent decrease in handgrip strength (HGS) across both genders. The HINT-8 assessment further revealed that increased severity in pain and work-related issues led to reduced HGS in both men and women. This study highlights the relationship between HGS and Quality of Life (QoL), taking lung function into consideration, and underscores the importance of HGS as a potential marker of physical health and fitness.


Asunto(s)
Fuerza de la Mano , Calidad de Vida , Adulto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Pulmón , Ansiedad , Dolor
15.
Diagn Microbiol Infect Dis ; 108(4): 116187, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38340485

RESUMEN

We investigated colistin heteroresistance in Citrobacter freundii isolates from Korean hospitals. Using population analysis profiling (PAP), we detected colistin heteroresistance in 31.3% of isolates. Among these, ST217 was the most prevalent clone (58.5%), particularly within colistin-heteroresistant isolates (80.0%). Interestingly, the second most common clone, ST248, was not found in heteroresistant isolates. We identified amino acid changes in PhoQ, PmrA, and PmrB, along with mRNA overexpression in pmrB and arnD. Colistin monotherapy showed no efficacy, but a combination of colistin and ciprofloxacin successfully eradicated all five isolates, even at 0.5 × minimum inhibitory concentrations. This study underscores the high prevalence of colistin heteroresistance in C. freundii isolates, limiting the effectiveness of colistin monotherapy. Combining colistin with ciprofloxacin may offer a viable treatment option for C. freundii infections.


Asunto(s)
Antibacterianos , Colistina , Humanos , Colistina/farmacología , Antibacterianos/farmacología , Citrobacter freundii/genética , Citrobacter freundii/metabolismo , Ciprofloxacina , República de Corea/epidemiología , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo
16.
Cell Genom ; 4(2): 100499, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38359788

RESUMEN

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.


Asunto(s)
Reordenamiento Génico , Translocación Genética , Humanos , Animales , Ratones , Mutación , Genómica , Inversión Cromosómica , Mamíferos
17.
ACS Nano ; 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38324887

RESUMEN

Electrolyte-gated transistors (EGTs) are promising candidates as artificial synapses owing to their precise conductance controllability, quick response times, and especially their low operating voltages resulting from ion-assisted signal transmission. However, it is still vague how ion-related physiochemical elements and working mechanisms impact synaptic performance. Here, to address the unclear correlations, we suggest a methodical approach based on electrochemical analysis using poly(ethylene oxide) EGTs with three alkali ions: Li+, Na+, and K+. Cyclic voltammetry is employed to identify the kind of electrochemical reactions taking place at the channel/electrolyte interface, which determines the nonvolatile memory functionality of the EGTs. Additionally, using electrochemical impedance spectroscopy and qualitative analysis of electrolytes, we confirm that the intrinsic properties of electrolytes (such as crystallinity, solubility, and ion conductivity) and ion dynamics ultimately define the linearity/symmetricity of conductance modulation. Through simple but systematic electrochemical analysis, these results offer useful insights for the selection of components for high-performing artificial synapses.

18.
Gerontology ; 70(3): 269-278, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38219723

RESUMEN

INTRODUCTION: In aging populations, the coexistence of multiple health comorbidities represents a significant challenge for clinicians and researchers. Leveraging advances in omics techniques to characterize these health conditions may provide insight into disease pathogenesis as well as reveal biomarkers for monitoring, prognostication, and diagnosis. Researchers have previously established the utility of big data approaches with respect to comprehensive health outcome measurements in younger populations, identifying protein markers that may provide significant health information with a single blood sample. METHODS: Here, we employed a similar approach in two cohorts of older adults, the Baltimore Longitudinal Study of Aging (mean age = 76.12 years) and InCHIANTI Study (mean age = 66.05 years), examining the relationship between levels of serum proteins and 5 key health outcomes: kidney function, fasting glucose, physical activity, lean body mass, and percent body fat. RESULTS: Correlations between proteins and health outcomes were primarily shared across both older adult cohorts. We further identified that most proteins associated with health outcomes in the older adult cohorts were not associated with the same outcomes in a prior study of a younger population. A subset of proteins, adiponectin, MIC-1, and NCAM-120, were associated with at least three health outcomes in both older adult cohorts but not in the previously published younger cohort, suggesting that they may represent plausible markers of general health in older adult populations. CONCLUSION: Taken together, these findings suggest that comprehensive protein health markers have utility in aging populations and are distinct from those identified in younger adults, indicating unique mechanisms of disease with aging.


Asunto(s)
Envejecimiento , Proteómica , Humanos , Anciano , Estudios Longitudinales , Composición Corporal , Evaluación de Resultado en la Atención de Salud
19.
Nat Commun ; 15(1): 49, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38169460

RESUMEN

Repurposing the intrinsic properties of natural enzymes can offer a viable solution to current synthetic challenges through the development of novel biocatalytic processes. Although amino acid racemases are ubiquitous in living organisms, an amine racemase (AR) has not yet been discovered despite its synthetic potential for producing chiral amines. Here, we report the creation of an AR based on the serendipitous discovery that amine transaminases (ATAs) can perform stereoinversion of 2-aminobutane. Kinetic modeling revealed that the unexpected off-pathway activity results from stereochemically promiscuous futile cycles due to incomplete stereoselectivity for 2-aminobutane. This finding motivated us to engineer an S-selective ATA through in silico alanine scanning and empirical combinatorial mutations, creating an AR with broad substrate specificity. The resulting AR, carrying double point mutations, enables the racemization of both enantiomers of diverse chiral amines in the presence of a cognate ketone. This strategy may be generally applicable to a wide range of transaminases, paving the way for the development of new-to-nature racemases.


Asunto(s)
Aminas , Racemasas y Epimerasas , Aminas/química , Racemasas y Epimerasas/genética , Racemasas y Epimerasas/metabolismo , Ciclo del Sustrato , Biocatálisis , Transaminasas/metabolismo , Especificidad por Sustrato , Estereoisomerismo
20.
ACS Nano ; 18(2): 1543-1554, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38173253

RESUMEN

Multivalued logic (MVL) technology is a promising solution for improving data density and reducing power consumption in comparison to complementary metal-oxide-semiconductor (CMOS) technology. Currently, heterojunction transistors (TRs) with negative differential transconductance (NDT) characteristics, which play an important role in the function of MVL circuits, adopt organic or 2D semiconductors as active layers, but it is still difficult to apply conventional CMOS processes. Herein, we demonstrate an oxide semiconductor (OS) heterojunction TR with NDT characteristics composed of p-type copper(I) oxide (Cu2O) and n-type indium gallium zinc oxide (IGZO) using the conventional CMOS manufacturing processes. The electrical characteristics of the fabricated device exhibit a high Ion/Ioff ratio (∼3 × 103), wide NDT ranges (∼29 V), and high peak-to-valley current ratios (PVCR ≈ 25). The electrical properties of 15 devices were measured, confirming uniform performance in the PVCR, NDT range, and Ion/Ioff ratio. We analyze the device operation by varying the source/drain (S/D) position and changing the device geometry and the thickness of the Cu2O layer. Additionally, we demonstrate heterojunction ambipolar TR to elucidate the transport mechanism of NDT devices at a high gate voltage (VGS). To confirm the feasibility of the MVL circuit, we present a ternary inverter with three clearly expressed logic states that have a long intermediate state and greater margin of error induced by wide NDT regions and high PVCR.

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