Single molecule fluorescence spectroscopy is at the heart of molecular biophysics research and the most sensitive biosensing assays. The growing demand for precision medicine and environmental ...monitoring requires the creation of miniaturized and portable sensing platforms. However, the need for highly sophisticated objective lenses has precluded the development of single molecule detection systems for truly portable devices. Here, we propose a dielectric metalens device of submicrometer thickness to excite and collect light from fluorescent molecules instead of an objective lens. The high numerical aperture, high focusing efficiency, and dual-wavelength operation of the metalens enable the implementation of fluorescence correlation spectroscopy with a single Alexa 647 molecule in the focal volume. Moreover, the metalens enables real-time monitoring of individual fluorescent nanoparticle transitions and identification of hydrodynamic diameters ranging from a few to hundreds of nanometers. This advancement in sensitivity extends the application of the metalens technology to ultracompact single-molecule sensors.
Photoacoustic microscopy is advancing with research on utilizing ultraviolet and visible light. Dual-wavelength approaches are sought for observing DNA/RNA- and vascular-related disorders. However, ...the availability of high numerical aperture lenses covering both ultraviolet and visible wavelengths is severely limited due to challenges such as chromatic aberration in the optics. Herein, we present a groundbreaking proposal as a pioneering simulation study for incorporating multilayer metalenses into ultraviolet-visible photoacoustic microscopy. The proposed metalens has a thickness of 1.4 µm and high numerical aperture of 0.8. By arranging cylindrical hafnium oxide nanopillars, we design an achromatic transmissive lens for 266 and 532 nm wavelengths. The metalens achieves a diffraction-limited focal spot, surpassing commercially available objective lenses. Through three-dimensional photoacoustic simulation, we demonstrate high-resolution imaging with superior endogenous contrast of targets with ultraviolet and visible optical absorption bands. This metalens will open new possibilities for downsized multispectral photoacoustic microscopy in clinical and preclinical applications.
A newly designed TEMPO-FRIPS reagent, 4-(2,2,6,6-tetramethylpiperidine-1-oxyl) methyl benzyl succinic acid N-hydroxysuccinimide ester or p-TEMPO-Bn-Sc-NHS, was synthesized to achieve single-step free ...radical-initiated peptide sequencing mass spectrometry (FRIPS MS) for a number of model peptides, including phosphopeptides. The p-TEMPO-Bn-Sc-NHS reagent was conjugated to target peptides, and the resulting peptides were subjected to collisional activation. The peptide backbone dissociation behaviors of the MS/MS and MS
experiments were monitored in positive ion mode. Fragment ions were observed even at the single-step thermal activation of the p-TEMPO-Bn-Sc-peptides, showing mainly a-/x- and c-/z-type fragments and neutral loss ions. This confirms that radical-driven peptide backbone dissociations occurred with the p-TEMPO-Bn-Sc-peptides. Compared to the previous version of the TEMPO reagent, i.e., o-TEMPO-Bz-C(O)-NHS, the newly designed p-TEMPO-Bn-Sc-NHS has better conjugation efficiency for the target peptides owing to its improved structural flexibility and solubility in the experimental reagents. An energetic interpretation using the survival fraction as a function of applied normalized collision energy (NCE) ascertained the difference in the thermal activation between p-TEMPO-Bn-Sc- and o-TEMPO-Bz-C(O)- radical initiators. This study clearly demonstrates that the application of the p-TEMPO-Bn-Sc- radical initiator can improve the duty cycle, and this FRIPS MS approach has the potential to be implemented in proteomics studies, including phosphoproteomics.
Systemic rheumatic disease is characterized by autoimmunity and systemic inflammation and affects multiple organs. Few studies have investigated whether autoimmune diseases increase the risk of ...dementia. Herein, we evaluate the relationship between systemic rheumatic disease and dementia through a population-based study using the Korean National Health Insurance Service (NHIS) claims database.
We conducted a nationwide population-based study using the Korean NHIS database, consisting of individuals who submitted medical claims from 2002-2013. Dementia was defined as having an acetylcholinesterase inhibitors (AChEIs) prescription along with symptoms satisfying the Alzhemier's disease (AD) International Classification of Diseases (ICD)-10 codes (F00 or G30), or vascular dementia (VaD; ICD-10 or F01) criteria. Control subjects were matched to the dementia patients by age and sex. The study group was limited to those diagnosed with rheumatic disease at least 6 months prior to diagnosis of dementia. Rheumatic disease was defined by the following ICD-10 codes: Rheumatoid arthritis (RA: M05), Sjögren's syndrome (SS: M35), systemic lupus erythematosus (SLE: M32), and Behcet's disease (BD: M35.2).
Of the 6,028 dementia patients, 261 (4.3%) had RA, 108 (1.6%) had SS, 12 (0.2%) had SLE, and 6 (0.1%) had BD. SLE history was significantly higher in dementia patients (0.2%) than in controls (0.1%) and was associated with dementia (odds ratio OR, 2.48; 95% confidence interval CI, 1.19-5.15). In subgroup analysis, SLE significantly increased dementia risk, regardless of dementia type (AD: OR, 2.29; 95% CI, 1.06-4.91; VaD: OR, 4.54; 95% CI, 1.36-15.14). However, these associations were not sustained in the mild CCI or elderly group.
SLE was independently associated with a higher risk of dementia, including AD and VaD when compared to the control group, even after adjustment. SLE patients (<65 years old) are a high-risk group for early vascular dementia and require screening for early detection and active prevention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Insect immunity defends against the virulence of various entomopathogens, including Bacillus thuringiensis (Bt). This study tested a hypothesis that any suppression of immune responses enhances Bt ...virulence. In a previous study, the entomopathogenic bacterium, Xenorhabdus hominickii (Xh), was shown to produce secondary metabolites to suppress insect immune responses. Indeed, the addition of Xh culture broth (XhE) significantly enhanced the insecticidal activity of Bt against S. exigua. To analyze the virulence enhanced by the addition of Xh metabolites, four bacterial secondary metabolites were individually added to the Bt treatment. Each metabolite significantly enhanced the Bt insecticidal activity, along with significant suppression of the induced immune responses. A bacterial mixture was prepared by adding freeze-dried XhE to Bt spores, and the optimal mixture ratio to kill the insects was determined. The formulated bacterial mixture was applied to S. exigua larvae infesting Welsh onions in a greenhouse and showed enhanced control efficacy compared to Bt alone. The bacterial mixture was also effective in controlling other Spodopteran species such as S. litura and S. frugiperda but not other insect genera or orders. This suggests that Bt+XhE can effectively control Spodoptera-associated pests by suppressing the immune defenses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Diabetes mellitus is a risk factor for tuberculosis (TB) disease. There is evidence that diabetes also influences TB severity and treatment outcomes but information is incomplete and some published ...results have been inconsistent.
A longitudinal cohort study was conducted at the National Masan Tuberculosis Hospital in the Republic of Korea. Subjects presenting with a first episode of TB or for retreatment of TB were followed from enrollment through completion of treatment. Demographic, clinical, and microbiological variables were recorded, along with assessment of outcomes. Results were compared in TB patients with and without diabetes or smoking history. Data were adjusted for gender, age, cohort, educational level and alcohol consumption.
The combined cohorts comprised 657 subjects. Diabetes was present in 25% and was associated with greater radiographic severity and with recurrent or relapsed TB. Diabetes and cigarette smoking independently increased the risk of death in the first 12 months after enrollment. Estimating the combined impact of diabetes and smoking yielded a hazard ratio of 5.78. Only 20% of diabetic subjects were non-smokers; 54% smoked ≥1 pack daily. In this cohort, the impact of diabetes on mortality was greater in patients younger than 50 years, compared to older patients.
In this cohort of Korean patients, diabetes exacerbated the severity of TB disease. Diabetic subjects who smoked ≥1 pack of cigarettes daily were at particularly high risk of death from TB. Strategies to improve TB outcomes could productively focus resources for patient education and TB prevention on the vulnerable population of younger diabetics, particularly those who also smoke.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The diagnostic yields and safety profiles of transbronchial lung biopsy have not been evaluated in inexperienced physicians using the combined modality of radial probe endobronchial ultrasound and a ...guide sheath (EBUS-GS). This study assessed the utility and safety of EBUS-GS during the learning phase by referring to a database of performed EBUS-GS procedures.
From December 2015 to January 2017, all of the consecutive patients who underwent EBUS-GS were registered. During the study period, two physicians with no previous experience performed the procedure. To assess the diagnostic yields, learning curve, and safety profile of EBUS-GS performed by these inexperienced physicians, the first 100 consecutive EBUS-GS procedures were included in the evaluation.
The overall diagnostic yield of EBUS-GS performed by two physicans in 200 patients with a peripheral lung lesion was 73.0%. Learning curve analyses showed that the diagnostic yields were stable, even when the procedure was performed by beginners. Complications related to EBUS-GS occurred in three patients (1.5%): pneumothorax developed in two patients (1%) and resolved spontaneously without chest tube drainage; another patient (0.5%) developed a pulmonary infection after EBUS-GS. There were no cases of pneumothorax requiring chest tube drainage, severe hemorrhage, respiratory failure, premature termination of the procedure, or procedure-related mortality.
EBUS-GS is a safe and stable procedure with an acceptable diagnostic yield, even when performed by physicians with no previous experience.
Despite an abundance of research related to the functional and structural changes of the brain in patients with geriatric depression, knowledge related to early alterations such as decreased white ...matter connectivity and their association with cognitive decline remains lacking. We aimed to investigate early alterations in hippocampal microstructure and identify their associations with memory function in geriatric patients with subclinical depression. Nineteen participants with subclinical geriatric depression and 19 healthy controls aged ≥65 years exhibiting general cognitive function within the normal range were included in the study and underwent assessments of verbal memory. Hippocampal subfield volumes were determined based on T1-weighted magnetization-prepared rapid gradient echo (T1-MPRAGE) images, while group tractography and connectometry analyses were conducted using diffusion tensor images. Our findings indicated that the volumes of whole bilateral hippocampus, cornus ammonis (CA) 1, molecular layer, left subiculum, CA3, hippocampal tail, right CA4, and granule cell/molecular layers of the dentate gyrus (GC-ML-DG) were significantly smaller in the subclinical depression group than in the control group. In the subclinical depression group, verbal learning was positively correlated with the volumes of the CA1, GC-ML-DG, molecular layer, and whole hippocampus in the right hemisphere. The fractional anisotropy of the bilateral fornix was also significantly lower in the subclinical depression group and exhibited a positive correlation with verbal learning and recall in both groups. Our results suggest that hippocampal microstructure is disrupted and associated with memory in patients with subclinical depression.
We investigated the differences in cognitive and emotional empathic ability between adolescents and adults, and the differences of the brain activation during cognitive and emotional empathy tasks.
...Adolescents (aged 13-15 years, n=14) and adults (aged 19-29 years, n=17) completed a range of empathic ability questionnaires and were scanned functional magnetic resonance imaging (fMRI) during both cognitive and emotional empathy task. Differences in empathic ability and brain activation between the groups were analyzed.
Both cognitive and emotional empathic ability were significantly lower in the adolescent compared to the adult group. Comparing the adolescent to the adult group showed that brain activation was significantly greater in the right transverse temporal gyrus (BA 41), right insula (BA 13), right superior parietal lobule (BA 7), right precentral gyrus (BA 4), and right thalamus whilst performing emotional empathy tasks. No brain regions showed significantly greater activation in the adolescent compared to the adult group while performing cognitive empathy task. In the adolescent group, scores of the Fantasy Subscale in the Interpersonal Reactivity Index, which reflects cognitive empathic ability, negatively correlated with activity of right superior parietal lobule during emotional empathic situations (r=-0.739, p=0.006).
These results strongly suggest that adolescents possess lower cognitive and emotional empathic abilities than adults do and require compensatory hyperactivation of the brain regions associated with emotional empathy or embodiment in emotional empathic situation. Compensatory hyperactivation in the emotional empathy-related brain areas among adolescents are likely associated with their lower cognitive empathic ability.
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