Investigating the effects of Carpesii fructus extract on the liver transcriptome of olive flounder (Paralichthys olivaceus) as a potential antiparasitic agent.

Olive flounder (Paralichthys olivaceus), a popular aquaculture species, is plagued by the disease scuticociliatosis caused by Miamiensis avidus, which has a high mortality rate and is typically treated with chemicals such as formalin and hydrogen peroxide. However, Carpesii fructus extract has shown potential as a natural therapeutic agent by reducing the motility of M. avidus. However, despite its potential importance, the effect of the extract on fish metabolism remains unknown. In this study, the effect of Carpesii fructus extract and formalin on fish metabolism was analysed by whole transcriptome analysis in the liver of P. olivaceus. A total of 37,796 transcripts were generated and differential expression genes (DEGs) were identified in the liver of P. olivaceus treated with Carpesii fructus extract or formalin. In addition, functional analysis of DEGs between treatment groups was presented using Gene Ontology. These results will be crucial for the study of scuticociliatosis in various fish species, including P. olivaceus, and for the development of therapeutic agents for other diseases.

Lipid kinase PIP5Kα contributes to Hippo pathway activation via interaction with Merlin and by mediating plasma membrane targeting of LATS1.

BACKGROUND: The Hippo pathway plays a critical role in controlled cell proliferation. The tumor suppressor Merlin and large tumor suppressor kinase 1 (LATS1) mediate activation of Hippo pathway, consequently inhibiting the primary effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Phosphatidylinositol 4,5-bisphosphate (PIP2), a lipid present in the plasma membrane (PM), binds to and activates Merlin. Phosphatidylinositol 4-phosphate 5-kinase α (PIP5Kα) is an enzyme responsible for PIP2 production. However, the functional role of PIP5Kα in regulation of Merlin and LATS1 under Hippo signaling conditions remains unclear. METHODS: PIP5Kα, Merlin, or LATS1 knockout or knockdown cells and transfected cells with them were used. LATS1, YAP, and TAZ activities were measured using biochemical methods and PIP2 levels were evaluated using cell imaging. Low/high cell density and serum starvation/stimulation conditions were tested. Colocalization of PIP5Kα and PIP2 with Merlin and LATS1, and their protein interactions were examined using transfection, confocal imaging, immunoprecipitation, western blotting, and/or pull-down experiments. Colony formation and adipocyte differentiation assays were performed. RESULTS: We found that PIP5Kα induced LATS1 activation and YAP/TAZ inhibition in a kinase activity-dependent manner. Consistent with these findings, PIP5Kα suppressed cell proliferation and enhanced adipocyte differentiation of mesenchymal stem cells. Moreover, PIP5Kα protein stability and PIP2 levels were elevated at high cell density compared with those at low cell density, and both PIP2 and YAP phosphorylation levels initially declined, then recovered upon serum stimulation. Under these conditions, YAP/TAZ activity was aberrantly regulated by PIP5Kα deficiency. Mechanistically, either Merlin deficiency or LATS1 deficiency abrogated PIP5Kα-mediated YAP/TAZ inactivation. Additionally, the catalytic domain of PIP5Kα directly interacted with the band 4.1/ezrin/radixin/moesin domain of Merlin, and this interaction reinforced interaction of Merlin with LATS1. In accordance with these findings, PIP5Kα and PIP2 colocalized with Merlin and LATS1 in the PM. In PIP5Kα-deficient cells, Merlin colocalization with PIP2 was reduced, and LATS1 solubility increased. CONCLUSIONS: Collectively, our results support that PIP5Kα serves as an activator of the Hippo pathway through interaction and colocalization with Merlin, which promotes PIP2-dependent Merlin activation and induces local recruitment of LATS1 to the PIP2-rich PM and its activation, thereby negatively regulating YAP/TAZ activity. Video Abstract.

Printable organometallic perovskite enables large-area, low-dose X-ray imaging.

Medical X-ray imaging procedures require digital flat detectors operating at low doses to reduce radiation health risks. Solution-processed organic-inorganic hybrid perovskites have characteristics that make them good candidates for the photoconductive layer of such sensitive detectors. However, such detectors have not yet been built on thin-film transistor arrays because it has been difficult to prepare thick perovskite films (more than a few hundred micrometres) over large areas (a detector is typically 50 centimetres by 50 centimetres). We report here an all-solution-based (in contrast to conventional vacuum processing) synthetic route to producing printable polycrystalline perovskites with sharply faceted large grains having morphologies and optoelectronic properties comparable to those of single crystals. High sensitivities of up to 11 microcoulombs per air KERMA of milligray per square centimetre (µC mGyair-1 cm-2) are achieved under irradiation with a 100-kilovolt bremsstrahlung source, which are at least one order of magnitude higher than the sensitivities achieved with currently used amorphous selenium or thallium-doped cesium iodide detectors. We demonstrate X-ray imaging in a conventional thin-film transistor substrate by embedding an 830-micrometre-thick perovskite film and an additional two interlayers of polymer/perovskite composites to provide conformal interfaces between perovskite films and electrodes that control dark currents and temporal charge carrier transportation. Such an all-solution-based perovskite detector could enable low-dose X-ray imaging, and could also be used in photoconductive devices for radiation imaging, sensing and energy harvesting.

Preliminary analysis of predicting the first recurrence in patients with neovascular age-related macular degeneration using deep learning.

BACKGROUND: To predict, using deep learning, the first recurrence in patients with neovascular age-related macular degeneration (nAMD) after three monthly loading injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: Optical coherence tomography (OCT) images were obtained at baseline and after the loading phase. The first recurrence was defined as the initial appearance of a new retinal hemorrhage or intra/subretinal fluid accumulation after the initial resolution of exudative changes after three loading injections. Standard U-Net architecture was used to identify the three retinal fluid compartments, which include pigment epithelial detachment, subretinal fluid, and intraretinal fluid. To predict the first recurrence of nAMD, classification learning was conducted to determine whether the first recurrence occurred within three months after the loading phase. The recurrence classification architecture was built using ResNet50. The model with retinal regions of interest of the entire region and fluid region on OCT at baseline and after the loading phase is presented. RESULTS: A total of 1,444 eyes of 1,302 patients were included. The mean duration until the first recurrence after the loading phase was 8.20 ± 15.56 months. The recurrence classification system revealed that the model with the fluid region of OCT after the loading phase provided the highest classification performance, with an area under the receiver operating characteristic curve (AUC) of 0.725 ± 0.012. Heatmap analysis revealed that three pathological fluids, subsided choroidal neovascularization lesions, and hyperreflective foci were important areas for the first recurrence. CONCLUSIONS: The deep learning algorithm allowed for the prediction of the first recurrence for three months after the loading phase with adequate feasibility. An automated prediction system may assist in establishing patient-specific treatment plans and the provision of individualized medical care for patients with nAMD.

Combined exercise and nutrition intervention for older women with spinal sarcopenia: an open-label single-arm trial.

PURPOSE: Spinal sarcopenia is a multifactorial disorder associated with atrophy and fatty changes in paraspinal muscles. Interventional studies for spinal sarcopenia are limited. We aimed to evaluate the effectiveness of a combined exercise and nutrition intervention for the treatment of spinal sarcopenia. METHODS: 35 community-dwelling older women diagnosed with spinal sarcopenia in a previous cohort study were included. The 12-week combined intervention consisted of back extensor strengthening exercises and protein supplementation. The following outcomes were measured at baseline (week 0), after the intervention (week 12), and follow-up (week 24): conventional variables of sarcopenia (appendicular skeletal muscle mass, handgrip strength, 6-meter gait speed, and short physical performance battery); lumbar extensor muscle mass; lumbar extensor muscle volume and signal intensity; back extensor isokinetic strength; and back performance scale. We used the intention-to-treat analysis method, and repeated measures analysis of variance was used to analyze the data. RESULTS: Of the total 35 potential participants, 26 older women participated in the study (mean age 72.5 ± 4.0 years old). After 12 weeks of combined exercise and nutrition intervention, there were no changes in the appendicular skeletal muscle mass, lumbar extensor muscle mass, volume, or signal intensity. Handgrip strength and back extensor isokinetic strength did not change significantly. Short physical performance battery significantly increased (P = 0.042) from 11.46 ± 0.86 to 11.77 ± 0.53 at week 12 and 11.82 ± 0.40 at week 24. The back performance scale sum score also significantly improved (P = 0.034) from 2.68 ± 1.81 to 1.95 ± 1.21 at week 12 and 2.09 ± 1.34 at week 24. CONCLUSION: The combined exercise and nutrition intervention for community-dwelling older women with spinal sarcopenia could be feasible and helpful in improving the physical performance as well as back performance.

PIP5Kγ Mediates PI(4,5)P2/Merlin/LATS1 Signaling Activation and Interplays with Hsc70 in Hippo-YAP Pathway Regulation.

The type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family produces the critical lipid regulator phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in the plasma membrane (PM). Here, we investigated the potential role of PIP5Kγ, a PIP5K isoform, in the Hippo pathway. The ectopic expression of PIP5Kγ87 or PIP5Kγ90, two major PIP5Kγ splice variants, activated large tumor suppressor kinase 1 (LATS1) and inhibited Yes-associated protein (YAP), whereas PIP5Kγ knockdown yielded opposite effects. The regulatory effects of PIP5Kγ were dependent on its catalytic activity and the presence of Merlin and LATS1. PIP5Kγ knockdown weakened the restoration of YAP phosphorylation upon stimulation with epidermal growth factor or lysophosphatidic acid. We further found that PIP5Kγ90 bound to the Merlin's band 4.1/ezrin/radixin/moesin (FERM) domain, forming a complex with PI(4,5)P2 and LATS1 at the PM. Notably, PIP5Kγ90, but not its kinase-deficient mutant, potentiated Merlin-LATS1 interaction and recruited LATS1 to the PM. Consistently, PIP5Kγ knockdown or inhibitor (UNC3230) enhanced colony formation in carcinoma cell lines YAP-dependently. In addition, PIP5Kγ90 interacted with heat shock cognate 71-kDa protein (Hsc70), which also contributed to Hippo pathway activation. Collectively, our results suggest that PIP5Kγ regulates the Hippo-YAP pathway by forming a functional complex with Merlin and LATS1 at the PI(4,5)P2-rich PM and via interplay with Hsc70.

Rural-urban differences of sarcopenia and spinal health in the older women: a comparative observational study.

INTRODUCTION: We aimed to investigate the correlation between spinal sarcopenia, spinal sagittal balance (SSB), and spinal function in older women living in rural areas versus those of the older urban women in our previous study. METHODS: Twenty-five older rural-dwelling women aged more than 70 years were compared with 24 older urban-dwelling women from our previous study. Demographic variables, conventional and spinal sarcopenic indices, variable functional outcome parameters, occupational state, and exercise participation rate were evaluated. We also measured the isometric back extensor strength, radiological parameters for SSB on whole-spine radiography, and volumetric parameters of the lumbar extensor muscle on computed tomography. RESULTS: There were no significant intergroup differences in demographic variables or the prevalence of sarcopenia. Older women in rural areas had greater handgrip strength than those in urban areas (22.7±3.7 kg v 20.0±3.4 kg, p=0.010). However, their mean lumbar lordosis angle was lower (31.7±15.3° v 42.3±11.2°, p=0.012). Isometric back extensor strength was lower in rural women than in urban women. The vocational activity participation rate of rural women was significantly higher (84% v 12.5%, p<0.001), whereas their exercise participation rate was significantly lower (60% v 92%, p<0.001). CONCLUSION: Older women in rural areas had greater handgrip strength and vocational participation rates but lower back extensor strength and exercise participation rates. Therefore, more attention is needed for healthcare services to support their spinal health and exercise habits.

VISUAL PROGNOSTIC VALUE OF NEUTROPHIL-TO-LYMPHOCYTE RATIO AND PLATELET-TO-LYMPHOCYTE RATIO IN BEHÇET UVEITIS.

PURPOSE: To investigate the significance of systemic indicators, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as long-term visual prognostic factors in patients with Behçet uveitis. METHODS: This study comprised 114 eyes from 114 patients diagnosed with Behçet uveitis. Ophthalmologic evaluations and biochemical measurements including NLR and PLR values were consecutively obtained at each visit. Patients were divided into good and poor visual outcome groups, based on the visual acuity of 0.5 logarithm of the minimum angle of resolution in the worse-seeing eyes at the last visit. Factors associated with poor visual outcomes were analyzed, and optimal cutoff values of NLR and PLR were also evaluated. RESULTS: Sixty-six eyes (57.9%) were included in the good visual outcome group. Multivariate regression analysis showed that younger age of onset (odds ratio = 0.939; P = 0.010), longer disease duration (odds ratio = 1.164; P < 0.001), higher maximum NLR (odds ratio = 1.215; P = 0.033), and higher initial PLR (odds ratio = 1.014; P = 0.039) were significantly associated with poor visual outcomes. The optimal cutoff value for patients with poor visual outcome was 5.608 for NLR and 128.078 for PLR. CONCLUSION: A higher maximum NLR and higher initial PLR, as well as a younger age of onset and longer disease duration, were significantly associated with poor visual outcomes. Systemic inflammatory factors might be important indicators of visual prognosis in Behçet uveitis.

RETINITIS PIGMENTOSA SINE PIGMENTO: Clinical Spectrum and Pigment Development.

PURPOSE: To investigate the clinical findings, natural course, and pigment development of patients with retinitis pigmentosa (RP) sine pigmento using multimodal imaging. METHODS: We reviewed the medical records of 810 consecutive patients with RP and assessed serial ultra-widefield fundus photography, fundus autofluorescence, and optical coherence tomography images. Electrophysiological and visual field analysis findings were also reviewed. RESULTS: Of the 774 patients with RP who met the inclusion criteria, 88 were diagnosed with RP sine pigmento, with a prevalence of 11.4%. The mean age of the patients was 35.57 years compared with 49.83 years for patients with typical RP. Fifty-nine patients (67%) demonstrated minimal color change, whereas 29 (33%) presented with grayish flecks in the retinal pigment epithelium on fundus photography. All patients with RP sine pigmento had abnormalities on fundus autofluorescence, and the commonest fundus autofluorescence findings were punctate or reticular hypoautofluorescence. Of the 62 patients without pigmentation at the first visit and at the follow-up visits, 14 (22.6%) had developed pigmentation at their follow-up visit, with an average time of 3.92 years. Most patients retained a visual acuity of ≥20/50 within the age of 50 years. CONCLUSION: Diagnosing RP sine pigmento based solely on ophthalmoscopic findings is more difficult than in more typical cases. Multimodal imaging can provide insights into the clinical characteristics to facilitate the diagnosis, classification, and follow-up of patients.

Natural aging course of lumbar extensor muscle mass and strength in community-dwelling older women: a 1-year prospective observational study.

BACKGROUND: Although the loss of skeletal limb muscle mass and muscle strength in the elderly have been demonstrated, the aging process of the back muscles to maintain core stability is not well known. This 1-year prospective observational study aimed to investigate the natural aging course of the lumbar extensor muscles (LEMs) compared with the extremity muscles and determine whether muscle strength or mass decreases more in community-dwelling older women. METHODS: Twenty-four older urban-dwelling women aged 70 years or older were initially enrolled. Their demographic variables, conventional and spinal sarcopenia indices, and functional outcome parameters were evaluated. We also measured back extensor strength, radiological parameters for spinal sagittal balance on whole-spine radiography, and volumetric parameters of the LEM on computed tomography. RESULTS: After the exclusion of 6 subjects, 18 older women were finally analyzed. All variables related to extremity muscle mass, muscle strength, physical performance, and LEM volume declined over the study period, but the changes were insignificant. However, back extensor strength decreased significantly (median, first, and third quartile: 35.20 [30.80, 44.00] N to 31.40 [29.25, 37.90] N, P = 0.026). Among spinal sagittal balance-related parameters, lumbar lordosis (44.25 [39.30, 47.35]° to 43.15 [31.43, 45.75]°, P = 0.043) and sagittal vertical axis (33.85 [3.57, 58.75] mm to 45.15 [25.35, 58.68] mm, P = 0.004) showed significant changes during the study. CONCLUSIONS: When the natural aging course of LEM in women aged 70 years or older was observed for 1 year, muscle mass decreased less than back extensor strength and spinal sagittal balance. Measurements of back extensor strength and spinal sagittal balance are necessary for the clinical evaluation of spinal aging.

A safe and sustainable bacterial cellulose nanofiber separator for lithium rechargeable batteries.

Bacterial cellulose nanofiber (BCNF) with high thermal stability produced by an ecofriendly process has emerged as a promising solution to realize safe and sustainable materials in the large-scale battery. However, an understanding of the actual thermal behavior of the BCNF in the full-cell battery has been lacking, and the yield is still limited for commercialization. Here, we report the entire process of BCNF production and battery manufacture. We systematically constructed a strain with the highest yield (31.5%) by increasing metabolic flux and improved safety by introducing a Lewis base to overcome thermochemical degradation in the battery. This report will open ways of exploiting the BCNF as a "single-layer" separator, a good alternative to the existing chemical-derived one, and thus can greatly contribute to solving the environmental and safety issues.

Characterization of aquaporin-1ab (Aqp1ab) mRNA in mud loach (Misgurnus mizolepis) exposed to heavy metal and immunostimulant stimuli.

Aquaporins (AQPs) are key proteins that regulate fluid homeostasis in cells via modulating osmotic water transport. In the present study, we identified three variants of Aqp1ab transcript (mmAQP1ab x1, mmAQP1ab x2, and mmAQP1ab x3) in mud loaches (Misgurnus mizolepis), and their expression patterns were examined in response to heavy metal and immunostimulant exposure. Mud loach Aqp1ab gene has a somewhat different organizational structure (i.e. five exons interrupted by four introns) compared to most other teleostean Aqp1ab orthologues, which have four exons. The 5'-flanking regulatory region of Aqp gene showed diverse transcription factor binding motifs, particularly those associated with stress/immune responses. Developmental expression patterns indicated that Aqp1ab mRNA was maternally inherited, presumably important for fine-tuning gene expression during embryonic and early larval developments. Expression of mud loach Aqp1ab mRNA was significantly and differentially modulated in several tissues (intestine, kidneys, spleen, and liver) in response to various heavy metal treatments. In addition, Aqp1ab gene expression was highly induced in response to immune challenge (LPS and polyI:C injections). Collectively, our results suggested that AQPs are multifunctional effectors playing diverse roles in cellular pathways relevant to immune and/or stress adaptation responses, in addition to their involvement in osmoregulation.

Complexities of Prostate Cancer.

Prostate cancer has a long disease history and a wide variety and uncertainty in individual patients' clinical progress. In recent years, we have seen a revolutionary advance in both prostate cancer patient care and in the research field. The power of deep sequencing has provided cistromic and transcriptomic knowledge of prostate cancer that has not discovered before. Our understanding of prostate cancer biology, from bedside and molecular imaging techniques, has also been greatly advanced. It is important that our current theragnostic schemes, including our diagnostic modalities, therapeutic responses, and the drugs available to target non-AR signaling should be improved. This review article discusses the current progress in the understanding of prostate cancer biology and the recent advances in diagnostic and therapeutic strategies.

MicroPET Imaging Assessment of Brain Tau and Amyloid Deposition in 6 × Tg Alzheimer's Disease Model Mice.

Alzheimer's disease (AD) is characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of neurofibrillary tangles (NFT). Amyloid beta (Aß) and tau imaging are widely used for diagnosing and monitoring AD in clinical settings. We evaluated the pathology of a recently developed 6 × Tg - AD (6 × Tg) mouse model by crossbreeding 5 × FAD mice with mice expressing mutant (P301L) tau protein using micro-positron emission tomography (PET) image analysis. PET studies were performed in these 6 × Tg mice using [18F]Flutemetamol, which is an amyloid PET radiotracer; [18F]THK5351 and [18F]MK6240, which are tau PET radiotracers; moreover, [18F]DPA714, which is a translocator protein (TSPO) radiotracer, and comparisons were made with age-matched mice of their respective parental strains. We compared group differences in standardized uptake value ratio (SUVR), kinetic parameters, biodistribution, and histopathology. [18F]Flutemetamol images showed prominent cortical uptake and matched well with 6E10 staining images from 2-month-old 6 × Tg mice. [18F]Flutemetamol images showed a significant correlation with [18F]DPA714 in the cortex and hippocampus. [18F]THK5351 images revealed prominent hippocampal uptake and matched well with AT8 immunostaining images in 4-month-old 6 × Tg mice. Moreover, [18F]THK5351 images were confirmed using [18F]MK6240, which revealed significant correlations in the cortex and hippocampus. Uptake of [18F]THK5351 or [18F]MK6240 was highly correlated with [18F]Flutemetamol in 4-month-old 6 × Tg mice. In conclusion, PET imaging revealed significant age-related uptake of Aß, tau, and TSPO in 6 × Tg mice, which was highly correlated with age-dependent pathology.

Synthesis and Characterization of Diketopyrrolopyrrole-Based Aggregation-Induced Emission Nanoparticles for Bioimaging.

Conventional fluorescent dyes have the property of decreasing fluorescence due to aggregation-caused quenching effects at high concentrations, whereas aggregation-induced emission dyes have the property of increasing fluorescence as they aggregate with each other. In this study, diketopyrrolopyrrole-based long-wavelength aggregation-induced emission dyes were used to prepare biocompatible nanoparticles suitable for bioimaging. Aggregation-induced emission nanoparticles with the best morphology and photoluminescence intensity were obtained through a fast, simple preparation method using an ultrasonicator. The optimally prepared nanoparticles from 3,6-bis(4-((E)-4-(bis(40-(1,2,2-triphenylvinyl)-[1,10-biphenyl]-4-yl)amino)styryl)phenyl)-2,5-dihexyl-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione (DP-R2) with two functional groups having aggregation-induced emission properties and additional donating groups at the end of the triphenylamine groups were considered to have the greatest potential as a fluorescent probe for bioimaging. Furthermore, it was found that the tendency for aggregation-induced emission, which was apparent for the dye itself, became much more marked after the dyes were incorporated within nanoparticles. While the photoluminescence intensities of the dyes were observed to decrease rapidly over time, the prepared nanoparticles encapsulated within the biocompatible polymers maintained their initial optical properties very well. Lastly, when the cell viability test was conducted, excellent biocompatibility was demonstrated for each of the prepared nanoparticles.

Influence of comorbidities on functional outcomes in patients with surgically treated fragility hip fractures: a retrospective cohort study.

BACKGROUND: The incidence and number of fragility hip fractures are gradually increasing, resulting in a wide consumption of medical resources. Various factors affecting functional recovery in patients with fragility hip fractures are known, and comorbid diseases are one of them. The purpose of this study is to determine the effect of comorbidities on functional outcomes in patients surgically treated for fragility hip fractures, thereby contributing to the efficient distribution of medical resources. METHODS: This was a retrospective cohort study performed in the three tertiary rehabilitation facilities. A total of 211 patients (50 men and 161 women; average age 81.6 ± 6.7 years) who had undergone surgery for fragility hip fractures were followed up from immediately after transfer to the Department of Rehabilitation Medicine to 6 months postoperatively. Comorbidities referred to a summary of the following conditions: hypertension, diabetes mellitus, chronic liver disease, dementia, cerebrovascular accident, and osteoporosis. Functional outcomes included Koval's grade, Functional Ambulatory Category (FAC), Functional Independence Measure (FIM)-locomotion, Modified Rivermead Mobility Index, Berg Balance Scale (BBS), 4-Meter Walking speed Test (4MWT), the Korean version of the Mini-Mental State Examination(K-MMSE), Geriatric Depression Scale (GDS), EuroQol Five-Dimension (EQ-5D) questionnaire, the Korean version of the Modified Barthel Index (K-MBI), the Korean version of the Instrumental Activities of Daily Living (K-IADL), and Korean version of Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight scale (K-FRAIL). For all tests, each patient was assessed immediately after transfer and 6 months post-surgery. RESULTS: Multivariate linear regression analyses adjusted for age, sex, the initial variable of the functional outcomes, and comorbidities revealed that dementia had a significant negative impact on Koval's grade and K-FRAIL 6 months postoperatively. Diabetes mellitus had a significant negative impact on the FAC, GDS, EQ-5D, K-IADL, and K-FRAIL 6 months postoperatively. Patients with osteoporosis showed a significant negative outcome of FIM-locomotion 6 months postoperatively. A cerebrovascular accident revealed a significant negative impact on the BBS 6 months postoperatively. In addition, hypertension led to significantly less favorable outcomes of the K-FRAIL 6 months postoperatively. CONCLUSIONS: This study confirmed that comorbidities, particularly dementia and diabetes mellitus, significantly influence functional outcomes 6 months after fragility hip fracture surgeries.

Relationship Between Low Handgrip Strength and Chronic Kidney Disease: KNHANES 2014-2017.

OBJECTIVE: Accelerated loss of muscle mass is common in patients with chronic kidney disease (CKD). Various factors associated with CKD, such as nutritional deficiencies, metabolic acidosis, and chronic inflammation, contribute to muscle wasting. This study aimed to investigate the relationship between CKD and handgrip strength (HGS) in the Korean population. DESIGN AND METHODS: This is a population-based, cross-sectional study of a nationally representative sample of 18,765 patients aged ≥19 years from the Korea National Health and Nutrition Examination Survey in 2014-2017. We measured HGS using a digital hand dynamometer and determined the cutoff for low HGS by deriving -2 standard deviation values of sex-matched healthy young adults (19-39 years old). We defined CKD as eGFR <60 mL/min/1.73 m2 or the presence of CKD based on a self-reported questionnaire. RESULTS: The prevalence of CKD was 4.0% in the total population. The cutoff values for the low HGS were 29.5 kg for men and 16.8 kg for women. The prevalence of low HGS was 6.2% in patients without CKD, and 25.2% in patients with CKD. There was a significant correlation between HGS and eGFR in both men and women. In multivariate logistic regression adjusted by age group, diabetes, hypertension, and obesity, CKD showed an independent relationship with low HGS in both men (odds ratio [OR] 1.910, 95% confidence interval [CI] 1.468-2.485) and women (OR 1.570, 95% CI 1.202-2.052). CONCLUSIONS: The prevalence of low HGS was higher in patients with CKD. We suggest that the sarcopenia should be evaluated in patients with CKD.

COVID-19 doesn't need lockdowns to destroy jobs: The effect of local outbreaks in Korea.

Unlike most countries, Korea did not implement a lockdown in its battle against COVID-19, instead successfully relying on testing and contact tracing. Until the summer of 2020, only one region, Daegu-Gyeongbuk, had a significant number of infections, traced to a religious sect. This allows us to estimate the causal effect of the outbreak on the labor market using difference-in-differences. We find that a one per thousand increase in infections caused a 2 to 3 percent drop in local employment in the early spring. We also find that employment losses caused by local outbreaks in the absence of lockdowns were (i) mainly due to reduced hiring by small establishments, (ii) concentrated in the accommodation/food, education, real estate, and transportation industries, and (iii) worst for economically vulnerable workers who are less educated, young, in low-wage occupations, and on temporary contracts, even controlling for industry effects. These patterns are similar to what we observed in the US and UK: The unequal effects of COVID-19 were the same with or without lockdowns. Our findings are consistent with the lifting of lockdowns having led to only modest employment recoveries in the US and UK, absent larger drops in infection rates.

Honokiol ameliorates angiotensin II-induced hypertension and endothelial dysfunction by inhibiting HDAC6-mediated cystathionine γ-lyase degradation.

Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Hydrogen sulphide (H2 S) produced by cystathionine γ-lyase (CSE) promotes vascular relaxation and lowers hypertension. Honokiol (HNK), a natural compound in the Magnolia plant, has been shown to retain multifunctional properties such as anti-oxidative and anti-inflammatory activities. However, a potential role of HNK in regulating CSE and hypertension remains largely unknown. Here, we aimed to demonstrate that HNK co-treatment attenuated the vasoconstriction, hypertension and H2 S reduction caused by angiotensin II (AngII), a well-established inducer of hypertension. We previously found that histone deacetylase 6 (HDAC6) mediates AngII-induced deacetylation of CSE, which facilitates its ubiquitination and proteasomal degradation. Our current results indicated that HNK increased endothelial CSE protein levels by enhancing its stability in a sirtuin-3-independent manner. Notably, HNK could increase CSE acetylation levels by inhibiting HDAC6 catalytic activity, thereby blocking the AngII-induced degradative ubiquitination of CSE. CSE acetylation and ubiquitination occurred mainly on the lysine 73 (K73) residue. Conversely, its mutant (K73R) was resistant to both acetylation and ubiquitination, exhibiting higher protein stability than that of wild-type CSE. Collectively, our findings suggested that HNK treatment protects CSE against HDAC6-mediated degradation and may constitute an alternative for preventing endothelial dysfunction and hypertensive disorders.

Absolute Quantification of N-Glycosylation of Alpha-Fetoprotein Using Parallel Reaction Monitoring with Stable Isotope-Labeled N-Glycopeptide as an Internal Standard.

Alpha-fetoprotein (AFP) is a well-established serum biomarker for hepatocellular carcinoma (HCC) in clinical laboratories. However, AFP levels can often be high in benign liver diseases such as liver cirrhosis. For this reason, specifically, the level of the aberrant N-glycosylation of AFP has been proposed as a HCC biomarker to improve diagnostic performance using targeted mass spectrometry (MS). In this study, we developed an endoglycosidase-assisted absolute quantification (AQUA) method by which to measure N-glycosylated AFP levels in serum using liquid chromatography-parallel reaction monitoring with immunoprecipitation. Especially, an isotopically labeled synthetic N-glycopeptide with N-acetylhexosamine (HexNAc) attached to asparagine (N) was used as an internal standard. The efficacy of this method was demonstrated by quantifying the N-glycosylation of AFP in human serum. As a result, we showed that the lower limit of the quantification of a stable isotope-labeled N-glycopeptide reached an attomolar level. Our method also had a linear dynamic range from 2 to 6000 ng/mL for N-glycosylated AFP levels. Finally, the N-glycosylation levels of AFP were measured in HCC patients and in healthy donors with the coefficient of variation in both cases (<10% CV). To the best of our knowledge, this is the first report of the AQUA of N-glycosylated AFP in human sera using a stable isotope-labeled glycopeptide as an internal standard. The results demonstrate that our method can facilitate the discovery and verification of aberrant glycoprotein biomarkers in human serum and plasma through sensitive and precise quantification.