Mitigating aluminum toxicity and promoting plant resilience in acidic soil with Penicillium olsonii TLL1.

Aluminum (Al), prevalent in the crust of the Earth, jeopardizes plant health in acidic soils, hindering root growth and overall development. In this study, we first analysed the Al- and pH- tolerance of the Penicillium olsonii TLL1 strain (POT1; NRRL:68252) and investigated the potential for enhancing plant resilience under Al-rich acidic soil conditions. Our research illustrates the extraordinary tolerance of POT1 to both high Al concentrations and acidic conditions, showcasing its potential to alleviate Al-induced stress in plants. Metabolite analysis revealed that POT1 detoxifies Al through organic acid-dependent chelation mechanisms, significantly reducing Al stress in Arabidopsis and Pak Choi plants. Consequently, plant growth conditions improved, and the Al content in plant tissues decreased. Transcriptome analysis indicated that POT1 treatment downregulates genes associated with Al and oxidative stress such as MATE, ALS3, NIP1-2 and several peroxidases, highlighting its effectiveness in lessening Al-induced damage. Comparative assessments highlight the superior performance of POT1 compared to other Al-tolerant Penicillium species, attributed to its ability to thrive in diverse pH levels and effectively detoxify Al. These findings position POT1 as a promising agent for enhancing crop resilience in Al-compromised acidic soils, offering new avenues for promoting plant health and bolstering food security through increased crop yield and safety.

Temporal Muscle Thickness and Sarcopenia Components in Healthy Adults, Validated through Allgeun Diagnostic Tool.

Sarcopenia, characterized by progressive muscle loss and functional decline, poses significant risks, including falls, impaired daily activities, and increased mortality. We developed Allgeun, a novel device that measures handgrip strength, muscle mass, and physical performance. This study aimed to investigate whether temporal muscle thickness (TMT) could be used as a sarcopenia marker and to evaluate the usability of Allgeun. This prospective study enrolled 28 participants without medical or neurological disorders. They underwent three-dimensional T1-weighted imaging using a 3 Tesla magnetic resonance imaging scanner. TMT was measured based on T1-weighted images by a board-certified neuroradiologist. Allgeun was used to measure the following three key components of sarcopenia: muscle strength (handgrip strength), muscle mass (calf and thigh circumference), and physical performance (five times the chair stand test). Correlation analysis was conducted between TMT and the results of the handgrip strength, calf and thigh circumferences, and chair stand tests. There were moderate positive correlations between TMT and calf circumference (r = 0.413, p = 0.029), thigh circumference (r = 0.486, p = 0.008), and handgrip strength (r = 0.444, p = 0.018). However, no significant correlation was observed between TMT and physical performance (r = -0.000, p = 0.998). Our findings underscore TMT's potential as an indicator of sarcopenia, particularly regarding muscle mass and strength. Additionally, we demonstrated that the new device, Allgeun, is useful for screening and diagnosing the severity of sarcopenia.

Correlation of diffusion tensor tractography with obstructive sleep apnea severity.

INTRODUCTION: Using correlation tractography, this study aimed to find statistically significant correlations between white matter (WM) tracts in participants with obstructive sleep apnea (OSA) and OSA severity. We hypothesized that changes in certain WM tracts could be related to OSA severity. METHODS: We enrolled 40 participants with OSA who underwent diffusion tensor imaging (DTI) using a 3.0 Tesla MRI scanner. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and quantitative anisotropy (QA)-values were used in the connectometry analysis. The apnea-hypopnea index (AHI) is a representative measure of the severity of OSA. Diffusion MRI connectometry that was used to derive correlational tractography revealed changes in the values of FA, MD, AD, RD, and QA when correlated with the AHI. A false-discovery rate threshold of 0.05 was used to select tracts to conduct multiple corrections. RESULTS: Connectometry analysis revealed that the AHI in participants with OSA was negatively correlated with FA values in WM tracts that included the cingulum, corpus callosum, cerebellum, inferior longitudinal fasciculus, fornices, thalamic radiations, inferior fronto-occipital fasciculus, superior and posterior corticostriatal tracts, medial lemnisci, and arcuate fasciculus. However, there were no statistically significant results in the WM tracts, in which FA values were positively correlated with the AHI. In addition, connectometry analysis did not reveal statistically significant results in WM tracts, in which MD, AD, RD, and QA values were positively or negatively correlated with the AHI. CONCLUSION: Several WM tract changes were correlated with OSA severity. However, WM changes in OSA likely involve tissue edema and not neuronal changes, such as axonal loss. Connectometry analyses are valuable tools for detecting WM changes in sleep disorders.

Plant growth promotion under phosphate deficiency and improved phosphate acquisition by new fungal strain, Penicillium olsonii TLL1.

Microbiomes in soil ecosystems play a significant role in solubilizing insoluble inorganic and organic phosphate sources with low availability and mobility in the soil. They transfer the phosphate ion to plants, thereby promoting plant growth. In this study, we isolated an unidentified fungal strain, POT1 (Penicillium olsonii TLL1) from indoor dust samples, and confirmed its ability to promote root growth, especially under phosphate deficiency, as well as solubilizing activity for insoluble phosphates such as AlPO4, FePO4·4H2O, Ca3(PO4)2, and hydroxyapatite. Indeed, in vermiculite containing low and insoluble phosphate, the shoot fresh weight of Arabidopsis and leafy vegetables increased by 2-fold and 3-fold, respectively, with POT1 inoculation. We also conducted tests on crops in Singapore's local soil, which contains highly insoluble phosphate. We confirmed that with POT1, Bok Choy showed a 2-fold increase in shoot fresh weight, and Rice displayed a 2-fold increase in grain yield. Furthermore, we demonstrated that plant growth promotion and phosphate solubilizing activity of POT1 were more effective than those of four different Penicillium strains such as Penicillium bilaiae, Penicillium chrysogenum, Penicillium janthinellum, and Penicillium simplicissimum under phosphate-limiting conditions. Our findings uncover a new fungal strain, provide a better understanding of symbiotic plant-fungal interactions, and suggest the potential use of POT1 as a biofertilizer to improve phosphate uptake and use efficiency in phosphate-limiting conditions.

The effects of the dialysis on the white matter tracts in patients with end-stage renal disease using differential tractography study.

This study aimed to determine whether white matter tracts correlate with kidney function using correlation tractography, and to investigate the effects of dialysis on white matter tracts in patients with end-stage renal disease (ESRD) using differential tractography. Ten patients with ESRD, who had a glomerular filtration rate of < 15 mL/min/1.73 m2, were enrolled in this prospective study. Diffusion tensor imaging (DTI) was performed both before and after dialysis. We discovered that white matter tracts correlated with the estimated glomerular filtration rate based on pre- and post-dialysis DTI using correlation tractography and investigated the differences in the white matter tracts between pre- and post-dialysis DTI in patients with ESRD using differential tractography. Correlation tractography revealed no quantitative anisotropy of the white matter tracts that correlated with the estimated glomerular filtration rate in pre- and post-dialysis patients with ESRD. Differential tractography revealed significant differences in several white matter tracts, particularly the cingulum, thalamic radiation, corpus callosum, and superior longitudinal fasciculus, between pre- and post-dialysis DTI, which revealed increased diffusion density after dialysis. We demonstrated the significant effects of dialysis on several white matter tracts in patients with ESRD using differential tractography, which showed increased diffusion density after dialysis. In this study, we confirmed the effects of dialysis on brain structure, especially white matter tracts.

Structural brain network changes in patients with neurofibromatosis type 1: A retrospective study.

We investigated the changes in structural connectivity (using diffusion tensor imaging [DTI]) and the structural covariance network based on structural volume using graph theory in patients with neurofibromatosis type 1 (NF1) compared to a healthy control group. We included 14 patients with NF1, according to international consensus recommendations, and 16 healthy individuals formed the control group. This was retrospectively observational study followed STROBE guideline. Both groups underwent brain magnetic resonance imaging including DTI and 3-dimensional T1-weighted imaging. We analyzed structural connectivity using DTI and Diffusion Spectrum Imaging Studio software and evaluated the structural covariance network based on the structural volumes using FreeSurfer and Brain Analysis Using Graph Theory software. There were no differences in the global structural connectivity between the 2 groups, but several brain regions showed significant differences in local structural connectivity. Additionally, there were differences between the global structural covariance networks. The characteristic path length was longer and the small-worldness index was lower in patients with NF1. Furthermore, several regions showed significant differences in the local structural covariance networks. We observed changes in structural connectivity and covariance networks in patients with NF1 compared to a healthy control group. We found that global structural efficiency is decreased in the brains of patients with NF1, and widespread changes in the local structural network were found. These results suggest that NF1 is a brain network disease, and our study provides direction for further research to elucidate the biological processes of NF1.

Difference in functional connectivity between end-stage renal disease patients with and without restless legs syndrome: A prospective study.

PURPOSE: The purpose of this study was to examine differences in functional connectivity between patients with end-stage renal disease (ESRD) with and without restless legs syndrome (RLS). In addition, the study aimed to identify any potential associations between RLS severity and functional connectivity. METHODS: We enrolled patients with ESRD who had been undergoing hemodialysis. Patients with and without RLS were separated into two groups. Using functional near-infrared spectroscopy (fNIRS) and a graph theory approach, we determined the functional connectivity of patients with ESRD. The data were collected during a 300-s resting state evaluation performed in the dialysis room prior to dialysis. RESULTS: Eighteen of 48 patients with ESRD were diagnosed with RLS, whereas 30 patients did not exhibit RLS symptoms. Notably, functional connectivity metrics differed significantly between patients with and without RLS. Specifically, patients with ESRD and RLS displayed higher values for mean clustering coefficient (0.474 vs. 0.352, p = 0.001), global efficiency (0.520 vs. 0.414, p = 0.001), strength (6.538 vs. 4.783, p = 0.001), and transitivity (0.714 vs. 0.521, p = 0.001), while values for diameter (5.451 vs. 7.338, p = 0.002), eccentricity (4.598 vs. 5.985, p = 0.004), and characteristic path length (2.520 vs. 3.271, p = 0.002) were lower in patients with ESRD and RLS compared to those without RLS. In addition, there were correlations between the RLS severity score and the assortative coefficient (r = 0.479, p = 0.044), the small-worldness index (r = -0.475, p = 0.046), and transitivity (r = 0.500, p = 0.034). CONCLUSIONS: We demonstrated differences in functional connectivity between patients with ESRD with and without RLS, which may shed light on the pathophysiology of RLS. Notably, a number of functional connectivity metrics demonstrated strong associations with RLS severity. Our study also confirmed the applicability of fNIRS as a tool for investigating functional connectivity in patients with RLS.

Changes in the glymphatic system before and after dialysis initiation in patients with end-stage kidney disease.

INTRODUCTION: The aims of this study were to evaluate 1) glymphatic system function in patients with end-stage kidney disease (ESKD) before initiating dialysis compared to healthy controls, and 2) changes in the glymphatic system function after kidney replacement therapy including dialysis in patients with ESKD using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. MATERIALS AND METHODS: This study was prospectively conducted at a single hospital. We enrolled 14 neurologically asymptomatic patients who first initiated hemodialysis or peritoneal dialysis for ESKD and 17 healthy controls. Patients had magnetic resonance imaging scans before initiating dialysis and again 3 months after initiating dialysis and the DTI-ALPS index was calculated. We compared the DTI-ALPS index before and after the initiation of dialysis and compared the DTI-ALPS index between the patients with ESKD and healthy control. RESULTS: There were differences in the DTI-ALPS index between ESKD patients before initiating dialysis and healthy controls (1.342 vs. 1.633, p = 0.003). DTI-ALPS index between ESKD patients before initiating dialysis and those after dialysis were not different (1.342 vs. 1.262, p = 0.386). There was a positive correlation between DTI-ALPS index and phosphate (r = 0.610, p = 0.020) in patients with ESKD. CONCLUSION: We confirmed the presence of glymphatic dysfunction in patients with ESKD. However, there was no difference in the glymphatic system before and after dialysis initiation. This finding may be related to uremic toxins that are not removed by dialysis in patients with ESKD. This study can be used for the development of pathophysiology of patients with ESKD.

Effects of Storage Temperatures on Nitrogen Assimilation and Remobilization during Post-Harvest Senescence of Pak Choi.

In the agricultural industry, the post-harvest leafy vegetable quality and shelf life significantly influence market value and consumer acceptability. This study examined the effects of different storage temperatures on leaf senescence, nitrogen assimilation, and remobilization in Pak Choi (Brassica rapa subsp. chinensis). Mature Pak Choi plants were harvested and stored at two different temperatures, 4 °C and 25 °C. Senescence was tracked via chlorophyll content and leaf yellowing. Concurrently, alterations in the total nitrogen, nitrate, and protein content were quantified on days 0, 3, 6, and 9 in old, mid, and young leaves of Pak Choi plants. As expected, 4 °C alleviated chlorophyll degradation and delayed senescence of Pak Choi compared to 25 °C. Total nitrogen and protein contents were inversely correlated, while the nitrate content remained nearly constant across leaf groups at 25 °C. Additionally, the transcript levels of genes involved in nitrogen assimilation and remobilization revealed key candidate genes that were differentially expressed between 4 °C and 25 °C, which might be targeted to extend the shelf life of the leafy vegetables. Thus, this study provides pivotal insights into the molecular and physiological responses of Pak Choi to post-harvest storage conditions.

Intrinsic prefrontal functional connectivity according to cognitive impairment in patients with end-stage renal disease.

Background: This study aimed to investigate differences in intrinsic prefrontal functional connectivity according to the presence of cognitive impairment in patients with end-stage renal disease (ESRD) using functional near-infrared spectroscopy (fNIRS). Methods: We prospectively enrolled 37 patients with ESRD who had been undergoing hemodialysis for more than 6 months and had no history of neurological or psychiatric disorders. All patients with ESRD underwent the Korean version of the Montreal Cognitive Assessment (MoCA-K) to assess cognitive function. The NIRSIT Lite device (OBELAB Inc.) was used to acquire fNIRS data, and the NIRSIT Lite Analysis Tool program was used to process the data and generate a functional connectivity matrix. We obtained functional connectivity measures by applying graph theory to the connectivity matrix using the BRAPH (brain analysis using graph theory) program. Results: Of the 37 patients with ESRD, 23 had cognitive impairment, whereas 14 patients showed no cognitive impairment. Intrinsic prefrontal functional connectivity was significantly different between groups. Network measures of strength, global efficiency, and mean clustering coefficient were lower in ESRD patients with cognitive impairment than in those without cognitive impairment (4.458 vs. 5.129, p = 0.02; 0.397 vs. 0.437, p = 0.03; and 0.316 vs. 0.421, p = 0.003; respectively). There were no significant correlations between MoCA-K scores and clinical characteristics. Conclusion: We demonstrated a significant association between cognitive function and intrinsic prefrontal functional connectivity in patients with ESRD. ESRD patients with cognitive impairment have reduced connectivity and segregation in the prefrontal brain network compared to those without cognitive impairment.

The effects of hemodialysis on the functional brain connectivity in patients with end-stage renal disease with functional near-infrared spectroscopy.

This study aimed to investigate functional brain connectivity in patients with end-stage renal disease (ESRD) undergoing hemodialysis using functional near-infrared spectroscopy (fNIRS) and to analyze the effect of hemodialysis on functional brain connectivity. We prospectively enrolled patients with ESRD undergoing hemodialysis for > 6 months without any history of neurological or psychiatric disorders. fNIRS data were acquired using a NIRSIT Lite device. Measurements were performed thrice in the resting state for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). We processed and exported all data, and created a weighted connectivity matrix using Pearson correlation analysis. We obtained functional connectivity measures from the connectivity matrix by applying a graph theoretical analysis. We then compared differences in functional connectivity measures according to hemodialysis status in patients with ESRD. We included 34 patients with ESRD. There were significant changes in the mean clustering coefficient, transitivity, and assortative coefficient between the pre- and post-HD periods (0.353 vs. 0.399, p = 0.047; 0.523 vs. 0.600, p = 0.042; and 0.043 vs. - 0.012, p = 0.044, respectively). However, there were no changes in the mean clustering coefficient, transitivity, and assortative coefficient between the pre- and mid-HD periods, or between the mid- and post-HD periods. In addition, there were no significant differences in the average strength, global efficiency, and local efficiency among the pre-, mid-, and post-HD periods. We demonstrated a significant effect of hemodialysis on functional brain connectivity in patients with ESRD. Functional brain connectivity changes more efficiently during hemodialysis.

Inositol polyphosphates-regulated polyubiquitination of PHR1 by NLA E3 ligase during phosphate starvation response in Arabidopsis.

Phosphate (Pi) availability is a major factor limiting plant growth and development. The key transcription factor controlling Pi-starvation response (PSR) is PHOSPHATE STARVATION RESPONSE 1 (PHR1) whose transcript levels do not change with changes in Pi levels. However, how PHR1 stability is regulated at the post-translational level is relatively unexplored in Arabidopsis thaliana. Inositol polyphosphates (InsPn) are important signal molecules that promote the association of stand-alone SPX domain proteins with PHR1 to regulate PSR. Here, we show that NITROGEN LIMITATION ADAPTATION (NLA) E3 ligase can associate with PHR1 through its conserved SPX domain and polyubiquitinate PHR1 in vitro. The association with PHR1 and its ubiquitination is enhanced by InsP6 but not by InsP5. Analysis of InsPn-related mutants and an overexpression plant shows PHR1 levels are more stable in itpk4-1 and vih2-4/VIH1amiRNA but less stable in ITPK4 overexpression plants. Under Pi-deficient conditions, nla seedlings contain high PHR1 levels, display long root hair and accumulate anthocyanin in shoots phenocopying PHR1 overexpression plants. By contrast, NLA overexpression plants phenocopy phr1 whose phenotypes are opposite to those of nla. Our results suggest NLA functions as a negative regulator of Pi response by modulating PHR1 stability and the NLA/PHR1 association depends on InsPn levels.

Humoral response to vaccination against SARS-CoV-2 in patients undergoing dialysis.

Patients undergoing maintenance dialysis have a higher mortality rate associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and response rates to vaccination against SARS-CoV-2 vary from 29.6% to 96.4% in such patients. This study aimed to assess the immunogenicity of SARS-CoV-2 vaccination in Korean patients undergoing dialysis. We enrolled 70 SARS-CoV-2-vaccinated patients undergoing dialysis, with 11 healthcare workers serving as healthy control subjects. Thirty-two patients had received a third vaccination, whereas 38 had received 2 vaccinations. The healthy control subjects completed the second vaccination. Immunoglobulin G (IgG) antibodies targeting the receptor-binding domain of the S1 subunit of the SARS-CoV-2 spike protein were measured The vaccination responder rates were 86% (37/43), 96% (26/27), and 91% (10/11) in the patients undergoing hemodialysis and peritoneal dialysis and healthy controls, respectively. IgG antibody levels were significantly higher when a third dose was administered, independent of the type of vaccine or the time interval between vaccination and the subsequent blood sampling date. When a third dose of vaccine was administered, there was no difference in IgG antibody levels between those receiving cross-vaccination or a single vaccine. There was no significant difference in IgG antibodies between healthy controls and patients undergoing dialysis. Patients on dialysis exhibited a sufficient antibody-related response to vaccination against SARS-CoV-2, even in those receiving cross-vaccination, and the antibody titer was higher after a third vaccination. Therefore, it is necessary to administer a third vaccine dose to Korean patients undergoing dialysis.

Glymphatic system dysfunction in patients with early chronic kidney disease.

Introduction: It is a recent finding that glymphatic system dysfunction contributes to various neurological problems. The purpose of this research was to assess the function of the glymphatic system in neurologically asymptomatic early chronic kidney disease (CKD) patients and healthy controls, using diffusion tensor image analysis along perivascular space (DTI-ALPS) index. Methods: In a prospective study, we included patients with early CKD who were asymptomatic for neurological issues and obtained clinical and laboratory data. In all participants, brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was conducted. We used DSI program for DTI preprocessing and DTI-ALPS index estimation. The DTI-ALPS index was compared between patients with early CKD and healthy controls, and the association between clinical characteristics and the DTI-ALPS index was investigated. Results: Eighteen patients with early CKD and 18 healthy controls were included in this study. Patients with early CKD had lower DTI-ALPS index than healthy controls (1.259 ± 0.199 vs. 1.477 ± 0.232, p = 0.004). In the correlation analysis, the DTI-ALPS index had no significant relationship with other clinical factors. Conclusion: We suggest dysfunction of glymphatic system in patients with early chronic kidney disease using the DTI-ALPS index. This may be related to the pathophysiology of neurological problems including impairment of cognition in patients with early CKD.

Glymphatic System Function in Patients with Transient Global Amnesia.

BACKGROUND: The purpose of this study was to examine glymphatic system function in patients with transient global amnesia (TGA), as well as to conduct a recurrence analysis. METHODS: We enrolled patients with TGA and healthy controls from our hospital retrospectively. The patients and healthy controls were all scanned with the same 3T scanner, which included diffusion tensor imaging (DTI). We investigated the function of the glymphatic system using DTI analysis along the perivascular space (DTI-ALPS). The ALPS index was compared between patients with TGA and healthy controls, as well as between patients who had recurrent TGA events and those who had only a single TGA event. RESULTS: Seventy-two patients with TGA and 53 healthy controls were enrolled. Sixty-five patients with TGA had a single TGA event, while seven patients had recurrent TGA events. The ALPS index did not differ significantly between patients with TGA and healthy controls (1.665 vs. 1.618, p = 0.436). The ALPS index, on the other hand, varied significantly according to recurrence in patients with TGA. The ALPS index was significantly higher in patients with recurrent TGA events compared to those with a single event (1.928 vs. 1.636, p = 0.049). CONCLUSIONS: We investigated the glymphatic system function in patients with TGA compared to healthy controls for the first time using the DTI-ALPS method. We discovered that these groups did not differ in terms of glymphatic system function. However, glymphatic system function in patients with TGA may differ according to recurrence. Additional research is required to substantiate these findings.

Glymphatic system dysfunction in patients with cluster headache.

INTRODUCTION: The aim of this study was to investigate alterations of the glymphatic system function in patients with cluster headache. METHODS: We enrolled patients with cluster headache and healthy controls, and they underwent brain magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI). We used the MRIcron and DSI studio programs for DTI preprocessing and DTI analysis with perivascular space (DTI-ALPS) index calculation. RESULTS: Fourteen patients with cluster headache and 23 healthy controls were enrolled. The DTI-ALPS indexes of the groups were significantly different. The DTI-ALPS index for the patients with cluster headache was lower than that for the healthy controls (1.586 vs. 1.786, p = 0.044). There was a significant negative correlation between the DTI-ALPS index and age in the patients with cluster headache (r = -0.549, p = 0.042). However, the DTI-ALPS index was not associated with other clinical characteristics, including disease duration and headache intensity (r = -0.405, p = 0.150; r = -0.048, p = 0.869, respectively). CONCLUSION: Patients with cluster headache had a lower DTI-ALPS index than the healthy controls; this might indicate glymphatic system dysfunction in the patients with cluster headache. Further research is required to determine whether glymphatic system dysfunction is related to the pathophysiology of cluster headache.

Glymphatic system dysfunction in temporal lobe epilepsy patients with hippocampal sclerosis.

OBJECTIVE: This study aimed to evaluate glymphatic system function in temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (HS) in comparison to healthy controls, using diffusion tensor imaging (DTI)-analysis along the perivascular space (ALPS) method. We hypothesized that there is glymphatic system dysfunction in TLE patients with HS. METHODS: We retrospectively enrolled 25 TLE patients with HS and 26 age- and sex-matched healthy controls. All participants underwent DTI with the same 3T magnetic resonance imaging scanner, and the DTI-ALPS index was calculated. We evaluated the differences in the DTI-ALPS index between TLE patients with HS and healthy controls. Moreover, we evaluated the correlation between the DTI-ALPS index and clinical characteristics of epilepsy, including age, age at seizure onset, duration of epilepsy, and number of anti-seizure medications (ASMs). RESULTS: There was a difference in the DTI-ALPS index between TLE patients with HS and healthy controls. The DTI-ALPS index in TLE patients with HS was lower than that in healthy controls (1.497 vs. 1.668, P = .015). However, there was no difference in the DTI-ALPS index between the newly diagnosed TLE patients with HS and the chronic TLE patients with HS. The DTI-ALPS index was negatively correlated with age (r = -0.420, P = .036). However, the DTI-ALPS index was not correlated with other clinical characteristics, including age at seizure onset, duration of epilepsy, and number of ASMs. SIGNIFICANCE: Our findings showed that the DTI-ALPS index was significantly lower in TLE patients with HS than in healthy controls, indicating the presence of glymphatic system dysfunction in TLE patients with HS. Our study also suggests that the DTI-ALPS method may be useful for evaluating glymphatic system function in epilepsy.

Glymphatic system function in patients with newly diagnosed focal epilepsy.

INTRODUCTION: The aim of this study was to analyze the glymphatic system function and its relationship with clinical characteristics, global diffusion tensor imaging (DTI) parameters, and global structural connectivity in treatment-naïve patients with newly diagnosed focal epilepsy. METHODS: This retrospective single-center study investigated patients with focal epilepsy and healthy controls. All participants underwent routine brain magnetic resonance imaging and DTI. DTI analysis along the perivascular space (DTI-ALPS) was used to evaluate glymphatic system function. We also calculated the measures of global DTI parameters, including whole-brain fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), and performed a graph theoretical network analysis to measure global structural connectivity. RESULTS: A total of 109 patients with focal epilepsy and 88 healthy controls were analyzed. There were no significant differences in the DTI-ALPS index (1.67 vs. 1.68, p = 0.861) between the groups. However, statistically significant associations were found between the DTI-ALPS index and age (r = -0.242, p = 0.01), FA (r = 0.257, p = 0.007), MD (r = -0.469, p < 0.001), AD (r = -0.303, p = 0.001), RD (r = -0.434, p < 0.001), and the assortative coefficient (r = 0.230, p = 0.016) in patients with focal epilepsy. CONCLUSION: The main finding of this study is that DTI-ALPS index is significantly correlated with global DTI parameters and structural connectivity measures of the brain in patients with focal epilepsy. In addition, DTI-ALPS index decreases with age in these patients. We conclude that the DTI-ALPS index can be used to investigate glymphatic system function in patients with focal epilepsy.

Melatonin Attenuates RANKL-Induced Osteoclastogenesis via Inhibition of Atp6v0d2 and DC-STAMP through MAPK and NFATc1 Signaling Pathways.

Melatonin is a hormone secreted by the pineal gland that is involved in the biorhythm of reproductive activities. The present study investigated the inhibitory effects of melatonin on osteoclastogenesis in RAW 264.7 cells according to changes in V-ATPase and the corresponding inhibition of the MAPK and NFATc1 signaling processes. METHODS: the cytotoxic effect of melatonin was investigated by MTT assay. Osteoclast differentiation and gene expression of osteoclast-related factors were confirmed via TRAP staining, pit formation assay, immunofluorescence imaging, western blot, and real-time PCR. RESULTS: melatonin was found to inactivate the p38 and JNK of MAP kinase in RAW264.7 cells treated with RANKL and treated with a combination RANKL and melatonin for 1, 3, and 5 days. The melatonin treatment group showed a reduction in osteoclastogenesis transcription factors and ATP6v0d2 gene expression. CONCLUSIONS: melatonin inhibits osteoclast differentiation and cell fusion by inhibiting the expression of Atp6v0d2 through the inactivation of MAPK and NFATc1 signaling in RANKL-stimulated RAW264.7 macrophages. The findings of the present study suggest that melatonin could be a suitable therapy for bone loss and imply a potential role of melatonin in bone health.

Chrysophanol-Induced Autophagy Disrupts Apoptosis via the PI3K/Akt/mTOR Pathway in Oral Squamous Cell Carcinoma Cells.

Background and Objectives: Natural products are necessary sources for drug discovery and have contributed to cancer chemotherapy over the past few decades. Furthermore, substances derived from plants have fewer side effects. Chrysophanol is an anthraquinone derivative that is isolated from rhubarb. Although the anticancer effect of chrysophanol on several cancer cells has been reported, studies on the antitumor effect of chrysophanol on oral squamous-cell carcinoma (OSCC) cells have yet to be elucidated. Therefore, in this study, we investigated the anticancer effect of chrysophanol on OSCC cells (CAL-27 and Ca9-22) via apoptosis and autophagy, among the cell death pathways. Results: It was found that chrysophanol inhibited the growth and viability of CAL-27 and Ca9-22 and induced apoptosis through the intrinsic pathway. It was also found that chrysophanol activates autophagy-related factors (ATG5, beclin-1, and P62/SQSTM1) and LC3B conversion. That is, chrysophanol activated both apoptosis and autophagy. Here, we focused on the roles of chrysophanol-induced apoptosis and the autophagy pathway. When the autophagy inhibitor 3-MA and PI3K/Akt inhibitor were used to inhibit the autophagy induced by chrysophanol, it was confirmed that the rate of apoptosis significantly increased. Therefore, we confirmed that chrysophanol induces apoptosis and autophagy at the same time, and the induced autophagy plays a role in interfering with apoptosis processes. Conclusions: Therefore, the potential of chrysophanol as an excellent anticancer agent in OSCC was confirmed via this study. Furthermore, the combined treatment of drugs that can inhibit chrysophanol-induced autophagy is expected to have a tremendous synergistic effect in overcoming oral cancer.