Spontaneous parametric downconversion photon pair generation in small footprint X-cut periodically poled lithium niobate micro-resonator.

Spontaneous parametric downconversion (SPDC) has been crucial for producing non-classical light, such as correlated photon pairs and squeezed states, essential for optical quantum technologies. Recently, thin-film lithium niobate (TFLN)-based devices have enabled high-performance SPDC in on-chip integrated photonic platforms. Here, we developed an X-cut periodically poled lithium niobate (PPLN) racetrack micro-resonator with a compact footprint and demonstrated bright SPDC photon pair generation characterized by distinct resonances and high extraction efficiency. We separately assessed the internal and loaded photon pair generation rates, measuring them at 4.525 MHz/µW and 62.73 kHz/µW, respectively. Our platform is integrated with maturing electro-/thermo-optic TFLN circuit elements and has meaningful potential for advancing active quantum photonic applications.

Hyperband electro-optic modulator based on a two-pulley coupled lithium niobate racetrack resonator.

Integrated optical modulators (IOMs) are crucial components of on-chip photonic circuits. However, most conventional IOMs are restricted to specific spectral bands. Here, we leveraged the wide transparency window of lithium niobate in conjunction with the two-pulley coupled resonator method. This approach led to the development of a hyperband electro-optic (EO) modulator that operates over an expansive spectral range from 775 to 1550 nm on a single device. The demonstrated EO modulator exhibits half-wave voltage-length products of 0.25, 0.93, and 0.68 V·cm at wavelengths of 1539.50, 969.70, and 775.17 nm, respectively.

Effect of RANKL on Lower Depressive Symptoms In Hemodialysis Patients.

Depression and osteoporosis are common diseases in dialysis patients. In addition, patients with osteoporosis are more susceptible to depression. Contrary to previous anti-osteoporosis agents, denosumab and romosozumab could be used in dialysis patients and have similar action mechanisms for blocking RANKL. RANKL causes bone resorption after binding RANKL, but binding with OPG leads to suppress of bone resorption. In recent mice study, inhibition of RANKL with denosumab improved depressive-like phenotype. Besides, it was found that OPG was associated with depression. Therefore, this study aimed to investigate the association of depressive symptoms with RANKL and OPG in hemodialysis patients. We conducted a cross-sectional study with a total of 172 hemodialysis patients. The participants were measured for plasma RANKL, OPG, MMP-2, and MMP-9 levels. Logistic regression analysis was performed to evaluate the effect of RANKL and OPG on the presence of depressive symptoms. The depressive symptoms were observed in 90 (52.3%) subjects. RANKL tertile 3 had negative association with BDI score (ß - 4.527, 95% CI - 8.310 to - 0.743) in univariate analysis, and this association persisted even after multivariate adjustments (ß - 5.603, 95% CI - 9.715 to -1.491) in linear regression. In logistic regression between RANKL tertiles and depressive symptoms, RANKL tertile 3 had significantly lower unadjusted OR (0.40, 95% CI 0.19-0.86), and multivariate-adjusted OR (0.31, 95% CI 0.12-0.82) for depressive symptoms. OPG was not significantly associated with depressive symptoms. Higher plasma RANKL concentrations were significantly associated with lower depressive symptoms in HD patients.Trial registration WHO registry, No. KCT0003281, date: January 12, 2017.

Understanding the Korean Dialysis Cohort for Mineral, Vascular Calcification, and Fracture (ORCHESTRA) Study: Design, Method, and Baseline Characteristics.

INTRODUCTION: End-stage renal disease (ESRD) is a growing disease worldwide, including Korea. This is an important condition that affects patient outcome. To provide optimal management for mineral disturbance, vascular calcification, and bone disease in ESRD patients, the Korean dialysis cohort for mineral, vascular calcification, and fracture (ORCHESTRA) study was conducted by enrolling Korean dialysis patients. METHODS: Sixteen university-affiliated hospitals and one Veterans' Health Service Medical Center participated in this study. This prospective cohort study enrolled approximately 900 consecutive patients on dialysis between May 2019 and January 2021. Enrolled subjects were evaluated at baseline for demographic information, laboratory tests, radiologic imaging, and bone mineral densitometry (BMD) scans. After enrollment, regular assessments of the patients were performed, and their biospecimens were collected according to the study protocol. The primary outcomes were the occurrence of major adverse cardiovascular events, invasive treatment for peripheral artery disease, and osteoporotic fractures. The secondary outcomes were hospitalization for cerebrovascular disease or progression of abdominal aortic calcification. Participants will be assessed for up to 3 years to determine whether primary or secondary outcomes occur. RESULTS: Between May 2019 and January 2021, all participating centers recruited 900 consecutive dialysis patients, including 786 undergoing hemodialysis (HD) and 114 undergoing peritoneal dialysis (PD). The mean age of the subjects was 60.4 ± 12.3 years. Males accounted for 57.7% of the total population. The mean dialysis vintage was 6.1 ± 6.0 years. The HD group was significantly older, had a longer dialysis vintage, and more comorbidities. Overall, the severity of vascular calcification was higher and the level of BMD was lower in the HD group than in the PD group. CONCLUSION: This nationwide, multicenter, prospective cohort study focused on chronic kidney disease-mineral and bone disorder and aimed to provide clinical evidence to establish optimal treatment guidelines for Asian dialysis patients.

Clinical significance of urinary inflammatory biomarkers in patients with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, although the definitive markers are unknown. We aimed to investigate the clinical significance of urinary cytokines in patients with IgAN. METHODS: From 2009 to 2018, the patients were divided into three groups: IgAN (n = 191), disease control (n = 53), and normal control (n = 76). We used a multiplex enzyme-linked immunosorbent assay to measure 16 selected urinary inflammatory cytokines, evaluated the correlation between clinical and pathological features following regression analysis on progression. RESULTS: The IgAN group exhibited significantly different levels of urinary cytokines compared to the normal control and disease control groups. Urinary levels of B-cell-activating factor, vascular endothelial growth factor receptor-2, monocyte chemoattractant protein-1, C-X-C motif chemokine 10, C-X-C motif ligand 16, epidermal growth factor (EGF), endocan, endostatin, growth/differentiation factor-15 (GDF-15), interleukin-6 (IL-6), mannose-binding lectin, transferrin receptor, and kidney injury molecule-1 were significantly correlated with both the estimated glomerular filtration rate and urine protein-creatinine ratio. In a multivariate Cox regression analysis, urinary EGF (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.17-0.95, P = 0.04), GDF-15 (HR 2.45, 95% CI 1.01-5.94, P = 0.048), and IL-6 (HR 3.02, 95% CI 1.05-8.64, P = 0.04) were associated with progression in IgAN. CONCLUSIONS: Urinary inflammatory biomarkers may serve as alternative predictive biomarkers in patients with IgAN. Further studies are needed to elucidate the physiological mechanisms and confirm the results.

ABCA9, an ER cholesterol transporter, inhibits breast cancer cell proliferation via SREBP-2 signaling.

The association between cholesterol metabolism and cancer development and progression has been recently highlighted. However, the role and function of many cholesterol transporters remain largely unknown. Here, we focused on the ATP-binding cassette subfamily A member 9 (ABCA9) transporter given that its expression is significantly downregulated in both canine mammary tumors and human breast cancers, which in breast cancer patients correlates with poor prognosis. We found that ABCA9 is mainly present in the endoplasmic reticulum (ER) and is responsible for promoting cholesterol accumulation in this structure. Accordingly, ABCA9 inhibited sterol-regulatory element binding protein-2 (SREBP-2) translocation from the ER to the nucleus, a crucial step for cholesterol synthesis, resulting in the downregulation of cholesterol synthesis gene expression. ABCA9 expression in breast cancer cells attenuated cell proliferation and reduced their colony-forming abilities. We identified ABCA9 expression to be regulated by Forkhead box O1 (FOXO1). Inhibition of PI3K induced enhanced ABCA9 expression through the activation of the PI3K-Akt-FOXO1 pathway in breast cancer cells. Altogether, our study suggests that ABCA9 functions as an ER cholesterol transporter that suppresses cholesterol synthesis via the inhibition of SREBP-2 signaling and that its restoration halts breast cancer cell proliferation. Our findings provide novel insight into the vital role of ABCA9 in breast cancer progression.

How obesity and metabolic syndrome affect cardiovascular events, progression to kidney failure and all-cause mortality in chronic kidney disease.

BACKGROUND: Obesity and metabolic syndrome (MetS) are prevalent among chronic kidney disease (CKD) patients. However, it is unclear whether obesity without MetS is associated with a higher risk of adverse clinical outcomes in CKD patients. METHODS: We searched the National Health Insurance Service database of Korea for patients who underwent national health screenings in 2009-2011 and identified 59 725 CKD patients. Obesity was defined as a body mass index ≥25 kg/m2. MetS was defined as the presence of ≥3 metabolic risks. RESULTS: The cumulative event rate of cardiovascular events, progression to end-stage kidney disease (ESKD), and all-cause mortality was the lowest among obese patients without MetS (all P < 0.001). In multivariable analysis, obese (versus non-obese) patients without MetS were not at increased risks of cardiovascular events (adjusted hazard ratio [HR] 1.02; 95% confidence interval 0.94-1.11) or progression to ESKD (0.92; 0.77-1.09). Their risk of all-cause mortality was significantly decreased (0.82; 0.75-0.90). These findings were consistently observed in overweight, obese, and morbidly obese patients without MetS. Moreover, despite a linear increase in HR for each additional metabolic abnormality in both obese and non-obese patients, the slope of HR increase for cardiovascular events was significantly slower in obese patients (P for interaction = 0.038). CONCLUSIONS: Obesity without MetS did not increase the risk of cardiovascular complications or progression to ESKD. The healthy effect of obesity on all-cause mortality risk and its weakening effect on the association between metabolic hazards and cardiovascular risk should be considered in CKD patients.

Clinical implications of changes in metabolic syndrome status after kidney transplantation: a nationwide prospective cohort study.

BACKGROUND: Metabolic syndrome (MetS) is prevalent in patients with end-stage kidney disease, and kidney transplantation is expected to modify the metabolic status. However, whether changes in metabolic status at the time of transplantation affect recipient outcomes remains unclear. METHODS: We analyzed 4187 recipients registered in a nationwide prospective cohort from 2014 to 2020. MetS was defined as the presence of three or more components of the metabolic syndrome. Patients were classified based on the pre- and post-transplant MetS status: MetS-free, MetS-developed, MetS-recovered and MetS-persistent. Study outcomes were occurrence of death-censored graft loss and a composite of cardiovascular events and death. RESULTS: Among recipients without pre-transplant MetS, 19.6% (419/2135) developed post-transplant MetS, and MetS disappeared in 38.7% (794/2052) of the recipients with pre-transplant MetS. Among the four groups, the MetS-developed group showed the worst graft survival rate, and the MetS-persistent group had a poorer composite event-free survival rate. Compared with the MetS-free group, the MetS-developed group was associated with an increased risk of graft loss [adjusted hazard ratio (aHR) 2.35; 95% confidence interval (CI) 1.17-4.98] and the risk of graft loss increased with increasing numbers of dysfunctional MetS components. MetS-persistent was associated with increased risks of cardiovascular events and death (aHR 2.46; 95% CI 1.12-5.63), but changes in the number of dysfunctional MetS components was not. CONCLUSION: Kidney transplantation significantly alters the metabolic status. Newly developed MetS after transplantation was associated with an increased risk of graft loss, whereas persistent MetS exposure before and after transplantation was associated with increased risks cardiovascular events and patient survival.

Electro-optic control of the external coupling strength of a high-quality-factor lithium niobate micro-resonator.

Controlling the optical coupling between a micro-resonator and waveguide plays a key role in on-chip photonic circuits. Here, we demonstrate a two-point coupled lithium niobate (LN) racetrack micro-resonator that enables us to electro-optically traverse a full set of the zero-, under-, critical-, and over-coupling regimes with minimized disturbance of the intrinsic properties of the resonant mode. The modulation between the zero- and critical-coupling conditions cost a resonant frequency shift of only ∼344.2 MHz and rarely changed the intrinsic quality (Q) factor of 4.6 × 105. Our device is a promising element in on-chip coherent photon storage/retrieval and its applications.

Glucosylceramide synthase regulates adipo-osteogenic differentiation through synergistic activation of PPARγ with GlcCer.

Dysregulation of the adipo-osteogenic differentiation balance of mesenchymal stem cells (MSCs), which are common progenitor cells of adipocytes and osteoblasts, has been associated with many pathophysiologic diseases, such as obesity, osteopenia, and osteoporosis. Growing evidence suggests that lipid metabolism is crucial for maintaining stem cell homeostasis and cell differentiation; however, the detailed underlying mechanisms are largely unknown. Here, we demonstrate that glucosylceramide (GlcCer) and its synthase, glucosylceramide synthase (GCS), are key determinants of MSC differentiation into adipocytes or osteoblasts. GCS expression was increased during adipogenesis and decreased during osteogenesis. Targeting GCS using RNA interference or a chemical inhibitor enhanced osteogenesis and inhibited adipogenesis by controlling the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ). Treatment with GlcCer sufficiently rescued adipogenesis and inhibited osteogenesis in GCS knockdown MSCs. Mechanistically, GlcCer interacted directly with PPARγ through A/B domain and synergistically enhanced rosiglitazone-induced PPARγ activation without changing PPARγ expression, thereby treatment with exogenous GlcCer increased adipogenesis and inhibited osteogenesis. Animal studies demonstrated that inhibiting GCS reduced adipocyte formation in white adipose tissues under normal chow diet and high-fat diet feeding and accelerated bone repair in a calvarial defect model. Taken together, our findings identify a novel lipid metabolic regulator for the control of MSC differentiation and may have important therapeutic implications.

Non-Contact Respiration Measurement Method Based on RGB Camera Using 1D Convolutional Neural Networks.

Conventional respiration measurement requires a separate device and/or can cause discomfort, so it is difficult to perform routinely, even for patients with respiratory diseases. The development of contactless respiration measurement technology would reduce discomfort and help detect and prevent fatal diseases. Therefore, we propose a respiration measurement method using a learning-based region-of-interest detector and a clustering-based respiration pixel estimation technique. The proposed method consists of a model for classifying whether a pixel conveys respiration information based on its variance and a method for classifying pixels with clear breathing components using the symmetry of the respiration signals. The proposed method was evaluated with the data of 14 men and women acquired in an actual environment, and it was confirmed that the average error was within approximately 0.1 bpm. In addition, a Bland-Altman analysis confirmed that the measurement result had no error bias, and regression analysis confirmed that the correlation of the results with the reference is high. The proposed method, designed to be inexpensive, fast, and robust to noise, is potentially suitable for practical use in clinical scenarios.

Thermoregulation of Pseudomonas aeruginosa Biofilm Formation.

We investigated the effect of temperature on the biofilm formation of Pseudomonas aeruginosa and revealed that the biofilm formation increased rapidly at temperatures lower than 25°C. P. aeruginosa formed the most robust biofilm of a conspicuous mushroom-like structure at 20°C. However, when the temperature increased to 25°C, the biofilm formation rapidly decreased. Above 25°C, as the temperature rose, the biofilm formation increased again little by little despite its less-structured form, indicating that 25°C is the low point of biofilm formation. The intracellular 3',5'-cyclic diguanylate (c-di-GMP) levels also decreased rapidly as the temperature rose from 20 to 25°C. The expression levels of pelA, algD, and pslA encoding Pel, alginate, and Psl, respectively, were also dramatically affected by temperature, with pelA being regulated in a pattern similar to that of the intracellular c-di-GMP levels, and the pattern seen for algD regulation was the most similar to the actual biofilm formation pattern. Total exopolysaccharide production was thermoregulated and followed the regulation pattern of c-di-GMP. Interestingly, the thermoregulation patterns in biofilm formation were different depending on the strain of P. aeruginosa Unlike PAO1, another strain, PA14, showed a gradual decrease in biofilm formation and c-di-GMP in the range of 20 to 37°C, and P. aeruginosa clinical isolates also showed slightly different patterns in biofilm formation in conjunction with temperature change, suggesting that different strains may sense different temperature ranges for biofilm formation. However, it is obvious that P. aeruginosa forms more biofilms at lower temperatures and that temperature is an important factor in determining the biofilm formation.IMPORTANCE Biofilm formation is an important protection mechanism used by most microorganisms and provides cells with many advantages, like high infectivity, antibiotic resistance, and strong survivability. Since most persistent bacterial infections are believed to be associated with biofilms, biofilm control is an important issue in medicine, environmental engineering, and industry. Biofilm formation is influenced by various environmental factors. Temperature is the most direct environmental cue encountered by microorganisms. Here, we investigated the effect of temperature on the biofilm formation of P. aeruginosa, a notorious pathogen, and found that temperature is an important factor determining the amount and structure of biofilms. Low temperatures greatly increase biofilm formation and give biofilms a highly conspicuous structure. Although thermoregulation of biofilm formation is mainly mediated by c-di-GMP, some c-di-GMP-independent regulations were also observed. This study shows how biofilms are formed at various temperatures and provides new insights to control biofilms using temperature.

Phospholipase C-ß1 potentiates glucose-stimulated insulin secretion.

PLC-ß exerts biologic influences through GPCR. GPCRs are involved in regulating glucose-stimulated insulin secretion (GSIS). Previous studies have suggested that PLC-ßs might play an important role in pancreatic ß cells. However, because of a lack of the specific inhibitors of PLC-ß isozymes and appropriate genetic models, the in vivo function of specific PLC-ß isozymes in pancreatic ß cells and their physiologic relevance in the regulation of insulin secretion have not been studied so far. The present study showed that PLC-ß1 was crucial for ß-cell function by generation of each PLC-ß conditional knockout mouse. Mice lacking PLC-ß1 in ß cells exhibited a marked defect in GSIS, leading to glucose intolerance. In ex vivo studies, the secreted insulin level and Ca2+ response in Plcb1f/f; pancreas/duodenum homeobox protein 1 (Pdx1)-Cre recombinase-estrogen receptor T2 (CreERt2) islets was lower than those in the Plcb1f/f islets under the high-glucose condition. PLC-ß1 led to potentiate insulin secretion via stimulation of particular Gq-protein-coupled receptors. Plcb1f/f; Pdx1-CreERt2 mice fed a high-fat diet developed more severe glucose intolerance because of a defect in insulin secretion. The present study identified PLC-ß1 as an important molecule that regulates ß cell insulin secretion and can be considered a candidate for therapeutic intervention in diabetes mellitus.-Hwang, H.-J., Yang, Y. R., Kim, H. Y., Choi, Y., Park, K.-S., Lee, H., Ma, J. S., Yamamoto, M., Kim, J., Chae, Y. C., Choi, J. H., Cocco, L., Berggren, P.-O., Jang, H.-J., Suh, P.-G. Phospholipase Cß1 potentiates glucose-stimulated insulin secretion.

Distribution of hepatitis B virus genotypes in the general population of Myanmar via nationwide study.

BACKGROUND: Hepatitis B virus (HBV) infections are a severe health concern worldwide. HBV is a DNA virus with a rapid rate of mutation. Based on heterogeneity of the nucleotide sequence, the HBV strains are divided into nine genotypes, each with a characteristic geographical distribution. Identifying and tracking alterations of HBV genotypes is important in epidemiological and transmission studies, and contributes to predicting the risk for development of severe liver disease and response to antiviral treatment. The present study was undertaken to detect HBV genotypes and sub-genotypes in the general population of different states and regions in Myanmar. METHODS: In 2015, a total of 5547 adults of the general population, residing in seven states, seven regions and the Nay Pyi Taw Union Territory, were screened for Hepatitis B Surface antigen (HBsAg) by the immunochromatographic test (ICT). Of the 353 HBsAg positive samples, the HBVDNA was identified using polymerase chain reactions (PCR) targeting the DNA sequences encoding the Pre-S region. A total of 153 PCR positive samples were subsequently subjected to genotyping by partial genome sequencing in both directions. The resulting sequences were then edited, aligned, and compared with reference sequences using the National Centre for Biotechnology Information (NCBI) web-based genotyping tool. RESULTS: Three HBV genotypes (HBV genotype B, genotype C and genotype D) were detected in Myanmar, of which genotype HBV genotype C (66.7%) was the most prevalent, followed by HBV genotype D (32%) and HBV genotype B (1.3%). Sub-genotyping revealed a total of 7 variants within the B, C and D genotypes: 2 (B4 and B5) in HBV genotype B, 3 (C1, C5 and C7) in HBV genotype C, and 2 (D3 and D6) in HBV genotype D. CONCLUSION: HBV genotype C, sub-genotype C1 was predominantly distributed in all states and regions of Myanmar. This study is the first report on the nationwide distribution of HBV genotypes and sub-genotypes in Myanmar. We believe our findings will enable huge support for the hepatitis disease surveillance program, since HBV infection is one of the National Priority Diseases in Myanmar.

Renal dysfunction is associated with decline of cognitive function in community-dwelling older adults: Korean frailty and aging cohort study.

BACKGROUND: Cognitive decline is common in older adults. Similarly, the prevalence of renal dysfunction is also increased in the elderly population. We conducted this study to clarify the relationship between renal dysfunction and decline of cognitive function in community-dwelling elderly population. METHODS: A cross-sectional analysis was performed using data from the Korean Frailty and Aging Cohort Study, a nationwide cohort study. Total 2847 (1333 men, 1514 women) eligible participants were enrolled for this study. The estimated glomerular filtration rate (eGFR, mL/min/1.73m2) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Global cognitive function was assessed with the Mini-mental State Examination-Korean version. Other domains of cognitive function were tested with the Consortium to Establish a Registry for Alzheimer's disease and the Frontal Assessment Battery. RESULTS: The mean age of all participants was 76.0 ± 3.9 years and eGFR (all in mL/min/1.73 m2) was 77.5 ± 14.3. And the mean eGFR was 91.7 ± 3.2 in quartile 1, 84.9 ± 1.8 in quartile 2, 76.1 ± 3.7 in quartile 3, and 57.2 ± 10.8 in quartile 4. In baseline characteristics, participants with lower eGFR tend to have lower cognitive function scores than participant with higher eGFR. In linear regression analysis, eGFR was correlated with the word list memory (ß = 0.53, P = 0.005), word list recall (ß = 0.86, P < 0.001), and word list recognition (ß = 0.43, P = 0.030) after adjustment of confounding variables. Moreover, after multivariate adjustment the association with cognitive impairment in quartile 2 was stronger (adjusted OR: 1.535, 95% CI: 1.111-2.120, P = 0.009), and the ORs of cognitive impairment were 1.501 (95% CI: 1.084-2.079, P = 0.014) in quartile 3 and 1.423 (95% CI: 1.022-1.983, P = 0.037) in quartile 4. CONCLUSION: In older adults, the immediate, recent memory, and recognition domains were significantly related to renal function. Also, the mild renal dysfunction was independently associated with impairment of global cognitive function. These results suggest that the early stages of renal dysfunction could be an effective target to prevent worsening of cognitive impairment. Therefore, regular monitoring and early detection of mild renal dysfunction in elderly population might be needed.

Epidemiology, risk factors, and clinical impact of early post-transplant infection in older kidney transplant recipients: the Korean organ transplantation registry study.

BACKGROUND: As in younger recipients, post-transplant infection is a frequent and devastating complication after kidney transplantation (KT) in older recipients. However, few studies have analyzed characteristics of post-transplant infection in older kidney recipients. In this study of a nation-wide cohort of older kidney recipients, we investigated the current epidemiology, risk factors, and clinical impacts of early post-transplant infection, which was defined as infectious complications requiring hospitalization within the first 6 months after KT. METHODS: Three thousand seven hundred thirty-eight kidney recipients registered in the Korean Organ Transplantation Registry between 2014 and 2017 were enrolled. Recipients were divided into two groups, younger (n = 3081) and older (n = 657), with a cutoff age of 60 years. We observed characteristics of early post-transplant infection, and investigated risk factors for the development of infection. We also analyzed the association of early post-transplant infection with clinical outcomes including cardiac events, rejection, graft loss, and all-cause mortality. RESULTS: The incidence of early post-transplant infection was more frequent in older recipients (16.9% in younger group and 22.7% in older group). Bacteria were the most common causative pathogens of early post-transplant infection, and the most frequent site of infection was the urinary tract in both older and younger recipients. Older recipients experienced more mycobacterial infections, co-infections, and multiple site infections compared with younger recipients. In older recipients, female sex (HR 1.398, 95% CI 1.199-1.631), older donor age (HR 1.010, 95% CI 1.004-1.016), longer hospitalization after KT (HR 1.010, 95% CI 1.006-1.014), and experience of acute rejection (HR 2.907, 95% CI 2.471-3.419) were independent risk factors for the development of early post-transplant infection. Experiencing infection significantly increases the incidence of rejection, graft loss, and all-cause mortality. CONCLUSION: Our results illustrate current trends, risk factors, and clinical impacts of early post-transplant infection after KT in older recipients. Considering the poor outcomes associated with early post-transplant infection, careful screening of recipients at high risk for infection and monitoring of recipients who experience infection are advised. In addition, since older recipients exhibit different clinical characteristics than younger recipients, further studies are needed to establish effective strategies for treating older recipients.

Gait speed and handgrip strength as predictors of all-cause mortality and cardiovascular events in hemodialysis patients.

BACKGROUND: Low physical performance in patients undergoing maintenance hemodialysis is associated with a high mortality rate. We investigated the clinical relevance of gait speed and handgrip strength, the two most commonly used methods of assessing physical performance. METHODS: We obtained data regarding gait speed and handgrip strength from 277 hemodialysis patients and evaluated their relationships with baseline parameters, mental health, plasma inflammatory markers, and major adverse clinical outcomes. Low physical performance was defined by the recommendations suggested by the Asian Working Group on Sarcopenia. RESULTS: The prevalence of low gait speed and handgrip strength was 28.2 and 44.8%, respectively. Old age, low serum albumin levels, high comorbidity index score, and impaired cognitive functions were associated with low physical performance. Patients with isolated low gait speed exhibited a general trend for worse quality of life than those with isolated low handgrip strength. Gait speed and handgrip strength showed very weak correlations with different determining factors (older age, the presence of diabetes, and lower serum albumin level for low gait speed, and lower body mass index and the presence of previous cardiovascular events for low handgrip strength). Patients with low gait speed and handgrip strength had elevated levels of plasma endocan and matrix metalloproteinase-7 and the highest risks for all-cause mortality and cardiovascular events among the groups (adjusted hazard ratio of 2.72, p = 0.024). Elderly patients with low gait speed and handgrip strength were at the highest risk for poor clinical outcomes. CONCLUSION: Gait speed and handgrip strength reflected distinctive aspects of patient characteristics and the use of both factors improved the prediction of adverse clinical outcomes in hemodialysis patients. Gait speed seems to be a better indicator of poor patient outcomes than is handgrip strength.

Long Non-Coding RNA Associated with Cholesterol Homeostasis and Its Involvement in Metabolic Diseases.

Cholesterol is an essential cell component that functions to create and maintain all kinds of cell membranes and lipoprotein particles. It is crucial to maintain the proper amount of cholesterol at both the cellular and systemic level. Recently, the importance of cholesterol has been reported not only in various cell development processes but also in the development of diseases. Furthermore, the involvement of long non-coding RNAs (lncRNAs), which are regarded as important epigenetic regulators in gene expression, has also been reported in cholesterol homeostasis. It is thus necessary to summarize the research on lncRNAs related to cholesterol with increased interest. This review organized the role of lncRNAs according to the major issues in cholesterol homeostasis: efflux, metabolism and synthesis, and disease process.

Cilastatin Preconditioning Attenuates Renal Ischemia-Reperfusion Injury via Hypoxia Inducible Factor-1α Activation.

Cilastatin is a specific inhibitor of renal dehydrodipeptidase-1. We investigated whether cilastatin preconditioning attenuates renal ischemia-reperfusion (IR) injury via hypoxia inducible factor-1α (HIF-1α) activation. Human proximal tubular cell line (HK-2) was exposed to ischemia, and male C57BL/6 mice were subjected to bilateral kidney ischemia and reperfusion. The effects of cilastatin preconditioning were investigated both in vitro and in vivo. In HK-2 cells, cilastatin upregulated HIF-1α expression in a time- and dose-dependent manner. Cilastatin enhanced HIF-1α translation via the phosphorylation of Akt and mTOR was followed by the upregulation of erythropoietin (EPO) and vascular endothelial growth factor (VEGF). Cilastatin did not affect the expressions of PHD and VHL. However, HIF-1α ubiquitination was significantly decreased after cilastatin treatment. Cilastatin prevented the IR-induced cell death. These cilastatin effects were reversed by co-treatment of HIF-1α inhibitor or HIF-1α small interfering RNA. Similarly, HIF-1α expression and its upstream and downstream signaling were significantly enhanced in cilastatin-treated kidney. In mouse kidney with IR injury, cilastatin treatment decreased HIF-1α ubiquitination independent of PHD and VHL expression. Serum creatinine level and tubular necrosis, and apoptosis were reduced in cilastatin-treated kidney with IR injury, and co-treatment of cilastatin with an HIF-1α inhibitor reversed these effects. Thus, cilastatin preconditioning attenuated renal IR injury via HIF-1α activation.

Rhabdomyolysis-Induced AKI Was Ameliorated in NLRP3 KO Mice via Alleviation of Mitochondrial Lipid Peroxidation in Renal Tubular Cells.

INTRODUCTION: A recent study showed that early renal tubular injury is ameliorated in Nod-like receptor pyrin domain-containing protein 3 (NLRP3) KO mice with rhabdomyolysis-induced acute kidney injury (RIAKI). However, the precise mechanism has not been determined. Therefore, we investigated the role of NLRP3 in renal tubular cells in RIAKI. METHODS: Glycerol-mediated RIAKI was induced in NLRP3 KO and wild-type (WT) mice. The mice were euthanized 24 h after glycerol injection, and both kidneys and plasma were collected. HKC-8 cells were treated with ferrous myoglobin to mimic a rhabdomyolytic environment. RESULTS: Glycerol injection led to increase serum creatinine, aspartate aminotransferase (AST), and renal kidney injury molecule-1 (KIM-1) level; renal tubular necrosis; and apoptosis. Renal injury was attenuated in NLRP3 KO mice, while muscle damage and renal neutrophil recruitment did not differ between NLRP3 KO mice and WT mice. Following glycerin injection, increases in cleaved caspase-3, poly (ADP-ribose) polymerase (PARP), and a decrease in the glutathione peroxidase 4 (GPX-4) level were observed in the kidneys of mice with RIAKI, and these changes were alleviated in the kidneys of NLRP3 KO mice. NLRP3 was upregulated, and cell viability was suppressed in HKC-8 cells treated with ferrous myoglobin. Myoglobin-induced apoptosis and lipid peroxidation were significantly decreased in siNLRP3-treated HKC-8 cells compared to ferrous myoglobin-treated HKC-8 cells. Myoglobin reduced the mitochondrial membrane potential and increased mitochondrial fission and reactive oxygen species (ROS) and lipid peroxidation levels, which were restored to normal levels in NLRP3-depleted HKC-8 cells. CONCLUSIONS: NLRP3 depletion ameliorated renal tubular injury in a murine glycerol-induced acute kidney injury (AKI) model. A lack of NLRP3 improved tubular cell viability via attenuation of myoglobin-induced mitochondrial injury and lipid peroxidation, which might be the critical factor in protecting the kidney.