Tailless Information-Energy Metasurface.

Programmable metasurface technology can achieve flexible manipulations of electromagnetic waves in real time by adjusting the surface structure and material properties and has shown extraordinary potential in many fields such as wireless communications and the Internet of Things. However, most of the programmable metasurfaces have a common feature: a tail (electrical wires and DC powers), which is difficult to supply in some particular application scenarios such as canyons and mountains. To eliminate the limitation of DC power supply, the programmable metasurface and wireless power transfer technology are combined to propose a tailless information-energy metasurface (IEMS). The tailless IEMS platform can dynamically control electromagnetic waves without relying on an external DC power supply; instead, the required DC power is provided internally by the IEMS platform itself. In the tailless IEMS experiments, the concept is demonstrated through the dynamic regulation of wireless channels and the wireless transmission of DC power. This work provides a self-powered method for programmable metasurfaces, expands the application scenarios, facilitates the miniaturization of systems, and makes it easy to integrate with other systems.

Blocking pathogenic Leptospira invasion with aptamer molecules targeting outer membrane LipL32 protein.

This study aimed to develop aptamers targeting LipL32, a most abundant lipoprotein in pathogenic Leptospira, to hinder bacterial invasion. The objectives were to identify high-affinity aptamers through SELEX and evaluate their specificity and inhibitory effects. SELEX was employed to generate LipL32 aptamers (L32APs) over 15 rounds of selection. L32APs' binding affinity and specificity for pathogenic Leptospira were assessed. Their ability to inhibit LipL32-ECM interaction and Leptospira invasion was investigated. Animal studies were conducted to evaluate the impact of L32AP treatment on survival rates, Leptospira colonization, and kidney damage. Three L32APs with strong binding affinity were identified. They selectively detected pathogenic Leptospira, sparing non-pathogenic strains. L32APs inhibited LipL32-ECM interaction and Leptospira invasion. In animal studies, L32AP administration significantly improved survival rates, reduced Leptospira colonies, and mitigated kidney damage compared to infection alone. This pioneering research developed functional aptamers targeting pathogenic Leptospira. The identified L32APs exhibited high affinity, pathogen selectivity, and inhibition of invasion and ECM interaction. L32AP treatment showed promising results, enhancing survival rates and reducing Leptospira colonization and kidney damage. These findings demonstrate the potential of aptamers to impede pathogenic Leptospira invasion and aid in recovery from Leptospira-induced kidney injury (190 words).

Interferon-alpha and MxA inhibit BK polyomavirus replication by interaction with polyomavirus large T antigen.

INTRODUCTION: BK Polyomavirus (BKPyV) infection is a common complication in kidney transplant recipients and can result in poor outcome and graft failure. Currently, there is no known effective antiviral agent. This study investigated the possible antiviral effects of Interferon alpha (IFNα) and its induced protein, MxA, against BKPyV. METHODS: In vitro cell culture experiments were conducted using human primary renal proximal tubular epithelial cells (HRPTECs). We also did animal studies using Balb/c mice with unilateral kidney ischemic reperfusion injury. RESULTS: Our results demonstrated that IFNα effectively inhibited BKPyV in vitro and murine polyomavirus in animal models. Additionally, IFNα and MxA were found to suppress BKPyV TAg and VP1 production. Silencing MxA attenuated the antiviral efficacy of IFNα.We observed that MxA interacted with BKPyV TAg, causing it to remain in the cytosol and preventing its nuclear translocation. To determine MxA's essential domain for its antiviral activities, different mutant MxA constructs were generated. The MxA mutant K83A retained its interaction with BKPyV TAg, and its antiviral effects were intact. The MxA T103A mutant, on the other hand, abolished GTPase activity and lost its protein-protein interaction with BKPyV TAg, and lost its antiviral effect. CONCLUSION: IFNα and its downstream protein, MxA, have potent antiviral properties against BKPyV. Furthermore, our findings indicate that the interaction between MxA and BKVPyV TAg plays a crucial role in determining the anti-BKPyV effects of MxA.

The essential role of the ERK activation in large T antigen of BK polyomavirus regulated cell migration.

Recent studies have suggested that BK polyomavirus (BKPyV) may be associated with the development of urothelial carcinoma. In Merkel cell carcinoma, TAg and tAg are the major viral proteins of Merkel cell polyomavirus with oncogenic potential. In this study, we aimed to distinguish the role of TAg and tAg in cell migration. Our result demonstrated that ERK was phosphorylated in human renal tubular cells expressing its TAg and tAg after BKPyV infection. Treatment with the ERK inhibitor U0126 suppressed BKPyV gene expression and reduced BKPyV replication. Both TAg and tAg induced cell migration via ERK-dependent signaling. Furthermore, the expression of TAg and tAg had a significant regulatory effect on focal adhesion molecules in renal proximal tubular cells, which strongly suggests that alterations in the focal adhesion complexes are critically involved in TAg and tAg-induced cell migration. Gelatin zymography profiling revealed that TAg regulates the expression and activity of MMP-2 and MMP-9, but not tAg. Interestingly, TAg regulates the expression and activity of MMP-9 through ERK signaling, whereas MMP-2 is regulated through an ERK-independent pathway. Unbalanced ERK pathway activity is frequently observed in many cancers, while MMP proteins are usually overexpressed in aggressive tumors. These findings support the view that BKPyV is an oncogenic virus.

Clinical Benefits of Laparoscopic Adhesiolysis during Peritoneal Dialysis Catheter Insertion: A Single-Center Experience.

Background and Objectives: In peritoneal dialysis (PD) therapy, intra-abdominal adhesions (IAAs) can cause catheter insertion failure, poor dialysis function, and decreased PD adequacy. Unfortunately, IAAs are not readily visible to currently available imaging methods. The laparoscopic approach for inserting PD catheters enables direct visualization of IAAs and simultaneously performs adhesiolysis. However, a limited number of studies have investigated the benefit/risk profile of laparoscopic adhesiolysis in patients receiving PD catheter placement. This retrospective study aimed to address this issue. Materials and Methods: This study enrolled 440 patients who received laparoscopic PD catheter insertion at our hospital between January 2013 and May 2020. Adhesiolysis was performed in all cases with IAA identified via laparoscopy. We retrospectively reviewed data, including clinical characteristics, operative details, and PD-related clinical outcomes. Results: These patients were classified into the adhesiolysis group (n = 47) and the non-IAA group (n = 393). The clinical characteristics and operative details had no remarkable between-group differences, except the percentage of prior abdominal operation history was higher and the median operative time was longer in the adhesiolysis group. PD-related clinical outcomes, including incidence rate of mechanical obstruction, PD adequacy (Kt/V urea and weekly creatinine clearance), and overall catheter survival, were all comparable between the adhesiolysis and non-IAA groups. None of the patients in the adhesiolysis group suffered adhesiolysis-related complications. Conclusions: Laparoscopic adhesiolysis in patients with IAA confers clinical benefits in achieving PD-related outcomes comparable to those without IAA. It is a safe and reasonable approach. Our findings provide new evidence to support the benefits of this laparoscopic approach, especially in patients with a risk of IAAs.

Crystal structure of Leptospira LSS_01692 reveals a dimeric structure and induces inflammatory responses through Toll-like receptor 2-dependent NF-κB and MAPK signal transduction pathways.

Leptospirosis is a commonly overlooked zoonotic disease that occurs in tropical and subtropical regions. Recent studies have divided the Leptospira spp. into three groups based on virulence, including pathogenic, intermediate, and saprophytic species. Pathogenic species express a protein family with leucine-rich repeat (LRR) domains, which are less expressed or absent in nonpathogenic species, highlighting the importance of this protein family in leptospirosis. However, the role of LRR domain proteins in the pathogenesis of leptospirosis is still unknown and requires further investigation. In this study, the 3D structure of LSS_01692 (rLRR38) was obtained using X-ray crystallography at a resolution of 3.2 Å. The results showed that rLRR38 forms a typical horseshoe structure with 11 α-helices and 11 ß-sheets and an antiparallel dimeric structure. The interactions of rLRR38 with extracellular matrix and cell surface receptors were evaluated using ELISA and single-molecule atomic force microscopy. The results showed that rLRR38 interacted with fibronectin, collagen IV, and Toll-like receptor 2 (TLR2). Incubating HK2 cells with rLRR38 induced two downstream inflammation responses (IL-6 and MCP-1) in the TLR2 signal transduction pathway. The TLR2-TLR1 complex showed the most significant upregulation effects under rLRR38 treatment. Inhibitors also significantly inhibited nuclear factor κB and mitogen-activated protein kinases signals transduction under rLRR38 stimulation. In conclusion, rLRR38 was determined to be a novel LRR domain protein in 3D structure and demonstrated as a TLR2-binding protein that induces inflammatory responses. These structural and functional studies provide a deeper understanding of the pathogenesis of leptospirosis.

Transcriptome landscape reveals the chronic inflammatory response in kidneys affected by the combinatory effect of leptospirosis and nephrotoxic injury.

Leptospirosis can cause chronic kidney damage, putting patients at risk of additional kidney injury due to other factors that can lead to renal failure. To understand the combined effect, the transcriptome profiles of kidneys of mice with adenine-induced and chronically Leptospira-infected kidneys were analysed. Chronic inflammation and T-helper 17 immune responses were activated and a high-level expression of Indoleamine 2,3-dioxygenase 1 protein was found. The results indicate that the combination may predispose patients to chronic inflammation, kidney function disruption, and symptoms seen in progressive chronic kidney disease (CKD). Furthermore, immunometabolic regulation may contribute to renal injury caused by chronic leptospirosis with secondary nephrotoxic injury. This study identified several significantly disrupted genes that could serve as potential targets for the diagnosis or treatment of CKD. Our work provides insight into the combined effect of leptospirosis and secondary kidney damage and the molecular basis for rapid progression of CKD.

Tuberculous peritonitis in patients on peritoneal dialysis: a 35-year experience from a large medical center in Northern Taiwan.

INTRODUCTION: Tuberculous peritonitis (TBP) is a rare but fatal complication in patients on peritoneal dialysis (PD). In this study, we aimed to determine the demographic features, clinical features, laboratory parameters, and clinical outcomes of PD patients with TBP and to clarify possible risk factors for mortality. MATERIALS AND METHODS: We retrospectively reviewed 2084 PD patients from January 1985 to December 2019. The diagnosis of TBP was established by positive peritoneal fluid culture for Mycobacterium tuberculosis. RESULTS: 18 patients were diagnosed with TBP. The incidence was 2.029 episodes per 1000 patient-years. The most common symptom was fever (94.4%), followed by cloudy effluent (83.3%) and abdominal pain (83.3%). The average peritoneal dialysis effluent (PDE) white blood cell (WBC) count was 172.7 cells/µL. Nine patients (50%) had WBC counts lower than 100 cells/µL and 13 patients (72.2%) had neutrophilic predominant WBC counts. Acid fast stain (AFS) was positive in 7 patients (38.9%). Only 2 patients (11.1%) continued with PD after TB infection, while 10 patients (55.6%) changed to hemodialysis. Seven patients (38.9%) died within 1 year. Significant differences were observed in sex (p = 0.040), the presence of diabetes mellitus (p = 0.024), and PD catheter removal (p < 0.001) between TBP patients with and without mortality. However, none of them was a significant factor for 1-year mortality in multivariate Cox regression model. CONCLUSION: Physicians should pay attention to the unusual presentations of peritonitis, especially if symptoms include fever or an initial low PDE WBC count. Catheter removal is not mandatory if early diagnosis and appropriate therapy are available.

Ultrafiltration in patients on automated peritoneal dialysis with Homechoice Claria connected to Sharesource: A pilot study.

INTRODUCTION: Fluid overload is an unavoidable problem in patients on peritoneal dialysis (PD) and is associated with poor outcomes. The aim of our study was to estimate ultrafiltration (UF) under different dextrose concentrations (DCs) and four peritoneal transport levels. MATERIALS AND METHODS: 70 patients, with a total of 1,848 daily treatment records and 8,266 single dwells on automated PD (APD) through Homechoice Claria with Sharesource were followed in October 2020 and categorized into two groups according to the DC (D1.5% and D2.5% groups). Baseline characteristics, peritoneal membrane characteristics, and daily PD treatment records from Sharesource were obtained. We compared UF under the different conditions. RESULTS: The mean night UF per cycle, the mean night UF corrected by fill volume (FV) per cycle, and the mean night UF corrected by FV and dwelling time (DT) per cycle were all significantly higher in the D2.5% group than in the D1.5% group (95.8 vs. 220.3 mL, 5.5 vs. 12.0%, and 5.0 vs. 11.6 0/000/minutes, all p < 0.001). However, there was no significant difference among the four transport categories in any group. CONCLUSION: This retrospective study presents precise UF measurements with two solutions at different DCs and four peritoneal transport levels. With a 2-L indwell (DT ranging from ~ 1 to 3 hours), the mean net UF rate was 1.0 mL/min in the D1.5% group and 2.3 mL/min in the D2.5% group.

Land-use diversity can better predict urban spontaneous plant richness than impervious surface coverage at finer spatial scales.

Urban spontaneous plants, that are not intentionally propagated by humans and do not belong to the remnants of the natural habitats, not only occur in green spaces but are also distributed in diverse microhabitats in impervious surface areas. Impervious surface coverage is commonly used in studies on spontaneous plant diversity patterns in human-dominated landscapes; however, the role of habitat diversity (i.e., land-use diversity) has been overlooked. Here, we surveyed spontaneous plant composition and land uses (12 types) in 321 0.25 ha sampling sites on the Chongming District islands, Shanghai, to determine the role of land-use diversity in explaining species richness. We examined the linear relationships between species richness and land-use diversity, and quantified the importance of impervious surface coverage and land-use diversity using the random forest (RF) method. All these analyses were conducted for spatial scales from 0.25 to 5 ha in 0.25 ha increments. We found an overall positive relationship between species richness and land-use diversity, and the RF model predicted approximately 50% of the species richness variation at the smallest spatial scale. However, the positive relationship weakened with spatial scale increase, and a rapid decline in explanatory power occurred for all predictor variables in the RF model. Besides impervious surface coverage, both the vegetated and non-vegetated land-use diversity contributed substantially to the prediction of species richness at finer spatial scales. The findings clarify how land-use diversity, both in green spaces and impervious surface areas, affect urban spontaneous plant richness and should be considered in urban biodiversity conservation strategies at the neighborhood scale.

Effects of Suramin on Polycystic Kidney Disease in a Mouse Model of Polycystin-1 Deficiency.

The aberrant activation of the purinergic signaling pathway has been shown to promote cyst growth and fluid secretion in autosomal dominant polycystic kidney disease (ADPKD). Suramin is an anti-parasitic drug that has strong anti-purinergic properties. Whether suramin could have a therapeutic effect on ADPKD has not been fully investigated. We examined the effect of suramin on cyst progression in a Pkd1 microRNAs transgenic mouse model that presented stable Pkd1 knockdown and moderate disease progression. The Pkd1-deficient mice were treated with suramin (60 mg/kg) by intraperitoneal injection twice a week from postnatal days 35 to 90. Kidney-to-body weight ratios, cyst indices, and blood urea nitrogen (BUN) levels were measured. Cell proliferation and macrophage infiltration were determined by immunohistochemistry. The suramin-treated group had significantly lower renal cyst densities, cell proliferation, and macrophage infiltration compared with saline-treated controls. Suramin significantly inhibited ERK phosphorylation and the expression of Il1b, Il6, Nlrp3, Tgfb, Fn1, P2rx7, and P2ry2 mRNAs in the kidneys. However, BUN levels remained high despite the reduction in cyst growth. Furthermore, plasma cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) levels were significantly higher in the suramin-treated group compared with the control group. Periodic acid-Schiff staining revealed degenerative changes and epithelial cell vacuolation in the non-cystic renal tubules, which indicated phospholipidosis following suramin treatment. These results suggest that suramin may reduce renal cyst growth and inflammation, but the associated tubular cell injuries could limit its therapeutic potential. Other purinergic receptor antagonists with less nephrotoxicity may deserve further investigation for the treatment of ADPKD.

Implication of the IL-10-Expression Signature in the Pathogenicity of Leptospira-Infected Macrophages.

Leptospirosis, an emerging infectious disease caused by pathogenic Leptospira spp., occurs in ecoregions with heavy rainfall and has public health implications. Macrophages are the major anti-Leptospira phagocytes that infiltrate the kidneys during renal leptospirosis, which is caused by leptospires residing in the renal tubules. The pathogenicity of Leptospira spp. in immune effector cells such as macrophages is not well understood. To evaluate this pathogenesis, we characterized and compared the transcriptome-wide alterations in macrophages infected with pathogenic and nonpathogenic Leptospira spp. Using transcriptome data and quantitative reverse transcription PCR analysis, at 2 h postinfection, the hypoxia-inducible factor-1α-dependent glycolysis pathway was implicated in pathogenic Leptospira-infected macrophages but not in nonpathogenic leptospiral infections. Immune-related biological processes were mostly activated in pathogenic Leptospira-infected macrophages, and flow cytometry investigations revealed that classically activated macrophages represent the predominant polarization status. At 24 h after infection, biological pathways associated with interleukin-10, IL-10, signaling the induction of macrophage tolerance, as well as higher levels of IL-10 mRNA and protein expression, were observed in nonpathogenic Leptospira-infected macrophages compared to in pathogenic leptospiral infection. Following leptospiral infection of macrophages, strong IL-10-expressing transcriptome signatures were observed following nonpathogenic leptospiral infection. The transcriptional programs generated in Leptospira-infected macrophages revealed an inflammatory milieu following the production of a critical anti-inflammatory cytokine, IL-10, which is implicated in controlling the pathogenicity of activated macrophages. These findings imply that IL-10-mediated anti-inflammatory responses and tolerance in activated macrophages induced by nonpathogenic Leptospira spp. infection reduce inflammation and tissue damage, thus providing a potential therapeutic target for leptospirosis. IMPORTANCE Activation of macrophages by Leptospira spp. infection is thought to be involved in the pathogenesis of leptospirosis. To evaluate the innate macrophage responses to Leptospira spp., specifically pathogenic versus nonpathogenic Leptospira spp., we characterized the entire transcriptome-wide alterations in infected macrophages. We showed that hypoxia-inducible factor-1α and immune-related pathways are activated in pathogenic leptospiral-infected macrophages. We confirmed the significantly high levels of IL-10-expressing signatures and tolerance in activated macrophages caused by nonpathogenic Leptospira infection. Furthermore, nonpathogenic leptospiral infections attenuated macrophage activation responses. These findings suggest a potential therapeutic strategy for the immune microenvironment caused by macrophage activation driven by IL-10 overexpression, which may contribute to regulating inflammation in leptospirosis.

Consistent temperature-dependent patterns of leaf lifespan across spatial and temporal gradients for deciduous trees in Europe.

Temperature affects leaf lifespan (LL) across either space or time, driving long-term adaptation and short-term thermal acclimation, respectively. However, a comprehensive understanding of the phenomenon and the underlying phenological mechanisms remain poorly understood. The present study investigated the relationship between LL and temperature in six common deciduous trees across both spatial and temporal gradients, then explained the LL variation patterns based on phenological shifts. Using long-term (1971-2000) phenological records of six deciduous tree species at 54 sites across central Europe, we analyzed spatial and temporal variations of LL and leaf phenology along temperature gradients. We assessed the relative contribution of phenological shifts to LL variations by comparing absolute changes in leaf-out and leaf fall. We reported positive LL-temperature relationships across all observations along both spatial (+3.32 days/°C) and temporal (+4.43 days/°C) gradients. The paired t-test of the six deciduous tree species showed no significant difference in regression slopes of LL- temperature between the two gradients (t = -1.50, df = 5, P = 0.194). Prolonged LL can be explained mainly by earlier leaf-out induced by warmer temperatures both spatially (-3.22 days/°C) and temporally (-4.08 days/°C). The converging temperature-dependent patterns of LL across time and space indicate that short-term thermal acclimation keeps pace with long-term genetic adaptation for deciduous trees in Europe. Earlier leaf-out is the key force shaping the LL-temperature relationship. These results provide insights for predicting future vegetation dynamics under global warming.

Metformin induces lactate accumulation and accelerates renal cyst progression in Pkd1-deficient mice.

Metabolic reprogramming is a potential treatment strategy for autosomal dominant polycystic kidney disease (ADPKD). Metformin has been shown to inhibit the early stages of cyst formation in animal models. However, metformin can lead to lactic acidosis in diabetic patients with advanced chronic kidney disease, and its efficacy in ADPKD is still not fully understood. Here, we investigated the effect of metformin in an established hypomorphic mouse model of PKD that presents stable and heritable knockdown of Pkd1. The Pkd1 miRNA transgenic mice of both genders were randomized to receive metformin or saline injections. Metformin was administrated through daily intraperitoneal injection from postnatal day 35 for 4 weeks. Unexpectedly, metformin treatment at a concentration of 150 mg/kg increased disease severity, including kidney-to-body weight ratio, cystic index and plasma BUN levels, and was associated with increased renal tubular cell proliferation and plasma lactate levels. Functional enrichment analysis for cDNA microarrays from kidney samples revealed significant enrichment of several pro-proliferative pathways including ß-catenin, hypoxia-inducible factor-1α, protein kinase Cα and Notch signaling pathways in the metformin-treated mutant mice. The plasma metformin concentrations were still within the recommended therapeutic range for type 2 diabetic patients. Short-term metformin treatment in a second Pkd1 hypomorphic model (Pkd1RC/RC) was however neutral. These results demonstrate that metformin may exacerbate late-stage cyst growth associated with the activation of lactate-related signaling pathways in Pkd1 deficiency. Our findings indicate that using metformin in the later stage of ADPKD might accelerate disease progression and call for the cautious use of metformin in these patients.

LncRNA OIP5-AS1 reduces renal epithelial cell apoptosis in cisplatin-induced AKI by regulating the miR-144-5p/PKM2 axis.

BACKGROUND: The abnormal expression of long non-coding RNA (lncRNA) Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) has been observed in many human cancers and the underlying mechanisms have been well studied. However, the function of OIP5-AS1 in acute kidney injury (AKI) remains unclear. METHODS: To explore the role of OIP5-AS1 in the progression of AKI, the cisplatin-induced AKI mouse and cell model were established. To confirm the potential protective effect of OIP5-AS1 during cisplatin-induced AKI, rescue experiments were performed. Targetscan was used to predict the potential targets of miR-144-5p. To further determine whether the effect of miR-144-5p during cisplatin-induced AKI was mediated by PMK2, the recuse experiments using PMK2 overexpressing vector was applied. RESULTS: OIP5-AS1 was significantly downregulated both in cisplatin-induced AKI mice and human renal tubular cell line HK-2 cells. Moreover, overexpression of OIP5-AS1 efficiently promoted cell growth and reduced cisplatin-induced apoptosis of HK-2 cells. Furthermore, OIP5-AS1 was identified as a sponge of miR-144-5p, and upregulation of miR-144-5p could significantly reverse overexpression of OIP5-AS1-induced protective effect on the damage of cisplatin to HK-2 cells. In addition, pyruvate kinase M2 (PKM2) was found to be a direct target of miR-144-5p, and overexpression of PKM2 efficiently reversed the effect of miR-144-5p mimics on the damage in cisplatin-stimulated HK-2 cells. CONCLUSIONS: OIP5-AS1 reduced the apoptosis of cisplatin-stimulated renal epithelial cells by targeting the miR-144-5p/PKM2 axis, which extended the regulatory network of lncRNAs in cisplatin-induced AKI and also provided a novel therapeutic target for AKI treatment.

Crosstalk between E-Cadherin/ß-Catenin and NF-κB Signaling Pathways: The Regulation of Host-Pathogen Interaction during Leptospirosis.

Approximately 1 million cases of leptospirosis, an emerging infectious zoonotic disease, are reported each year. Pathogenic Leptospira species express leucine-rich repeat (LRR) proteins that are rarely expressed in non-pathogenic Leptospira species. The LRR domain-containing protein family is vital for the virulence of pathogenic Leptospira species. In this study, the biological mechanisms of an essential LRR domain protein from pathogenic Leptospira were examined. The effects of Leptospira and recombinant LRR20 (rLRR20) on the expression levels of factors involved in signal transduction were examined using microarray, quantitative real-time polymerase chain reaction, and western blotting. The secreted biomarkers were measured using an enzyme-linked immunosorbent assay. rLRR20 colocalized with E-cadherin on the cell surface and activated the downstream transcription factor ß-catenin, which subsequently promoted the expression of MMP7, a kidney injury biomarker. Additionally, MMP7 inhibitors were used to demonstrate that the secreted MMP7 degrades surface E-cadherin. This feedback inhibition mechanism downregulated surface E-cadherin expression and inhibited the colonization of Leptospira. The degradation of surface E-cadherin activated the NF-κB signal transduction pathway. Leptospirosis-associated acute kidney injury is associated with the secretion of NGAL, a downstream upregulated biomarker of the NF-κB signal transduction pathway. A working model was proposed to illustrate the crosstalk between E-cadherin/ß-catenin and NF-κB signal transduction pathways during Leptospira infection. Thus, rLRR20 of Leptospira induces kidney injury in host cells and inhibits the adhesion and invasion of Leptospira through the upregulation of MMP7 and NGAL.

Challenges for the Applications of Human Pluripotent Stem Cell-Derived Liver Organoids.

The current organoid culture systems allow pluripotent and adult stem cells to self-organize to form three-dimensional (3D) structures that provide a faithful recapitulation of the architecture and function of in vivo organs. In particular, human pluripotent stem cell-derived liver organoids (PSC-LOs) can be used in regenerative medicine and preclinical applications, such as disease modeling and drug discovery. New bioengineering tools, such as microfluidics, biomaterial scaffolds, and 3D bioprinting, are combined with organoid technologies to increase the efficiency of hepatic differentiation and enhance the functional maturity of human PSC-LOs by precise control of cellular microenvironment. Long-term stabilization of hepatocellular functions of in vitro liver organoids requires the combination of hepatic endodermal, endothelial, and mesenchymal cells. To improve the biological function and scalability of human PSC-LOs, bioengineering methods have been used to identify diverse and zonal hepatocyte populations in liver organoids for capturing heterogeneous pathologies. Therefore, constructing engineered liver organoids generated from human PSCs will be an extremely versatile tool in in vitro disease models and regenerative medicine in future. In this review, we aim to discuss the recent advances in bioengineering technologies in liver organoid culture systems that provide a timely and necessary study to model disease pathology and support drug discovery in vitro and to generate cell therapy products for transplantation.

The protective effect of beta-hydroxybutyric acid on renal glomerular epithelial cells in adriamycin-induced injury.

Beta-hydroxybutyric acid (BHB) exerts a protective effect in experimental of kidney disease models. However, the mechanisms underlying this activity are not well defined. BHB stands out for its ability to inhibit the Nε-lysine acetylation of histone and non-histone proteins, which may affect cellular processes and protein functions. In adriamycin-injured murine glomerular podocytes, BHB ameliorates podocyte damage and preserves actin cytoskeleton integrity, reminiscent of the effect of MS275, a highly selective inhibitor of lysine deacetylase. Further research found that adriamycin causes the reduced acetylation of nephrin, WT-1, and GSK3ß. This process is abrogated by the lysine deacetylase inhibitor or BHB, suggesting that the acetylation of these molecules regulates their activity. In contrast, anacardic acid, a selective inhibitor of acetyltransferase, decreases the acetylation of nephrin, WT-1, and GSK3ß and mitigates the podocyte protective effects of BHB. Taken together, BHB attenuates adriamycin-elicited glomerular epithelial cell injury, at least in part, by inhibiting the deacetylation of the key molecules implicated in glomerular injury.

Changes in anti-müllerian hormone after ultrasound guided aspiration and ethanol sclerotic therapy of ovarian cyst.

OBJECTIVE: To evaluate the effect of transvaginal ultrasound-guided aspiration and ethanol sclerotherapy on anti-müllerian hormone (AMH) in patients with ovarian endometriomas. SETTING: Teaching hospital affiliated with Chang Gung University, Taipei. MATERIAL AND METHODS: We retrospectively reviewed 124 patients, with ovarian endometriomas who underwent transvaginal aspiration and sclerotherapy of endometrioma(s) at a tertiary medical center, Chang Gung Memorial Hospital, Taipei, Taiwan. Preoperative evaluation included AMH, midcycle serum CA-125 level, and ultrasonography to exclude possibility of malignancies. Patients underwent ultrasonographic guided transvaginal aspiration and sclerotherapy with 95% ethanol irrigation of the cystic cavity. Patients were grouped into group 1, n = 44, retention of ethanol, and group 2, n = 80, no retention. Serum AMH level was checked at 6 months after aspiration. Those who were infertile prior to therapy were followed up for subsequent pregnancies (either by assisted reproductive technologies, or by natural conception). RESULTS: The mean pre-operative AMH levels for the group without retention of ethanol and with ethanol retention were 3.80 and 3.06 respectively (p > 0.05). The change in AMH at 6-month follow up for retained group patients was significantly more than for non-retained group patients, with mean decrease of 0.72 (23.6%) and 0.10 (2.7%) respectively (p < 0.05). 54.5% (retained) and 47.2% (non-retained) of patients failed to achieve pregnancy during the observation period. CONCLUSIONS: Transvaginal aspiration of endometriomas followed by sclerotherapy with ethanol can be effective in preserving ovarian reserve, provided that no ethanol is left in situ.

Low central blood pressure and sympathetic activity predispose for the development of intradialytic hypotension.

ABSTRACT: Intradialytic hypotension (IDH) may lead to a poor life quality and was associated with cardiovascular mortality in patients under hemodialysis. This study investigated the autonomic nerve and cardiovascular function in the IDH episodes.In this case-control study, 70 end stage renal disease patients (198 visits) were recruited. Pulse wave analysis and heart rate variability were evaluated before hemodialysis. Two definitions of IDH were confirmed by medical records. IDH-f indicated a drop of systolic blood pressure or mean arterial pressure, accompanied with symptoms; IDH-n indicated a low nadir systolic pressure during the hemodialysis. All parameters were evaluated for the possible predisposing factors under each definition.A total of 24 IDH-f and 37 IDH-n were noted in 177 visits. For both definitions, central pulse pressure seemed to be a consistent predisposing factor. Furthermore, lower sympathetic activity (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.35-0.87), lower pulse pressure (OR 0.95; 95% CI 0.92-0.98), and higher augmentation index (OR 17.36; 95% CI 1.48-204.10) were the possible predisposing factors for IDH-f. On the contrary, lower mean arterial pressure (OR 0.87; 95% CI 0.78-0.98) was identified as the possible factor for IDH-n.It was suggested that the lower central pulse pressure and sympathetic activity might be involved in the development of IDH.