Impact of cardiac rehabilitation on ventricular-arterial coupling and left ventricular function in patients with acute myocardial infarction.

To maintain efficient myocardial function, optimal coordination between ventricular contraction and the arterial system is required. Exercise-based cardiac rehabilitation (CR) has been demonstrated to improve left ventricular (LV) function. This study aimed to investigate the impact of CR on ventricular-arterial coupling (VAC) and its components, as well as their associations with changes in LV function in patients with acute myocardial infarction (AMI) and preserved or mildly reduced ejection fraction (EF). Effective arterial elastance (EA) and index (EAI) were calculated from the stroke volume and brachial systolic blood pressure. Effective LV end-systolic elastance (ELV) and index (ELVI) were obtained using the single-beat method. The characteristic impedance (Zc) of the aortic root was calculated after Fourier transformation of both aortic pressure and flow waveforms. Pulse wave separation analysis was performed to obtain the reflection magnitude (RM). An exercise-based, outpatient cardiac rehabilitation (CR) program was administered for up to 6 months. Twenty-nine patients were studied. However, eight patients declined to participate in the CR program and were subsequently classified as the non-CR group. At baseline, E' velocity showed significant associations with EAI (beta -0.393; P = 0.027) and VAC (beta -0.375; P = 0.037). There were also significant associations of LV global longitudinal strain (LV GLS) with EAI (beta 0.467; P = 0.011). Follow-up studies after a minimum of 6 months demonstrated a significant increase in E' velocity (P = 0.035), improved EF (P = 0.010), and LV GLS (P = 0.001), and a decreased EAI (P = 0.025) only in the CR group. Changes in E' velocity were significantly associated with changes in EAI (beta -0.424; P = 0.033). Increased aortic afterload and VA mismatch were associated with a negative impact on both LV diastolic and systolic function. The outpatient CR program effectively decreased aortic afterload and improved LV diastolic and systolic dysfunction in patients with AMI and preserved or mildly reduced EF.

Biomedical Applications of CNT-Based Fibers.

Carbon nanotubes (CNTs) have been regarded as emerging materials in various applications. However, the range of biomedical applications is limited due to the aggregation and potential toxicity of powder-type CNTs. To overcome these issues, techniques to assemble them into various macroscopic structures, such as one-dimensional fibers, two-dimensional films, and three-dimensional aerogels, have been developed. Among them, carbon nanotube fiber (CNTF) is a one-dimensional aggregate of CNTs, which can be used to solve the potential toxicity problem of individual CNTs. Furthermore, since it has unique properties due to the one-dimensional nature of CNTs, CNTF has beneficial potential for biomedical applications. This review summarizes the biomedical applications using CNTF, such as the detection of biomolecules or signals for biosensors, strain sensors for wearable healthcare devices, and tissue engineering for regenerating human tissues. In addition, by considering the challenges and perspectives of CNTF for biomedical applications, the feasibility of CNTF in biomedical applications is discussed.

All-in-one IQ toggle switches with high versatilities for fine-tuning of transgene expression in mammalian cells and tissues.

The transgene toggling device is recognized as a powerful tool for gene- and cell-based biological research and precision medicine. However, many of these devices often operate in binary mode, exhibit unacceptable leakiness, suffer from transgene silencing, show cytotoxicity, and have low potency. Here, we present a novel transgene switch, SIQ, wherein all the elements for gene toggling are packed into a single vector. SIQ has superior potency in inducing transgene expression in response to tebufenozide compared with the Gal4/UAS system, while completely avoiding transgene leakiness. Additionally, the ease and versatility of SIQ make it possible with a single construct to perform transient transfection, establish stable cell lines by targeting a predetermined genomic locus, and simultaneously produce adenovirus for transduction into cells and mammalian tissues. Furthermore, we integrated a cumate switch into SIQ, called SIQmate, to operate a Boolean AND logic gate, enabling swift toggling-off of the transgene after the removal of chemical inducers, tebufenozide and cumate. Both SIQ and SIQmate offer precise transgene toggling, making them adjustable for various researches, including synthetic biology, genome engineering, and therapeutics.

Drosophila Gut Immune Pathway Suppresses Host Development-Promoting Effects of Acetic Acid Bacteria.

The physiology of most organisms, including Drosophila, is heavily influenced by their interactions with certain types of commensal bacteria. Acetobacter and Lactobacillus, two of the most representative Drosophila commensal bacteria, have stimulatory effects on host larval development and growth. However, how these effects are related to host immune activity remains largely unknown. Here, we show that the Drosophila development-promoting effects of commensal bacteria are suppressed by host immune activity. Mono-association of germ-free Drosophila larvae with Acetobacter pomorum stimulated larval development, which was accelerated when host immune deficiency (IMD) pathway genes were mutated. This phenomenon was not observed in the case of mono-association with Lactobacillus plantarum. Moreover, the mutation of Toll pathway, which constitutes the other branch of the Drosophila immune pathway, did not accelerate A. pomorum-stimulated larval development. The mechanism of action of the IMD pathway-dependent effects of A. pomorum did not appear to involve previously known host mechanisms and bacterial metabolites such as gut peptidase expression, acetic acid, and thiamine, but appeared to involve larval serum proteins. These findings may shed light on the interaction between the beneficial effects of commensal bacteria and host immune activity.

A Graphene-Based Polymer-Dispersed Liquid Crystal Device Enabled through a Water-Induced Interface Cleaning Process.

We report the use of four-layer graphene (4LG) as a highly reliable transparent conductive electrode (TCE) for polymer-dispersed liquid crystal (PDLC)-based smart window devices. The adhesion between 4LG and the substrate was successfully improved through a water-induced interface-cleaning (WIIC) process. We compared the performance of a device with a WIIC-processed 4LG electrode with that of devices with a conventional indium tin oxide (ITO) electrode and a 4LG electrode without a WIIC. With the application of the WIIC process, the PDLC smart window with a 4LG electrode exhibited reduced turn-on voltage and haze compared to 4LG without the WIIC process and characteristics comparable to those of the ITO electrode. The WIIC-processed 4LG electrode demonstrated enhanced electrical properties and better optical performance, leading to improved device efficiency and reliability. Furthermore, our study revealed that the WIIC process not only improved the adhesion between 4LG and the substrate but also enhanced the compatibility and interfacial interactions, resulting in the superior performance of the smart window device. These findings suggest that 4LG with WIIC holds great promise as a transparent conductive electrode for flexible smart windows, offering a cost-effective and efficient alternative to conventional ITO electrodes.

A Novel Incisionless Disposable Vaginal Device for Female Stress Urinary Incontinence: Efficacy and Quality of Life.

PURPOSE: This clinical study sought to evaluate the possible clinical effectiveness and practicality of URINO, an innovative, incisionless, and disposable intravaginal device, designed for patients suffering from stress urinary incontinence. METHODS: A prospective, multicenter, single-arm clinical trial was carried out, involving women diagnosed with stress urinary incontinence who used a self-inserted, disposable intravaginal pessary device. Comparisons were made between the results of the 20-minute pad-weight gain (PWG) test at baseline and visit 3, where the device was applied. After 1 week of device usage, compliance, satisfaction, the sensation of a foreign body, and adverse events were assessed. RESULTS: Out of 45 participants, 39 completed the trial and expressed satisfaction within the modified intention-to-treat group. The average 20-minute PWG of participants was 17.2±33.6 g at baseline and significantly dropped to 5.3±16.2 g at visit 3 with device application. A total of 87.2% of participants exhibited a reduction ratio of PWG by 50% or more, surpassing the clinical trial success benchmark of 76%. The mean compliance was recorded as 76.6%±26.6%, the average visual analogue scale score for patient satisfaction was 6.4±2.6, and the sensation of a foreign body, measured on a 5-point Likert scale, was 3.1±1.2 after 1 week of device use. No serious adverse events were reported; there was 1 instance of microscopic hematuria and 2 cases of pyuria, all of which recovered. CONCLUSION: The investigated device demonstrated significant clinical effectiveness and safety for patients with stress urinary incontinence. It was easy to use, showing favorable patient compliance. We propose that these disposable intravaginal pessaries could potentially be an alternative treatment for patients with stress urinary incontinence who are seeking nonsurgical options or are unable to undergo surgery. Trial Registration: The study was registered as a clinical trial (KCT0008369).

Secreted Akkermansia muciniphila threonyl-tRNA synthetase functions to monitor and modulate immune homeostasis.

Commensal bacteria are critically involved in the establishment of tolerance against inflammatory challenges, the molecular mechanisms of which are just being uncovered. All kingdoms of life produce aminoacyl-tRNA synthetases (ARSs). Thus far, the non-translational roles of ARSs have largely been reported in eukaryotes. Here, we report that the threonyl-tRNA synthetase (AmTARS) of the gut-associated bacterium Akkermansia muciniphila is secreted and functions to monitor and modulate immune homeostasis. Secreted AmTARS triggers M2 macrophage polarization and orchestrates the production of anti-inflammatory IL-10 via its unique, evolutionary-acquired regions, which mediates specific interactions with TLR2. This interaction activates the MAPK and PI3K/AKT signaling pathways, which converge on CREB, leading to an efficient production of IL-10 and suppression of the central inflammatory mediator NF-κB. AmTARS restores IL-10-positive macrophages, increases IL-10 levels in the serum, and attenuates the pathological effects in colitis mice. Thus, commensal tRNA synthetases can act as intrinsic mediators that maintain homeostasis.

Impact of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers on clinical outcomes in hypertensive patients with acute myocardial infarction.

There has been a concern that angiotensin receptor blockers (ARB) may increase myocardial infarction (MI) in hypertensive patients compared with other classes of anti-hypertensive drugs. Angiotensin-converting enzyme inhibitor (ACEI) is recommended as a first-line inhibitor of renin-angiotensin system (RASI) in patients with acute MI (AMI), but ARB is also frequently used to control blood pressure. This study investigated the association of ARB vs. ACEI with the long-term clinical outcomes in hypertensive patients with AMI. Among patients enrolled in the nationwide AMI database of South Korea, the KAMIR-NIH, 4,827 hypertensive patients, who survived the initial attack and were taking ARB or ACEI at discharge, were selected for this study. ARB therapy was associated with higher incidence of 2-year major adverse cardiac events, cardiac death, all-cause death, MI than ACEI therapy in entire cohort. After propensity score-matching, ARB therapy was still associated with higher incidence of 2-year cardiac death (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.20-2.14; P = 0.001), all-cause death (HR, 1.81; 95% CI, 1.44-2.28; P < 0.001), and MI (HR, 1.76; 95% CI, 1.25-2.46; P = 0.001) than the ACEI therapy. It was concluded that ARB therapy at discharge in hypertensive patients with AMI was inferior to ACEI therapy with regard to the incidence of CD, all-cause death, and MI at 2-year. These data suggested that ACEI be a more appropriate RASI than ARB to control BP in hypertensive patients with AMI.

Engineered multi-scale roughness of carbon nanofiller-embedded 3D printed spacers for membrane distillation.

Membrane distillation (MD) transfers heat and mass simultaneously through a hydrophobic membrane. Hence, it is sensitive to both concentration and temperature polarisation (CP and TP) effects. In this study, we fabricated feed spacers to improve MD efficiency by alleviating the polarisation effects. First, a 3D printed spacer design was optimised to show superior performance amongst the others tested. Then, to further enhance spacer performance, we incorporated highly thermally stable carbon nanofillers, including carbon nanotubes (CNT) and graphene, in the fabrication of filaments for 3D printing. All the fabricated spacers had a degree of engineered multi-scale roughness, which was relatively high compared to that of the polylactic acid (PLA) spacer (control). The use of nanomaterial-incorporated spacers increased the mean permeate flux significantly compared to the PLA spacer (27.1 L/m2h (LMH)): a 43% and 75% increase when using the 1% graphene-incorporated spacer (38.9 LMH) and 2% CNT incorporated spacer (47.5 LMH), respectively. This could be attributed to the locally enhanced turbulence owing to the multi-scale roughness formed on the spacer, which further increased the vaporisation rate through the membrane. Interestingly, only the CNT-embedded spacer markedly reduced the ion permeation through the membrane, which may be due to the effective reduction of CP. This further decreased with increasing CNT concentration, confirming that the CNT spacer can simultaneously reduce the CP and TP effects in the MD process. Finally, we successfully proved that the multi-scale roughness of the spacer surface induces micromixing near the membrane walls, which can improve the MD performance via computational fluid dynamics.

The effect of home-based cardiac rehabilitation on arterial stiffness and peak oxygen consumption in patients with myocardial infarction.

Objectives: This study aims to investigate the effectiveness of home-based cardiac rehabilitation (CR) on arterial stiffness in patients with acute myocardial infarction (AMI). Patients and methods: Between January 2015 and December 2017, a total of 135 patients (120 males, 15 females; mean age: 58.8±11.1 years) with AMI who were referred for CR were included. Home-based CR was prescribed based on a cardiopulmonary exercise test (CPET) for at least six months. All patients completed three consecutive CPETs and brachial-ankle pulse wave velocity (baPWV) measurements at one, four, and seven months after onset. Results: After six months of CR, there was an improvement in peak oxygen consumption (pVO2) (Month 1, 28.7±6.4 mL/kg/min; Month 4, 31.6±6.3 mL/kg/min; Month 7, 31.2±7.1 mL/kg/min, p<0.001) and a reduction in baPWV (Month 1, left, 1546.0±311.2 cm/sec, right 1545.5±301.5 cm/sec; Month 4, left, 1374.9±282.5 cm/sec, right 1371.6±287.5 cm/sec; Month 7, left, 1362.9±287.0 cm/sec, right 1365.5±281.1 cm/sec, p<0.001). Conclusion: In patients with AMI, arterial stiffness and aerobic capacity improved after six months of home-based CR, particularly in the early stages of rehabilitation. These results suggest that changes in baPWV are useful in determining the effectiveness of CR and pVO2 in the initial stages of CR.

Bayesian Optimization of Wet-Impregnated Co-Mo/Al2O3 Catalyst for Maximizing the Yield of Carbon Nanotube Synthesis.

Multimetallic catalysts have demonstrated their high potential for the controlled synthesis of carbon nanotubes (CNTs), but their development requires a more complicated optimization than that of monometallic catalysts. Here, we employed Bayesian optimization (BO) to optimize the preparation of Co-Mo/Al2O3 catalyst using wet impregnation, with the goal of maximizing carbon yield in the chemical vapor deposition (CVD) synthesis of CNTs. In the catalyst preparation process, we selected four parameters to optimize: the weight percentage of metal, the ratio of Co to Mo in the catalyst, the drying temperature, and the calcination temperature. We ran two parallel BO processes to compare the performance of two types of acquisitions: expected improvement (EI), which does not consider noise, and one-shot knowledge gradient (OKG), which takes noise into account. As a result, both acquisition functions successfully optimized the carbon yield with similar performance. The result suggests that the use of EI, which has a lower computational load, is acceptable if the system has sufficient robustness. The investigation of the contour plots showed that the addition of Mo has a negative effect on carbon yield.

A bacteria-regulated gut peptide determines host dependence on specific bacteria to support host juvenile development and survival.

BACKGROUND: Commensal microorganisms have a significant impact on the physiology of host animals, including Drosophila. Lactobacillus and Acetobacter, the two most common commensal bacteria in Drosophila, stimulate fly development and growth, but the mechanisms underlying their functional interactions remain elusive. RESULTS: We found that imaginal morphogenesis protein-Late 2 (Imp-L2), a Drosophila homolog of insulin-like growth factor binding protein 7, is expressed in gut enterocytes in a bacteria-dependent manner, determining host dependence on specific bacteria for host development. Imp-L2 mutation abolished the stimulatory effects of Lactobacillus, but not of Acetobacter, on fly larval development. The lethality of the Imp-L2 mutant markedly increased under axenic conditions, which was reversed by Acetobacter, but not Lactobacillus, re-association. The host dependence on specific bacteria was determined by Imp-L2 expressed in enterocytes, which was repressed by Acetobacter, but not Lactobacillus. Mechanistically, Lactobacillus and Acetobacter differentially affected steroid hormone-mediated Imp-L2 expression and Imp-L2-specific FOXO regulation. CONCLUSIONS: Our finding may provide a way how host switches dependence between different bacterial species when benefiting from varying microbiota.

Association of the medical therapy with beta-blockers or inhibitors of renin-angiotensin system with clinical outcomes in patients with mildly reduced left ventricular ejection fraction after acute myocardial infarction.

In the era of the initial optimal interventional and medical therapy for acute myocardial infarction (AMI), a number of patients with mildly reduced left ventricular ejection fraction (EF) (41%-49%) have been increasing. This observational study aimed to investigate the association between the medical therapy with oral beta-blockers or inhibitors of renin-angiotensin system (RAS) and 2-year clinical outcomes in patients with mildly reduced EF after AMI. Among patients enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health, propensity-score matched patients who survived the initial attack and had mildly reduced EF were selected according to beta-blocker or RAS inhibitor therapy at discharge. Beta-blocker therapy at discharge was associated with lower 2-year major adverse cardiac events which was a composite of cardiac death, myocardial infarction, revascularization and re-hospitalization due to heart failure (8.7 vs 12.8/100 patient-years; hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.50-0.93; P = .015), and no significant interaction between EF ≤ 45% and > 45% was observed (Pinteraction = 0.354). This association was mainly driven by lower myocardial infarction in patients with beta-blockers (HR 0.50; 95% CI 0.26-0.95; P = .035). Inhibitors of RAS at discharge were associated with lower re-hospitalization due to heart failure (1.8 vs 3.5/100 patient-years; HR 0.53; 95% CI 0.33-0.86; P = .010) without a significant interaction between EF ≤ 45% and > 45% (Pinteraction = 0.333). In patients with mildly reduced EF after AMI, the medical therapy with beta-blockers or RAS inhibitors at discharge was associated with better 2-year clinical outcomes.

Intermediate cells of in vitro cellular reprogramming and in vivo tissue regeneration require desmoplakin.

Amphibians and fish show considerable regeneration potential via dedifferentiation of somatic cells into blastemal cells. In terms of dedifferentiation, in vitro cellular reprogramming has been proposed to share common processes with in vivo tissue regeneration, although the details are elusive. Here, we identified the cytoskeletal linker protein desmoplakin (Dsp) as a common factor mediating both reprogramming and regeneration. Our analysis revealed that Dsp expression is elevated in distinct intermediate cells during in vitro reprogramming. Knockdown of Dsp impedes in vitro reprogramming into induced pluripotent stem cells and induced neural stem/progenitor cells as well as in vivo regeneration of zebrafish fins. Notably, reduced Dsp expression impairs formation of the intermediate cells during cellular reprogramming and tissue regeneration. These findings suggest that there is a Dsp-mediated evolutionary link between cellular reprogramming in mammals and tissue regeneration in lower vertebrates and that the intermediate cells may provide alternative approaches for mammalian regenerative therapy.

Artificial intelligence for predicting survival following deceased donor liver transplantation: Retrospective multi-center study.

BACKGROUND: Previous studies have indicated that the model for end-stage liver disease (MELD) score may fail to predict post-transplantation patient survival. Similarly, other scores (donor MELD score, balance of risk score) that have been developed to predict transplant outcomes have not gained widespread use. These scores are typically derived using linear statistical models. This study aimed to compare the performance of traditional statistical models with machine learning approaches for predicting survival following liver transplantation. MATERIALS AND METHODS: Data were obtained from 785 deceased donor liver transplant recipients enrolled in the Korean Organ Transplant Registry (2014-2019). Five machine learning methods (random forest, artificial neural networks, decision tree, naïve Bayes, and support vector machine) and four traditional statistical models (Cox regression, MELD score, donor MELD score and balance of risk score) were compared to predict survival. RESULTS: Among the machine learning methods, the random forest yielded the highest area under the receiver operating characteristic curve (AUC-ROC) values (1-month = 0.80; 3-month = 0.85; and 12-month = 0.81) for predicting survival. The AUC-ROC values of the Cox regression analysis were 0.75, 0.86, and 0.77 for 1-month, 3-month, and 12-month post-transplant survival, respectively. However, the AUC-ROC values of the MELD, donor MELD, and balance of risk scores were all below 0.70. Based on the variable importance of the random forest analysis in this study, the major predictors associated with survival were cold ischemia time, donor ICU stay, recipient weight, recipient BMI, recipient age, recipient INR, and recipient albumin level. As with the Cox regression analysis, donor ICU stay, donor bilirubin level, BAR score, and recipient albumin levels were also important factors associated with post-transplant survival in the RF model. The coefficients of these variables were also statistically significant in the Cox model (p < 0.05). The SHAP ranges for selected predictors for the 12-month survival were (-0.02,0.10) for recipient albumin, (-0.05,0.07) for donor bilirubin and (-0.02,0.25) for recipient height. Surprisingly, although not statistically significant in the Cox model, recipient weight, recipient BMI, recipient age, or recipient INR were important factors in our random forest model for predicting post-transplantation survival. CONCLUSION: Machine learning algorithms such as the random forest were superior to conventional Cox regression and previously reported survival scores for predicting 1-month, 3-month, and 12-month survival following liver transplantation. Therefore, artificial intelligence may have significant potential in aiding clinical decision-making during liver transplantation, including matching donors and recipients.

Analysis of Dispersion of Carbon Nanotubes in m-Cresol.

We analyzed the dispersion state of carbon nanotubes (CNTs) in m-cresol using dispersion stability analysis, optical microscopy, and UV-vis spectroscopy. The high dispersion stability of CNT/m-cresol dispersion was observed when it was sufficiently treated with ultrasonication. Despite the high dispersion stability, optical microscopy and UV-vis spectroscopy analysis of various CNT/m-cresol dispersions revealed that CNT bundles in m-cresol were not dispersed into individual CNTs. We also propose that the blue-shift of the G peak of CNTs in m-cresol in the Raman spectrum, which had been reported as evidence of the formation of the charge-transfer complex between m-cresol and CNTs, is rather attributed to the interference of m-cresol's inherent peak at around 1600 cm-1.

Host tp53 mutation induces gut dysbiosis eliciting inflammation through disturbed sialic acid metabolism.

BACKGROUND: Host tp53 mutations are frequently found during the early stages of colitis-associated colorectal cancer (CAC), but whether such mutations induce gut microbiota dysbiosis and chronic intestinal inflammation that contributes to the development of CAC, remains unknown. RESULTS: We found that zebrafish tp53 mutant larvae exhibited elevated intestinal inflammation, by monitoring the NFκB activity in the mid-distal intestines of zebrafish larvae using an NFκB:EGFP transgenic reporter line in vivo as well as neutrophil infiltration into the intestine. This inflammation was due to dysbiotic gut microbiota with reduced diversity, revealed using both 16S rRNA amplicon sequencing and a germfree larva model. In this dysbiosis, Aeromonas spp. were aberrantly enriched as major pathobionts and exhibited the capacity for aggressive colonization in tp53 mutants. Importantly, the ex-germfree experiments supported the causality of the host tp53 mutation for inducing the inflammation. Transcriptome and high-performance liquid chromatography analyses of the host gastrointestinal tracts identified dysregulated sialic acid (SA) metabolism concomitant with increased host Neu5Gc levels as the key determinant of aberrant inflammation, which was reversed by the sialidase inhibitors oseltamivir and Philippin A. CONCLUSIONS: These results demonstrate a crucial role for host tp53 in maintaining symbiosis and immune homeostasis via SA metabolism. Disturbed SA metabolism via a tp53 mutation may be exploited by specific elements of the gut microbiome, eliciting both dysbiosis and inflammation. Manipulating sialometabolism may therefore provide an efficacious therapeutic strategy for tp53 mutation-induced dysbiosis, inflammation, and ultimately, related cancers. Video Abstract.

IQ-Switch is a QF-based innocuous, silencing-free, and inducible gene switch system in zebrafish.

Though various transgene expression switches have been adopted in a wide variety of organisms for basic and biomedical research, intrinsic obstacles of those existing systems, including toxicity and silencing, have been limiting their use in vertebrate transgenesis. Here we demonstrate a novel QF-based binary transgene switch (IQ-Switch) that is relatively free of driver toxicity and transgene silencing, and exhibits potent and highly tunable transgene activation by the chemical inducer tebufenozide, a non-toxic lipophilic molecule to developing zebrafish with negligible background. The interchangeable IQ-Switch makes it possible to elicit ubiquitous and tissue specific transgene expression in a spatiotemporal manner. We generated a RASopathy disease model using IQ-Switch and demonstrated that the RASopathy symptoms were ameliorated by the specific BRAF(V600E) inhibitor vemurafenib, validating the therapeutic use of the gene switch. The orthogonal IQ-Switch provides a state-of-the-art platform for flexible regulation of transgene expression in zebrafish, potentially applicable in cell-based systems and other model organisms.

Differential Clearance of Aß Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish.

The failure of amyloid beta (Aß) clearance is a major cause of Alzheimer's disease, and the brain lymphatic systems play a crucial role in clearing toxic proteins. Recently, brain lymphatic endothelial cells (BLECs), a non-lumenized lymphatic cell in the vertebrate brain, was identified, but Aß clearance via this novel cell is not fully understood. We established an in vivo zebrafish model using fluorescently labeled Aß42 to investigate the role of BLECs in Aß clearance. We discovered the efficient clearance of monomeric Aß42 (mAß42) compared to oligomeric Aß42 (oAß42), which was illustrated by the selective uptake of mAß42 by BLECs and peripheral transport. The genetic depletion, pharmacological inhibition via the blocking of the mannose receptor, or the laser ablation of BLECs resulted in the defective clearance of mAß42. The treatment with an Aß disaggregating agent facilitated the internalization of oAß42 into BLECs and improved the peripheral transport. Our findings reveal a new role of BLECs in the differential clearance of mAß42 from the brain and provide a novel therapeutic strategy based on promoting Aß clearance.

Sophisticated regulation of micturition: review of basic neurourology.

The neurological regulation of the lower urinary tract can be viewed separately from the perspective of sensory neurons and motor neurons. First, in the receptors of the bladder and urethra of sensory nerves, sensations are transmitted through the periaqueductal gray matter of the midbrain to the cerebral cortex, and the cerebrum goes through the process of decision-making. Motor neurons are divided into upper motor neurons (UMNs) and lower motor neurons (LMNs). UMNs coordinate storage and micturition in the brain stem so that synergic voiding can occur. LMNs facilitate muscle contractions in the spinal cord. The muscles involved in urinary storage and micturition are innervated by the somatic branches of sympathetic, parasympathetic, and peripheral nerves. Sympathetic nerves are responsible for contractions of urethral smooth muscles, while parasympathetic nerves originate from S2-S4 and are in charge of contractions of the bladder muscle. Somatic nerves originate from the motor neurons in Onuf's nucleus, which is a specific part of somatic nerves. In this review, we will investigate the structures of the nervous systems related to the lower urinary tract and the regulatory system of innervation for the urinary storage and micturition and discuss the clinical significance and future prospects of neurourological research.