Enhanced sludge dewatering using a novel synergistic iron/peroxymonosulfate-polyacrylamide method.

In the sludge dewatering process, a formidable challenge arises due to the robust interactions between extracellular polymeric substances (EPS) and bound water. This study introduces a novel, synergistic conditioning method that combines iron (Fe2+)/peroxymonosulfate (PMS) and polyacrylamide (PAM) to significantly enhance sludge dewatering efficiency. The application of the Fe2+/PMS-PAM conditioning method led to a substantial reduction in specific filtration resistance (SFR) by 82.75% and capillary suction time (CST) by 80.44%, marking a considerable improvement in dewatering performance. Comprehensive analyses revealed that pre-oxidation with Fe2+/PMS in the Fe2+/PMS-PAM process effectively degraded EPS, facilitating the release of bound water. Subsequently, PAM enhanced the flocculation of fine sludge particles resulting from the advanced oxidation processes (AOPs). Furthermore, analysis based on the Extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory demonstrated shifts in interaction energies, highlighting the breakdown of energy barriers within the sludge and a transition in surface characteristics from hydrophilic (3.79 mJ m-2) to hydrophobic (-61.86 mJ m-2). This shift promoted the spontaneous aggregation of sludge particles. The innovative use of the Flory-Huggins theory provided insights into the sludge filtration mechanism from a chemical potential perspective, linking these changes to SFR. The introduction of Fe2+/PMS-PAM conditioning disrupted the uniformity of the EPS-formed gel layer, significantly reducing the chemical potential difference between the permeate and the water in the gel layer, leading to a lower SFR and enhanced dewatering performance. This thermodynamic approach significantly enhances our understanding of sludge dewatering and conditioning. These findings represent a paradigm shift, offering innovative strategies for sludge treatment and expanding our comprehension of dewatering and conditioning techniques.

Accuracy of dental implant placement with a robotic system in partially edentulous patients: A prospective, single-arm clinical trial.

OBJECTIVES: This clinical study aimed to assess the accuracy of implant positions using a robotic system in partially edentulous patients. MATERIALS AND METHODS: Twenty-eight partially edentulous patients received 31 implants using the robotic system. Deviations between the planned and placed implants were calculated after surgery. The deviations were compared with objective performance goals (OPGs) from reported studies of fully guided static computer-assisted implant surgery (CAIS) and dynamic CAIS. A multiple linear regression analysis was performed to investigate the possible effects of the type and side of the arch, implant location, and implant dimensions on the deviations. RESULTS: The evaluation of 31 implants resulted in a mean angle deviation of 2.81 ± 1.13° (95% confidence interval (CI): 2.40-3.23°), while the 3D deviations at the implant shoulder and apex were 0.53 ± 0.23 mm (95% CI 0.45-0.62 mm) and 0.53 ± 0.24 mm (95% CI 0.44-0.61 mm), respectively. The upper limits of the 95% CI of 3D deviations were lower than those of the corresponding OPGs; however, the angle deviation was similar to that of the OPG. No statistically significant differences were found for the type and side of the arch, implant location, and implant dimensions to the deviations (p > .05). CONCLUSIONS: The robotic system appears to achieve higher accuracy in implant positions than static and dynamic CAIS in partially edentulous patients (Chinese Clinical Trial Registry ChiCTR2300067587).

Exploring training dental implant placement using static or dynamic devices among dental students.

BACKGROUND: Static computer-assisted surgery (s-CAIS) and dynamic computer-assisted implant surgery (d-CAIS) are the main digital approaches in guiding dental implant placement. PURPOSE: The aim of this study was to explore and compare the learning curves for s-CAIS and d-CAIS by beginners. MATERIALS AND METHODS: Three dental students used each dental model for drilling five positions with missing teeth. Operators performed the drilling test for five sets of dental models with an interval of 7 ± 1 days assisted by the d-CAIS system. After a six-month break, the same students performed the drilling test again in the same way but with the s-CAIS system. A total of thirty models were used, and 150 implants were inserted. The operation time and relative deviations were recorded and calculated. Correlations between various deviation parameters and attempts were tested with independent-samples Kruskal-Wallis tests. RESULTS: A significant difference between the two groups was found in the operation time (p < .001). For accuracy, the difference was found in the first attempt of coronal and apical deviations but disappeared as the training went on. As the practice progressed, improvement was evident in the d-CAIS group but not in the s-CAIS group. When reaching the plateau stage of the learning curve of the d-CAIS group (after five attempts), the influence of different methods of guidance was limited between the two groups. CONCLUSIONS: A learning curve effect was found in d-CAIS but not in s-CAIS in vitro tests by beginners. The operating procedure of dynamic navigated and static template-guided implant placement was easy to master.

Rapid fabrication of precise high-throughput filters from membrane protein nanosheets.

Biological membranes are ideal for separations as they provide high permeability while maintaining high solute selectivity due to the presence of specialized membrane protein (MP) channels. However, successful integration of MPs into manufactured membranes has remained a significant challenge. Here, we demonstrate a two-hour organic solvent method to develop 2D crystals and nanosheets of highly packed pore-forming MPs in block copolymers (BCPs). We then integrate these hybrid materials into scalable MP-BCP biomimetic membranes. These MP-BCP nanosheet membranes maintain the molecular selectivity of the three types of ß-barrel MP channels used, with pore sizes of 0.8 nm, 1.3 nm, and 1.5 nm. These biomimetic membranes demonstrate water permeability that is 20-1,000 times greater than that of commercial membranes and 1.5-45 times greater than that of the latest research membranes with comparable molecular exclusion ratings. This approach could provide high performance alternatives in the challenging sub-nanometre to few-nanometre size range.

Identification of two novel pathogenic variants of PIBF1 by whole exome sequencing in a 2-year-old boy with Joubert syndrome.

BACKGROUND: Joubert syndrome (OMIM 213300) is an autosomal recessive disorder with gene heterogeneity. Causal genes and their variants have been identified by sequencing or other technologies for Joubert syndrome subtypes. CASE PRESENTATION: A two-year-old boy was diagnosed with Joubert syndrome by global development delay and molar tooth sign of mid-brain. Whole exome sequencing was performed to detect the causative gene variants in this individual, and the candidate pathogenic variants were verified by Sanger sequencing. We identified two pathogenic variants (NM_006346.2: c.1147delC and c.1054A > G) of PIBF1 in this Joubert syndrome individual, which is consistent with the mode of autosomal recessive inheritance. CONCLUSION: In this study, we identified two novel pathogenic variants in PIBF1 in a Joubert syndrome individual using whole exome sequencing, thereby expanding the PIBF1 pathogenic variant spectrum of Joubert syndrome.

Development of liposome as a novel adsorbent for artificial liver support system in liver failure.

Artificial liver support systems (ALSS), represented by albumin dialysis, are designed to replace the liver detoxification function and to serve as supportive therapy until liver transplantation or liver regeneration. We introduce liposome, which is majorly formed by soybean lecithin as the adsorbent nanomaterial in dialysate for the removal of protein-bound and liver failure-related solutes. The binding rate was detected by ultrafiltration column. In vitro and in vivo dialysis was performed in a recirculation system. Unconjugated bilirubin (52.83-99.87%) and bile salts (50.54-94.75%) were bound by liposomes (5-80 g/L) in a dose-response relationship. The in vitro haemodialysis model showed that the concentration of unconjugated bilirubin (45.64 ± 0.90 µmol/L vs. 54.47 ± 3.48 µmol/L, p < 0.05) and bile salts (153.75 ± 7.72 µmol/L vs. 180.72 ± 7.95 µmol/L, p < 0.05) were significantly decreased in the liposome dialysis group than in the phosphate buffer saline group. The in vivo haemodialysis model showed that 40 g/L liposome-containing dialysate led to a significant higher reduction ratio in total bilirubin (6.56 ± 5.72% vs. -1.86 ± 5.99%, p < 0.05) and more total bile acids (7.63 ± 5.27 µmol vs. 2.13 ± 2.32 µmol, p < 0.05) extracted in the dialysate in comparison with the conventional dialysate. In conclusion, the liposome-added dialysate proved to impose good extraction effects on the unconjugated bilirubin and bile salts. These findings indicate that conventional dialysate supported by this nanomaterial can markedly improve the removal of protein-bound and liver failure-related solutes, thus suggesting a novel and promising liver dialysis system.

Bisphenol A analogs in patients with chronic kidney disease and dialysis therapy.

Bisphenol A (BPA) accumulates in patients with chronic kidney disease (CKD), and hemodialysis filters may contribute to bisphenol burden in patients on hemodialysis (HD). The serum levels of BPA and three BPA analogs, namely, bisphenol B (BPB), bisphenol S (BPS), and bisphenol F (BPF), in 58 patients with CKD, 66 patients on dialysis therapy and 30 healthy control were investigated. The content of four bisphenols (BPs) was also examined in three types of dialysis filters, followed by an in vitro elution experiment to test the release of BPs from the dialysis filters. The serum levels of BPA (r = -0.746, p < 0.05) and BPS (r = -0.433, p < 0.05) in 58 CKD patients and 30 healthy control were correlated with the decrease in estimated glomerular filtration rate. The serum levels of BPs in the HD patients were higher than those in the peritoneal dialysis patients (p < 0.05). In the in vitro study on the BP contents in dialysis filters, BPA was the main form of the BPs in the polysulfone membrane (20.86 ±â€¯1.18 ng/mg) and in the polyamide membrane (18.70 ±â€¯2.88 ng/mg), and a modicum of BPS (0.01 ±â€¯0.01 ng/mg) was detected in the polyethersulfone membrane. The results of the elution experiment were in accordance with the results of BPs content in the dialysis filters. Insufficient renal function may lead to BPs accumulation in patients with CKD, and BPs in dialysis products may cause BPs burden in patients on HD.

Creating cross-linked lamellar block copolymer supporting layers for biomimetic membranes.

The long-standing goal in membrane development is creating materials with superior transport properties, including both high flux and high selectivity. These properties are common in biological membranes, and thus mimicking nature is a promising strategy towards improved membrane design. In previous studies, we have shown that artificial water channels can have excellent water transport abilities that are comparable to biological water channel proteins, aquaporins. In this study, we propose a strategy for incorporation of artificial channels that mimic biological channels into stable polymeric membranes. Specifically, we synthesized an amphiphilic triblock copolymer, poly(isoprene)-block-poly(ethylene oxide)-block-poly(isoprene), which is a high molecular weight synthetic analog of naturally occurring lipids in terms of its self-assembled structure. This polymer was used to build stacked membranes composed of self-assembled lamellae. The resulting membranes resemble layers of natural lipid bilayers in living systems, but with superior mechanical properties suitable for real-world applications. The procedures used to synthesize the triblock copolymer resulted in membranes with increased stability due to the crosslinkability of the hydrophobic domains. Furthermore, the introduction of bridging hydrophilic domains leads to the preservation of the stacked membrane structure when the membrane is in contact with water, something that is challenging for diblock lamellae that tend to swell, and delaminate in aqueous solutions. This new method of membrane fabrication offers a practical model for making channel-based biomimetic membranes, which may lead to technological applications in reverse osmosis, nanofiltration, and ultrafiltration membranes.

Highly permeable artificial water channels that can self-assemble into two-dimensional arrays.

Bioinspired artificial water channels aim to combine the high permeability and selectivity of biological aquaporin (AQP) water channels with chemical stability. Here, we carefully characterized a class of artificial water channels, peptide-appended pillar[5]arenes (PAPs). The average single-channel osmotic water permeability for PAPs is 1.0(± 0.3) × 10(-14) cm(3)/s or 3.5(± 1.0) × 10(8) water molecules per s, which is in the range of AQPs (3.4 ∼ 40.3 × 10(8) water molecules per s) and their current synthetic analogs, carbon nanotubes (CNTs, 9.0 × 10(8) water molecules per s). This permeability is an order of magnitude higher than first-generation artificial water channels (20 to ∼ 10(7) water molecules per s). Furthermore, within lipid bilayers, PAP channels can self-assemble into 2D arrays. Relevant to permeable membrane design, the pore density of PAP channel arrays (∼ 2.6 × 10(5) pores per µm(2)) is two orders of magnitude higher than that of CNT membranes (0.1 ∼ 2.5 × 10(3) pores per µm(2)). PAP channels thus combine the advantages of biological channels and CNTs and improve upon them through their relatively simple synthesis, chemical stability, and propensity to form arrays.

An Off-Pump Repair Technique for Postinfarction Apical Left Ventricular Aneurysm.

PURPOSE: The conventional surgical treatment for postinfarction left ventricular aneurysm (LVA) is open-heart repair with cardiopulmonary bypass. However, the risk of the open-heart surgery under cardiopulmonary bypass may result in an unacceptable risk for many patients with multiple comorbidities. Here, we reported a new off-pump repair technique for postinfarction apical LVA. METHODS: A new off-pump repair technique, circular banding and occlusion technique, was applied to repair the postinfarction apical LVA in 12 patients. Clinical data of all those 12 patients were retrospectively reviewed. Patients were followed up prospectively by direct interviews and echocardiographic examination. RESULTS: The new repair technique was successfully performed in all these 12 patients. Acute reduction of the LVA mouth diameter, the left ventricular (LV) end-diastolic volume and end-systolic volume, and an increase in the LV ejection fraction (EF) were immediately obtained after the repair. Patients had an uneventful postoperative course. They were in New York Heart Association class 1-2, and the LV volume and EF detected by echocardiography remained unchanged during an average 28.4 ± 9.9 months (range 13 to 45 months) follow-up. CONCLUSIONS: Circular banding and occlusion is a simple, safe, and effective off-pump repair technique for postinfarction apical LVA. It can allow effective LV remodeling and improve heart function.

PEG300 Protects Mitochondrial Function By Upregulating PGC-1α to Delay Central Nervous System Oxygen Toxicity in Mice.

Central nervous system oxygen toxicity (CNS-OT) is a complication of hyperbaric oxygen (HBO) treatment, with limited prevention and treatment options available. In this study, we aimed to explore the effect of polyethylene glycol 300 (PEG300) on CNS-OT and underlying mechanisms. Motor and cognitive functions of mice in normobaric conditions were evaluated by Morris water maze, passive active avoidance, and rotarod tests. HBO was applied at 6 atmospheres absolute (ATA) for 30 min after drug administration. The latency period of convulsion in mice was recorded, and hippocampal tissues were extracted for biochemical experiments. Our experimental results showed that PEG300 extended the convulsion latencies in CNS-OT mice, reduced oxidative stress and inflammation levels in hippocampal tissues. Furthermore, PEG300 preserved mitochondrial integrity and maintained mitochondrial membrane potential in hippocampal tissue by upregulating Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α). This protective effect was enhanced following the administration of ZLN005, an agonist of PGC-1a. Hence, our study suggests that PEG300 might exert protective effects by upregulating PGC-1α expression and preserving mitochondrial health, offering promising prospects for CNS-OT treatment.

Self-Healing Micro Arc Oxidation and Dicalcium Phosphate Dihydrate Double-Passivated Coating on Magnesium Membrane for Enhanced Bone Integration Repair.

Magnesium is a revolutionary biomaterial for orthopedic implants, owing to its eminent mechanical properties and biocompatibility. However, its uncontrolled degradation rate remains a severe challenge for its potential applications. In this study, we developed a self-healing micro arc oxidation (MAO) and dicalcium phosphate dihydrate (DCPD) double-passivated coating on a magnesium membrane (Mg-MAO/DCPD) and investigated its potential for bone-defect healing. The Mg-MAO/DCPD membrane possessed a feasible self-repairing ability and good cytocompatibility. In vitro degradation experiments showed that the Mg contents on the coating surface were 0.3, 3.8, 4.1, 6.1, and 7.9% when the degradation times were 0, 1, 2, 3, and 4 weeks, respectively, exhibiting available corrosion resistance. The slow and sustained release of Mg2+ during the degradation process activated extracellular matrix proteins for bone regeneration, accelerating osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The extract solutions of Mg-MAO/DCPD considerably promoted the activation of the Wnt and PI3K/AKT signaling pathways. Furthermore, the evaluation of the rat skull defect model manifested the outstanding bone-healing efficiency of the Mg-MAO/DCPD membrane. Taken together, the Mg-MAO/DCPD membrane demonstrates an optimized degradation rate and excellent bioactivity and is believed to have great application prospects in bone tissue engineering.

Bomidin attenuates inflammation of periodontal ligament stem cells and periodontitis in mice via inhibiting ferroptosis.

AIM: Periodontitis is a prevalent oral immunoinflammatory condition that is distinguished by the compromised functionality of periodontal ligament stem cells (PDLSCs). Bomidin, a new recombinant antimicrobial peptide (AMP), exhibits antibacterial properties and modulates immune responses. Nevertheless, the precise anti-inflammatory impact of bomidin in periodontitis has yet to be fully elucidated. Thus, the study aimed to clarified the role of bomidin in modulating inflammation and its underlying mechanisms. METHODS: TNF-α was applied to treating PDLSCs for establishing a cell model of periodontitis. Bomidin, RSL3, ML385 and cycloheximide were also used to treat PDLSCs. Transcriptome sequencing, RT-qPCR, western blot, immunofluorescence, immunohistochemistry, Fe2+ detection probe, molecular docking, Co-IP assay, ubiquitination assay and murine models of periodontitis were used. RESULTS: Our study demonstrated that bomidin effectively suppressed inflammation in PDLSCs stimulated by TNF-α, through down-regulating the MAPK and NF-κB signaling pathways. Furthermore, bomidin exerted inhibitory effects on ferroptosis and activated the Keap1/Nrf2 pathway in the TNF-α group. There is a strong likelihood of bonding bomidin with Keap1 protein, which facilitated the degradation of Keap1 protein via the ubiquitin-proteasome pathway, leading to an enhanced translocation of Nrf2 protein to the nucleus. CONCLUSIONS: Bomidin can directly bond to Keap1 protein, resulting in the degradation of Keap1 through the ubiquitin-proteasome pathway, thereby further activating the Keap1/Nrf2 pathway. The upregulation of the Keap1/Nrf2 signaling pathway was found to contribute to the suppression of ferroptosis, ultimately alleviating inflammation in treatment of periodontitis.

A novel 1.38-kb deletion combined with a single nucleotide variant in KIAA0586 as a cause of Joubert syndrome.

BACKGROUND: KIAA0586, also known as Talpid3, plays critical roles in primary cilia formation and hedgehog signaling in humans. Variants in KIAA0586 could cause some different ciliopathies, including Joubert syndrome (JBTS), which is a clinically and genetically heterogeneous group of autosomal recessive neurological disorders. METHODS AND RESULTS: A 9-month-old girl was diagnosed as JBTS by the "molar tooth sign" of the mid-brain and global developmental delay. By whole-exome sequencing, we identified a single nucleotide variant c.3303G > A and a 1.38-kb deletion in KIAA0586 in the proband. These two variants of KIAA0586 were consistent with the mode of autosomal recessive inheritance in the family, which was verified using Sanger sequencing. CONCLUSIONS: This finding of a compound heterozygote with a 1.38-kb deletion and c.3303G > A gave a precise genetic diagnosis for the patient, and the novel 1.38-kb deletion also expanded the pathogenic variation spectrum of JBTS caused by KIAA0586.

Influence of grasping postures on skin deformation of hand.

To investigate the influence of different grasping postures on the hand's skin deformation, a handheld 3D EVA SCANNER was used to obtain 3D models of 111 women in five postures, including a straight posture and grasping cylinders with various diameters (4/6/8/10 cm). Skin relaxation strain ratio ([Formula: see text]) and surface area skin relaxation strain ratio ([Formula: see text]) were used as measures of skin deformation between two landmarks and multiple landmarks, respectively. The effects of grasping posture on skin deformation in different directions were analyzed. The results revealed significant variations in skin deformation among different grasping postures, except for the width of middle finger metacarpal and the length of middle finger's proximal phalanx. The [Formula: see text] increased with decreasing grasping object diameter, ranging from 5 to 18% on the coronal axis, and from 4 to 20% on the vertical axis. The overall variation of [Formula: see text] ranged from 5 to 37.5%, following the same trend as [Formula: see text] except for the surface area of tiger's mouth, which exhibited a maximum difference of 10.9% with significant differences. These findings have potential applications in improving the design of hand equipment and understanding hand movement characteristics.

Bioinspired Synthesis of Ag Nanoparticles onto Polytetrafluoroethylene with Enhanced Antibacterial Activity for Dental Implant Application.

BACKGROUND: Endosseous implants are widely used as a treatment for tooth loss, but gaps in the implant-abutment interface, and the cavity inside the implant, can cause inflammation of the tissue surrounding the implant. Currently available filling materials, however, cannot solve these problems. Therefore, the development of new antibacterial materials is key. In this study, we synthesized Ag nanoparticle-coated polytetrafluoroethylene (PTFE), analyzed the effect of Ag ion concentration, and estimated the antibacterial effects against oral pathogens in vitro. Method: The Ag nanoparticles (AgNPs)-modified PTFE was achieved using self-polymerized dopamine in an alkaline solution (2 mg/mL) and reduction reaction of Ag ions (0.01 mol/L and 0.05 mol/L). The surface features, chemical components, and wettability were characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS) and contact angle measurement. The antibacterial effect against Streptococcus mutans and Porphyromonas gingivalis was evaluated by counting colony-forming units on agar media and the visualization of bacteria present on the specimens by SEM and confocal laser scanning microscope (CLSM). RESULTS: The surface characterization results indicated that a polydopamine film was successfully formed on the PTFE membrane, and spherical AgNPs were successfully reduced. With increasing concentration of the Ag precursor, the contents of the AgNPs increased (p < 0.05). The antibacterial ratio of AgNP-coated PTFE against Streptococcus mutans and Porphyromonas gingivalis reached 94.2% and 80.6%, respectively. The results of antibacterial testing analyzed via SEM and CLSM also demonstrated the robust antibacterial ability of AgNPs-modified PTFE (p < 0.05). CONCLUSIONS: AgNPs-modified PTFE has great potential to function as an implant filling material with enhanced antibacterial properties, and has the potential to be a novel antimicrobial material for the prevention of peri-implantitis in the clinic.

High-density reconstitution of functional water channels into vesicular and planar block copolymer membranes.

The exquisite selectivity and unique transport properties of membrane proteins can be harnessed for a variety of engineering and biomedical applications if suitable membranes can be produced. Amphiphilic block copolymers (BCPs), developed as stable lipid analogs, form membranes that functionally incorporate membrane proteins and are ideal for such applications. While high protein density and planar membrane morphology are most desirable, BCP-membrane protein aggregates have so far been limited to low protein densities in either vesicular or bilayer morphologies. Here, we used dialysis to reproducibly form planar and vesicular BCP membranes with a high density of reconstituted aquaporin-0 (AQP0) water channels. We show that AQP0 retains its biological activity when incorporated at high density in BCP membranes, and that the morphology of the BCP-protein aggregates can be controlled by adjusting the amount of incorporated AQP0. We also show that BCPs can be used to form two-dimensional crystals of AQP0.

In vitro corrosion and in vivo behavior of high strength Mg-6Zn-1Mn alloy wire for gastrointestinal anastomosis nail application.

Ti and its alloy staples can be retained in the human body for a long period because of their excellent corrosion resistance and thus requires revision surgery for removal. In this study, biodegradable Mg-6Zn-1Mn alloy staples were fabricated using ∼99.8 % area reduction cold drawing, whose service performance was evaluated by in vitro corrosion and in vivo tests. The high strength (∼340 MPa) of staples is mainly attributed to the formation of fine grains, nanoparticles, and additional dislocations. Moreover, owing to the effect of fine grains, as well as the high Schmid factor of prismatic ⟨a⟩ slip and pyramidal ⟨c+a⟩ slip, the staples also exhibit acceptable ductility (∼10 %). The in vitro corrosion results indicate that staple fractures occurred after immersion for 21 h in a single PBS solution. With the addition of ∼0.5 g/L bovine serum albumin (BSA), the time required to maintain the mechanical integrity of staples can expand to 90 h. This is mainly related to the adsorption and chelating effects between BSA and Mg matrix. After the implantation surgery, all rabbits fully recovered with normal oral intake, and Mg ions generated by degradation effectively promoted the absorption of the alimentary system. Therefore, the Mg-6Zn-1Mn alloy staples fabricated in this study exhibit desired effect, and excellent clinical application prospects.

Polyethyleneimine-anchored liposomes as scavengers for improving the efficiency of protein-bound uremic toxin clearance during dialysis.

Protein-bound uremic toxins (PBUTs) are significant toxins that are closely related to the prognosis of chronic kidney disease. They cannot be effectively removed by conventional dialysis therapies due to their high albumin binding affinity. Our previous research revealed that cationic liposomes (i.e., polyethyleneimine [PEI]-decorated liposomes) could enhance the clearance of PBUTs via electrostatic interactions. However, the poor biocompatibility (hemolysis) restricted their applications in clinical dialysis treatment. Herein, we produced PEI-anchored, linoleic acid-decorated liposomes (CP-LA liposomes) via the conjugation of PEI to cholesterol chloroformate (Chol-PEI, CP), and linoleic acid (LA) was added to provide liposomal colloidal stability. The CP-LA liposomes outperformed the plain liposomes, demonstrating significantly higher PBUT binding rates and removal rates. In addition, in vitro dialysis simulation verified that the CP-LA liposomes had a better capacity for PBUT clearance than the plain liposomes, especially for PBUTs with a strong negative net charge. Hemolysis and cytotoxicity tests revealed that the biocompatibility of the CP-LA liposomes was better than that of the physically-decorated PEI-liposome. CP-LA liposomes possess great potential for PBUT clearance in clinical dialysis therapy.

Whole Exome Sequencing Identified Novel ARMC9 Variations in Two Cases With Joubert Syndrome.

Background: Biallelic variations in the armadillo repeat-containing 9 (ARMC9) gene were recently defined to cause Joubert syndrome (JS) type thirty. In this study, two unrelated families with probands displaying typical indications of JS were enrolled and underwent a series of clinical and genetic investigations. Methods: Routine evaluation including magnetic resonance imaging (MRI) was carried out. Whole-exome sequencing (WES) was performed on the probands to detect causative variants. Next, in silico structural and molecular dynamic (MD) analysis was conducted on the missense variant for analyzing its intramolecular impact. Meanwhile, an in vitro study with the minigene system was performed to explore the specific impact on mRNA splicing of another variant. Results: Two unrelated patients from two different families came to our hospital exhibiting typical JS presentations, such as the "molar tooth sign." Using WES, we identified that both probands carried the compound heterogeneous variants in ARMC9 (NM_025139.6), with c.1878+1G > A and c.895C > T (p.Arg299Ter) in family 1 and c.1878+1G > A and c.1027C > T (p.Arg343Cys) in family 2. These variants were inherited from their unaffected parents by Sanger sequencing, respectively, and ARMC9 c.895C > T (p.Arg299Ter) and c.1878+1G > A were novel variants. In silico analysis indicated the c.1027C > T (p.Arg343Cys) would likely affect the secondary structure of the ARMC9 protein. The minigene study demonstrated that the splice site variant c.1878+1G > A abolished the canonical donor site, resulting in an 18bp intronic retention of intron 20. Conclusion: The findings in this study expanded the mutation spectrum of ARMC9-associated JS, and we suggested that the function of ARMC9 in the pathogenesis of JS might involve the development of primary cilia, after discussing the function of the ARMC9 protein.