Significant Defects Research Articles

Predicting the wrinkling in AA5052 seamless tubes manufactured by free bending forming technology

Wrinkling is a significant defect during forming of thin-walled metallic tubes via free-bending forming (FBF) technology. Thus, it's quite important to predict the wrinkling in the tubes to improve the quality of the final products. Accordingly, new theoretical and numerical frameworks were proposed for predicting the wrinkling of the tubes manufactured via FBF technology. The theoretical wrinkling prediction model is based on the energy criteria and the thin shell theory. The numerical prediction model was constructed on the ABAQUS/Implicit FE code. Besides, The Knoop microhardness test characterized the anisotropy of the tube. The tube's imperfection was introduced to the numerical model through pure bending buckling analysis. The bending experiments were conducted to verify the results obtained from the proposed theoretical and numerical frameworks and showed good agreement with them. Furthermore, it was noticed that the additional axial force in the FBF process reduces the tube's ability to resist wrinkles. The larger additional axial force makes tubes more sensitive to imperfection in free bending than in other bending technologies. The numerical prediction model with the perfect tube exhibits good accuracy in predicting the initiation of the tube wrinkling in free bending but not in terms of the wrinkling shape. The model considering the imperfection can predict the onset and development of wrinkling properly.

An obturator prosthesis for a 4-year-old child following treatment of a juvenile trabecular ossifying fibroma with a maxillary resection

Juvenile trabecular ossifying fibroma (JTOF) is a benign fibro-osseous lesion that usually occurs in the maxilla or mandible. Individuals with JTOF of the maxilla will most commonly require a resection that can result in a significant palatal defect. Appearance and articulatory, masticatory, and deglutitory functions can be restored with a clasp-retained obturator. Providing a prosthetic obturator with adequate retention in situations where the teeth cannot accommodate clasps because of insufficient eruption can be challenging. This article describes a technique that has been developed for such instances—in this situation, a 4-year-old child who had undergone a maxillary resection because of a JTOF.

Nonmetal‐Mediated Atomic Spalling of Large‐Area Monolayer Transition Metal Dichalcogenide

Transition metal dichalcogenides (TMDCs) have attracted intense interest; however, despite the considerable effort of researchers, a universal manufacturing method that can guarantee both high material quality and throughput has not been realized to date. Herein, a universal approach to producing high‐quality monolayer TMDCs on a large scale via germanium (Ge)‐mediated atomic spalling is presented. Through the modified analytic model, the study verifies that the thin Ge film could be a suitable stressor that effectively reduces the crack propagation depth at the sub‐nanometer range. In particular, an acid‐etching process is not required in the overall atomic spalling process due to the water‐soluble nature of the Ge, enabling it widely applicable to various TMDCs. Under the optimized spalling conditions, a millimeter‐sized monolayer of stable MoS2, as well as unstable MoTe2, is successfully achieved. Through detailed spectroscopic and electrical characterizations, it is confirmed that the proposed methodology for obtaining large‐area atomic layers does not introduce any significant structural defects or chemical contaminations.

Reconstruction with an Anterolateral Thigh Free Flap Following a Skin Graft from the Same Donor Site for Tissue Use Efficacy: Two Case Reports

The coverage of extensive soft tissue defects requires several considerations, such as limited donor sites, reconstruction methods, and the outcome of functional recovery. In the cases described herein, when a significant soft tissue defect was present on an extremity, we opted for staged reconstruction. We first performed a split-thickness skin graft (STSG) to reduce the soft tissue defect, using the anterolateral thigh (ALT) as the donor site. In the second stage, the remaining soft tissue defect was reconstructed with an ALT free flap, utilizing the same lateral thigh area that had previously served as the STSG donor site. After the free flap procedure, we encountered several challenges in monitoring the ALT flap; however, all flaps ultimately survived. To the best of our knowledge, this is the first report of using an ALT free flap following STSG from the same donor site, demonstrating efficient tissue utilization. We believe this approach is beneficial for reconstructing extensive soft tissue defects, as it maximizes tissue use efficiency and reduces donor site morbidity when donor options are limited.

Combining Piezoelectric Stimulation and Extracellular Vesicles for Cartilage Regeneration

Numerous patients experience articular cartilage defects (ACDs), which are characterized by progressive cartilage degradation and often lead to osteoarthritis (OA). Consequently, 44.7% of OA patients suffer from dyskinesia or disability. Current clinical drug treatments offer limited effectiveness in fully curing the disease. In this study, we propose a collaborative approach that combines physical and biological cues to promote cartilage regeneration. A biodegradable piezoelectric poly (l-lactic acid) (PLLA) nanofiber scaffold facilitates in situ, battery-free electrical stimulation under natural joint loading, while extracellular vesicles (EVs) serve as communication mediators between cells and promote cell proliferation, migration, and secretion of type II collagen. In this combined approach, EVs attached to PLLA are gradually released by localized piezoelectric electrical stimulation and taken up by chondrocytes. This process results in the organization of type II collagen along the PLLA fiber surface, ultimately forming cartilage lacunae that facilitate the residence of new chondrocytes. As an outcome, a significant round cartilage defect (diameter: 3 mm and depth: 1 mm) in the PLLA/EVs group (rat and knee) was rapidly restored within six weeks. In contrast, individual EVs and PLLA groups demonstrated considerably weaker cartilage regeneration capabilities. This research suggests that the synergistic effect of electromechanical stimulation and EVs-based biological cues is a crucial intervention method for treating OA.

Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome.

Oral-facial-digital syndromes (OFDS) are a group of clinically and genetically heterogeneous disorders characterized by defects in the development of the face and oral cavity along with digit anomalies. Pathogenic variants in over twenty genes encoding ciliary proteins have been found to cause OFDS through deleterious structural or functional impacts on primary cilia. We identified by exome sequencing bi-allelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families. Affected individuals presented a novel form of OFDS (OFDS-RAB34) accompanied by cardiac, cerebral, skeletal, and anorectal defects. RAB34 encodes a member of the Rab GTPase superfamily and was recently identified as a key mediator of ciliary membrane formation. Unlike many genes required for cilium assembly, RAB34 acts selectively in cell types that use the intracellular ciliogenesis pathway, in which nascent cilia begin to form in the cytoplasm. We find that the protein products of these pathogenic variants, which are clustered near the RAB34 C-terminus, exhibit a strong loss of function. Although some variants retain the ability to be recruited to the mother centriole, cells expressing mutant RAB34 exhibit a significant defect in cilium assembly. While many Rab proteins have been previously linked to ciliogenesis, our studies establish RAB34 as the first small GTPase involved in OFDS and reveal the distinct clinical manifestations caused by impairment of intracellular ciliogenesis.

Defining the Roles of Pyruvate Oxidation, TCA Cycle, and Mannitol Metabolism in Methicillin-Resistant Staphylococcus aureus Catheter-Associated Urinary Tract Infection.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of complicated urinary tract infection (UTI) associated with the use of indwelling urinary catheters. Previous reports have revealed host and pathogen effectors critical for MRSA uropathogenesis. Here, we sought to determine the significance of specific metabolic pathways during MRSA UTI. First, we identified four mutants from the Nebraska transposon mutant library in the MRSA JE2 background that grew normally in rich medium but displayed significantly reduced growth in pooled human urine (HU). This prompted us to transduce the uropathogenic MRSA 1369 strain with the transposon mutants in sucD and fumC (tricarboxylic acid [TCA] cycle), mtlD (mannitol metabolism), and lpdA (pyruvate oxidation). Notably, sucD, fumC, and mtlD were also significantly upregulated in the MRSA 1369 strain upon exposure to HU. Compared to the WT, the MRSA 1369 lpdA mutant was significantly defective for (i) growth in HU, and (ii) colonization of the urinary tract and dissemination to the kidneys and the spleen in the mouse model of catheter-associated UTI (CAUTI), which may be attributed to its increased membrane hydrophobicity and higher susceptibility to killing by human blood. In contrast to their counterparts in the JE2 background, the sucD, fumC, and mtlD mutants in the MRSA 1369 background grew normally in HU; however, they displayed significant fitness defects in the CAUTI mouse model. Overall, identification of novel metabolic pathways important for the urinary fitness and survival of MRSA can be used for the development of novel therapeutics. IMPORTANCE While Staphylococcus aureus has historically not been considered a uropathogen, S. aureus urinary tract infection (UTI) is clinically significant in certain patient populations, including those with chronic indwelling urinary catheters. Moreover, most S. aureus strains causing catheter-associated UTI (CAUTI) are methicillin-resistant S. aureus (MRSA). MRSA is difficult to treat due to limited treatment options and the potential to deteriorate into life-threatening bacteremia, urosepsis, and shock. In this study, we found that pathways involved in pyruvate oxidation, TCA cycle, and mannitol metabolism are important for MRSA fitness and survival in the urinary tract. Improved understanding of the metabolic needs of MRSA in the urinary tract may help us develop novel inhibitors of MRSA metabolism that can be used to treat MRSA-CAUTI more effectively.

Functional Evaluation of a Novel GRIN2B Missense Variant Associated with Epilepsy and Intellectual Disability

Epilepsy, a neurological condition, is widely prevalent among individuals with intellectual disability (ID). It is well established that N-methyl-D-aspartate (NMDA) receptors play an important role in both epilepsy and ID. Autosomal dominant mutations in the GRIN2B gene, which encodes the GluN2B subunit of the NMDA receptor, have been reported to be associated with epilepsy and ID. However, the underlying mechanism of this association is not well-understood. In this study, we identified a novel GRIN2B mutation (c.3272A > C, p.K1091T) in a patient with epilepsy and ID. The proband was a one year and ten months old girl. GRIN2B variant was inherited from her mother. We further investigated the functional consequences of this mutation. Our findings revealed that the p.K1091T mutation created a Casein kinase 2 phosphorylation site. Using recombinant NMDA receptors containing the GluN2B-K1091T along with GluN1 in HEK 293T cells, we observed significant defects in its interactions with postsynaptic density 95. It is accompanied by reduced delivery of the receptors to the cell membrane and a decrease in glutamate affinity. Moreover, primary neurons expressing GluN2B-K1091T also exhibited impaired surface expression of NMDA receptors, a reduction in dendritic spine number and excitatory synaptic transmission. In summary, our study reports a novel GRIN2B mutation and provides functional characteristics of this mutation in vitro, thereby contributing to the understanding of GRIN2B variants in epilepsy and ID.

Characteristics of diagnostic defects in traumatic brain injury (forensic medical approach)

Diagnostic defects in the evaluation of TBI, such as the violation of protocols, neglect of neurological symptoms, and incorrect description of head injuries, can significantly impact the diagnosis and forensic assessment of TBI. The study of defects in the provision of medical care in traumatic brain injury (TBI) was conducted based on the data from forensic medical examinations of Kharkiv Regional Bureau of Forensic Medical Examination (KhRBFME) (307) and SI "Main Bureau of Forensic Medical Examination of the Ministry of Health of Ukraine" (SI MBFME) (226). The largest number of undiagnosed diagnostic and treatment measures related to clinically mild forms of TBI due to incomplete description of the neurological status, failure to consider the complete neurological symptomatology specific to a particular form of TBI, diagnosis based solely on subjective complaints of the patient and historical data (head injury, according to the patient's words), lack of patient examination by related specialists, and absence of additional investigations. Significant defects influencing the forensic medical assessment of TBI in the affected individuals included: incomplete description of neurological symptomatology (91±2.4%), absence of trauma history (23.5±1.8%), defects in describing external head injuries (67.9±2.0%), simulation, and aggravation.

Bmal1 downregulation leads to diabetic cardiomyopathy by promoting Bcl2/IP3R-mediated mitochondrial Ca2+ overload

Brain and muscle arnt-like protein 1 (Bmal1) is a crucial transcription factor, regulating circadian rhythm and involved in multiple heart diseases. However, it is unknown whether Bmal1 promotes diabetic cardiomyopathy (DCM) pathogenesis. The objective of this investigation was to ascertain the vital role of Bmal1 in the progression of DCM. Mice with T2D and H9c2 cardiomyoblasts exposed to high glucose and palmitic acid (HGHP) were used. Cardiomyocyte-specific knockout mouse of Bmal1 (CKB) was also generated, and cardiac Bmal1 was overexpressed in type 2 diabetes (T2D) mice using an adeno-associated virus. Bmal1 gene recombinant adenovirus was used to either knockdown or overexpress in H9c2 cardiomyoblasts. Bmal1 expression was significantly altered in diabetic mice hearts. Bmal1 downregulation in CKB and T2D mice heart accelerated cardiac hypertrophy and diastolic dysfunction, while Bmal1 overexpression ameliorated these pathological changes in DCM mice. Furthermore, DCM mice had significant mitochondrial ultrastructural defects, reactive oxygen species accumulation, and apoptosis, which could be alleviated by overexpressing Bmal1. In H9c2 cardiomyoblasts, genetic downregulation of Bmal1 or HGHP markedly decreased the binding of Bcl2 to IP3R, thus increasing Ca2+ release to mitochondria through mitochondria-associated endoplasmic reticulum membranes. Importantly, chromatin immunoprecipitation revealed Bmal1 could bind directly to the Bcl2 gene promoter region. Bmal1 overexpression augmented the Bmal1/Bcl2 binding, enhancing the inhibition of Bcl2 on IP3R activity, thus alleviating mitochondrial Ca2+ overload and subsequent cell apoptosis. These results show that Bmal1 is involved in the DCM development through Bcl2/IP3R-mediated mitochondria Ca2+ overload. Therapy targeting the circadian clock (Bmal1) can treat DCM.

Outcomes of Shoulder Instability Repair - Latarjet vs Arthroscopic Bankart Repair: A Retrospective Study

This retrospective study aimed to compare the outcomes of two surgical procedures, Latarjet repair and arthroscopic Bankart repair, for the treatment of anterior shoulder instability. The study included 31 patients between the ages of 16 and 40 years who underwent either Latarjet repair or arthroscopic Bankart repair. The patients were evaluated using the Constant Murley Shoulder Score (CMS) and the American Shoulder and Elbow Surgeons Score (ASES) at 3, 6, and 12 months postoperatively. The results showed a gradual improvement in functional outcomes for both groups during the follow-up period. At one year postoperative, the Bankart repair group exhibited a CMS score of 89.3 and an ASES score of 94.1, while the Latarjet repair group showed a CMS score of 87.8 and an ASES score of 91.3. Statistical analysis revealed no significant differences in the CMS scores at any follow-up time point. However, the ASES score at 12 months postoperative was significantly higher in the Bankart repair group compared to the Latarjet repair group. The findings of this study suggest that both Latarjet repair and arthroscopic Bankart repair yield favorable clinical outcomes in terms of functional improvement for patients with anterior shoulder instability. Although arthroscopic techniques are minimally invasive and preferred by surgeons, the Latarjet procedure offers comparable results with less expenditure. The choice of surgical approach should be based on factors such as the patient's age, level of activity, and the presence of significant bone defects or soft tissue deficiencies. Further comparative studies with long-term follow-ups are recommended to validate these findings and provide more comprehensive insights into the outcomes of these procedures.

Whole-exome sequencing identified novel DNAH5 homozygous variants in two consanguineous families with primary ciliary dyskinesia.

Whole-exome sequencing identified novel DNAH5 homozygous variants in two consanguineous families with primary ciliary dyskinesia.

Improving the surface quality of material extrusion additive manufacturing parts by using ultrasonic‐vibration machining

AbstractMaterial extrusion (ME) technique has been one of the most popular additive manufacturing techniques because of its environmental friendliness, low cost, simple operation, and so forth. However, significant surface defects occur on ME parts due to the discontinuity between adjacent layers. For this reason, a new method, using ultrasonic‐vibration machining, was innovatively proposed to improve the ME parts' surface quality. A theoretical surface roughness (SR) model of the ME parts processed by using ultrasonic vibration was established. An ultrasonic‐vibrating ME equipment was then set up by refitting an ordinary one and the samples built without and with ultrasonic‐vibration machining utilized were prepared, respectively. With the laser microscope, the built parts' SR was tested and determined. Compared the predicted SR results with the measured ones, the theoretical model was verified. The influence of different ultrasonic vibration on the surface quality of ME parts was also discussed, clarifying the corresponding mechanism.

Structural and Biophysical Analysis of Adeno-Associated Virus Serotype 2 Capsid Assembly Variants.

Adeno-associated virus (AAV) is a nonenveloped single-stranded DNA (ssDNA) icosahedral T=1 virus being developed as a vector for clinical gene delivery systems. Currently, there are approximately 160 AAV clinical trials, with AAV2 being the most widely studied serotype. To further understand the AAV gene delivery system, this study investigates the role of viral protein (VP) symmetry interactions on capsid assembly, genome packaging, stability, and infectivity. A total of 25 (seven 2-fold, nine 3-fold, and nine 5-fold symmetry interface) AAV2 VP variants were studied. Six 2-fold and two 5-fold variants did not assemble capsids based on native immunoblots and anti-AAV2 enzyme-linked immunosorbent assays (ELISAs). Seven of the 3-fold and seven of the 5-fold variants that assembled capsids were less stable, while the only 2-fold variant that assembled had ~2°C higher thermal stability (Tm) than recombinant wild-type AAV2 (wtAAV2). Three of the 3-fold variants (AAV2-R432A, AAV2-L510A, and N511R) had an approximately 3-log defect in genome packaging. Consistent with previous reports of the 5-fold axes, the region of the capsid is important for VP1u externalization and genome ejection, and one 5-fold variant (R404A) had a significant defect in viral infectivity. The structures of wtAAV2 packaged with a transgene (AAV2-full) and without a transgene (AAV2-empty) and one 5-fold variant (AAV2-R404A) were determined by cryo-electron microscopy and three dimensional (3D)-image reconstruction to 2.8, 2.9, and 3.6 Å resolution, respectively. These structures revealed the role of stabilizing interactions on the assembly, stability, packaging, and infectivity of the virus capsid. This study provides insight into the structural characterization and functional implications of the rational design of AAV vectors. IMPORTANCE Adeno-associated viruses (AAVs) have been shown to be useful vectors for gene therapy applications. Consequently, AAV has been approved as a biologic for the treatment of several monogenic disorders, and many additional clinical trials are ongoing. These successes have generated significant interest in all aspects of the basic biology of AAV. However, to date, there are limited data available on the importance of the capsid viral protein (VP) symmetry-related interactions required to assemble and maintain the stability of the AAV capsids and the infectivity of the AAV capsids. Characterizing the residue type and interactions at these symmetry-driven assembly interfaces of AAV2 has provided the foundation for understanding their role in AAV vectors (serotypes and engineered chimeras) and has determined the residues or regions of the capsid that can or cannot tolerate alterations.

Nickel promoted Si-rich ZSM-5 nanocatalyst remarkably converts LDPE plastic waste to gasoline range hydrocarbons in a dual-bed semi-batch reactor at atmospheric pressure

Catalytic pyrolysis is an environmentally friendly recycling method, which has attracted remarkable attention due to worldwide issues of the production and accumulation of plastic wastes. In this work, the catalytic pyrolysis of Low-density polyethylene (LDPE) was carried out in a dual-bed semi-batch reactor over the Si-rich Ni/ZSM-5 nanocatalyst at atmospheric pressure. The parent nanocatalyst was prepared by hydrothermal technique and modified with nickel promoter (0–25 wt%). The properties of the nanocatalysts were characterized by XRD, FTIR, FE-SEM, EDX, TEM, BET, NH3-TPD, and TG-DTA techniques. The results showed the high crystallinity, spherical particles, and high specific surface area (376 m2g−1). The impact of operational conditions was evaluated to maximize the production of the high value-added compounds. The high percentage of the Ni promoter (25 wt%) led to the highest amount of gasoline range hydrocarbons (61%). The appropriate operational conditions were temperature of 525 °C, catalyst to plastic ratio of 1:20, and 2.5 ml min−1 nitrogen flow rate, resulting in the best product distribution: aromatics (39.4%), olefins (28.3%), and paraffins (15%). The reusability of the nanocatalyst showed high performance and more aromatic production. The characterization results of the used nanocatalyst confirmed the high stability through the pyrolysis reaction and lack of significant structural defect. The developed nanocatalyst represented the high activity through the pyrolysis of the real LDPE plastic waste, including the major product distribution in the gasoline range hydrocarbons.

Homogeneity of Bored Piles According to Results of Four-Channel Cross-Well Ultrasonic Monitoring

The homogeneity of the structure of the boired pile shaft has been studied based on the results of four-channel inter-well ultrasonic (US) monitoring. The actual lengthy of the piles has been determined with the detection of defragmentation of the pile shaft, the compressive defects have been determined, and continuity defects have been identified based on a joint analysis of data from the method of interwell ultrasonic monitoring. The use of four channels allows to control separately the peripheral and central areas of the pile in six directions. The data of the seismoacoustic method coincided with the parameters of ultrasonic monitoring in terms of identifying zones of concrete heterogeneity, reducing the pile cross section, etc. For all of the listed piles, data are not registered by the named test methods indicating defragmentation of the pile shaft – the presence of sections in the cross sections of which there is no concrete at all. These test methods for all piles confirmed the compliance of their actual length with the design values. A significant defect in the continuity of the concrete of the 40op pile, according to the data of ultrasonic monitoring and seismoacoustic method, was registered in the interval of marks – (17.5–18) m, manifesting itself a sa decrease in the propagation velocity of the ultrasonic pulse from 25 to 50 % in two sounding directions, inclu-ding diametrical. This defect can be interpreted as a decrease in the effective section of the pile to 25–50 % of the average value. Defective sections of piles were found in their upper part at depth marks from 0 to –1.5 m, counting from the end surface of the head. At the same time, differences in the physical and mechanical parameters of concrete at these marks were also observed within the cross section of piles [1–5].

Expression level of SOR1 is a bottleneck for efficient sorbitol utilization by yeast Komagataella kurtzmanii.

The yeast strain Komagataella kurtzmanii VKPM Y-727 shows a significant defect in sorbitol utilization compared to closely related yeast K.phaffii (including strains formerly identified as Pichia pastoris). Our aim was to investigate the factors that determine the phenotype of the wild-type strain and to obtain a K. kurtzmanii strain with an improved ability to utilize sorbitol. We sequenced and annotated the genome of K. kurtzmanii VKPM Y-727 and compared it with that of K. phaffii GS115. Five K. phaffii GS115 genes that might be involved in sorbitol metabolism were selected and transferred into K. kurtzmanii Y-727. The transfer of the modified SOR1 gene resulted in an increased growth rate of K. kurtzmanii in sorbitol, despite the fact that Y-727 already contains its own SOR1 gene without any apparent mutations. The enzymes encoded by the SOR1 genes were analyzed in vitro and found to have similar properties. Differences in promoter activity were assessed using lacZ as a reporter gene, and the PSDH727 (promoter of SOR1 (SDH727) from K. kurtzmanii Y-727) promoter was shown to be 1.5-2.0 times weaker than PSDH115 (promoter of SOR1 (SDH115) from K. phaffii GS115). Moreover, both promoters were less active in K. kurtzmanii than in K. phaffii when evaluated in cells grown in synthetic complete media with glucose or sorbitol. Thus, SOR1 gene expression was identified as a bottleneck in sorbitol metabolism in K. kurtzmanii. Also, the positive effect of additional modified SOR1 gene copies was observed in both yeasts, as K. kurtzmanii and K. phaffii could grow on synthetic complete media with sorbitolthree times faster than the original K. phaffii GS115 strain.

A Displacement-Dependent Limit-Equilibrium Slice Method for Slope Stability Analysis

Displacement and factor of safety are two crucial pieces of information about slope stability, but the traditional limit-equilibrium slice method has a significant defect; that is, it cannot reflect slope displacement. In this paper, a displacement-dependent limit-equilibrium slice method is proposed based on the soil shear constitutive model and Morgenstern–Price assumption of interslice forces to establish the relationship between the factor of safety and displacement. In addition to the overall factor of safety, point factors of safety and point displacements can also be obtained using the proposed method to characterize the displacement-dependent slope stability. The point factor of safety and shear displacement of each soil slice calculated using the proposed method are slightly higher and smaller than those calculated by the modified displacement-dependent Janbu method. The iterative process of the proposed method is simpler and more stable than that of the modified displacement-dependent Janbu method. Calculation results of four examples show that the point factors of safety at the upper and lower ends of the slide mass are generally smaller than those at the middle part of the slip body, and the shear displacement of the soil slice near the slope top is generally larger than those at the other positions. The proposed method associates the factors of safety with slope displacements, which allows us to quantitatively assess the slope stability immediately in practice by monitoring the displacements of some key points on it.

EGF-Receptor–Dependent TLR7 Signaling in Macrophages Promotes Glomerular Injury in Crescentic Glomerulonephritis

Glomerulonephritis (GN) is a group of inflammatory diseases and an important cause of morbidity and mortality worldwide. The initiation of the inflammatory process is quite different for each type of GN; however, each GN is characterized commonly and variably by acute inflammation with neutrophils and macrophages and crescent formation, leading to glomerular death. Toll-like receptor (TLR) 7 is a sensor for self-RNA and implicated in the pathogenesis of human and murine GN. Here, we show that TLR7 exacerbates glomerular injury in nephrotoxic serum nephritis (NTN), a murine model of severe crescentic GN. TLR7−/− mice were resistant to NTN, although TLR7−/− mice manifested comparable immune-complex deposition to wild-type mice without significant defects in humoral immunity, suggesting that endogenous TLR7 ligands accelerate glomerular injury. TLR7 was expressed exclusively in macrophages in glomeruli in GN but not in glomerular resident cells or neutrophils. Furthermore, we discovered that epidermal growth factor receptor (EGFR), a receptor-type tyrosine kinase, is essential for TLR7 signaling in macrophages. Mechanistically, EGFR physically interacted with TLR7 upon TLR7 stimulation, and EGFR inhibitor completely blocked the phosphorylation of TLR7 tyrosine residue(s). EGFR inhibitor attenuated glomerular damage in wild-type mice, and no additional glomerular protective effects by EGFR inhibitor were observed in TLR7−/− mice. Finally, mice lacking EGFR in macrophages were resistant to NTN. This study clearly demonstrated that EGFR-dependent TLR7 signaling in macrophages is essential for glomerular injury in crescentic GN.

Investigation on the improvement of mechanical properties and surface quality of the polylactic acid (PLA) fused filament fabrication parts manufactured without and with vibrations dependent utilization

Fused Filament Fabrication (FFF), is one of the most widely used additive manufacturing technologies today, which has been used for a variety of applications. Due to the layer-by-layer manufacturing process, FFF parts are inferior to those fabricated by traditional methods in terms of tensile properties, which is one of the most significant defects that hinder the development of this technique. In this study, a vibration was utilized during the FFF process by piezoelectric ceramics electric plates to improve the mechanical properties of the built parts and surface quality of PLA FFF parts. Subsequently, an investigation of the tensile and the surface quality of PLA FFF specimens built-in X and Z-direction fabricated individually without and with vibrations utilized has been done. Furthermore, a theoretical model has been established to predict the tensile strength and plasticity of FFF parts fabricated without and with vibrations utilized based on classical laminated plate theory, with the anisotropic and laminated characteristics taken into consideration. Young's modulus model has been established based on the laminated plate theory and flexural vibration theoretical approaches of a plate for the PLA FFF parts manufactured without and with vibrations utilized respectively. Compared with the previous models this model provides the tensile strength and plasticity of FFF parts both manufactured without and with vibrations utilized. The results indicate that the predicted tensile strength and plasticity of the PLA FFF parts manufactured with vibrations utilized have a good consistency with the experimental ones, meanwhile, vibration utilization can significantly improve the surface quality of the PLA FFF samples manufactured in the Z-direction, and the scanning electron microscopy (SEM) analysis confirmed that vibration utilization can improve the forming quality of FFF manufactured parts.