Molecular Dynamics Simulation of Droplet Impact on a Hydrophobic 3D Elastic Surface.

The phenomenon of droplets impacting elastic surfaces is common in nature and in many engineering applications. It has been shown that droplet impact on an elastic surface drastically reduces droplet contact time and hinders droplet spreading. However, most of the current studies are based on experiments, and the analysis of the influence mechanism of the elastic substrate on the dynamic behavior of droplets is not complete. In addition, the simulations of droplet impact on elastic substrates are mainly focused on 2D elastic films or vibrating rigid substrates, ignoring the effect of 3D elastic substrate deformation on the droplet dynamic behavior. Therefore, in this paper, we propose to model the droplet impact on a 3D hydrophobic elastic substrate using the molecular dynamics method. We find that droplet pancake rebound can substantially reduce the droplet contact time. Moreover, we record the conditions required for the pancake rebound of the droplet. Furthermore, we investigated the effects of the elastic modulus of the substrate and the initial velocity of the droplet on the droplet contact time, contact area, and spreading factor. This study further elucidates the influence mechanism of the elastic substrate on the dynamic behavior of the droplet and provides theoretical guidance for regulating the dynamic behavior of the droplet in related fields.

A retrospective study of the accuracy of Invisalign Progress Assessment with clear aligners.

The objective of this study was to detective the accuracy of model superimposition and automatic analysis for upper and lower dentition width in Invisalign Progress Assessment during the process of clear aligners. 19 cases were included in this study. Pre-treatment dental cast (T0) and post-treatment dental cast after staged treatment (T1) were available for three-dimensional model superimposition. Subsequently, movements of maxillary teeth in the horizontal plane (cross-section) after staged treatment and width of upper and lower dentition were measured by three-dimensional model superimposition in the real world and Invisalign Progress Assessment separately. Consequently, the data collected from these two methods were compared. In Invisalign Progress Assessment, movements of maxillary teeth in the horizontal plane after staged treatment was 2.31 (1.59,3.22) [median (upper quartile, lower quartile)] millimeter (mm), while in three-dimensional model superimposition, the result was 1.79 (1.21,3.03) mm. The difference between the two groups is significant (P < 0.05). Intercanine width upper, intermolar width upper, intercanine width lower, and intermolar width lower were 36.55 ± 2.76 mm, 56.98 ± 2.62 mm, 28.16 ± 1.85 mm, 53.21 ± 2.72 mm separately in Invisalign Progress Assessment and were 36.48 ± 2.78 mm, 56.89 ± 2.58 mm, 28.05 ± 1.85 mm, 53.16 ± 2.64 mm separately in three-dimensional model analysis, which was no significant difference among these groups (P > 0.05). The data from Invisalign Progress Assessment was not in parallel with what was achieved from model superimposition with palate as a reference completely. The accuracy of model superimposition in Invisalign Progress Assessment needs further investigation, whereas the accuracy of model analysis in Invisalign Progress Assessment was accurate. Thereby, results from Invisalign Progress Assessment should be interpreted with caution by the orthodontist in the clinic.

[A preliminary study on the effects of fecal microbiota transplantation on the intestinal microecology of patients with severe pneumonia during the convalescence period].

OBJECTIVE: To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period. METHODS: A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group. RESULTS: The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and ß diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030). CONCLUSIONS: FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.

Squeeze-Printing Ultrathin 2D Gallium Oxide out of Liquid Metal for Forming-Free Neuromorphic Memristors.

Two-dimensional (2D) metal oxides exhibit extraordinary mechanical and electronic properties, leading to new paradigms in the design of electronic and optical systems. However, as a representative, a 2D Ga2O3-based memristor has rarely been touched, which is hindered by challenges associated with large-scale material synthesis. In this work, the ultrathin 2D Ga2O3 layer (∼3 nm thick) formation on the liquid gallium (Ga) surface is transferred with lateral dimensions over several centimeters on a substrate via the squeeze-printing strategy. 2D Ga2O3-based memristors exhibit forming-free and bipolar switching behaviors, which also reveal essential functions of biological synapse, including paired-pulse facilitation, spiking timing-dependent plasticity, and long-term depression and potentiation. These results demonstrate the potential of 2D Ga2O3 material for neuromorphic computing and open up an avenue for future electronics application, such as deep UV photodetectors, multimode nanoresonators, and power switching devices.

Juvenile CLN3 disease is a lysosomal cholesterol storage disorder: similarities with Niemann-Pick type C disease.

BACKGROUND: The most common form of neuronal ceroid lipofuscinosis (NCL) is juvenile CLN3 disease (JNCL), a currently incurable neurodegenerative disorder caused by mutations in the CLN3 gene. Based on our previous work and on the premise that CLN3 affects the trafficking of the cation-independent mannose-6 phosphate receptor and its ligand NPC2, we hypothesised that dysfunction of CLN3 leads to the aberrant accumulation of cholesterol in the late endosomes/lysosomes (LE/Lys) of JNCL patients' brains. METHODS: An immunopurification strategy was used to isolate intact LE/Lys from frozen autopsy brain samples. LE/Lys isolated from samples of JNCL patients were compared with age-matched unaffected controls and Niemann-Pick Type C (NPC) disease patients. Indeed, mutations in NPC1 or NPC2 result in the accumulation of cholesterol in LE/Lys of NPC disease samples, thus providing a positive control. The lipid and protein content of LE/Lys was then analysed using lipidomics and proteomics, respectively. FINDINGS: Lipid and protein profiles of LE/Lys isolated from JNCL patients were profoundly altered compared to controls. Importantly, cholesterol accumulated in LE/Lys of JNCL samples to a comparable extent than in NPC samples. Lipid profiles of LE/Lys were similar in JNCL and NPC patients, except for levels of bis(monoacylglycero)phosphate (BMP). Protein profiles detected in LE/Lys of JNCL and NPC patients appeared identical, except for levels of NPC1. INTERPRETATION: Our results support that JNCL is a lysosomal cholesterol storage disorder. Our findings also support that JNCL and NPC disease share pathogenic pathways leading to aberrant lysosomal accumulation of lipids and proteins, and thus suggest that the treatments available for NPC disease may be beneficial to JNCL patients. This work opens new avenues for further mechanistic studies in model systems of JNCL and possible therapeutic interventions for this disorder. FUNDING: San Francisco Foundation.

Lysosomal phospholipase A2 contributes to the biosynthesis of the atypical late endosome lipid bis(monoacylglycero)phosphate.

The late endosome/lysosome (LE/Lys) lipid bis(monoacylglycero)phosphate (BMP) plays major roles in cargo sorting and degradation, regulation of cholesterol and intercellular communication and has been linked to viral infection and neurodegeneration. Although BMP was initially described over fifty years ago, the enzymes regulating its synthesis remain unknown. The first step in the BMP biosynthetic pathway is the conversion of phosphatidylglycerol (PG) into lysophosphatidylglycerol (LPG) by a phospholipase A2 (PLA2) enzyme. Here we report that this enzyme is lysosomal PLA2 (LPLA2). We show that LPLA2 is sufficient to convert PG into LPG in vitro. We show that modulating LPLA2 levels regulates BMP levels in HeLa cells, and affects downstream pathways such as LE/Lys morphology and cholesterol levels. Finally, we show that in a model of Niemann-Pick disease type C, overexpressing LPLA2 alleviates the LE/Lys cholesterol accumulation phenotype. Altogether, we shed new light on BMP biosynthesis and contribute tools to regulate BMP-dependent pathways.

Alzheimer's-Associated Upregulation of Mitochondria-Associated ER Membranes After Traumatic Brain Injury.

Traumatic brain injury (TBI) can lead to neurodegenerative diseases such as Alzheimer's disease (AD) through mechanisms that remain incompletely characterized. Similar to AD, TBI models present with cellular metabolic alterations and modulated cleavage of amyloid precursor protein (APP). Specifically, AD and TBI tissues display increases in amyloid-ß as well as its precursor, the APP C-terminal fragment of 99 a.a. (C99). Our recent data in cell models of AD indicate that C99, due to its affinity for cholesterol, induces the formation of transient lipid raft domains in the ER known as mitochondria-associated endoplasmic reticulum (ER) membranes ("MAM" domains). The formation of these domains recruits and activates specific lipid metabolic enzymes that regulate cellular cholesterol trafficking and sphingolipid turnover. Increased C99 levels in AD cell models promote MAM formation and significantly modulate cellular lipid homeostasis. Here, these phenotypes were recapitulated in the controlled cortical impact (CCI) model of TBI in adult mice. Specifically, the injured cortex and hippocampus displayed significant increases in C99 and MAM activity, as measured by phospholipid synthesis, sphingomyelinase activity and cholesterol turnover. In addition, our cell type-specific lipidomics analyses revealed significant changes in microglial lipid composition that are consistent with the observed alterations in MAM-resident enzymes. Altogether, we propose that alterations in the regulation of MAM and relevant lipid metabolic pathways could contribute to the epidemiological connection between TBI and AD.

Fluorinated covalent organic frameworks for efficient drug delivery.

In this study, two novel fluorine-functionalized crystalline covalent organic frameworks (COFs), namely DF-TAPB-COF and DF-TATB-COF, were synthesized, and their ordered structure, porosity, suitable pore size, and abundant fluorine groups were expected to serve as effective carriers in drug delivery. The excellent cell viability of DF-TAPB-COF and DF-TATB-COF was verified using MTT assays. Both COFs exhibited very high loading capacities in terms of drug loading performance, in particular the drug loading rate of DF-TAPB-COF for 5-fluorouracil (5-FU) was up to 69%. They also exhibited efficient drug release performance in a simulated body fluid environment. Cell endocytosis experiments demonstrated that DF-TAPB-COF and DF-TATB-COF could be effectively endocytosed by cells. Hence, this study offers new insight into the design and development of COF-based drug carrier systems.

Accuracy of progress assessment with clear aligners.

OBJECTIVES: This study aimed to investigate the accuracy of model superimposition and automatic analysis for upper and lower dentition widths in iTero Progress Assessment during the clear aligner process. METHODS: Nineteen cases were included in this retrospective case control study. Pretreatment dental cast (T0) and post treatment dental cast after staged treatment (T1) were available for three-dimensional (3D) model superimposition. The movements of maxillary teeth in the horizontal plane (cross section) after staged treatment and the widths of upper and lower dentitions were measured by 3D model superimposition in real world and iTero Progress Assessment. The data collected from the two methods were compared. RESULTS: The movements [Median (upper and lower quartiles)] of maxillary teeth in the horizontal plane after staged treatment were 2.31 (1.59, 3.22) and 1.79 (1.21, 3.03) mm in iTero Progress Assessment and 3D model analysis, respectively. Significant difference was observed between the two groups (P<0.05). In the measurement of upper and lower dentition width, four indicators were measured, including intercanine width upper, intermolar width upper, intercanine width lower, and intermolar width lower. Before treatment, the measurement of iTero Progress Assessment were (35.78±2.49), (56.21±2.51), (27.43±1.38), (52.26±2.91) mm, respectively, and actual measurement were (35.77±2.53), (56.17±2.47), (27.40±1.41), (52.30±2.86) mm, respectively, without significant difference (P>0.05). After stage treatment, the measurement of iTero Progress Assessment were (37.37±2.86), (57.76±2.56), (28.89±2.00), (54.16±2.19) mm, respectively, and actual measurement were (37.29±2.94), (57.71±2.63), (28.88±2.05), (54.01±2.15) mm, respectively, and there was no significant difference (P>0.05). CONCLUSIONS: The data from iTero Progress Assessment did not coincide with the model superimposition results with palate as reference. The accuracy of model superimposition in iTero Progress Assessment needs further investigation, whereas the arch width analysis is accurate. Therefore, iTero Progress Assessment results should be interpreted with caution by orthodontists in clinical applications.

Molecular Dynamics Simulation of Nanodroplets Impacting Stripe-Textured Surfaces.

The dynamic behavior of droplets impacting on textured surfaces has an important influence on many engineering applications, such as anti-icing and self-cleaning. However, the mechanism and law of the effect of textured surfaces on the impact behavior of nanodroplets has not been fully revealed yet. In this paper, the molecular dynamics (MD) method is used to model the dynamic behavior of nanodroplets after impacting the solid surface with a striped texture. The influences of texture gap and texture angle on the real contact area, spreading factor, contact time, and bounce velocity of the droplet after impact are also quantitatively analyzed. It is shown that the striped texture produces significant anisotropy in the spreading and contraction behavior of nanodroplets after impact, and the anisotropy is more pronounced on the ridged texture surface than on the grooved texture surface. In addition, we find that the texture gap has little effect on the dynamic behavior of nanodroplets impacting the textured surface. However, as the bottom angle of the texture increases, the real contact area and bounce velocity of the nanodroplet increase significantly, while the contact time and spreading factor decrease. This work further elucidates the characteristics and mechanisms of nanodroplets impacting on stripe-textured surfaces and provides a theoretical basis for the design of nanostructured surfaces in relevant applications.

Integration of Neuroscience and Entrepreneurship: A Systematic Review and Bibliometric Analysis.

In this study, we investigated the integration between neuroscience and entrepreneurship. First, we explored the concept of neuroentrepreneurship and the investigation of neuroentrepreneurship using scientific research methods. Second, we constructed a road map for entrepreneurial researchers interested in conducting neuroentrepreneurship-related research. This is an emerging research area; therefore, to more clearly analyze the dynamics of the research trends, we used a bibliometric method to capture patterns in current publications on subjects related to neuroentrepreneurship, examining papers published between 1999 and 2021 using the keywords "neuroscience" and "entrepreneurship" or "neuroentrepreneurship." To identify the keywords, we used two academic databases-the Social Science Citation Index and Science Citation Index-accessed through the Web of Science website. The three keywords were identified from studies integrating neuroscience with entrepreneurship. After carefully reviewing the research papers, we identified neuroentrepreneurship as a novel research area. The outcomes of this study provide a guide for describing the theoretical connection between neuroscience and entrepreneurship. In the future, this field of study should be empirically investigated.

Effects of APOE4 allelic dosage on lipidomic signatures in the entorhinal cortex of aged mice.

Apolipoprotein E ε4 (APOE4) is the primary genetic risk factor for the late-onset form of Alzheimer's disease (AD). Although the reason for this association is not completely understood, researchers have uncovered numerous effects of APOE4 expression on AD-relevant brain processes, including amyloid beta (Aß) accumulation, lipid metabolism, endosomal-lysosomal trafficking, and bioenergetics. In this study, we aimed to determine the effect of APOE4 allelic dosage on regional brain lipid composition in aged mice, as well as in cultured neurons. We performed a targeted lipidomic analysis on an AD-vulnerable brain region (entorhinal cortex; EC) and an AD-resistant brain region (primary visual cortex; PVC) from 14-15 month-old APOE3/3, APOE3/4, and APOE4/4 targeted replacement mice, as well as on neurons cultured with conditioned media from APOE3/3 or APOE4/4 astrocytes. Our results reveal that the EC possesses increased susceptibility to APOE4-associated lipid alterations compared to the PVC. In the EC, APOE4 expression showed a dominant effect in decreasing diacylglycerol (DAG) levels, and a semi-dominant, additive effect in the upregulation of multiple ceramide, glycosylated sphingolipid, and bis(monoacylglycerol)phosphate (BMP) species, lipids known to accumulate as a result of endosomal-lysosomal dysfunction. Neurons treated with conditioned media from APOE4/4 vs. APOE3/3 astrocytes showed similar alterations of DAG and BMP species to those observed in the mouse EC. Our results suggest that APOE4 expression differentially modulates regional neuronal lipid signatures, which may underlie the increased susceptibility of EC-localized neurons to AD pathology.

The Alzheimer's disease-associated C99 fragment of APP regulates cellular cholesterol trafficking.

The link between cholesterol homeostasis and cleavage of the amyloid precursor protein (APP), and how this relationship relates to Alzheimer's disease (AD) pathogenesis, is still unknown. Cellular cholesterol levels are regulated through crosstalk between the plasma membrane (PM), where most cellular cholesterol resides, and the endoplasmic reticulum (ER), where the protein machinery that regulates cholesterol levels resides. The intracellular transport of cholesterol from the PM to the ER is believed to be activated by a lipid-sensing peptide(s) in the ER that can cluster PM-derived cholesterol into transient detergent-resistant membrane domains (DRMs) within the ER, also called the ER regulatory pool of cholesterol. When formed, these cholesterol-rich domains in the ER maintain cellular homeostasis by inducing cholesterol esterification as a mechanism of detoxification while attenuating its de novo synthesis. In this manuscript, we propose that the 99-aa C-terminal fragment of APP (C99), when delivered to the ER for cleavage by γ-secretase, acts as a lipid-sensing peptide that forms regulatory DRMs in the ER, called mitochondria-associated ER membranes (MAM). Our data in cellular AD models indicates that increased levels of uncleaved C99 in the ER, an early phenotype of the disease, upregulates the formation of these transient DRMs by inducing the internalization of extracellular cholesterol and its trafficking from the PM to the ER. These results suggest a novel role for C99 as a mediator of cholesterol disturbances in AD, potentially explaining early hallmarks of the disease.

Phospholipase D1 Ablation Disrupts Mouse Longitudinal Hippocampal Axis Organization and Functioning.

Phosphatidic acid (PA) is a signaling lipid involved in the modulation of synaptic structure and functioning. Based on previous work showing a decreasing PA gradient along the longitudinal axis of the rodent hippocampus, we asked whether the dorsal hippocampus (DH) and the ventral hippocampus (VH) are differentially affected by PA modulation. Here, we show that phospholipase D1 (PLD1) is a major hippocampal PA source, compared to PLD2, and that PLD1 ablation affects predominantly the lipidome of the DH. Moreover, Pld1 knockout (KO) mice show specific deficits in novel object recognition and social interaction and disruption in the DH-VH dendritic arborization differentiation in CA1/CA3 pyramidal neurons. Also, Pld1 KO animals present reduced long-term depression (LTD) induction and reduced GluN2A and SNAP-25 protein levels in the DH. Overall, we observe that PLD1-derived PA reduction leads to differential lipid signatures along the longitudinal hippocampal axis, predominantly affecting DH organization and functioning.

Decreased surfactant lipids correlate with lung function in chronic obstructive pulmonary disease (COPD).

Smoke exposure is known to decrease total pulmonary surfactant and alter its composition, but the role of surfactant in chronic obstructive pulmonary disease (COPD) remains unknown. We aimed to analyze the compositional changes in the surfactant lipidome in COPD and identify specific lipids associated with pulmonary function decline. Bronchoalveolar lavage (BAL) fluid was obtained from 12 former smokers with COPD and 5 non-smoking, non-asthmatic healthy control volunteers. Lipids were extracted and analyzed by liquid chromatography and mass spectrometry. Pulmonary function data were obtained by spirometry, and correlations of lung function with lipid species were determined. Wild-type C57BL/6 mice were exposed to 6 months of second-hand smoke in a full-body chamber. Surfactant lipids were decreased by 60% in subjects with COPD. All phospholipid classes were dramatically decreased, including ether phospholipids, which have not been studied in pulmonary surfactant. Availability of phospholipid, cholesterol, and sphingomyelin in BAL strongly correlated with pulmonary function and this was attributable to specific lipid species of phosphatidylcholine with surface tension reducing properties, and of phosphatidylglycerol with antimicrobial roles, as well as to other less studied lipid species. Mice exposed to smoke for six months recapitulated surfactant lipidomic changes observed in human subjects with COPD. In summary, we show that the surfactant lipidome is substantially altered in subjects with COPD, and decreased availability of phospholipids correlated with decreased pulmonary function. Further investigation of surfactant alterations in COPD would improve our understanding of its physiopathology and reveal new potential therapeutic targets.

Synergistic effects of titanium dioxide and cellulose on the properties of glassionomer cement.

In this study, we evaluate the effect of co-doping with TiO2 nanoparticles and sisal cellulose nanocrystals (CNCs) on the physical and biological properties of a conventional glass-ionomer cement (GIC). Test samples were characterized by scanning electron microscopy, and Fourier-transform infrared spectroscopy, and subjected to mechanical tests to evaluate the mechanical performances. Antimicrobial activity was evaluated against Candida albicans, and cytotoxicity experiments were conducted using L-929 cells. Unmodified GIC served as a control. Compared with the control group, the co-doped group demonstrated an increased compressive strength of 18.9%, an increased shear bond strength of 51%, the dissolution decreased by 18.3%, the volume wear rate was reduced by 5%. The antifungal effect against C. albicans was increased by 22%. In cytotoxicity experiments, the co-doped group had a slightly negative effect on the viability of L-929 cells.

Knitted silk mesh-like scaffold incorporated with sponge-like regenerated silk fibroin/collagen I and seeded with mesenchymal stem cells for repairing Achilles tendon in rabbits.

A scaffold knit with natural sericin-free silk fibroin fiber possesses desirable mechanical properties, biocompatibility, ease of fabrication, and slow degradability. However, regenerated silk fibroin degrades faster than natural silk. In this study, natural silk fibroin fiber mesh-like scaffolds were prepared by a weft-knitting method and the pores were filled with sponge-like regenerated silk fibroin-collagen I. The microporous sponge and mesh-like scaffolds were fused to achieve gradient degradation of the scaffolds, and rabbit bone marrow mesenchymal stem cells (BMSCs) were seeded onto the scaffolds to form scaffold-BMSCs composites. The composites were implanted into gap defects made in the rabbit Achilles tendon. Twenty weeks after implantation, histological observation showed that tendon-like tissue had formed, collagen I mRNA was expressed, abundant collagen was generated, and that there was no obvious degradation of silk. The maximum load of the neo-Achilles tendon was 62.14% that of the natural Achilles tendon. These outcomes were superior to those obtained in the group implanted with a scaffold without BMSCs. These findings suggest the feasibility of constructing tissue-engineered tendons using weft-knitted silk scaffolds incorporated with sponge-like regenerated silk fibroin/collagen I and seeded with BMSCs, and show potential of the scaffold-BMSCs composites to repair Achilles tendon defects.

CoQ10 supplementation rescues nephrotic syndrome through normalization of H2S oxidation pathway.

Nephrotic syndrome (NS), a frequent chronic kidney disease in children and young adults, is the most common phenotype associated with primary coenzyme Q10 (CoQ10) deficiency and is very responsive to CoQ10 supplementation, although the pathomechanism is not clear. Here, using a mouse model of CoQ deficiency-associated NS, we show that long-term oral CoQ10 supplementation prevents kidney failure by rescuing defects of sulfides oxidation and ameliorating oxidative stress, despite only incomplete normalization of kidney CoQ levels and lack of rescue of CoQ-dependent respiratory enzymes activities. Liver and kidney lipidomics, and urine metabolomics analyses, did not show CoQ metabolites. To further demonstrate that sulfides metabolism defects cause oxidative stress in CoQ deficiency, we show that silencing of sulfide quinone oxido-reductase (SQOR) in wild-type HeLa cells leads to similar increases of reactive oxygen species (ROS) observed in HeLa cells depleted of the CoQ biosynthesis regulatory protein COQ8A. While CoQ10 supplementation of COQ8A depleted cells decreases ROS and increases SQOR protein levels, knock-down of SQOR prevents CoQ10 antioxidant effects. We conclude that kidney failure in CoQ deficiency-associated NS is caused by oxidative stress mediated by impaired sulfides oxidation and propose that CoQ supplementation does not significantly increase the kidney pool of CoQ bound to the respiratory supercomplexes, but rather enhances the free pool of CoQ, which stabilizes SQOR protein levels rescuing oxidative stress.