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1.
Polymers (Basel) ; 16(10)2024 May 09.
Article in English | MEDLINE | ID: mdl-38794526

ABSTRACT

In this paper, the solid-state shear milling (S3M) strategy featuring a very strong three-dimensional shear stress field was adopted to prepare the high-performance polyoxymethylene (POM)/molybdenum disulfide (MoS2) functional nanocomposite. The transmission electron microscope and Raman measurement results confirmed that the bulk MoS2 particle was successfully exfoliated into few-layer MoS2 nanoplatelets by the above simple S3M physical method. The polarized optical microscope (PLM) observation indicated the pan-milled nanoscale MoS2 particles presented a better dispersion performance in the POM matrix. The results of the tribological test indicated that the incorporation of MoS2 could substantially improve the wear resistance performance of POM. Moreover, the pan-milled exfoliated MoS2 nanosheets could further substantially decrease the friction coefficient of POM. Scanning electron microscope observations on the worn scar revealed the tribological mechanism of the POM/MoS2 nanocomposite prepared by solid-state shear milling. The tensile test results showed that the pan-milled POM/MoS2 nanocomposite has much higher elongation at break than the conventionally melt-compounded material. The solid-state shear milling strategy shows a promising prospect in the preparation of functional nanocomposite with excellent comprehensive performance at a large scale.

2.
Adv Sci (Weinh) ; 11(13): e2306986, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38240347

ABSTRACT

Previously a ring finger protein 20 (RNF20) is found to be essential for meiotic recombination and mediates H2B ubiquitination during spermatogenesis. However, its role in meiotic division is still unknown. Here, it is shown that RNF20 is localized at both centromeres and spindle poles, and it is required for oocyte acentrosomal spindle organization and female fertility. RNF20-depleted oocytes exhibit severely abnormal spindle and chromosome misalignment caused by defective bipolar organization. Notably, it is found that the function of RNF20 in spindle assembly is not dependent on its E3 ligase activity. Instead, RNF20 regulates spindle assembly by recruiting tropomyosin3 (TPM3) to both centromeres and spindle poles with its coiled-coil motif. The RNF20-TPM3 interaction is essential for acentrosomal meiotic spindle assembly. Together, the studies uncover a novel function for RNF20 in mediating TPM3 recruitment to both centromeres and spindle poles during oocyte spindle assembly.


Subject(s)
Meiosis , Spindle Apparatus , Male , Female , Humans , Spindle Apparatus/metabolism , Oocytes/metabolism , Spindle Poles/metabolism , Centromere
3.
Nanomicro Lett ; 16(1): 85, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38214822

ABSTRACT

Electromagnetic interference shielding (EMI SE) modules are the core component of modern electronics. However, the traditional metal-based SE modules always take up indispensable three-dimensional space inside electronics, posing a major obstacle to the integration of electronics. The innovation of integrating 3D-printed conformal shielding (c-SE) modules with packaging materials onto core electronics offers infinite possibilities to satisfy ideal SE function without occupying additional space. Herein, the 3D printable carbon-based inks with various proportions of graphene and carbon nanotube nanoparticles are well-formulated by manipulating their rheological peculiarity. Accordingly, the free-constructed architectures with arbitrarily-customized structure and multifunctionality are created via 3D printing. In particular, the SE performance of 3D-printed frame is up to 61.4 dB, simultaneously accompanied with an ultralight architecture of 0.076 g cm-3 and a superhigh specific shielding of 802.4 dB cm3 g-1. Moreover, as a proof-of-concept, the 3D-printed c-SE module is in situ integrated into core electronics, successfully replacing the traditional metal-based module to afford multiple functions for electromagnetic compatibility and thermal dissipation. Thus, this scientific innovation completely makes up the blank for assembling carbon-based c-SE modules and sheds a brilliant light on developing the next generation of high-performance shielding materials with arbitrarily-customized structure for integrated electronics.

5.
Cell Mol Life Sci ; 81(1): 1, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38038747

ABSTRACT

Multiple morphological abnormalities of the flagella (MMAF) is a severe disease of male infertility, while the pathogenetic mechanisms of MMAF are still incompletely understood. Previously, we found that the deficiency of Ccdc38 might be associated with MMAF. To understand the underlying mechanism of this disease, we identified the potential partner of this protein and found that the coiled-coil domain containing 146 (CCDC146) can interact with CCDC38. It is predominantly expressed in the testes, and the knockout of this gene resulted in complete infertility in male mice but not in females. The knockout of Ccdc146 impaired spermiogenesis, mainly due to flagellum and manchette organization defects, finally led to MMAF-like phenotype. Furthermore, we demonstrated that CCDC146 could interact with both CCDC38 and CCDC42. It also interacts with intraflagellar transport (IFT) complexes IFT88 and IFT20. The knockout of this gene led to the decrease of ODF2, IFT88, and IFT20 protein levels, but did not affect CCDC38, CCDC42, or ODF1 expression. Additionally, we predicted and validated the detailed interactions between CCDC146 and CCDC38 or CCDC42, and built the interaction models at the atomic level. Our results suggest that the testis predominantly expressed gene Ccdc146 is essential for sperm flagellum biogenesis and male fertility, and its mutations might be associated with MMAF in some patients.


Subject(s)
Infertility, Male , Microtubule-Associated Proteins , Sperm Tail , Animals , Male , Mice , Fertility/genetics , Heat-Shock Proteins/metabolism , Infertility, Male/metabolism , Mice, Knockout , Semen , Sperm Tail/metabolism , Sperm Tail/pathology , Spermatozoa/metabolism , Testis/metabolism , Microtubule-Associated Proteins/genetics
6.
ACS Biomater Sci Eng ; 9(12): 6734-6744, 2023 Dec 11.
Article in English | MEDLINE | ID: mdl-37939039

ABSTRACT

Poly(vinyl alcohol) (PVA) exhibits a wide range of potential applications in the biomedical field due to its favorable mechanical properties and biocompatibility. However, few studies have been carried out on selective laser sintering (SLS) of PVA due to its poor thermal processability. In this study, in order to impart PVA powder the excellent thermal processability, the molecular complexation technology was performed to destroy the strong hydrogen bonds in PVA and thus significantly reduced the PVA melting point and crystallinity to 190.9 °C and 27.9%, respectively. The modified PVA (MPVA) was then compounded with hydroxyapatite (HA) to prepare PVA/HA composite powders suitable for SLS 3D printing. The final SLS 3D-printed MPVA/HA composite porous scaffolds show high precision and interconnected pores with a porosity as high as 68.3%. The in vitro cell culture experiments revealed that the sintered composite scaffolds could significantly promote the adhesion and proliferation of osteoblasts and facilitate bone regeneration, and the quantitative real-time polymerase chain reaction results further demonstrate that the printed MPVA/20HA scaffold could significantly enhance the expression levels of both early osteogenic-specific marker of alkaline phosphatase stain and runt-related transcription factor 2. Meanwhile, in in vivo experiments, it is encouragingly found that the resultant MPVA/20HA SLS 3D-printed part has an obvious effect on promoting the growth of new bone tissue as well as a better bone regeneration capability. This work could provide a promising strategy for fabrication of PVA scaffolds through SLS 3D printing, exhibiting a great potential for clinical applications in bone tissue engineering.


Subject(s)
Durapatite , Tissue Scaffolds , Durapatite/pharmacology , Durapatite/chemistry , Tissue Scaffolds/chemistry , Porosity , Polyvinyl Alcohol/chemistry , Ethanol , Printing, Three-Dimensional
7.
Elife ; 122023 10 17.
Article in English | MEDLINE | ID: mdl-37847146

ABSTRACT

The landscape of extrachromosomal circular DNA (eccDNA) during mammalian spermatogenesis, as well as the biogenesis mechanism, remains to be explored. Here, we revealed widespread eccDNA formation in human sperms and mouse spermatogenesis. We noted that germline eccDNAs are derived from oligonucleosomal DNA fragmentation in cells likely undergoing cell death, providing a potential new way for quality assessment of human sperms. Interestingly, small-sized eccDNAs are associated with euchromatin, while large-sized ones are preferentially generated from heterochromatin. By comparing sperm eccDNAs with meiotic recombination hotspots and structural variations, we found that they are barely associated with de novo germline deletions. We further developed a bioinformatics pipeline to achieve nucleotide-resolution eccDNA detection even with the presence of microhomologous sequences that interfere with precise breakpoint identification. Empowered by our method, we provided strong evidence to show that microhomology-mediated end joining is the major eccDNA biogenesis mechanism. Together, our results shed light on eccDNA biogenesis mechanism in mammalian germline cells.


Subject(s)
DNA, Circular , Semen , Male , Animals , Humans , Mice , DNA, Circular/genetics , Chromosomes , Spermatogenesis/genetics , Mammals/genetics
8.
PeerJ ; 11: e15673, 2023.
Article in English | MEDLINE | ID: mdl-37551344

ABSTRACT

Background: Infertility is recognized as a common and worrisome problem of human reproduction worldwide. Based on previous studies, male factors account for about half of all infertility cases. Exposure to environmental toxicants is an important contributor to male infertility. Bisphenol A (BPA) is the most prominent toxic environmental contaminant worldwide affecting the male reproductive system. BPA can impair the function of the Golgi apparatus which is important in spermatogenesis. GGA1 is known as Golgi-localized, gamma adaptin ear-containing, ARF-binding protein 1. Previously, it has been shown that GGA1 is associated with spermatogenesis in Drosophila, however, its function in mammalian spermatogenesis remains unclear. Methods: Gga1 knockout mice were generated using the CRISPR/Cas9 system. Gga1-/- male mice and wild-type littermates received intraperitoneal (i.p.) injections of BPA (40 µg/kg) once daily for 2 weeks. Histological and immunofluorescence staining were performed to analyze the phenotypes of these mice. Results: Male mice lacking Gga1 had normal fertility without any obvious defects in spermatogenesis, sperm count and sperm morphology. Gga1 ablation led to infertility in male mice exposed to BPA, along with a significant reduction in sperm count, sperm motility and the percentage of normal sperm. Histological analysis of the seminiferous epithelium showed that spermatogenesis was severely disorganized, while apoptotic germ cells were significantly increased in the Gga1 null mice exposed to BPA. Our findings suggest that Gga1 protects spermatogenesis against damage induced by environmental pollutants.


Subject(s)
Adaptor Proteins, Vesicular Transport , Infertility, Male , Sperm Motility , Animals , Male , Mice , Infertility, Male/chemically induced , Semen , Spermatogenesis/genetics , Spermatozoa/metabolism , Adaptor Proteins, Vesicular Transport/genetics , Adaptor Proteins, Vesicular Transport/metabolism
9.
Nucleic Acids Res ; 51(14): 7357-7375, 2023 08 11.
Article in English | MEDLINE | ID: mdl-37378420

ABSTRACT

DNA-RNA hybrids play various roles in many physiological progresses, but how this chromatin structure is dynamically regulated during spermatogenesis remains largely unknown. Here, we show that germ cell-specific knockout of Rnaseh1, a specialized enzyme that degrades the RNA within DNA-RNA hybrids, impairs spermatogenesis and causes male infertility. Notably, Rnaseh1 knockout results in incomplete DNA repair and meiotic prophase I arrest. These defects arise from the altered RAD51 and DMC1 recruitment in zygotene spermatocytes. Furthermore, single-molecule experiments show that RNase H1 promotes recombinase recruitment to DNA by degrading RNA within DNA-RNA hybrids and allows nucleoprotein filaments formation. Overall, we uncover a function of RNase H1 in meiotic recombination, during which it processes DNA-RNA hybrids and facilitates recombinase recruitment.


Subject(s)
Meiosis , Ribonuclease H , Humans , Male , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , DNA/genetics , DNA/metabolism , Rad51 Recombinase/genetics , Rad51 Recombinase/metabolism , Recombinases/genetics , Spermatocytes/metabolism , Ribonuclease H/metabolism
10.
Polymers (Basel) ; 15(10)2023 May 09.
Article in English | MEDLINE | ID: mdl-37242809

ABSTRACT

Poly(lactic acid) (PLA) microneedles have been explored extensively, but the current regular fabrication strategy, such as thermoforming, is inefficient and poorly conformable. In addition, PLA needs to be modified as the application of microneedle arrays made of pure PLA is limited because of their easy tip fracture and poor skin adhesion. For this purpose, in this article, we reported a facile and scalable strategy to fabricate the microneedle arrays of the blend of PLA matrix and poly(p-dioxanone) (PPDO) dispersed phase with complementary mechanical properties through microinjection molding technology. The results showed that the PPDO dispersed phase could be in situ fibrillated under the effect of the strong shear stress field generated in micro-injection molding. These in situ fibrillated PPDO dispersed phases could hence induce the formation of the shish-kebab structures in the PLA matrix. Particularly for PLA/PPDO (90/10) blend, there are the densest and most perfect shish-kebab structures formed. The above microscopic structure evolution could be also advantageous to the enhancement in the mechanical properties of microparts of PLA/PPDO blend (tensile microparts and microneedle arrays), e.g., the elongation at break of the blend is almost double that of pure PLA while still maintaining the high stiffness (Young's modulus of 2.7 GPa) and the high strength (tensile strength of 68.3 MPa) in the tensile test, and relative to pure PLA, there is 100% or more increase in the load and displacement of microneedle in the compression test. This could open up new spaces for expanding the industrial application of the fabricated microneedle arrays.

11.
Cell Biosci ; 13(1): 82, 2023 May 11.
Article in English | MEDLINE | ID: mdl-37170281

ABSTRACT

BACKGROUND: Meiotic recombination is initiated by Spo11-dependent programmed DNA double-strand breaks (DSBs) that are preferentially concentrated within genomic regions called hotspots; however, the factor(s) that specify the positions of meiotic DSB hotspots remain unclear. RESULTS: Here, we examined the frequency and distribution of R-loops, a type of functional chromatin structure comprising single-stranded DNA and a DNA:RNA hybrid, during budding yeast meiosis and found that the R-loops were changed dramatically throughout meiosis. We detected the formation of multiple de novo R-loops in the pachytene stage and found that these R-loops were associated with meiotic recombination during yeast meiosis. We show that transcription-replication head-on collisions could promote R-loop formation during meiotic DNA replication, and these R-loops are associated with Spo11. Furthermore, meiotic recombination hotspots can be eliminated by reversing the direction of transcription or replication, and reversing both of these directions can reconstitute the hotspots. CONCLUSIONS: Our study reveals that R-loops may play dual roles in meiotic recombination. In addition to participation in meiotic DSB processing, some meiotic DSB hotspots may be originated from the transcription-replication head-on collisions during meiotic DNA replication.

12.
Polymers (Basel) ; 15(2)2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36679255

ABSTRACT

In this study, a ternary hydrogen (H)-bonded complex intumescent flame retardant (TH-IFR) of melamine (ME) · phosphoric acid (PA)…pentaerythritol (PER) was synthesized through hydrothermal reaction. The combination of the synthesized TH-IFR with 4A molecular sieve as the synergist was used for the first time to improve the flame retardancy of polypropylene (PP). The involved structure, morphology, flame retardancy, flame-retarding mechanism and mechanical properties of the prepared PP composites were systematically investigated. The results show that incorporation of 1 wt% synergist 4A shows the optimum synergistic effect, and the flame retardancy and mechanical properties of the flame-retarded (FR) PP composites are significantly improved. Incorporation of 4A could change the pyrolysis process of the entire system and promote the char-forming chemical interaction, thereby further enhancing the flame retardancy of FR PP composite. The synergistically flame-retarding mechanism of 4A is explained by the significantly improved quality and quantity of the solid-phase char layer, which is formed through generation of SiO2 and Al2O3 substances, and also participation of PP macromolecular chains in the final char layer formation during burning. Furthermore, the improved dispersion and compatibility of TH-IFR in the composite is largely beneficial to the improvement of flame retardancy and mechanical properties.

13.
Autophagy ; 19(2): 644-659, 2023 02.
Article in English | MEDLINE | ID: mdl-35786405

ABSTRACT

Primary ovarian insufficiency (POI), also known as premature ovarian failure, is an ovarian defect in humans characterized by the premature depletion of ovarian follicles before the age of 40. However, the mechanisms underlying POI remain largely unknown. Here, we show that knockout of Epg5 (ectopic P-granules autophagy protein 5 homolog (C. elegans)) results in subfertility in female mice, which exhibit a POI-like phenotype. Single-cell RNA sequencing analysis revealed that the knockout of Epg5 affected the differentiation of granulosa cells (GCs). Further investigation demonstrated that knockout of Epg5 blocks macroautophagic/autophagic flux, resulting in the accumulation of WT1 (WT1 transcription factor), an essential transcription factor for GCs, suggesting WT1 needs to be selectively degraded by the autophagy pathway. We found that the insufficient degradation of WT1 in the antral follicular stage contributes to reduced expression of steroidogenesis-related genes, thereby disrupting GC differentiation. Collectively, our studies show that EPG5 promotes WT1 degradation in GCs, indicating that the dysregulation of Epg5 in GCs can trigger POI pathogenesis.Abbreviations: 3-MA, 3-methyladenine; CHX, cycloheximide; CQ, chloroquine; EPG5, ectopic P-granules autophagy protein 5 homolog (C. elegans); GC, granulosa cell; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; MII, metaphase II; POI, primary ovarian insufficiency; PB1, polar body 1; SQSTM1/p62, sequestosome 1; WT1, WT1 transcription factor.


Subject(s)
Primary Ovarian Insufficiency , Animals , Female , Mice , Autophagy/genetics , Autophagy-Related Protein 5/metabolism , Autophagy-Related Proteins/metabolism , Caenorhabditis elegans/metabolism , Granulosa Cells/metabolism , Primary Ovarian Insufficiency/genetics , Primary Ovarian Insufficiency/metabolism , Primary Ovarian Insufficiency/pathology , Transcription Factors/metabolism , Vesicular Transport Proteins/metabolism , WT1 Proteins/genetics , WT1 Proteins/metabolism
14.
Nutrients ; 14(22)2022 Nov 20.
Article in English | MEDLINE | ID: mdl-36432597

ABSTRACT

Lipid droplet is a dynamic organelle that undergoes periods of biogenesis and degradation under environmental stimuli. The excessive accumulation of lipid droplets is the major characteristic of non-alcoholic fatty liver disease (NAFLD). Moderate aerobic exercise is a powerful intervention protecting against the progress of NAFLD. However, its impact on lipid droplet dynamics remains ambiguous. Mice were fed with 15 weeks of high-fat diet in order to induce NAFLD. Meanwhile, the mice performed 15 weeks of treadmill exercise. Our results showed that 15 weeks of regular moderate treadmill exercise alleviated obesity, insulin intolerance, hyperlipidemia, and hyperglycemia induced by HFD. Importantly, exercise improved histological phenotypes of NAFLD, including hepatic steatosis, inflammation, and locular ballooning, as well as prevented liver fat deposition and liver injury induced by HFD. Exercise reduced hepatic lipid droplet size, and moreover, it reduced PLIN2 protein level and increased PLIN3 protein level in the liver of HFD mice. Interestingly, our results showed that exercise did not significantly affect the gene expressions of DGAT1, DGAT2, or SEIPIN, which were involved in TG synthesis. However, it did reduce the expressions of FITM2, CIDEA, and FSP27, which were major involved in lipid droplet growth and budding, and lipid droplet expansion. In addition, exercise reduced ATGL protein level in HFD mice, and regulated lipophagy-related markers, including increasing ATG5, LAMP1, LAMP2, LAL, and CTSD, decreasing LC3II/I and p62, and promoting colocalization of LAMP1 with LDs. In summary, our data suggested that 15 weeks of moderate treadmill exercise was beneficial for regulating liver lipid droplet dynamics in HFD mice by inhibiting abnormal lipid droplets expansion and enhancing clearance of lipid droplets by lysosomes during the lipophagic process, which might provide highly flexible turnover for lipid mobilization and metabolism. Abbreviations: ß-actin: actin beta; ATG5: autophagy related 5; LAMP2: lysosomal-associated membrane protein 2; LAMP1: lysosomal-associated membrane protein 1; SQSTM1/p62: sequestosome 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ATGL: adipose triglyceride lipase; CSTD: cathepsin D; LAL: lysosomal acid lipase; DGAT1: diacylglycerol-o-acyltransferase 1; DGAT2: diacylglycerol-o-acyltransferase 2; CIDEA: cell death inducing dffa-like effector a; CIDEC/FSP27: cell death inducing dffa-like effector c; FITM2: fat storage-inducing transmembrane protein 2; PLIN2: adipose differentiation related protein; PLN3: tail-interacting protein 47; HSP90: heat shock protein 90; SREBP1c: sterol regulatory element binding protein-1c; chREBP: carbohydrate response element binding protein.


Subject(s)
Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/metabolism , Lipid Droplets/metabolism , Diglycerides , Autophagy , Perilipin-2/genetics , Perilipin-2/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , Diacylglycerol O-Acyltransferase/metabolism
15.
Mol Ther Nucleic Acids ; 30: 451-464, 2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36420210

ABSTRACT

Infertility affects 10%-20% of the population in most countries, with approximately half of those cases resulting from male infertility. Although millions of infertile men are able to have children with the assistance of reproductive technology, individuals with non-obstructive azoospermia (NOA) syndrome are unable to do so because they lack functional sperm. Therefore, some other strategies for infertile NOA men are still urgently needed. Our current study uses an NOA-like mouse model to optimize microinjection and a subsequent electroporation method to test potential treatment strategies. We showed that the spermatogenetic process could be partially rescued in young Stra8-Rnf20 -/- mice with microinjection and subsequent electroporation of Rnf20 plasmids into the testes. All meiotic prophase I stages could be identified, and programmed DNA double-strand break repair factors could successfully be recruited to Stra8-Rnf20 -/- spermatocytes after electroporation. Moreover, by including an autophagy inhibitor in the treatment, electroporation significantly improved the spermatogenetic rescue efficiency of adult Stra8-Rnf20 -/- mice. Most importantly, infertility caused by Rnf20 depletions could be overcome by electroporation coupled with intracytoplasmic sperm injection. Our studies establish a relative safe and efficient testis electroporation system and provide a promising therapeutic strategy for patients with NOA.

16.
Chemosphere ; 307(Pt 1): 135751, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35863420

ABSTRACT

Fluxapyroxad (Flu), one of the succinate dehydrogenase-inhibited (SDHI) fungicides, has been extensively used in crop fungal disease control. Despite its increasing use in modern agriculture and long-term retention in the environment, the potentially toxic effects of Flu in vivo, especially on neurodevelopment, remain under-evaluated. In this study, zebrafish embryos were exposed to Flu at concentrations of 0.5, 0.75, and 1 mg/L for 96 h to evaluate the neurotoxicity of Flu. The results showed that Flu caused concentration-dependent malformations, including shorter body length, smaller head and eyes, and yolk sac edema. After exposure to Flu, larval zebrafish exhibited severe motor aberrations. Flu at a concentration of 1 mg/L significantly decreased dopamine level and notably altered acetylcholinesterase (AChE) activity and acetylcholine (ACh) content. Abnormal central nervous system (CNS) neurogenesis and disordered motor neuron development were observed in Tg (HUC-GFP) and Tg (hb9-GFP) zebrafish in Flu-treated groups. The expression of key genes involved in neurotransmission and neurodevelopment further proved that Flu impaired the zebrafish nervous system. This work contributes to our understanding of the neurotoxic effects and mechanisms induced by Flu in zebrafish and may help us take precautions against the neurotoxicity of Flu.


Subject(s)
Fungicides, Industrial , Neurotoxicity Syndromes , Acetylcholine/metabolism , Acetylcholinesterase/metabolism , Amides , Animals , Central Nervous System , Dopamine/metabolism , Embryo, Nonmammalian , Fungicides, Industrial/metabolism , Larva , Succinate Dehydrogenase , Zebrafish/metabolism
17.
J Cell Biol ; 221(7)2022 07 04.
Article in English | MEDLINE | ID: mdl-35674692

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal pathogen of the ongoing global pandemic of coronavirus disease 2019 (COVID-19). Loss of smell and taste are symptoms of COVID-19, and may be related to cilia dysfunction. Here, we found that the SARS-CoV-2 ORF10 increases the overall E3 ligase activity of the CUL2ZYG11B complex by interacting with ZYG11B. Enhanced CUL2ZYG11B activity by ORF10 causes increased ubiquitination and subsequent proteasome-mediated degradation of an intraflagellar transport (IFT) complex B protein, IFT46, thereby impairing both cilia biogenesis and maintenance. Further, we show that exposure of the respiratory tract of hACE2 mice to SARS-CoV-2 or SARS-CoV-2 ORF10 alone results in cilia-dysfunction-related phenotypes, and the ORF10 expression in primary human nasal epithelial cells (HNECs) also caused a rapid loss of the ciliary layer. Our study demonstrates how SARS-CoV-2 ORF10 hijacks CUL2ZYG11B to eliminate IFT46 and leads to cilia dysfunction, thereby offering a powerful etiopathological explanation for how SARS-CoV-2 causes multiple cilia-dysfunction-related symptoms specific to COVID-19.


Subject(s)
Cilia , SARS-CoV-2 , Ubiquitin-Protein Ligases , Animals , Cells, Cultured , Cilia/metabolism , Cilia/pathology , Cytoskeletal Proteins , Epithelial Cells/metabolism , Epithelial Cells/virology , Humans , Mice , SARS-CoV-2/pathogenicity , Smell , Ubiquitin-Protein Ligases/metabolism
18.
Development ; 149(11)2022 06 01.
Article in English | MEDLINE | ID: mdl-35587122

ABSTRACT

The sperm flagellum is essential for male fertility, and defects in flagellum biogenesis are associated with male infertility. Deficiency of coiled-coil domain-containing (CCDC) 42 (CCDC42) is specifically associated with malformation of mouse sperm flagella. Here, we find that the testis-specific protein CCDC38 interacts with CCDC42, localizing on the manchette and sperm tail during spermiogenesis. Inactivation of CCDC38 in male mice results in a distorted manchette, multiple morphological abnormalities of the flagella of spermatozoa and eventually male sterility. Furthermore, we find that CCDC38 interacts with intraflagellar transport protein 88 (IFT88), as well as outer dense fibrous 2 (ODF2), and the knockout of Ccdc38 reduces transport of ODF2 to the flagellum. Altogether, our results uncover the essential role of CCDC38 in sperm flagellum biogenesis, and suggest that some mutations of these genes might be associated with male infertility in humans.


Subject(s)
Fertility , Infertility, Male , Sperm Tail , Animals , Fertility/genetics , Heat-Shock Proteins/metabolism , Infertility, Male/genetics , Infertility, Male/metabolism , Male , Mice , Mice, Knockout , Sperm Tail/metabolism , Spermatozoa/metabolism , Testis/metabolism
19.
ACS Appl Mater Interfaces ; 14(13): 15346-15359, 2022 Apr 06.
Article in English | MEDLINE | ID: mdl-35324160

ABSTRACT

High-performance flexible piezoelectric polymer-ceramic composites are in high demand for increasing wearable energy-harvesting applications. In this work, a strategy combining solid-state shear milling (S3M) and fused filament fabrication (FFF) 3D-printing technology is proposed for the fabrication of high-performance biomimetic wearable piezoelectric poly(vinylidene fluoride) (PVDF)/tetraphenylphosphonium chloride (TPPC)/barium titanate (BaTiO3) nanocomposite energy harvesters with a biomimetic fish-scale-like metamaterial. The S3M technology could greatly improve the dispersion of BaTiO3 sub-micrometer particles and the interfacial compatibility, resulting in better processability and piezoelectric performance of the nanocomposites. Typically, the FFF 3D printed energy harvester incorporating 30 wt % BaTiO3 showed the highest piezoelectric outputs with an open-circuit voltage of 11.5 V and a short-circuit current of 220 nA. It could hence drive nine green LEDs to work normally. In addition, a 3D-printed biomimetic wearable energy harvester inspired by an environmentally adaptive fish-scale-like metamaterial was further fabricated. The fish-scale-like energy harvester could harvest energy through different deformation motions and successfully recharge a 4.7 µF capacitor by being mounted on a bicycle tire and the tire's rolling. This work not only provides a 3D printing strategy for designing diversified and complex geometric structures but also paves the way for further applications in flexible, wearable, self-powered electromechanical energy harvesters.


Subject(s)
Biomimetics , Wearable Electronic Devices , Animals , Fluorocarbon Polymers , Polyvinyls , Printing, Three-Dimensional
20.
ACS Omega ; 7(5): 4293-4304, 2022 Feb 08.
Article in English | MEDLINE | ID: mdl-35155922

ABSTRACT

The material design could be very critical in the preparation of conductive polymer composites for electromagnetic interference (EMI) shielding applications. In this work, two methods were proposed to prepare PA12 composite powders coated with CNTs, including ball-milling (BM) and ultrasonic dispersion-liquid phase deposition strategies. Then, by applying selective laser sintering printing (SLS) 3D printing, the segregated network structures were successfully constructed. Various characterization techniques were employed to validate the presence of the formed segregated network structure in the SLS 3D printed parts. The BM SLS 3D printed part at a loading of 5.66 wt % CNTs exhibited an optimum electrical conductivity of 3.0 S/m and an electromagnetic interference shielding (EMI SE) of 23.9 dB (2.0 mm thickness), while its electrical percolation threshold was found to be at 0.347 wt %. However, the EMI SE values of homogenous PA12/CNTs composites prepared by the melt compounding-cryogenic pulverization (MP) method and melt compounding-compression molding were only 9.8 and 15.6 dB, respectively. In addition, the incorporation of CNTs decreased the mechanical performance of the PA12/CNTs printed part due to their negative effect on the sintering. However, such a decrease could be inhibited by increasing the laser energy density. The related investigation could offer a solution to the preparation of the conductive polymer composite and the EMI shielded material through SLS 3D printing processing.

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