Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 342
Filtrar
1.
ACS Nano ; 18(20): 12917-12932, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38720520

RESUMO

Inflammatory bowel diseases (IBDs) refer to multifaceted disorders in the intestinal microenvironment and microbiota homeostasis. In view of the broad bioactivity and high compatibility of polyphenols, there is considerable interest in developing a polyphenol-based collaborative platform to remodel the IBD microenvironment and regulate microbiota. Here, we demonstrated the coordination assembly of nanostructured polyphenols to modify probiotics and simultaneously deliver drugs for IBD treatment. Inspired by the distinctive structure of tannic acid (TA), we fabricated nanostructured pBDT-TA by using a self-polymerizable aromatic dithiol (BDT) and TA, which exhibited excellent antioxidant and anti-inflammatory capability in vitro. We thus coated pBDT-TA and sodium alginate (SA) to the surface of Escherichia coli Nissle 1917 layer by layer to construct the collaborative platform EcN@SA-pBDT-TA. The modified probiotics showed improved resistance to oxidative and inflammatory stress, which resulted in superior colon accumulation and retention in IBD model mice. Further, EcN@SA-pBDT-TA could alleviate dextran sulfate sodium (DSS)-induced colitis by controlling the inflammatory response, repairing intestinal barriers, and modulating gut microbiota. Importantly, EcN@SA-pBDT-TA-mediated IBD drug delivery could achieve an improved therapeutic effect in DSS model mice. Given the availability and functionality of polyphenol and prebiotics, we expected that nanostructured polyphenol-modified probiotics provided a solution to develop a collaborative platform for IBD treatment.


Assuntos
Doenças Inflamatórias Intestinais , Nanopartículas , Polifenóis , Probióticos , Taninos , Animais , Probióticos/farmacologia , Probióticos/química , Probióticos/administração & dosagem , Polifenóis/química , Polifenóis/farmacologia , Camundongos , Nanopartículas/química , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/terapia , Taninos/química , Taninos/farmacologia , Camundongos Endogâmicos C57BL , Escherichia coli/efeitos dos fármacos , Sulfato de Dextrana/química , Alginatos/química , Alginatos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Antioxidantes/química , Antioxidantes/farmacologia
2.
Mitochondrial DNA B Resour ; 9(5): 588-591, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716394

RESUMO

Chlorophytum laxum of Asparagaceae is a valuable ornamental plant native to the tropical regions of Asia, Africa, and Australia. The plant also has medicinal properties and is used as source for folk medicine. Despite being commercially important, genetic studies of C. laxum are still limited. To expand the genomic information of this plant species, we sequenced, assembled, and characterized its complete chloroplast genome. The chloroplast genome was 153,678 bp in length, with a large single-copy region (83,225 bp) and a small single-copy region (18,031 bp) separated by a pair of inverted repeat regions (26,211 bp each). A total of 127 genes were predicted, including 81 protein-coding, 38 tRNA, and eight rRNA genes. The overall GC content was 37.3%. Based on current sampling size, phylogenetic analysis using the maximum likelihood based on the complete chloroplast genome sequence revealed that the relationship in Chlorophytum is well resolved; C. laxum was closely related to C. rhizopendulum.

3.
J Oral Implantol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716588

RESUMO

Perforation of the maxillary sinus membrane is a common complication during maxillary sinus elevation. Intraoperative perforation of the maxillary sinus membrane may complicate the procedure and indirectly lead to implant failure. Timely repair of the perforated maxillary sinus membrane can effectively improve the implant survival rate. This case describes a method of repairing a maxillary sinus membrane perforation with a suture-attached collagen membrane and shows stable repair results at a 31-month follow-up.

4.
BMC Genomics ; 25(1): 474, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745148

RESUMO

BACKGROUND: Flowering time has an important effect on regional adaptation and yields for crops. The tyrosine kinase-like (TKL) gene family is widely existed and participates in many biological processes in plants. Furthermore, only few TKLs have been characterized functions in controlling flowering time in wheat. RESULTS: Here, we report that TaCTR1, a tyrosine kinase-like (TKL) gene, regulates flowering time in wheat. Based on identification and evolutionary analysis of TKL_CTR1-DRK-2 subfamily in 15 plants, we proposed an evolutionary model for TaCTR1, suggesting that occurrence of some exon fusion events during evolution. The overexpression of TaCTR1 caused early flowering time in transgenic lines. Transcriptomics analysis enabled identification of mass differential expression genes including plant hormone (ET, ABA, IAA, BR) signaling, flavonoid biosynthesis, phenolamides and antioxidant, and flowering-related genes in TaCTR1 overexpression transgenic lines compared with WT plants. qRT-PCR results showed that the expression levels of ethylene (ET) signal-related genes (ETR, EIN, ERF) and flowering-related genes (FT, PPD1, CO, PRR, PHY) were altered in TaCTR1-overexpressing wheat compared with WT plants. Metabonomics analysis showed that flavonoid contents were altered. CONCLUSIONS: Thus, the results show that TaCTR1 plays a positive role in controlling flowering time by activating various signaling pathways and regulating flowering-related genes, and will provide new insights on the mechanisms of wheat flowering regulation.


Assuntos
Evolução Molecular , Flores , Regulação da Expressão Gênica de Plantas , Família Multigênica , Proteínas de Plantas , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Triticum/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Plantas Geneticamente Modificadas/genética , Reguladores de Crescimento de Plantas/metabolismo , Perfilação da Expressão Gênica , Genoma de Planta
5.
Int J Pediatr Otorhinolaryngol ; 181: 111979, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38739980

RESUMO

BACKGROUND: Maternally inherited hearing loss has been associated with mitochondrial genes, including MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE. Among these genes, MT-RNR1 is known to be a hotspot for pathogenic variants related to aminoglycoside ototoxicity and nonsyndromic hearing loss. However, the frequency and spectrum of variants in these genes, particularly in multi-ethnic hearing loss patients from Southwestern China, are still not fully understood. METHODS: In this study, we enrolled 460 hearing loss patients from various ethnic backgrounds (Han, Yi, Dai, Hani, etc.) in Southwestern China. Next-generation sequencing was used to analyze the mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes. Subsequently, bioinformatical methods were employed to evaluate the identified variants. RESULTS: Among the patients with hearing loss, we identified 70 variants in MT-RNR1 (78.6 %, 55/70), MT-TL1 (4.3 %, 3/70), MT-TS1 (4.3 %, 3/70), MT-TK (7.1 %, 5/70) and MT-TE (5.7 %, 4/70) genes. We found that 15 variants were associated with hearing loss, including m.1555 A > G and m.1095 T > C. Additionally, we discovered three reported mitochondrial variants (m.676 G > A, m.7465 insC, and m.7474 A > G) newly correlated with hearing loss. Notably, certain pathogenic variants, such as m.1555 A > G, displayed non-consistent distributions among the multi-ethnic patients with hearing loss. Furthermore, the number of variants associated with hearing loss was higher in the Sinitic group (n = 181) and Tibeto-Burman group (n = 215) compared to the Kra-Dai group (n = 38) and Hmong-Mien group (n = 26). CONCLUSIONS: This present study revealed the distribution of mitochondrial variants linked to hearing loss across various ethnic groups in Southwestern China. These data suggest a potential correlation between the distribution of mitochondrial variants associated with hearing loss and ethnic genetic backgrounds.

6.
Plant Dis ; 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38764344

RESUMO

Wurfbainia villosa var. villosa is a traditional Chinese herbal medicine under the family Zingiberaceae, and its ripe fruits (called Fructus Amomi) are widely used clinically for the treatment of gastrointestinal disorders (Yang et al. 2023; Chen et al. 2023). In September 2023, plants of W. villosa var. villosa exhibited anthracnose-like symptoms on leaf with a disease incidence of 35% (n = 100 investigated plants) in an approximately 90 m2 field in Guangning, China (N23°42'51.70″, E112°26'35.75″). Light yellowish-green spots (~2 mm diameter) initially appeared on the infected leaves, gradually formed sub-circular or irregular spots, then fused and expanded, resulting in wilting of the leaves. To identify the causal agent, 10 symptomatic leaves were collected and transferred to the laboratory. The symptomatic leaf samples were surface sterilized in 0.5% NaClO for 2 min, and in 70% ethanol for 30 s, then washed three times with sterile water and air-dried on sterile filter paper. The leaf tissues were placed on potato dextrose agar (PDA) medium containing 100 µg mL-1 of ampicillin (Sigma-Aldrich, St. Louis, MO) and incubated for 7 days at 28°C in darkness. Nine isolates with similar colony morphology were isolated from the 10 plated leaves. Three representative isolates (GNAF03, GNAF06, GNAF09 with approximately 3.5 cm in diameter after 3 days of incubation) appeared gray to dark brown with dense aerial hyphae at the front and gray to black colonies on the reverse of the plates. Conidia were cylindrical and measured 21.2 to 29.3 µm long × 7.1 to 9.6 µm wide (n = 50). Appressoria were formed by the tips of germ tubes or hyphae and were brown, ellipsoid, thick-walled, and smooth-margined, measuring 10.2 to 12.3 µm long × 6.4 to 8.2 µm wide (n = 50). Morphologically, the fungal isolates resembled Colletotrichum sp. (Weir et al. 2012). For molecular analysis, genomic DNA was extracted from fresh mycelia of the three isolates, and the primers ACT-512F/ACT-783R, CL1/CL2A, GDF/GDR, and ITS1/ITS4 were used to amplify partial regions of rDNA-ITS, actin (ACT), calmodulin (CAL), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) regions, respectively (Weir et al. 2012). The resulting sequences with more than 99% nucleotide identity to C. gloeosporioides were submitted to GenBank (accession numbers PP552725, PP552726, and OR827444 for ACT; PP552727, PP552728, and OR827443 for CAL; PP552729, PP552730, and OR827445 for GAPDH; PP549996, PP549999, and OR841394 for ITS). A phylogenetic tree was generated by the maximum likelihood method using the concatenated sequences of ACT, CAL, GADPH, and ITS by Polysuite software (Damm et al. 2020). Based on morphological and molecular analysis, the three isolates were characterized as C. gloeosporioides. The pathogenicity of the GNAF09 isolate was assessed on W. villosa var. villosa seedling leaves inoculated by spraying with 40 µL of conidial suspension at 106 conidia mL-1 or wounded with a sterile toothpick then inoculated with mycelial agar plugs (5 mm diameter). Control leaves were inoculated with 40 µL of sterile distilled water or agar plugs without mycelia. The inoculated plants were placed in a humid chamber at 28°C with 80% humidity and a 12 h light-dark photoperiod. Symptoms similar to those seen on naturally infected leaves were observed on all inoculated leaves after 7 days inoculation. Re-isolation was performed from 80% of the inoculated leaves and isolates were confirmed as C. gloeosporioides morphologically, confirming Koch's postulates, and by sequencing the ACT, CAL, GADPH, and ITS regions. The control groups remained asymptomatic. In previous studies, C. gloeosporioides has also caused anthracnose on Chinese medicinal plants, including Baishao (Radix paeoniae alba) (Zhang et al. 2017) and Rubia cordifolia L. (Tang et al. 2020). To our knowledge, this is the first report of C. gloeosporioides causing anthracnose on W. villosa var. villosa in China. The results of our report serve as valuable references for further research on this disease.

7.
Hum Brain Mapp ; 45(7): e26702, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38726998

RESUMO

Imaging studies of subthreshold depression (StD) have reported structural and functional abnormalities in a variety of spatially diverse brain regions. However, there is no consensus among different studies. In the present study, we applied a multimodal meta-analytic approach, the Activation Likelihood Estimation (ALE), to test the hypothesis that StD exhibits spatially convergent structural and functional brain abnormalities compared to healthy controls. A total of 31 articles with 25 experiments were included, collectively representing 1001 subjects with StD. We found consistent differences between StD and healthy controls mainly in the left insula across studies with various neuroimaging methods. Further exploratory analyses found structural atrophy and decreased functional activities in the right pallidum and thalamus in StD, and abnormal spontaneous activity converged to the middle frontal gyrus. Coordinate-based meta-analysis found spatially convergent structural and functional impairments in StD. These findings provide novel insights for understanding the neural underpinnings of subthreshold depression and enlighten the potential targets for its early screening and therapeutic interventions in the future.


Assuntos
Depressão , Humanos , Depressão/diagnóstico por imagem , Depressão/fisiopatologia , Depressão/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/patologia , Imageamento por Ressonância Magnética , Neuroimagem/métodos
8.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167162, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38604490

RESUMO

The molecular mechanism underlying the promotion of fracture healing by mechanical stimuli remains unclear. The present study aimed to investigate the role of zinc finger protein 36 like 2 (ZFP36L2)-histone deacetylase 1 (HDAC1) axis on the osteogenic responses to moderate mechanical stimulation. Appropriate stimulation of fluid shear stress (FSS) was performed on MC3T3-E1 cells transduced with ZFP36L2 and HDAC1 recombinant adenoviruses, aiming to validate the influence of mechanical stress on the expression of ZFP36L2-HDAC1 and the osteogenic differentiation and mineralization. The results showed that moderate FSS stimulation significantly upregulated the expression of ZFP36L2 in MC3T3-E1 cells (p < 0.01). The overexpression of ZFP36L1 markedly enhanced the levels of osteogenic differentiation markers, including bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), Osterix, and collagen type I alpha 1 (COL1A1) (p < 0.01). ZFP36L2 accelerated the degradation of HDAC1 by specifically binding to its 3' UTR region, thereby fulfilling its function at the post-transcriptional regulatory gene level and promoting the osteogenic differentiation and mineralization fate of cells. Mechanical unloading notably diminished/elevated the expression of ZFP36L2/HDAC1, decreased bone mineral density and bone volume fraction, hindered the release of osteogenic-related factors and vascular endothelial growth factor in callus tissue (p < 0.01), and was detrimental to fracture healing. Collectively, proper stress stimulation plays a crucial role in facilitating osteogenesis through the promotion of ZFP36L2 and subsequent degradation of HDAC1. Targeting ZFP36L2-HDAC1 axis may provide promising insights to enhance bone defect healing.


Assuntos
Diferenciação Celular , Histona Desacetilase 1 , Osteogênese , Estresse Mecânico , Animais , Camundongos , Histona Desacetilase 1/metabolismo , Histona Desacetilase 1/genética , Osteogênese/fisiologia , Linhagem Celular , Osso e Ossos/metabolismo , Osteoblastos/metabolismo
9.
Adv Sci (Weinh) ; : e2401952, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647398

RESUMO

The general strategy for n-type organic thermoelectric is to blend n-type conjugated polymer hosts with small molecule dopants. In this work, all-polymer n-type thermoelectric is reported by dissolving a novel n-type conjugated polymer and a polymer dopant, poly(ethyleneimine) (PEI), in alcohol solution, followed by spin-coating to give polymer host/polymer dopant blend film. To this end, an alcohol-soluble n-type conjugated polymer is developed by attaching polar and branched oligo (ethylene glycol) (OEG) side chains to a cyano-substituted poly(thiophene-alt-co-thiazole) main chain. The main chain results in the n-type property and the OEG side chain leads to the solubility in hexafluorineisopropanol (HFIP). In the polymer host/polymer dopant blend film, the Coulombic interaction between the dopant counterions and the negatively charged polymer chains is reduced and the ordered stacking of the polymer host is preserved. As a result, the polymer host/polymer dopant blend exhibits the power factor of 36.9 µW m-1 K-1, which is one time higher than that of the control polymer host/small molecule dopant blend. Moreover, the polymer host/polymer dopant blend shows much better thermal stability than the control polymer host/small molecule dopant blend. This research demonstrates the high performance and excellent stability of all-polymer n-type thermoelectric.

10.
Plants (Basel) ; 13(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38592831

RESUMO

Undaria pinnatifida can effectively deal with organotin pollution through its excellent accumulation and degradation capabilities found under laboratory conditions. However, nothing is known regarding its accumulation, degradation performance, and related impact factors in the wild farming area. In this study, we monitored triphenyltin chloride (TPTCL) contents and degradation products in different algal parts (blades, stipes, sporophylls, and holdfasts) of cultivated U. pinnatifida from December 2018 to May 2019. Our results showed that sporophytes had an accumulation and degradation capacity for TPTCL. The TPTCL contents and degradation products varied with the algal growth stages and algal parts. TPTCL accumulated in the blades at the growth stage and the blades, stipes, sporophylls, and holdfasts at the mature stage. The TPTCL content among algal parts was blades (74.92 ± 2.52 µg kg-1) > holdfasts (62.59 ± 1.42 µg kg-1) > sporophylls (47.24 ± 1.41 µg kg-1) > stipes (35.53 ± 0.55 µg kg-1). The primary degradation product DPTCL accumulated only in the blades at any stage, with a concentration of 69.30 ± 3.89 µg kg-1. The secondary degradation product MPTCL accumulated in the blades at the growth stage and in the blades, stipe, and sporophyll at the mature stage. The MPTCL content among algal parts was blades (52.80 ± 3.48 µg kg-1) > sporophylls (31.08 ± 1.53 µg kg-1) > stipes (20.44 ± 0.85 µg kg-1). The accumulation pattern of TPTCL and its degradation products seems closely related to nutrient allocation in U. pinnatifida. These results provide the basis for applying cultivated U. pinnatifida in the bioremediation of organotin pollution and the food safety evaluation of edible algae.

11.
Plant Dis ; 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616389

RESUMO

Ammopiptanthus mongolicus is the only evergreen broad-leaved shrub in the desert region of Northwest China, which is one of the dominant species in the desert vegetation of the region, playing an important role in maintaining the stability of the local desert ecosystem. A. mongolicus is also very hardy and drought resistant and can survive extreme temperatures (Liu et al. 2013; Yang et al. 2022). The large-scale death of A. mongolicus could cause desertification in the region. Two months after the discovery of Fusarium verticillioides causing blight on A. mongolicus in Etuoke county, Inner Mongolia Autonomous Region in September 2023 (Yang et al. 2024), a large number of A. mongolicus plants with symptoms of blights were found in Lingwu city, Ningxia Hui Autonomous Region, China (106.442368°E, 37.734026°N) in November 2023. The incidence of diseased plants in this field was about 30%. The field symptoms in Lingwu city were similar to those observed in Etuoke county. The diseased leaves initially turned yellow, then wilted and dehisced, eventually resulting in plant death (Figure 1). The roots of the diseased plants were cut diagonally and the central cylinder showed a brown color (Figure 2). In order to investigate whether the death of A. mongolicus was caused by the same pathogen as those identified previously, 30 roots were collected from 10 diseased plants. After rinsing and surface sterilization (70% ethanol for 3 min and 2.5% NaClO for 5 min, rinsed 3 times with sterile distilled water), diseased tissues (10×10 mm) were placed on potato dextrose agar (PDA) (3 pieces per plate) and incubated from 3 to 5 days at 25°C. The strain AmP5 was isolated and used for further study. After 3 days on PDA medium, fungal colonies were white to milky, the undersides of the cultures were yellowish to orange-brown (Figure 3). After 7 days on synthetic nutrient-poor agar (SNA), microconidia were ovoidal or with a rounded apex and truncate base, 10.5 ± 1.5 µm × 1.6 ± 0.2 µm (×400). The macroconidia were slightly curved or arcuate, 40.5 ± 3.5 µm × 5 ± 0.5 µm (×400) (Figure 4) (Sisic et al. 2018). The pathogen was confirmed to be Neocosmospora pisi by multigene phylogenetic analysis of TEF, RPB1 and RPB2 genes using primers EF1/EF2, F5/G2R and 5F2/11AR, respectively (O'Donnell et al. 2022). The sequences of PCR products were deposited in GenBank with accession numbers OR944631 (RPB1), OR988086 (TEF) and OR988087 (RPB2), respectively. The results of pairwise alignment in Fusarioid-ID database (Crous et al. 2021) showed 99.84% similarity and 83.96% overlap of the EF1-α sequence to the corresponding sequence LR583636 of ex-epitype CBS 123669 of Neocosmospora pisi (syn. Fusarium solani f. sp. pisi), 99.72% similarity and 85.66% overlap of the RPB1 sequence to the corresponding sequence MW834242 of ex-epitype CBS 123669 of N. pisi, and 99.47% similarity and 78.26% overlap of RPB2 sequence to the corresponding sequence LR583862 of ex-epitype CBS 123669 of N. pisi. Moreover, the result of polyphasic identification in the Fusarioid-ID database also showed EF1-a, RPB1, and RPB2 sequences had 99.15% similarity to the corresponding sequences of CBS 1233669. The pathogenicity of AmP5 was tested on potted 64 days old seedlings A. mongolicus plants. The roots of 3 seedlings were inoculated with conidial suspension (1×106 /ml), and another 3 used as controls were inoculated with sterile water, by gently peeling off the soil around the roots during inoculation, and pouring the conidial suspension around the roots (10 ml/seedling). All plants were placed in a growth chamber at 18-25℃ (10 h light; 14 h dark). After incubation for 3-5 days, the symptoms similar to those observed in the field (Figure 5), including brown rot of steles (Figure 6), developed on plants inoculated with conidial suspension, whereas no symptoms were observed on the control plants. The same pathogen was reisolated from inoculated roots and confirmed as N. pisi based on morphological and molecular analyses (TEF, RPB1 and RPB2). To our knowledge, this is the first report of blight on A. mongolicus caused by N. pisi in China. This study also indicates that blight on A. mongolicus can be caused by different fungal pathogens. Blight caused by different pathogens may have different in terms of control measures and pathogenic mechanisms, so the study of blight caused by different pathogens is of profound value.

12.
Asian J Androl ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38445955

RESUMO

ABSTRACT: Failure of oocyte activation, including polyspermy and defects in pronuclear (PN) formation, triggers early embryonic developmental arrest. Many studies have shown that phospholipase C zeta 1 ( PLCZ1 ) mutations cause failure of PN formation following intracytoplasmic sperm injection (ICSI); however, whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization (IVF) remains unknown. Whole-exome sequencing (WES) was performed to identify candidate mutations in couples with primary infertility. Sanger sequencing was used to validate the mutations. Multiple PLCZ1 -mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced. Assisted oocyte activation (AOA) after ICSI was performed to overcome the failure of oocyte activation. We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles, including a novel missense mutation c.1154C>T, p.R385Q. PN formation failure was observed during the ICSI cycle. However, injection of multiple PLCZ1 -mutated sperm induced PN formation, suggesting that the Ca 2+ oscillations induced by the sperm exceeded the necessary threshold for PN formation. AOA after ICSI enabled normal fertilization, and all patients achieved successful pregnancies. These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy. Furthermore, this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

14.
Autophagy ; : 1-23, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38513669

RESUMO

PLD1 has been implicated in cytoskeletal reorganization and vesicle trafficking in somatic cells; however, its function remains unclear in oocyte meiosis. Herein, we found PLD1 stably expresses in mouse oocytes meiosis, with direct interaction with spindle, RAB11A+ vesicles and macroautophagic/autophagic vacuoles. The genetic or chemical inhibition of PLD1 disturbed MTOC clustering, spindle assembly and its cortical migration, also decreased PtdIns(4,5)P2, phosphorylated CFL1 (p-CFL1 [Ser3]) and ACTR2, and their local distribution on MTOC, spindle and vesicles. Furthermore in PLD1-suppressed oocytes, vesicle size was significantly reduced while F-actin density was dramatically increased in the cytoplasm, the asymmetric distribution of autophagic vacuoles was broken and the whole autophagic process was substantially enhanced, as illustrated with characteristic changes in autophagosomes, autolysosome formation and levels of ATG5, BECN1, LC3-II, SQSTM1 and UB. Exogenous administration of PtdIns(4,5)P2 or overexpression of CFL1 hyperphosphorylation mutant (CFL1S3E) could significantly improve polar MTOC focusing and spindle structure in PLD1-depleted oocytes, whereas overexpression of ACTR2 could rescue not only MTOC clustering, and spindle assembly but also its asymmetric positioning. Interestingly, autophagy activation induced similar defects in spindle structure and positioning; instead, its inhibition alleviated the alterations in PLD1-depleted oocytes, and this was highly attributed to the restored levels of PtdIns(4,5)P2, ACTR2 and p-CFL1 (Ser3). Together, PLD1 promotes spindle assembly and migration in oocyte meiosis, by maintaining rational levels of ACTR2, PtdIns(4,5)P2 and p-CFL1 (Ser3) in a manner of modulating autophagy flux. This study for the first time introduces a unique perspective on autophagic activity and function in oocyte meiotic development.Abbreviations: ACTR2/ARP2: actin related protein 2; ACTR3/ARP3: actin related protein 3; ATG5: autophagy related 5; Baf-A1: bafilomycin A1; BFA: brefeldin A; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GOLGA2/GM130: golgin A2; GV: germinal vesicle; GVBD: germinal vesicle breakdown; IVM: in vitro maturation; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MI: metaphase of meiosis I; MII: metaphase of meiosis II; MO: morpholino; MTOC: microtubule-organizing center; MTOR: mechanistic target of rapamycin kinase; PB1: first polar body; PLA: proximity ligation assay; PLD1: phospholipase D1; PtdIns(4,5)P2/PIP2: phosphatidylinositol 4,5-bisphosphate; RAB11A: RAB11A, member RAS oncogene family; RPS6KB1/S6K1: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TUBA/α-tubulin: tubulin alpha; TUBG/γ-tubulin: tubulin gamma; UB: ubiquitin; WASL/N-WASP: WASP like actin nucleation promoting factor.

15.
Cancer Manag Res ; 16: 177-183, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525374

RESUMO

Objective: Cystic brain metastases (BMs) are rare in small cell lung cancer (SCLC), and there are limited data on the treatment and prognosis of cystic BMs. Whole brain radiotherapy has been the mainstay for BMs since several years. Immune checkpoint inhibitors in extensive stage small cell lung cancer (ES-SCLC) have been shown to be suitable for patients who experienced better overall survival and progress-free survival and have been approved as the first-line treatment for ES-SCLC. In this report, we described two ES-SCLC patients developed cystic BMs after immunotherapy, after which the patients continued to treat the primary lesion with immune checkpoint inhibitors and the cystic BMs with radiotherapy. Case Description: Two male patients were diagnosed with ES-SCLC at the first admission and were subsequently treated with immunotherapy plus platinum therapy, during which cystic BMs developed. One patient received whole brain radiotherapy and the other received whole brain radiotherapy and Gamma knife radiosurgery (GKRS). Immunotherapy was continued after the brain lesions were controlled. It has been 33 months since the first patient was diagnosed and is now in stable condition. The other patient achieved an overall survival of 30 months. Conclusion: This report describes two patients with cystic brain metastases in ES-SCLC. Whole brain radiotherapy has a good effect on local control of cystic brain metastases in small cell lung cancer and can significantly improve the symptoms of patients. At the same time, we treat immunotherapy as the first-line treatment, and then perform cross-immunotherapy after disease progression, combined with anti-vascular targeting drugs. The patient did not develop severe iRAEs.

16.
Heliyon ; 10(6): e27678, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38533058

RESUMO

Background: Aortic dissection refers to the true and false two-lumen separation of the aortic wall, in which the blood in the aortic lumen enters the aortic mesomembrane from the tear of the aortic intima to separate the mesomembrane and expand along the long axis of the aorta. Purpose: In view of the problems of individual differences, complex complications and many small targets in clinical aortic dissection detection, this paper proposes a convolution neural network MFF-FPN (Multi-scale Feature Fusion based Feature Pyramid Network) for the detection of aortic dissection complications. Methods: The proposed model uses Resnet50 as the backbone for feature extraction and builds a pyramid structure to fuse low-level and high-level feature information. We add an attention mechanism to the backbone network, which can establish inter-dependencies between feature graph channels and enhance the representation quality of CNN. Results: The proposed method has a mean average precision (MAP) of 99.40% in the task of multi object detection for aortic dissection and complications, which is higher than the accuracy of 96.3% on SSD model and 99.05% on YoloV7 model. It greatly improves the accuracy of small target detection such as cysts, making it more suitable for clinical focus detection. Conclusions: The proposed deep learning model achieves feature reuse and focuses on local important information. By adding only a small number of model parameters, we are able to greatly improve the detection accuracy, which is effective in detecting small target lesions commonly found in clinical settings, and also performs well on other medical and natural datasets.

17.
Mol Neurobiol ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453793

RESUMO

Novel CHCHD2 mutations causing C-terminal truncation and interrupted CHCHD2 protein stability in Parkinson's disease (PD) patients were previously found. However, there is limited understanding of the underlying mechanism and impact of subsequent CHCHD2 loss-of-function on PD pathogenesis. The current study further identified the crucial motif (aa125-133) responsible for diminished CHCHD2 expression and the molecular interplay within the C1QBP/CHCHD2/CHCHD10 complex to regulate mitochondrial functions. Specifically, CHCHD2 deficiency led to decreased neural cell viability and mitochondrial structural and functional impairments, paralleling the upregulation of autophagy under cellular stresses. Meanwhile, as a binding partner of CHCHD2, C1QBP was found to regulate the stability of CHCHD2 and CHCHD10 proteins to maintain the integrity of the C1QBP/CHCHD2/CHCHD10 complex. Moreover, C1QBP-silenced neural cells displayed severe cell death phenotype along with mitochondrial damage that initiated a significant mitophagy process. Taken together, the evidence obtained from our in vitro and in vivo studies emphasized the critical role of CHCHD2 in regulating mitochondria functions via coordination among CHCHD2, CHCHD10, and C1QBP, suggesting the potential mechanism by which CHCHD2 function loss takes part in the progression of neurodegenerative diseases.

19.
Front Endocrinol (Lausanne) ; 15: 1361115, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298380
20.
Cell Metab ; 36(3): 598-616.e9, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38401546

RESUMO

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.


Assuntos
COVID-19 , Microbioma Gastrointestinal , Trombose , Humanos , Camundongos , Animais , Integrina alfa2beta1/genética , Integrina alfa2beta1/metabolismo , Colágeno/metabolismo , Plaquetas/metabolismo , COVID-19/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA