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1.
Mar Genomics ; 76: 101123, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39009499

RESUMO

Kushneria phosphatilytica YCWA18T (= CGMCC 1.9149T = NCCB 100306T) was isolated from sediment collected in a saltern on the eastern coast of Yellow Sea in China. The genome was sequenced and comprised of one circular chromosome with the size of 3,624,619 bp and DNA G + C content of 59.13%. A total of 3267 protein-coding genes, 64 tRNA genes and 12 rRNA genes were obtained. Genomic annotation indicated that the genome of K. phosphatilytica YCWA18T had 34 genes involved in phosphorus (P) solubilization/metabolism, e.g., gdh, pqq, phoA, phoD and phoX, which products can convert insoluble P-containing compounds to more bio-available dissolved inorganic P. Comparative genomic analysis of Kushneria strains revealed that gdh, pqq, phoA, phoD and phoX were widely distributed in these strains, indicating the genus Kushneria may play an important role in the P cycle. Additionally, a multitude of salt tolerance genes were detected in the genome of K. phosphatilytica YCWA18T. This study and the genome sequence data will be available for further research and will provide insights into potential biotechnological and agricultural applications of Kushneria strains.


Assuntos
Genoma Bacteriano , Fósforo , Sequenciamento Completo do Genoma , Fósforo/metabolismo , China
2.
PLoS One ; 19(7): e0305573, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38985778

RESUMO

OBJECTIVES: To evaluate the clinical efficacy of dexamethasone (DEX) implant, for the treatment of macular edema (ME) caused by retinal vein occlusion (RVO) and diabetic retinopathy (DR) through a systematic review and meta-analysis. METHODS: The PubMed, Embase and Cochrane Library databases were comprehensively searched from inception to November 21, 2022, for studies evaluating the clinical efficacy of DEX implant for patients with retinal vein occlusion macular edema (RVO-ME) or diabetic macular edema (DME). Randomized controlled trials (RCTs) published in English were considered eligible. The Cochrane Collaboration tool was applied to assess the risk of bias in each study. Effect estimates with 95% confidence intervals (CIs) were pooled using the random effects model. We also conducted subgroup analyses to explore the sources of heterogeneity and the stability of the results. RESULTS: This meta-analysis included 8 RCTs (RVO-ME [n = 2] and DME [n = 6]) assessing a total of 336 eyes. Compared with anti-VEGF therapy, DEX implant treatment achieved superior outcomes in terms of best corrected visual acuity (BCVA) (mean difference [MD] = -3.68 ([95% CI, -6.11 to -1.25], P = 0.003), and no heterogeneity was observed (P = 0.43, I2 = 0%). DEX implant treatment also significantly reduced central macular thickness (CMT) compared with anti-VEGF treatment (MD = -31.32 [95% CI, -57.92 to -4.72], P = 0.02), and there was a high level of heterogeneity between trials (P = 0.04, I2 = 54%). In terms of severe adverse events, DEX implant treatment had a higher risk of elevated intraocular pressure than anti-VEGF therapy (RR = 6.98; 95% CI: 2.16 to 22.50; P = 0.001), and there was no significant difference in cataract progression between the two groups (RR = 1.83; 95% CI: 0.63 to 5.27, P = 0.31). CONCLUSIONS: Compared with anti-VEGF therapy, DEX implant treatment is more effective in improving BCVA and reducing ME. Additionally, DEX implant treatment has a higher risk of elevated intraocular pressure. Due to the small number of studies and the short follow-up period, the results should be interpreted with caution. The long-term effects of the two treatments need to be further determined. TRIAL REGISTRATION: Prospero Registration Number CRD42021243185.


Assuntos
Dexametasona , Retinopatia Diabética , Implantes de Medicamento , Edema Macular , Fator A de Crescimento do Endotélio Vascular , Edema Macular/tratamento farmacológico , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Humanos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Retinopatia Diabética/tratamento farmacológico , Acuidade Visual/efeitos dos fármacos , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/complicações , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem
3.
Bioinformatics ; 40(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38963312

RESUMO

MOTIVATION: Gene regulatory networks (GRNs) are vital tools for delineating regulatory relationships between transcription factors and their target genes. The boom in computational biology and various biotechnologies has made inferring GRNs from multi-omics data a hot topic. However, when networks are constructed from gene expression data, they often suffer from false-positive problem due to the transitive effects of correlation. The presence of spurious noise edges obscures the real gene interactions, which makes downstream analyses, such as detecting gene function modules and predicting disease-related genes, difficult and inefficient. Therefore, there is an urgent and compelling need to develop network denoising methods to improve the accuracy of GRN inference. RESULTS: In this study, we proposed a novel network denoising method named REverse Network Diffusion On Random walks (RENDOR). RENDOR is designed to enhance the accuracy of GRNs afflicted by indirect effects. RENDOR takes noisy networks as input, models higher-order indirect interactions between genes by transitive closure, eliminates false-positive effects using the inverse network diffusion method, and produces refined networks as output. We conducted a comparative assessment of GRN inference accuracy before and after denoising on simulated networks and real GRNs. Our results emphasized that the network derived from RENDOR more accurately and effectively captures gene interactions. This study demonstrates the significance of removing network indirect noise and highlights the effectiveness of the proposed method in enhancing the signal-to-noise ratio of noisy networks. AVAILABILITY AND IMPLEMENTATION: The R package RENDOR is provided at https://github.com/Wu-Lab/RENDOR and other source code and data are available at https://github.com/Wu-Lab/RENDOR-reproduce.


Assuntos
Algoritmos , Biologia Computacional , Redes Reguladoras de Genes , Biologia Computacional/métodos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
4.
Environ Pollut ; : 124565, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033842

RESUMO

Antibiotics and triazole fungicides coexist in varying concentrations in natural aquatic environments, resulting in complex mixtures. These mixtures can potentially affect aquatic ecosystems. Accurately distinguishing synergistic and antagonistic mixtures and predicting mixture toxicity are crucial for effective mixture risk assessment. We tested the toxicities of 75 binary mixtures of antibiotics and fungicides against Auxenochlorella pyrenoidosa. Both regression and classification models for these mixtures were developed using machine learning models: random forest (RF), k-nearest neighbors (KNN), and kernel k-nearest neighbors (KKNN). The KKNN model emerged as the best regression model with high values of determination coefficient (R2 = 0.977), explained variance in prediction leave-one-out (Q2LOO = 0.894), and explained variance in external prediction (Q2F1 = 0.929, Q2F2 = 0.929, and Q2F3 = 0.923). The RF model, the leading classifier, exhibited high accuracy (accuracy = 1 for the training set and 0.905 for the test set) in distinguishing the synergistic and antagonistic mixtures. These results provide crucial value for the risk assessment of mixtures.

5.
Langmuir ; 40(29): 14900-14907, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38982885

RESUMO

The transfer of chirality from molecules to synthesized nanomaterials has recently attracted significant attention. Although most studies have focused on graphene and plasmonic metal nanostructures, layered transition metal dichalcogenides (TMDs), particularly MoS2, have recently garnered considerable attention due to their semiconducting and electrocatalytic characteristics. Herein, we report a new approach for the synthesis of chiral molybdenum sulfide nanomaterials based on a bottom-up synthesis method in the presence of chiral cysteine enantiomers. In the synthesis process, molybdenum trioxide and sodium hydrosulfide serve as molybdenum and sulfur sources, respectively. In addition, ascorbic acid acts as a reducing agent, resulting in the formation of zero-dimensional MoS2 nanodots. Moreover, the addition of cysteine enantiomers to the growth solutions contributes to the chirality evolution of the MoS2 nanostructures. The chirality is attributed to the cysteine enantiomer-induced preferential folding of the MoS2 planes. The growth mechanism and chiral structure of the nanomaterials are confirmed through a series of characterization techniques. This work combines chirality with the bottom-up synthesis of MoS2 nanodots, thereby expanding the synthetic methods for chiral nanomaterials. This simple synthesis approach provides new insights for the construction of other chiral TMD nanomaterials with emerging structures and properties. More significantly, the as-formed MoS2 nanodots exhibited highly defect-rich structures and chiroptical performance, thereby inspiring a high potential for emerging optical and electronic applications.

6.
Nat Nanotechnol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009756

RESUMO

The movement of ions along the pressure-driven water flow in narrow channels, known as downstream ionic transport, has been observed since 1859 to induce a streaming potential and has enabled the creation of various hydrovoltaic devices. In contrast, here we demonstrate that proton movement opposing the water flow in two-dimensional nanochannels of MXene/poly(vinyl alcohol) films, termed upstream proton diffusion, can also generate electricity. The infiltrated water into the channel causes the dissociation of protons from functional groups on the channel surface, resulting in a high proton concentration inside the channel that drives the upstream proton diffusion. Combined with the particularly sluggish water diffusion in the channels, a small water droplet of 5 µl can generate a voltage of ~400 mV for over 330 min. Benefiting from the ultrathin and flexible nature of the film, a wearable device is built for collecting energy from human skin sweat.

7.
Reprod Toxicol ; : 108671, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39038764

RESUMO

Maternal prenatal hypoxia is an important contributor to intrauterine growth restriction (IUGR), which impedes fetal lung maturation and leads to the development of chronic lung diseases. Although evidence suggests the involvement of pyroptosis in IUGR, the molecular mechanism of pyroptosis is still unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been found to potentially interact with gasdermin D (GSDMD), the key protein responsible for pyroptosis, indicating its crucial role in inhibiting pyroptosis. Therefore, we hypothesized that Nrf2 deficiency is a key molecular responsible for lung pyroptosis in maternal hypoxia-induced IUGR offspring mice. Pregnant WT and Nrf2-/- mice were exposed to hypoxia (10.5% O2) to mimic IUGR model. We assessed body weight, lung histopathology, pulmonary angiogenesis, oxidative stress levels, as well as mRNA and protein expressions related to inflammation in the 2-week-old offspring. Additionally, we conducted a dual-luciferase reporter assay to confirm the targeting relationship between Nrf2 and GSDMD. Our findings revealed that offspring with maternal hypoxia-induced IUGR exhibited reduced birth weight, catch-up growth delay, and pulmonary dysplasia. Furthermore, we observed impaired nuclear translocation of Nrf2 and increased GSDMD-mediated pyroptosis in these offspring with IUGR. Moreover, the dual-luciferase reporter assay demonstrated that Nrf2 could directly inhibit GSDMD transcription; deficiency of Nrf2 exacerbated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR. Collectively, our findings suggest that Nrf2 deficiency induces GSDMD-mediated pyroptosis and pulmonary dysplasia in offspring with maternal hypoxia-induced IUGR; thus highlighting the potential therapeutic approach of targeting Nrf2 for treating prenatal hypoxia-induced pulmonary dysplasia in offspring.

8.
Small ; : e2400587, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837673

RESUMO

Precise integration of diverse therapeutic approaches into nanomaterials is the key to the development of multimodal synergistic cancer therapy. In this work, tadpole-like carbon nanotubes with Fe nanoparticle encapsulated at the head and Zn single-atom anchored on the body (Fe@CNT-Zn) is precisely designed and facilely prepared via one-pot carbonization. In vitro studies revealed the integration of chemotherapy (CT), chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT) in Fe@CNT-Zn as well as the near-infrared light (NIR)-responsive cascade therapeutic efficacy. Furthermore, in vivo studies demonstrated the NIR-triggered cascade-amplifying synergistic cancer therapy in a B16 tumor-bearing mouse model. The results not only showcased the Fe@CNT-Zn as a potential tetramodal therapeutic platform, but also demonstrated a proof-of-concept on metal-organic framework-based "one stone for multiple birds" strategy for in situ functionalization of carbon materials.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38934277

RESUMO

AIM: The purpose of this study was to analyze the relationship between serum indicators and high-throughput drug screening (HDS) results, aiming to achieve specific therapy for hepatocellular carcinoma (HCC). METHODS: This study recruited patients with HCC who underwent surgical resection at the Hepatobiliary Surgery Center of the First Affiliated Hospital of Chongqing Medical University from December 2019 to December 2021. HCC tissues were obtained from patients during surgery and subjected to in vitro cell culture, and then HDS testing was performed on the cultured tissue samples. We used Spearman's correlation analysis to examine the relationships between drug sensitivity results for anti-hepatocellular carcinoma drugs, other antitumor drugs, and serological indicators, the Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammatory Index (SII), Systemic Inflammatory Response Index (SIRI), Prognostic Nutritional Index (PNI), and Lymphocyte Monocyte Ratio (LMR). A significant correlation was considered when P<0.05 and |r|>0.40. Furthermore, linear regression analysis was conducted to elucidate the relationship between serological indicators and drug susceptibility, with significant results indicated by P<0.05 and R²≥0.50. RESULTS: In this study, 82 patients with HCC who had undergone hepatectomy and completed in vitro cell culture and HDS testing were evaluated. Using Spearman's correlation with a significance threshold of P<0.05 and |r|>0.40, we identified significant associations between serological indicators and specific drug regimens: NLR correlated with 5-Fluorouracil, 5- Fluorouracil+Calcium folinate (FOLFOX4), and Capecitabine + Cisplatin (XP); PLR with FOLFOX4; SII with XP, FOLFOX4, Doxorubicin + Oxaliplatin (ADM+L-OHP); and SIRI with XP and FOLFOX4. No correlations were found between PNI or LMR and any drug inhibition rates. A comprehensive evaluation using linear regression analysis-which included variables such as sex, age, hepatitis B virus and liver cirrhosis status, size and number of lesions, alphafetoprotein, total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, and prothrombin time, alongside NLR, PLR, SII, and SIRI was conducted in relation to drug regimens. This analysis revealed that NLR, SII, and SIRI are significant predictors of FOLFOX4 inhibition rate, while NLR predicts the inhibition rate of XP effectively. However, no significant links were established between molecular targeted drugs, other antitumor drugs, and serological indicators. CONCLUSIONS: NLR, SII, and SIRI were correlated with FOLFOX4, and the higher the values of NLR, SII, and SIRI, the higher the in vitro inhibition of FOLFOX. Also, NLR was correlated with XP, and the higher the value of NLR, the higher the in vitro inhibition of XP.

10.
Int J Biol Macromol ; 274(Pt 1): 133209, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906348

RESUMO

This study synthesized a robust, magnetically responsive hydrogel from Sophora flavescens-modified cellulose and chitosan, employing Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA and DTG), and scanning electron microscopy (SEM) to confirm the preservation of cellulose's intrinsic properties and the hydrogel's remarkable elasticity, toughness, and porosity. These hydrogels integrate cellulose's structural backbone with functional moieties from chitosan, enhancing adsorption capabilities for Cu2+ ions and Congo red (CR) dye. Kinetic and thermodynamic analyses reveal that adsorption is spontaneous and endothermic, following a pseudo-second-order model and the Freundlich isotherm. Notably, Cu2+ adsorption capacity increases with pH, while CR adsorption initially decreases before rising, demonstrating the hydrogels' potential as effective, sustainable adsorbents for removing pollutants from water.

11.
Cancer Lett ; 597: 217008, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38849012

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and it lacks specific therapeutic targets and effective treatment protocols. By analyzing a proteomic TNBC dataset, we found significant upregulation of sideroflexin 1 (SFXN1) in tumor tissues. However, the precise function of SFXN1 in TNBC remains unclear. Immunoblotting was performed to determine SFXN1 expression levels. Label-free quantitative proteomics and liquid chromatography-tandem mass spectrometry were used to identify the downstream targets of SFXN1. Mechanistic studies of SFXN1 and cellular inhibitor of PP2A (CIP2A) were performed using immunoblotting, immunofluorescence staining, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Functional experiments were used to investigate the role of SFXN1 in TNBC cells. SFXN1 was significantly overexpressed in TNBC tumor tissues and was associated with unfavorable outcomes in patients with TNBC. Functional experiments demonstrated that SFXN1 promoted TNBC growth and metastasis in vitro and in vivo. Mechanistic studies revealed that SFXN1 promoted TNBC progression by inhibiting the autophagy receptor TOLLIP (toll interacting protein)-mediated autophagic degradation of CIP2A. The pro-tumorigenic effect of SFXN1 overexpression was partially prevented by lapatinib-mediated inhibition of the CIP2A/PP2A/p-AKT pathway. These findings may provide a new targeted therapy for patients with TNBC.

12.
Heliyon ; 10(11): e31878, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38882332

RESUMO

The molecular pathology of lung injury in patients with Corona Virus Disease 2019 (COVID-19) remain unclear. In this study, we performed a proteomic study of lung tissues from seven patients with COVID-19, and eight without. Lung parenchymal tissues with COVID-19 were obtained from autopsy samples, while control samples were obtained from paracancerous tissues. Proteins were extracted using phenol extraction. A tandem mass tag-based quantitative proteomic approach combined with bioinformatic analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues. A total of 6,602, and 6,549 proteins were identified in replicates 1 and 2, respectively. Of these, 307, and 278, respectively, were identified as differentially expressed proteins (DEPs). In total, 216 DEPs were identified in this study. These proteins were enriched in 189 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The downregulated proteins are mainly involved in focal adhesion (n = 5), and the PI3K-Akt signaling pathway (n = 4). The upregulated proteins were related to neutrophil extracellular trap (NET) formation (n = 16), and the phagosome pathway (n = 11). The upregulated proteins in these two pathways interact with one another. Further immunohistochemistry verified NET enrichment in the tissues with COVID-19 compared to the controls. Our results systematically outlined the proteomic profiles of the lung's response to SARS-CoV-2 infection and indicated that NET formation was hyper-activated. These results will hopefully provide new evidence for understanding the mechanism behind fatal COVID-19.

13.
Am J Transl Res ; 16(5): 1550-1567, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883343

RESUMO

OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.

14.
Front Neurol ; 15: 1353248, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872815

RESUMO

Introduction: The pattern of extraocular muscle involvement in ocular myasthenia gravis varies across different reports, diverging from our own observations. Thus, we employed two novel tools to discern this pattern. Methods: A retrospective analysis was conducted to collect and organize clinical data from 43 patients diagnosed with ocular myasthenia gravis. Each patient underwent both the computerized diplopia test and the Ocular Motor Nerve Palsy Scale assessment to evaluate the involvement of extraocular muscles. Results: Among the patients, there were 30 male and 13 female individuals, with a total of 113 affected extraocular muscles identified. Among all the affected extraocular muscles, the involvement of the levator palpebrae superioris muscle accounted for 35.40%, medial rectus muscle 7.7%, lateral rectus muscle 16.81%, superior rectus muscle 13.27%, inferior rectus muscle 12.39%, superior oblique muscle 1.77%, and inferior oblique muscle 2.65% of the total affected extraocular muscles. The positivity rates of the Neostigmine test were 89.19%, AChR antibody detection was 59.38%, and repetitive nerve stimulation was 34.38%. The AChR antibody positive rate among patients with only diplopia was 100%; among those with only ptosis, it was 80%; and among those with both diplopia and ptosis, it was 86.67%. Conclusion: The involvement of the extraocular muscles is not uniform. The levator palpebrae superioris exhibits the highest incidence rate, followed by the four rectus muscles and two oblique muscles. The inferior oblique involvement typically occurs when four or more EOMs are affected. Moreover, the levator palpebrae superioris and medial rectus show a higher tendency for bilateral involvement compared with other extraocular muscles.

15.
Mol Neurobiol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865078

RESUMO

Chronic inflammatory pain caused by neuronal hyperactivity is a common and refractory disease. Kv3.1, a member of the Kv3 family of voltage-dependent K+ channels, is a major determinant of the ability of neurons to generate high-frequency action potentials. However, little is known about its role in chronic inflammatory pain. Here, we show that although Kv3.1 mRNA expression was unchanged, Kv3.1 protein expression was decreased in the dorsal spinal horn of mice after plantar injection of complete Freund's adjuvant (CFA), a mouse model of inflammatory pain. Upregulating Kv3.1 expression alleviated CFA-induced mechanical allodynia and heat hyperalgesia, whereas downregulating Kv3.1 induced nociception-like behaviors. Additionally, we found that ubiquitin protein ligase E3 component n-recognin 5 (UBR5), a key factor in the initiation of chronic pain, binds directly to Kv3.1 to drive its ubiquitin degradation. Intrathecal injection of the peptide TP-CH-401, a Kv3.1 ubiquitination motif sequence, rescued the decrease in Kv3.1 expression and Kv currents through competitive binding to UBR5, and consequently attenuated mechanical and thermal hypersensitivity. These findings demonstrate a previously unrecognized pathway of Kv3.1 abrogation by UBR5 and indicate that Kv3.1 is critically involved in the regulation of nociceptive behavior. Kv3.1 is thus a promising new target for treating inflammatory pain.

16.
Se Pu ; 42(6): 572-580, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38845518

RESUMO

Perfluorooctanoic acid (PFOA) is a persistent contaminant with detrimental effects on the natural environment. This persistence leads to potential enrichment and osmotic transfer, which can affect normal circulation in the environment. PFOA poses significant threats to both the natural environment and human health. Therefore, the development of cost-effective, highly efficient, and environment-friendly PFOA adsorbents is a crucial endeavor. This paper presents the catalyst-free one-pot synthesis of fluorinated nitrogen-rich porous organic polymers (POP-3F) via a Schiff-base condensation reaction. The reaction between the nitrogen-rich compound 1,4-bis(2,4-diamino-1,3,5-triazine)benzene and p-trifluoromethylbenzaldehyde yielded POP-3F. The introduction of fluorine atoms into the nitrogen-rich porous organic polymer enhanced its hydrophobicity, thereby facilitating favorable fluoro-fluorine interactions with PFOA and, thus, improving the efficacy of the adsorbent. Scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), solid-state nuclear magnetic resonance (ssNMR) spectroscopy, X-ray photoelectron spectroscopy (XPS), nitrogen adsorption-desorption analysis, and thermogravimetric analysis (TGA) were used to confirm the successful synthesis and characterization of POP-3F. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was conducted in negative electrospray ionization (ESI) mode coupled with multi-reaction monitoring mode (MRM). The instrument was equipped with an Atlantis T3 column (100 mm×2.1 mm, 3 µm), and analysis was conducted using an external standard method. The influences of various factors on PFOA adsorption by POP-3F, including pH, salt concentration, and humic acid presence, were investigated. The highest PFOA removal rate (98.6%) was achieved at a pH of 2, indicating the applicability of POP-3F for the effective removal of PFOA from acidic industrial wastewater. The removal rate of PFOA was unaffected by increases in NaCl concentration. This phenomenon can be attributed to electrostatic interactions between the protonated secondary amines in POP-3F and deprotonated PFOA. Upon the addition of NaCl, a double electric layer is formed on the POP-3F surface, with Cl- ions in the outer layer and Na+ ions in the inner layer, which weakened these interactions. Humic acid is competitively adsorbed with PFOA. However, POP-3F demonstrated good removal rates even in the presence of high humic acid concentrations in water. Adsorption isotherm and kinetics experiments were conducted at the optimal pH to explore the relevant adsorption mechanism. The results showed a rapid initial adsorption rate, with 95.4% PFOA removal within 5 min. Optimal adsorption equilibrium was achieved within 6 h, and the removal rate decreased by only 0.3% after 24 h. This finding indicates that POP-3F exhibits sustained efficacy for PFOA removal. Langmuir fitting analysis revealed a theoretical maximum adsorption capacity of 191 mg/g for POP-3F; this value surpasses those of activated carbon materials and most other adsorbents, highlighting the superior PFOA-adsorption performance of POP-3F. Additionally, matrix effects minimally affected the removal of PFOA by POP-3F, with only a slight reduction (0.1%) observed in simulated natural water. The recyclability of POP-3F was assessed over five adsorption-desorption cycles. The removal efficenecy exhibited a minor decrease of only 0.67% after five cycles. These results demonstrate the recyclability of the proposed adsorbent, which translates into cost reduction through reusability. This characteristic renders POP-3F a promising candidate for the economical and efficient removal of PFOA from wastewater in practical applications.

17.
NPJ Digit Med ; 7(1): 169, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926552

RESUMO

Gait impairments are among the most common and disabling symptoms of Parkinson's disease and worsen as the disease progresses. Early detection and diagnosis of subtype-specific gait deficits, as well as progression monitoring, can help to implement effective and preventive personalized treatment for PD patients. Yet, the gait features have not been fully studied in PD and its motor subtypes. To characterize comprehensive and objective gait alterations and to identify the potential gait biomarkers for early diagnosis, subtype differentiation, and disease severity monitoring. We analyzed gait parameters related to upper/lower limbs, trunk and lumbar, and postural transitions from 24 tremor-dominant (TD) and 20 postural instability gait difficulty (PIGD) dominant PD patients who were in early stage and 39 matched healthy controls (HC) during the Timed Up and Go test using wearable sensors. Results show: (1) Both TD and PIGD groups showed restricted backswing range in bilateral lower extremities and more affected side (MAS) arm, reduced trunk and lumbar rotation range in the coronal plane, and low turning efficiency. The receiver operating characteristic (ROC) analysis revealed these objective gait features had high discriminative value in distinguishing both PD subtypes from the HC with the area under the curve (AUC) values of 0.7~0.9 (p < 0.01). (2) Subtle but measurable gait differences existed between TD and PIGD patients before the onset of clinically apparent gait impairment. (3) Specific gait parameters were significantly associated with disease severity in TD and PIGD subtypes. Objective gait biomarkers based on wearable sensors may facilitate timely and personalized gait treatments in PD subtypes through early diagnosis, subtype differentiation, and disease severity monitoring.

18.
Genome Biol ; 25(1): 148, 2024 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845023

RESUMO

BACKGROUND: Sheep and goats have undergone domestication and improvement to produce similar phenotypes, which have been greatly impacted by structural variants (SVs). Here, we report a high-quality chromosome-level reference genome of Asiatic mouflon, and implement a comprehensive analysis of SVs in 897 genomes of worldwide wild and domestic populations of sheep and goats to reveal genetic signatures underlying convergent evolution. RESULTS: We characterize the SV landscapes in terms of genetic diversity, chromosomal distribution and their links with genes, QTLs and transposable elements, and examine their impacts on regulatory elements. We identify several novel SVs and annotate corresponding genes (e.g., BMPR1B, BMPR2, RALYL, COL21A1, and LRP1B) associated with important production traits such as fertility, meat and milk production, and wool/hair fineness. We detect signatures of selection involving the parallel evolution of orthologous SV-associated genes during domestication, local environmental adaptation, and improvement. In particular, we find that fecundity traits experienced convergent selection targeting the gene BMPR1B, with the DEL00067921 deletion explaining ~10.4% of the phenotypic variation observed in goats. CONCLUSIONS: Our results provide new insights into the convergent evolution of SVs and serve as a rich resource for the future improvement of sheep, goats, and related livestock.


Assuntos
Cabras , Animais , Cabras/genética , Ovinos/genética , Evolução Molecular , Variação Estrutural do Genoma , Locos de Características Quantitativas , Genoma , Variação Genética , Domesticação , Fenótipo , Seleção Genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética
19.
MAGMA ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904745

RESUMO

RATIONALE AND OBJECTIVES: Defacing research MRI brain scans is often a mandatory step. With current defacing software, there are issues with Windows compatibility and researcher doubt regarding the adequacy of preservation of brain voxels in non-T1w scans. To address this, we developed PyFaceWipe, a multiplatform software for multiple MRI contrasts, which was evaluated based on its anonymisation ability and effect on downstream processing. MATERIALS AND METHODS: Multiple MRI brain scan contrasts from the OASIS-3 dataset were defaced with PyFaceWipe and PyDeface and manually assessed for brain voxel preservation, remnant facial features and effect on automated face detection. Original and PyFaceWipe-defaced data from locally acquired T1w structural scans underwent volumetry with FastSurfer and brain atlas generation with ANTS. RESULTS: 214 MRI scans of several contrasts from OASIS-3 were successfully processed with both PyFaceWipe and PyDeface. PyFaceWipe maintained complete brain voxel preservation in all tested contrasts except ASL (45%) and DWI (90%), and PyDeface in all tested contrasts except ASL (95%), BOLD (25%), DWI (40%) and T2* (25%). Manual review of PyFaceWipe showed no failures of facial feature removal. Pinna removal was less successful (6% of T1 scans showed residual complete pinna). PyDeface achieved 5.1% failure rate. Automated detection found no faces in PyFaceWipe-defaced scans, 19 faces in PyDeface scans compared with 78 from the 224 original scans. Brain atlas generation showed no significant difference between atlases created from original and defaced data in both young adulthood and late elderly cohorts. Structural volumetry dice scores were ≥ 0.98 for all structures except for grey matter which had 0.93. PyFaceWipe output was identical across the tested operating systems. CONCLUSION: PyFaceWipe is a promising multiplatform defacing tool, demonstrating excellent brain voxel preservation and competitive defacing in multiple MRI contrasts, performing favourably against PyDeface. ASL, BOLD, DWI and T2* scans did not produce recognisable 3D renders and hence should not require defacing. Structural volumetry dice scores (≥ 0.98) were higher than previously published FreeSurfer results, except for grey matter which were comparable. The effect is measurable and care should be exercised during studies. ANTS atlas creation showed no significant effect from PyFaceWipe defacing.

20.
Cancer Immunol Immunother ; 73(8): 143, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832955

RESUMO

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.


Assuntos
Linfócitos do Interstício Tumoral , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Microambiente Tumoral
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