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1.
Biomed Environ Sci ; 37(3): 266-277, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582991

RESUMO

Objective: The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area, namely, Qunlu Practice Base, Peach Blossom Garden, and Huangtong Animal Husbandry, and whether vectors carry any bacterial pathogens that may cause diseases to humans, to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods: Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit (OPU) analysis, we characterized the species-level microbial community structure of two important vector species, biting midges and ticks, including 33 arthropod samples comprising 3,885 individuals, collected around Poyang Lake. Results: A total of 662 OPUs were classified in biting midges, including 195 known species and 373 potentially new species, and 618 OPUs were classified in ticks, including 217 known species and 326 potentially new species. Surprisingly, OPUs with potentially pathogenicity were detected in both arthropod vectors, with 66 known species of biting midges reported to carry potential pathogens, including Asaia lannensis and Rickettsia bellii, compared to 50 in ticks, such as Acinetobacter lwoffii and Staphylococcus sciuri. We found that Proteobacteria was the most dominant group in both midges and ticks. Furthermore, the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria. Pantoea sp7 was predominant in biting midges, while Coxiella sp1 was enriched in ticks. Meanwhile, Coxiella spp., which may be essential for the survival of Haemaphysalis longicornis Neumann, were detected in all tick samples. The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion: Biting midges and ticks carry large numbers of known and potentially novel bacteria, and carry a wide range of potentially pathogenic bacteria, which may pose a risk of infection to humans and animals. The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.


Assuntos
Ceratopogonidae , Microbiota , Carrapatos , Animais , Humanos , Carrapatos/microbiologia , Ceratopogonidae/genética , Filogenia , RNA Ribossômico 16S/genética , Estudos Prospectivos , Coxiella/genética
2.
Angew Chem Int Ed Engl ; : e202405514, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584585

RESUMO

Pyroelectric materials hold significant potential for energy harvesting, sensing, and imaging applications. However, achieving high-performance pyroelectricity across a wide temperature range near room temperature remains a significant challenge. Herein, we demonstrate a single crystal of Fe(II) spin-crossover compound shows remarkable pyroelectric properties accompanied by a thermally controlled spin transition. In this material, the uniaxial alignment of polar molecules results in a polarization of the lattice. As the molecular geometry is modulated during a gradual spin transition, the polar axis experiences a colossal thermal expansion with a coefficient of 796 × 10-6 K-1. Consequently, the material's polarization undergoes significant modulation as a secondary pyroelectric effect. The considerable shift in polarization (pyroelectric coefficient, p = 3.7~22 nC K-1cm-2), coupled with a low dielectric constant (ε' = 4.4~5.4) over a remarkably wide temperature range of 298 to 400 K, suggests this material is a high-performance pyroelectric. The demonstration of pyroelectricity combined with magnetic switching in this study will inspire further investigations in the field of molecular electronics and magnetism.

3.
Nat Commun ; 15(1): 2896, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575592

RESUMO

The synthesis of dynamic chiral lanthanide complex emitters has always been difficult. Herein, we report three pairs of dynamic chiral EuIII complex emitters (R/S-Eu-R-1, R = Et/Me; R/S-Eu-Et-2) with aggregation-induced emission. In the molecular state, these EuIII complexes have almost no obvious emission, while in the aggregate state, they greatly enhance the EuIII emission through restriction of intramolecular rotation and restriction of intramolecular vibration. The asymmetry factor and the circularly polarized luminescence brightness are as high as 0.64 (5D0 → 7F1) and 2429 M-1cm-1 of R-Eu-Et-1, achieving a rare double improvement. R-Eu-Et-1/2 exhibit excellent sensing properties for low concentrations of CuII ions, and their detection limits are as low as 2.55 and 4.44 nM, respectively. Dynamic EuIII complexes are constructed by using chiral ligands with rotor structures or vibration units, an approach that opens a door for the construction of dynamic chiral luminescent materials.

4.
Apoptosis ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581529

RESUMO

Since the discovery of copper induces cell death(cuprotosis) in 2022, it has been one of the biggest research hotspots. cuprotosis related genes (CRGs) has been demonstrated to be a potential therapeutic target for cancer, however, the molecular mechanism of CRGs in coronavirus disease 2019 (COVID-19) infected in DLBCL patients has not been reported yet. Therefore, our research objective is first to elucidate the mechanism and role of CRGs in COVID-19. Secondly, we conducted univariate and multivariate analysis and machine learning to screen for CRGs with common expression differences in COVID-19 and DLBCL. Finally, the functional role and immune mechanism of genes in DLBCL were confirmed through cell experiments and immune analysis. The research results show that CRGs play an important role in the occurrence and development of COVID-19. Univariate analysis and machine learning confirm that dihydrolipoamide dehydrogenase (DLD) is the common key gene of COVID-19 and DLBCL. Inhibiting the expression of DLD can significantly inhibit the cycle progression and promote cell apoptosis of DLBCL cells and can target positive regulation of Lysine-specific demethylase 1 (LSD1, also known as KDM1A) to inhibit the proliferation of DLBCL cells and promote cell apoptosis. The immune analysis results show that high-expression of DLD may reduce T cell-mediated anti-tumor immunity by regulating immune infiltration of CD8 + T cells and positively regulating immune checkpoints LAG3 and CD276. Reducing the expression of DLD can effectively enhance T cell-mediated anti-tumor immunity, thereby clearing cancer cells and preventing cancer growth. In conclusion, DLD may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our research provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL.

5.
Front Immunol ; 15: 1337489, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38566988

RESUMO

Introduction: Chimeric antigen receptor natural killer (CAR-NK) cells have been found to be successful in treating hematologic malignancies and present potential for usage in solid tumors. Methods: In this study, we created CD276-targeted CAR-expressing NK cells from pluripotent stem cells (iPSC CD276-targeted CAR-NK cells) and evaluated their cytotoxicity against esophageal squamous cell carcinoma (ESCC) using patient-specific organoid (PSO) models comprising of both CD276-positive and CD276-negative adjacent epithelium PSO models (normal control PSO, NC PSO) as well as primary culture of ESCC cell models. In addition, in vitro and in vivo models such as KYSE-150 were also examined. iPSC NK cells and NK-free media were used as the CAR-free and NK-free controls, respectively. Results: The positive CD276 staining was specifically detected on the ESCC membrane in 51.43% (54/105) of the patients of all stages, and in 51.35% (38/74) of stages III and IV. The iPS CD276-targeted CAR-NK cells, comparing with the iPS NK cells and the NK-free medium, exhibited specific and significant cytotoxic activity against CD276-positive ESCC PSO rather than CD276-negative NC PSO, and exhibited significant cytotoxicity against CD276-expressing cultured ESCC cells, as well as against CD276-expressing KYSE-150 in vitro and in BNDG mouse xenograft. Discussion: The efficacy of the iPSC CD276-targeted CAR-NK cells demonstrated by their successful treatment of CD276-expressing ESCC in a multitude of pre-clinical models implied that they hold tremendous therapeutic potential for treating patients with CD276-expressing ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Células-Tronco Pluripotentes Induzidas , Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas do Esôfago/terapia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/metabolismo , Células Matadoras Naturais , Antígenos B7/metabolismo
6.
J Neuroinflammation ; 21(1): 83, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581043

RESUMO

BACKGROUND: It is well established that traumatic brain injury (TBI) causes acute and chronic alterations in systemic immune function and that systemic immune changes contribute to posttraumatic neuroinflammation and neurodegeneration. However, how TBI affects bone marrow (BM) hematopoietic stem/progenitor cells chronically and to what extent such changes may negatively impact innate immunity and neurological function has not been examined. METHODS: To further understand the role of BM cell derivatives on TBI outcome, we generated BM chimeric mice by transplanting BM from chronically injured or sham (i.e., 90 days post-surgery) congenic donor mice into otherwise healthy, age-matched, irradiated CD45.2 C57BL/6 (WT) hosts. Immune changes were evaluated by flow cytometry, multiplex ELISA, and NanoString technology. Moderate-to-severe TBI was induced by controlled cortical impact injury and neurological function was measured using a battery of behavioral tests. RESULTS: TBI induced chronic alterations in the transcriptome of BM lineage-c-Kit+Sca1+ (LSK+) cells in C57BL/6 mice, including modified epigenetic and senescence pathways. After 8 weeks of reconstitution, peripheral myeloid cells from TBI→WT mice showed significantly higher oxidative stress levels and reduced phagocytic activity. At eight months after reconstitution, TBI→WT chimeric mice were leukopenic, with continued alterations in phagocytosis and oxidative stress responses, as well as persistent neurological deficits. Gene expression analysis revealed BM-driven changes in neuroinflammation and neuropathology after 8 weeks and 8 months of reconstitution, respectively. Chimeric mice subjected to TBI at 8 weeks and 8 months post-reconstitution showed that longer reconstitution periods (i.e., time post-injury) were associated with increased microgliosis and leukocyte infiltration. Pre-treatment with a senolytic agent, ABT-263, significantly improved behavioral performance of aged C57BL/6 mice at baseline, although it did not attenuate neuroinflammation in the acutely injured brain. CONCLUSIONS: TBI causes chronic activation and progressive dysfunction of the BM stem/progenitor cell pool, which drives long-term deficits in hematopoiesis, innate immunity, and neurological function, as well as altered sensitivity to subsequent brain injury.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Camundongos , Animais , Doenças Neuroinflamatórias , Camundongos Endogâmicos C57BL , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas/patologia , Encéfalo/metabolismo
7.
Can Respir J ; 2024: 5554886, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584671

RESUMO

Objective: To investigate the mechanism through which Astragalus and Panax notoginseng decoction (APD) facilitates the treatment of ferroptosis-mediated pulmonary fibrosis. Materials and Methods: First, the electromedical measurement systems were used to measure respiratory function in mice; the lungs were then collected for histological staining. Potential pharmacologic targets were predicted via network pharmacology. Finally, tests including immunohistochemistry, reverse transcription-quantitative polymerase chain reaction, and western blotting were used to evaluate the relative expression levels of collagen, transforming growth factor ß, α-smooth muscle actin, hydroxyproline, and ferroptosis-related genes (GPX4, SLC7A11, ACSL4, and PTGS2) and candidates involved in the mediation of pathways associated with ferroptosis (Hif-1α and EGFR). Results: APD prevented the occurrence of restrictive ventilation dysfunction induced by ferroptosis. Extracellular matrix and collagen fiber deposition were significantly reduced when the APD group compared with the model group; furthermore, ferroptosis was attenuated, expression of PTGS2 and ACSL4 increased, and expression of GPX4 and SLC7A11 decreased. In the APD group, the candidates related to the mediation of ferroptosis (Hif-1α and EGFR) decreased compared with the model group. Discussion and Conclusions. APD may ameliorate restrictive ventilatory dysfunction through the inhibition of ferroptosis. This was achieved through the attenuation of collagen deposition and inflammatory recruitment in pulmonary fibrosis. The underlying mechanisms might involve Hif-1α and EGFR.


Assuntos
Ferroptose , Panax notoginseng , Fibrose Pulmonar , Animais , Camundongos , Fibrose Pulmonar/tratamento farmacológico , Ciclo-Oxigenase 2 , Colágeno , Receptores ErbB
8.
Cell Rep Med ; : 101488, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38565146

RESUMO

Most recurrences of lung cancer (LC) occur within 3 years after surgery, but the underlying mechanism remains unclear. Here, we collect LC tissues with shorter (<3 years, recurrence group) and longer (>3 years, non-recurrence group) recurrence-free survival. By using 16S sequencing, we find that intratumor microbiome diversity is lower in the recurrence group and butyrate-producing bacteria are enriched in the recurrence group. The intratumor microbiome signature and circulating microbiome DNA can accurately predict LC recurrence. We prove that intratumor injection of butyrate-producing bacteria Roseburia can promote subcutaneous tumor growth. Mechanistically, bacteria-derived butyrate promotes LC metastasis by increasing expression of H19 in tumor cells through inhibiting HDAC2 and increasing H3K27 acetylation at the H19 promoter and inducing M2 macrophage polarization. Depletion of macrophages partially abolishes the metastasis-promoting effect of butyrate. Our results provide evidence for the cross-talk between the intratumor microbiome and LC metastasis and suggest the potential prognostic and therapeutic value of the intratumor microbiome.

9.
Aging Cell ; : e14163, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566438

RESUMO

The transition from ordered to noisy is a significant epigenetic signature of aging and age-related disease. As a paradigm of healthy human aging and longevity, long-lived individuals (LLI, >90 years old) may possess characteristic strategies in coping with the disordered epigenetic regulation. In this study, we constructed high-resolution blood epigenetic noise landscapes for this cohort by a methylation entropy (ME) method using whole genome bisulfite sequencing (WGBS). Although a universal increase in global ME occurred with chronological age in general control samples, this trend was suppressed in LLIs. Importantly, we identified 38,923 genomic regions with LLI-specific lower ME (LLI-specific lower entropy regions, for short, LLI-specific LERs). These regions were overrepresented in promoters, which likely function in transcriptional noise suppression. Genes associated with LLI-specific LERs have a considerable impact on SNP-based heritability of some aging-related disorders (e.g., asthma and stroke). Furthermore, neutrophil was identified as the primary cell type sustaining LLI-specific LERs. Our results highlight the stability of epigenetic order in promoters of genes involved with aging and age-related disorders within LLI epigenomes. This unique epigenetic feature reveals a previously unknown role of epigenetic order maintenance in specific genomic regions of LLIs, which helps open a new avenue on the epigenetic regulation mechanism in human healthy aging and longevity.

10.
Sci Rep ; 14(1): 7638, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561452

RESUMO

Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.


Assuntos
Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central , Masculino , Feminino , Humanos , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Mutação , Fenótipo , Atrofia , RNA de Transferência , RNA Polimerase III/genética , RNA Polimerase III/metabolismo
11.
Front Cell Infect Microbiol ; 14: 1210857, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590441

RESUMO

Background: Timely diagnosis and appropriate antifungal therapy are critical for improving the prognosis of patients with invasive fungal disease (IFD) after hematopoietic stem cell transplantation (HSCT). We evaluated the performance of metagenomic next-generation sequencing (mNGS) and conventional microbiological testing (CMT), as well as the diagnosis, therapeutic management, and outcomes of IFD after HSCT. Methods: We retrospectively studied 189 patients who underwent HSCT and were considered at risk for IFD. In total, 46 patients with IFD were enrolled in this study. The IFD consensus was followed for classifying IFD incidents. Results: Forty-six patients were diagnosed with proven/probable (n = 12), possible (n = 27), and undefined (n = 7) IFD. Aspergillus was the most commonly detected fungal genus. Mucormycosis was found in 15 patients; two had Aspergillus, and one had Candida infections. Compared to CMT, mNGS significantly reduced the time required to identify pathogens (P = 0.0016). mNGS had a much higher sensitivity than CMT (84.78% vs. 36.96%; P < 0.0001). A total of 76.09% of patients received antifungal prophylaxis during fungal infections. All Pneumocystis infections occurred later than 100 days after transplantation. Among patients with Pneumocystis infection, 71.43% occurred following sulfonamide withdrawal, and subsequent treatment with sulfonamide alone or in combination with other drugs was effective. Based on the empirical antifungal treatment, the dosages, modes of administration, frequency of administration, or antifungal of 55.26% of the patients were changed according to the mNGS results. The 4-year overall survival rate of patients diagnosed with IFD after transplantation was 71.55% (95% CI, 55.18%-85.82%). Hypoproteinemia and corticosteroid use are independent risk factors for IFD. Conclusion: mNGS, which has a high sensitivity and a short detection time, aids in the diagnosis and prognosis of pathogenic fungi. As a powerful technology, mNGS can influence treatment decisions in patients with IFD following HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas , Micoses , Humanos , Antifúngicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Micoses/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala , Sulfonamidas/uso terapêutico
12.
J Ethnopharmacol ; : 118167, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38593964

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Diminished ovarian reserve (DOR) results in reduced fertility. Kuntai capsule, a Chinese patent medicine, which can nourish the heart and kidneys, has shown promising efficacy in its treatment. However, there is no enough clinical evidence to confirm the efficacy and safety of Kuntai capsule. AIM OF THE STUDY: This review aims to evaluate Kuntai capsule's potential benefits and detriments for diminished ovarian reserve. MATERIALS AND METHODS: Databases namely China National Knowledge Infrastructure, WANFANG Database, Chinese Science and Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Cochrane Library, and Embase were searched from their inception to July 2023. We included randomized controlled trials (RCTs) comparing Kuntai capsule to hormone therapy (HT) and Kuntai capsule in combination with HT to HT alone for DOR treatment. The risk of bias was evaluated using RoB1.0. A Meta-analysis was performed using RevMan 5.4 software. The primary outcomes were antral follicle count (AFC) and serum anti-Müllerian hormone (AMH), secondary outcomes were follicle-stimulating hormone (FSH) and adverse reactions. RESULTS: A Meta-analysis of 12 randomized controlled trials (RCTs), encompassing a total of 905 DOR patients was conducted. The results indicated that the combination of Kuntai capsule with HT exhibited superior efficacy in enhancing AFC (MD=1.34, 95% CI [0.96,1.72]) and AMH levels (MD=1.09 (ng/mL) 95% CI[0.80,1.38]), Kuntai capsule demonstrated improvements in AFC (MD=0.65, 95% CI [0.48,0.83]) in DOR patients compared to HT alone. CONCLUSIONS: Based on the available results, the combination of Kuntai capsule with HT appears to improve the AFC, AMH and FSH levels of DOR patients. Kuntai capsule alone appears to improve the AFC and FSH levels of DOR patients. However, included trials had methodological quality issues, further standardized research is required.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38588463

RESUMO

For patients with Biliary atresia, antibiotic prophylaxis after Kasai portoenterostomy is a common practice. Societal guidelines often cite one reference as supportive evidence for this practice. In this paper, we go back to review the quality of this evidence and suggest more research is required to demonstrate the efficacy of antibiotic prophylaxis in this population.

14.
Int J Biol Macromol ; : 131484, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38599421

RESUMO

Adopting effective and efficient techniques for the treatment of heavy metal pollution in water bodies plays an important role in guaranteeing the quality of water and the sustainable development of water resources. In this study, GO, MMT and SA were used as raw materials to compare the adsorption behaviors of three alginate-based adsorbents crosslinked with different valence metal ions (Ca2+, Fe3+ and Zr4+) on Cu(II). The aerogels were based on sodium alginate as the matrix material with unique slit-shaped pore structures formed by stacking effect of sheets and chemical bonding. It was found that the pore structures of the aerogels were denser and more orderly with the increase of the valence states of the crosslinked ions, and the affinity for Cu(II) in planar configuration was stronger. The Zr4+-GMSA aerogel had the maximum adsorption capacity of 126.68 mg/g and the Kd of Cu(II) was up to 50.80 L/g, which exhibited good preferential adsorption performance. The adsorption mechanism of Mn+-GMSA aerogels on Cu(II) was mainly ionic exchange, surface complexation and physical adsorption, which was explored by combining XPS and EDS characterizations of Mn+-GMSA before and after adsorption. This scheme can provide valuable and meaningful contribution to realize the selective recovery of Cu(II).

15.
Heliyon ; 10(7): e29100, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601629

RESUMO

C-X3-C motif chemokine ligand 1 (CX3CL1) is a transmembrane protein, and the membranal and soluble forms of CX3CL1 exhibit different functions, although both bind to the CX3CR1 chemokine receptor. The CX3CL1/CX3CR1 axis induces many cellular responses relevant to cancer, such as proliferation, migration, invasion, and apoptosis resistance. Here we attempt to elucidate whether CX3CL1/CX3CR1 is associated with paclitaxel (PTX) resistance in gastric cancer (GC). The Gene Expression Omnibus database was queried to screen for differentially expressed genes in GC cells caused by drug resistance, and CX3CL1 was selected as a candidate. CX3CL1 was overexpressed in PTX-resistant cells and tissues. CX3CL1 loss sensitized GC cells to PTX, promoted apoptosis and DNA damage, and inhibited cell proliferation, migration, and invasion. CX3CR1 reversed the ameliorative effect of CX3CL1 silencing on PTX sensitivity in GC cells. The promotion of PTX resistance by CX3CL1/CX3CR1 was inhibited by impairment of the small GTPase Ras homolog gene family member A (RhoA) pathway in vitro and in vivo. These findings indicate that the CX3CL1/CX3CR1 expedites PTX resistance through the RhoA signaling in GC cells.

16.
Elife ; 132024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602170

RESUMO

Stains are known to be anti-inflammatory, but the mechanism remains poorly understood. Here we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the ATP synthase in the inner mitochondrial membrane (IMM) and changes the proton gradient in the mitochondria. This activates NFkB and Jmjd3 expression to remove the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus LPS (M1), both macrophages treated with statins in vitro or isolated from statin-treated mice in vivo, express lower levels pro-inflammatory cytokines than controls, while augmenting anti-inflammatory Il10 expression. On the other hand, when macrophages are alternatively activated by IL4 (M2), statins promote the expression of Arg1, Ym1, and Mrc1. The enhanced expression is correlated with the statin-induced removal of H3K27me3 from these genes prior to activation. In addition, Jmjd3 and its demethylase activity are necessary for cholesterol to modulate both M1 and M2 activation. We conclude that upregulation of Jmjd3 is a key event for the anti-inflammatory function of statins on macrophages.

18.
Seizure ; 116: 87-92, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38523034

RESUMO

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.


Assuntos
Epilepsia , Deficiência Intelectual , Malformações do Desenvolvimento Cortical , Transtornos do Neurodesenvolvimento , Humanos , Deficiência Intelectual/genética , Epilepsia/genética , Transtornos do Neurodesenvolvimento/genética , Mutação de Sentido Incorreto , Fenótipo , Proteínas do Citoesqueleto/genética
19.
Inorg Chem ; 63(14): 6116-6121, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38518373

RESUMO

Obtaining compounds with large nonlinear-optical (NLO) coefficients and wide band gaps is challenging due to their competitive requirements for chemical bonds. Herein, the first member with mixed cations on the A site in the A-M3-Q5 or A-Ag-M6-Q10 (A = alkali metal; M = Ga, In; Q = S, Se, Te) family, viz. Na0.45Ag0.55Ga3Se5 (NAGSe), was obtained by a solid-state reaction. Its structure features [GaSe4] tetrahedra built three-dimensional {[Ga3Se5]-}∞ network, with Na and Na/Ag cations located at the octahedral cavities. Noncentrosymmetric (R32) NAGSe can also be transformed from centrosymmetric RbGa3S5 (P21/c) via multiple-site cosubstitution. NAGSe exhibits the highest NLO response (1.9 × AGS) in the A-Ag-M-Q family. Crystal structure analysis and theoretical calculations suggest that the NLO response is mainly contributed by the regularly arranged [GaSe4] units. This work enriches the exploration of the undeveloped A-M3-Q5 or A-Ag-M6-Q10 family as potential infrared NLO materials.

20.
Microbiol Spectr ; 12(4): e0405223, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38440971

RESUMO

"Candidatus Liberibacter asiaticus" (CLas), the causal agent of citrus Huanglongbing (HLB), is able to multiply to a high abundance in citrus fruit pith. However, little is known about the biological processes and phytochemical substances that are vital for CLas colonization and growth in fruit pith. In this study, CLas-infected fruit pith of three citrus cultivars ("Shatangju" mandarin, "Guanxi" pomelo, and "Shatian" pomelo) exhibiting different tolerance to CLas were collected and used for dual RNA-Seq and untargeted metabolome analysis. Comparative transcriptome analysis found that the activation of the CLas noncyclic TCA pathway and pathogenic-related effectors could contribute to the colonization and growth of CLas in fruit pith. The pre-established Type 2 prophage in the CLas genome and the induction of its CRISPR/cas system could enhance the phage resistance of CLas and, in turn, facilitate CLas population growth in fruit pith. CLas infection caused the accumulation of amino acids that were correlated with tolerance to CLas. The accumulation of most sugars and organic acids in CLas-infected fruit pith, which could be due to the phloem blockage caused by CLas infection, was thought to be beneficial for CLas growth in localized phloem tissue. The higher levels of flavonoids and terpenoids in the fruit pith of CLas-tolerant cultivars, particularly those known for their antimicrobial properties, could hinder the growth of CLas. This study advances our understanding of CLas multiplication in fruit pith and offers novel insight into metabolites that could be responsible for tolerance to CLas or essential to CLas population growth.IMPORTANCECitrus Huanglongbing (HLB, also called citrus greening disease) is a highly destructive disease currently threatening citrus production worldwide. HLB is caused by an unculturable bacterial pathogen, "Candidatus Liberibacter asiaticus" (CLas). However, the mechanism of CLas colonization and growth in citrus hosts is poorly understood. In this study, we utilized the fruit pith tissue, which was able to maintain the CLas at a high abundance, as the materials for dual RNA-Seq and untargeted metabolome analysis, aiming to reveal the biological processes and phytochemical substances that are vital for CLas colonization and growth. We provided a genome-wide CLas transcriptome landscape in the fruit pith of three citrus cultivars with different tolerance and identified the important genes/pathways that contribute to CLas colonization and growth in the fruit pith. Metabolome profiling identified the key metabolites, which were mainly affected by CLas infection and influenced the population dynamic of CLas in fruit pith.


Assuntos
Citrus , Liberibacter , Rhizobiaceae , Citrus/microbiologia , Rhizobiaceae/genética , Rhizobiaceae/metabolismo , Transcriptoma , Frutas/metabolismo , Metaboloma , Dinâmica Populacional , Compostos Fitoquímicos/metabolismo , Doenças das Plantas/microbiologia
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