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1.
Front Pediatr ; 12: 1342514, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560399

RESUMO

Background: Short sleep duration has been related to obesity in children and adolescents. However, it remains unknown whether late bedtime is also associated with obesity and whether the association is independent of sleep duration. A meta-analysis was performed to address this issue. Methods: In order to accomplish the aim of the meta-analysis, a comprehensive search was conducted on databases including PubMed, Embase, and Web of Science to identify observational studies. The cutoff to determine late bedtime in children in this meta-analysis was consistent with the value used among the included original studies. As for obesity, it was typically defined as a body mass index (BMI) > 95th percentile of age and sex specified reference standards or the International Obesity Task Force defined age- and gender-specific cut-off of BMI. The Cochrane Q test was employed to evaluate heterogeneity among the included studies, while the I2 statistic was estimated. Random-effects models were utilized to merge the results, considering the potential impact of heterogeneity. Results: Tweleve observational studies with 57,728 participants were included. Among them, 6,815 (11.8%) were obese. Pooled results showed that late bedtime reported by the participants or their caregivers was associated with obesity (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 1.16-1.39, p < 0.001; I2 = 0%). Subgroup analysis showed consistent results in studies with (OR: 1.33, 95% CI: 1.04-1.70, p = 0.02) and without adjustment of sleep duration (OR: 1.27, 95% CI: 1.14-1.41, p < 0.001). Further subgroup analysis also showed that the association was not significantly affected by study location, design, age of the participants, or diagnostic methods for obesity (p for subgroup difference all >0.05). Conclusion: Late bedtime is associated with obesity in children and adolescents, which may be independent of sleep duration.

2.
Talanta ; 274: 125975, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38599114

RESUMO

Sirtuin1 (SIRT1), an NAD+-dependent histone deacetylase, plays a crucial role in regulating molecular signaling pathways. Recently, inhibition of SIRT1 rather than its activation shows the therapeutic potential for central nervous system disorder, however, the discovered SIRT1 inhibitors remains limited. In this work, a dual recognition-based strategy was developed to screen SIRT1 inhibitors from natural resources in situ. This approach utilized a Ni-modified metal-organic framework (Ni@Tyr@UiO-66-NH2) along with cell lysate containing an engineered His-tagged SIRT1 protein, eliminating the need for purified proteins, pure compounds, and protein immobilization. The high-performance Ni@Tyr@UiO-66-NH2 was synthesized by modifying the surface of UiO-66-NH2 with Ni2+ ions to specifically capture His-tagged SIRT1 while persevering its enzyme activity. By employing dual recognition, in which Ni@Tyr@UiO-66-NH2 recognized SIRT1 and SIRT1 recognized its ligands, the process of identifying SIRT1 inhibitors from complex matrix was vastly streamlined. The developed method allowed the efficient discovery of 16 natural SIRT1 inhibitors from Chinese herbs. Among them, 6 compounds were fully characterized, and suffruticosol A was found to have an excellent IC50 value of 0.95 ±â€¯0.12 µM. Overall, an innovative dual recognition-based strategy was proposed to efficiently identify SIRT1 inhibitors in this study, offering scientific clues for the development of drugs targeting CNS disorders.

3.
Nat Commun ; 15(1): 2974, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582895

RESUMO

Linear ubiquitination catalyzed by HOIL-1-interacting protein (HOIP), the key component of the linear ubiquitination assembly complex, plays fundamental roles in tissue homeostasis by executing domain-specific regulatory functions. However, a proteome-wide analysis of the domain-specific interactome of HOIP across tissues is lacking. Here, we present a comprehensive mass spectrometry-based interactome profiling of four HOIP domains in nine mouse tissues. The interaction dataset provides a high-quality HOIP interactome resource with an average of approximately 90 interactors for each bait per tissue. HOIP tissue interactome presents a systematic understanding of linear ubiquitination functions in each tissue and also shows associations of tissue functions to genetic diseases. HOIP domain interactome characterizes a set of previously undefined linear ubiquitinated substrates and elucidates the cross-talk among HOIP domains in physiological and pathological processes. Moreover, we show that linear ubiquitination of Integrin-linked protein kinase (ILK) decreases focal adhesion formation and promotes the detachment of Shigella flexneri-infected cells. Meanwhile, Hoip deficiency decreases the linear ubiquitination of Smad ubiquitination regulatory factor 1 (SMURF1) and enhances its E3 activity, finally causing a reduced bone mass phenotype in mice. Overall, our work expands the knowledge of HOIP-interacting proteins and provides a platform for further discovery of linear ubiquitination functions in tissue homeostasis.


Assuntos
Ubiquitina-Proteína Ligases , Ubiquitina , Animais , Camundongos , Homeostase , NF-kappa B/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
4.
J Agric Food Chem ; 72(14): 8018-8026, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38557039

RESUMO

Phloretin is widely found in fruit and shows various biological activities. Here, we demonstrate the dimethylallylation, geranylation, and farnesylation, particularly the first dimethylallylation at the nonaromatic carbon of phloretin (1) by the fungal prenyltransferase AnaPT and its mutants. F265 was identified as a key amino acid residue related to dimethylallylation at the nonaromatic carbon of phloretin. Mutants AnaPT_F265D, AnaPT_F265G, AnaPT_F265P, AnaPT_F265C, and AnaPT_F265Y were discovered to generally increase prenylation activity toward 1. AnaPT_F265G catalyzes the O-geranylation selectively at the C-2' hydroxyl group, which involves an intramolecular hydrogen bond with the carbonyl group of 1. Seven products, 1D5, 1D7-1D9, 1G2, 1G4, and 1F2, have not been reported prior to this study. Twelve compounds, 1D3-1D9, 1G1-1G3, and 1F1-1F2, exhibited potential inhibitory effects on α-glucosidase with IC50 values ranging from 11.45 ± 0.87 to 193.80 ± 6.52 µg/mL. Among them, 1G1 with an IC50 value of 11.45 ± 0.87 µg/mL was the most potential α-glucosidase inhibitor, which is about 30 times stronger than the positive control acarbose with an IC50 value of 346.63 ± 15.65 µg/mL.


Assuntos
Dimetilaliltranstransferase , Floretina , Floretina/farmacologia , Indóis/química , Carbono , Catálise , Prenilação
5.
Artigo em Inglês | MEDLINE | ID: mdl-38629469

RESUMO

BACKGROUND: Riemerella anatipestifer encodes an iron acquisition system, but whether it encodes the iron efflux pump and its role in antibiotic resistance are largely unknown. OBJECTIVES: To screen and identify an iron efflux gene in R. anatipestifer and determine whether and how the iron efflux gene is involved in antibiotic resistance. METHODS: In this study, gene knockout, streptonigrin susceptibility assay and inductively coupled plasma mass spectrometry were used to screen for the iron efflux gene ietA. The MIC measurements, scanning electron microscopy and reactive oxygen species (ROS) detection were used to verify the role of IetA in aztreonam resistance and its mechanism. Mortality and colonization assay were used to investigate the role of IetA in virulence. RESULTS: The deletion mutant ΔietA showed heightened susceptibility to streptonigrin, and prominent intracellular iron accumulation was observed in ΔfurΔietA under excess iron conditions. Additionally, ΔietA exhibited increased sensitivity to H2O2-produced oxidative stress. Under aerobic conditions with abundant iron, ΔietA displayed increased susceptibility to the ß-lactam antibiotic aztreonam due to heightened ROS production. However, the killing efficacy of aztreonam was diminished in both WT and ΔietA under anaerobic or iron restriction conditions. Further experiments demonstrated that the efficiency of aztreonam against ΔietA was dependent on respiratory complexes Ⅰ and Ⅱ. Finally, in a duckling model, ΔietA had reduced virulence compared with the WT. CONCLUSION: Iron efflux is critical to alleviate oxidative stress damage and ß-lactam aztreonam killing in R. anatipestifer, which is linked by cellular respiration.

6.
Chemosphere ; 356: 141927, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38593954

RESUMO

Numerous animal studies have demonstrated the toxicity of hexavalent chromium [Cr(VI)] and the bioremediative effects of probiotics on the composition and functions of gut microbiota. Since the precise mechanisms of Cr(VI) detoxification and its interactions with human gut microbiota were unknown, a novel dual-chamber simulated intestinal (DCSI) system was developed to maintain both the stability of the simulated system and the composition of the gut microbiota. Probiotic GR-1 was found to regulate intestinal gut microbiota, thereby reducing the toxicity of Cr(VI) within the DCSI system. The results indicate that Cr(VI) levels were reduced from 2.260 ± 0.2438 µg/g to 1.7086 ± 0.1950 µg/g in the gut microbiota cell pellet, and Cr(VI) permeability decreased from 0.5521 ± 0.1132 µg/L to 0.3681 ± 0.0178 µg/L after 48 h in simulated gut fluid. Additionally, the removal rate of 1,1-Diphenyl-2-picrylhydrazyl (DPPH), reducibility (Vitamin C), and total antioxidant capacity (T-AOC) increased by 50.83%, 31.70%, and 27.56%, respectively, following probiotic treatment. The increase in antioxidant capacity correlated with total Cr removal (P < 0.05, r from -0.80 to 0.73). 16S rRNA sequencing analysis showed that gut microbiota composition was reshaped by the addition of probiotics, which regulated the recovery of the functional gut microbiota to normal levels, rather than restoring the entire gut microbiota composition for community function. Thus, this study not only demonstrates the feasibility and stability of culturing gut microbiota but also offers a new biotechnological approach to synthesizing functional communities with functional strains for environmental risk management.

7.
Soc Sci Med ; 348: 116785, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38569281

RESUMO

Identifying environmental determinants of health and clarifying their variations is crucial for health promotion in different cities by providing tailored intervention strategies. Although the association between perceived urban environment and health (e.g., self-rated health) has been repeatedly explored, most studies have focused on cities of a specific size, and it is still unknown whether either significant environment variables or the magnitude of the association would vary across different-sized cities. This study investigated how perceived urban environment variables significantly associated with individuals' self-rated health varied from small cities to mega cities in China, based on a national survey including 5963 valid respondents. The results showed that the relationship between self-rated health and city size was U-shaped, with respondents in medium and large cities reporting a low-level self-rated health. Perceived greenness, public facilities, housing supply, and medical services were positively and significantly associated with self-rated health, with the odds ratio (OR) of 1.37 (95%CI: 1.29-1.46), 1.27 (95%CI: 1.19-1.35), 1.14 (95%CI: 1.09-1.20), and 1.17 (95%CI: 1.10-1.24), respectively. Furthermore, the magnitude of the association was significantly larger in mega cities. These findings provide useful evidence for promoting public health in cities of different sizes for achieving health equity and indicate that smaller cities and their health-supportive environment need further attention.

8.
Opt Express ; 32(6): 9995-10004, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571222

RESUMO

We present a design of middle-infrared modulation absorbers based on vanadium dioxide (VO2). By using the electron beam evaporation technique, the Ag/SiO2/VO2/Ag/VO2 multilayer structure can achieve double band strong absorption in the mid-infrared, and dynamically adjust the absorption performance through VO2. The simulation results demonstrate a remarkable absorption rate of 91.8% and 98.9% at 9.09 µm and 10.25 µm, respectively. The high absorption is elucidated by analyzing the field strength distribution in each layer. Meanwhile, based on the phase change characteristics of VO2, the absorber has exceptional thermal regulation, with a remarkable 78% heat regulation range in the mid-infrared band. The size altering of the absorbing layer is effective in enhancing and optimizing the structure's absorption performance. The structure is used to characterize probe molecules of CV and R6 G by mid-infrared spectroscopy, which illustrates an impressive limit of detection (LOD) of 10-7 M for both substances. These results provide valuable insights for designing future high-performance tunable optical devices.

9.
Poult Sci ; 103(6): 103727, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38652953

RESUMO

Duck Tembusu virus (DTMUV) belongs to the Flaviviridae family and mainly infects ducks. Duck Tembusu virus genome encodes one polyprotein that undergoes cleavage to produce 10 proteins. Among these, NS4B, the largest transmembrane protein, plays a crucial role in the viral life cycle. In this study, we investigated the localization of NS4B and found that it is located in the endoplasmic reticulum, where it co-localizes with DTMUV dsRNA. Subsequently, we confirmed 5 different transmembrane domains of NS4B and discovered that only its transmembrane domain 3 (TMD3) can traverse ER membrane. Then mutations were introduced in the conserved amino acids of NS4B TMD3 of DTMUV replicon and infectious clone. The results showed that V111G, V117G, and I118G mutations enhanced viral RNA replication, while Q104A, T106A, A113L, M116A, H120A, Y121A, and A122G mutations reduced viral replication. Recombinant viruses with these mutations were rescued and studied in BHK21 cells. The findings demonstrated that A113L and H120A mutations led to higher viral titers than the wild-type strain, while Q104A, T106A, V111G, V117G, and Y121A mutations attenuated viral proliferation. Additionally, H120A, M116A, and A122G mutations enhanced viral proliferation. Furthermore, Q104A, T106A, V111G, M116A, V117G, Y121A, and A122G mutants showed reduced viral virulence to 10-d duck embryos. Animal experiments further indicated that all mutation viruses resulted in lower genome copy numbers in the spleen compared to the WT group 5 days postinfection. Our data provide insights into the topological model of DTMUV NS4B, highlighting the essential role of NS4B TMD3 in viral replication and proliferation.

10.
Microb Genom ; 10(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38630615

RESUMO

The ubiquitous and abundant marine phages play critical roles in shaping the composition and function of bacterial communities, impacting biogeochemical cycling in marine ecosystems. Autographiviridae is among the most abundant and ubiquitous phage families in the ocean. However, studies on the diversity and ecology of Autographiviridae phages in marine environments are restricted to isolates that infect SAR11 bacteria and cyanobacteria. In this study, ten new roseophages that infect marine Roseobacter strains were isolated from coastal waters. These new roseophages have a genome size ranging from 38 917 to 42 634 bp and G+C content of 44.6-50 %. Comparative genomics showed that they are similar to known Autographiviridae phages regarding gene content and architecture, thus representing the first Autographiviridae roseophages. Phylogenomic analysis based on concatenated conserved genes showed that the ten roseophages form three distinct subgroups within the Autographiviridae, and sequence analysis revealed that they belong to eight new genera. Finally, viromic read-mapping showed that these new Autographiviridae phages are widely distributed in global oceans, mostly inhabiting polar and estuarine locations. This study has expanded the current understanding of the genomic diversity, evolution and ecology of Autographiviridae phages and roseophages. We suggest that Autographiviridae phages play important roles in the mortality and community structure of roseobacters, and have broad ecological applications.


Assuntos
Bacteriófagos , Roseobacter , Humanos , Bacteriófagos/genética , Roseobacter/genética , Ecossistema , Genoma Viral , Genômica
12.
Int J Mol Sci ; 25(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38612914

RESUMO

Hematopoietic reconstitution after hematopoietic stem cell transplantation (HSCT) is influenced by the number of transplanted cells. However, under certain conditions donor cell counts are limited and impair clinical outcome. Hematopoietic stem and progenitor cell (HSPC) expansion prior to HSCT is a widely used method to achieve higher donor cell counts and minimize transplantation-related risks such as graft failure or delayed engraftment. Still, expansion in a non-physiological environment can trigger cell death mechanisms and hence counteract the desired effect. We have shown earlier that during HSCT a relevant amount of HSPCs were lost due to apoptosis and that cell death inhibition in donor HSPCs improved engraftment in xenotransplantation experiments. Here, we assessed the effect of combined ex vivo expansion and cell death inhibition on HSPC yield and their reconstitution potential in vivo. During expansion with cytokines and the small molecule inhibitor StemRegenin 1, concomitant lentiviral overexpression of antiapoptotic BCL-XL resulted in an increased yield of transduced HSPCs. Importantly, BCL-XL overexpression enhanced the reconstitution potential of HSPCs in xenotransplantation experiments in vivo. In contrast, treatment with caspase and necroptosis inhibitors had no favorable effects on HSPC yields nor on cell viability. We postulate that overexpression of antiapoptotic BCL-XL, both during ex vivo expansion and transplantation, is a promising approach to improve the outcome of HSCT in situations with limited donor cell numbers. However, such apoptosis inhibition needs to be transient to avoid long-term sequelae like leukemia.


Assuntos
Apoptose , Lentivirus , Transplante Heterólogo , Lentivirus/genética , Células-Tronco Hematopoéticas , Morte Celular
13.
Ergonomics ; : 1-14, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613399

RESUMO

Emotion is an important factor that can lead to the occurrence of aggressive driving. This paper proposes an association rule mining-based method for analysing contributing factors associated with aggressive driving behaviour among online car-hailing drivers. We collected drivers' emotion data in real time in a natural driving setting. The findings show that 29 of the top 50 association rules for aggressive driving are related to emotions, revealing a strong relationship between driver emotions and aggressive driving behaviour. The emotions of anger, surprised, happy and disgusted are frequently associated with aggressive driving behaviour. Negative emotions combined with other factors (for example, driving at high speeds and high acceleration rates and with no passengers in the vehicle) are more likely to lead to aggressive driving behaviour than negative emotions alone. The results of this study provide practical implications for the supervision and training of car-hailing drivers.


Based on the association rule mining method, we found a close connection between drivers' emotional states and the manifestation of aggressive driving behaviours. The findings indicate that the combination of negative emotions and various contributing factors significantly amplifies the likelihood of aggressive driving.

14.
Front Microbiol ; 15: 1355035, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650880

RESUMO

In the present study, small RNA (sRNA) data from Ascosphaera apis were filtered from sRNA-seq datasets from the gut tissues of A. apis-infected Apis mellifera ligustica worker larvae, which were combined with the previously gained sRNA-seq data from A. apis spores to screen differentially expressed milRNAs (DEmilRNAs), followed by trend analysis and investigation of the DEmilRNAs in relation to significant trends. Additionally, the interactions between the DEmilRNAs and their target mRNAs were verified using a dual-luciferase reporter assay. In total, 974 A. apis milRNAs were identified. The first base of these milRNAs was biased toward U. The expression of six milRNAs was confirmed by stem-loop RT-PCR, and the sequences of milR-3245-y and milR-10285-y were validated using Sanger sequencing. These miRNAs grouped into four significant trends, with the target mRNAs of DEmilRNAs involving 42 GO terms and 120 KEGG pathways, such as the fungal-type cell wall and biosynthesis of secondary metabolites. Further investigation demonstrated that 299 DEmilRNAs (novel-m0011-3p, milR-10048-y, bantam-y, etc.) potentially targeted nine genes encoding secondary metabolite-associated enzymes, while 258 (milR-25-y, milR-14-y, milR-932-x, etc.) and 419 (milR-4561-y, milR-10125-y, let-7-x, etc.) DEmilRNAs putatively targeted virulence factor-encoded genes and nine genes involved in the MAPK signaling pathway, respectively. Additionally, the interaction between ADM-B and milR-6882-x, as well as between PKIA and milR-7009-x were verified. Together, these results not only offer a basis for clarifying the mechanisms underlying DEmilRNA-regulated pathogenesis of A. apis and a novel insight into the interaction between A. apis and honey bee larvae, but also provide candidate DEmilRNA-gene axis for further investigation.

15.
Front Physiol ; 15: 1369174, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651044

RESUMO

In recent years, an increasing trend has been observed in the consumption of specific polyphenols, such as flavonoids and phenolic acids, derived from green tea, berries, and other similar sources. These compounds are believed to alleviate oxidative stress and inflammation resulting from exercise, potentially enhancing athletic performance. This systematic review critically examines the role of polyphenol supplementation in improving aerobic endurance among athletes and individuals with regular exercise habits. The review involved a thorough search of major literature databases, including PubMed, Web of Science, SCOPUS, SPORTDiscus, and Embase, covering re-search up to the year 2023. Out of 491 initially identified articles, 11 met the strict inclusion criteria for this review. These studies specifically focused on the incorporation of polyphenols or polyphenol-containing complexes in their experimental design, assessing their impact on aerobic endurance. The methodology adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the risk of bias was evaluated using the Cochrane bias risk assessment tool. While this review suggests that polyphenol supplementation might enhance certain aspects of aerobic endurance and promote fat oxidation, it is important to interpret these findings with caution, considering the limited number of studies available. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023453321.

16.
Front Immunol ; 15: 1365521, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38629064

RESUMO

3D polymerase, also known as RNA-dependent RNA polymerase, is encoded by all known picornaviruses, and their structures are highly conserved. In the process of picornavirus replication, 3D polymerase facilitates the assembly of replication complexes and directly catalyzes the synthesis of viral RNA. The nuclear localization signal carried by picornavirus 3D polymerase, combined with its ability to interact with other viral proteins, viral RNA and cellular proteins, indicate that its noncatalytic role is equally important in viral infections. Recent studies have shown that 3D polymerase has multiple effects on host cell biological functions, including inducing cell cycle arrest, regulating host cell translation, inducing autophagy, evading immune responses, and triggering inflammasome formation. Thus, 3D polymerase would be a very valuable target for the development of antiviral therapies. This review summarizes current studies on the structure of 3D polymerase and its regulation of host cell responses, thereby improving the understanding of picornavirus-mediated pathogenesis caused by 3D polymerase.


Assuntos
Infecções por Picornaviridae , Picornaviridae , Humanos , Replicação Viral/genética , Picornaviridae/genética , Proteínas Virais/genética , RNA Viral/genética
17.
J Cell Sci ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587100

RESUMO

During development neurons achieve a stereotyped neuron type-specific morphology, which relies on dynamic support by microtubules (MTs). An important player is augmin which binds to existing MT filaments and recruits the γ-Tubulin Ring Complex (γ-TuRC), to form branched MTs. In cultured neurons, augmin is important for neurite formation. However, little is known about the role of augmin during neurite formation in vivo. Here, we have revisited the role of mammalian augmin in culture and then turned towards the class four Drosophila dendritic arborization (c4da) neurons. We show that MT density is maintained through augmin in cooperation with the γ-TuRC in vivo. Mutant c4da neurons show a reduction of newly emerging higher-order dendritic branches and in turn also a reduced number of their characteristic space-filling higher-order branchlets. Taken together, our data reveal a cooperative function of the augmin complex with the γ-TuRC in forming enough MTs needed for the appropriate differentiation of morphologically complex dendrites in vivo.

18.
Mol Psychiatry ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519640

RESUMO

Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Aberrant activation of microglia in SCZ is one of the leading hypotheses for disease pathogenesis, but due to the lack of proper human cell models, the role of microglia in SCZ is not well studied. We used monozygotic twins discordant for SCZ and healthy individuals to generate human induced pluripotent stem cell-derived microglia to assess the transcriptional and functional differences in microglia between healthy controls, affected twins and unaffected twins. The microglia from affected twins had increased expression of several common inflammation-related genes compared to healthy individuals. Microglia from affected twins had also reduced response to interleukin 1 beta (IL1ß) treatment, but no significant differences in migration or phagocytotic activity. Ingenuity Pathway Analysis (IPA) showed abnormalities related to extracellular matrix signaling. RNA sequencing predicted downregulation of extracellular matrix structure constituent Gene Ontology (GO) terms and hepatic fibrosis pathway activation that were shared by microglia of both affected and unaffected twins, but the upregulation of major histocompatibility complex (MHC) class II receptors was observed only in affected twin microglia. Also, the microglia of affected twins had heterogeneous response to clozapine, minocycline, and sulforaphane treatments. Overall, despite the increased expression of inflammatory genes, we observed no clear functional signs of hyperactivation in microglia from patients with SCZ. We conclude that microglia of the patients with SCZ have gene expression aberrations related to inflammation response and extracellular matrix without contributing to increased microglial activation.

19.
Front Cell Infect Microbiol ; 14: 1351993, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524182

RESUMO

Acinetobacter baumannii (A. baumannii) is a popular clinical pathogen worldwide. Biofilm-associated antibiotic-resistant A. baumannii infection poses a great threat to human health. Bacteria in biofilms are highly resistant to antibiotics and disinfectants. Furthermore, inhibition or eradication of biofilms in husbandry, the food industry and clinics are almost impossible. Phages can move across the biofilm matrix and promote antibiotic penetration. In the present study, a lytic A. baumannii phage vB_AbaM-SHI, belonging to family Straboviridae, was isolated from sauce chop factory drain outlet in Wuxi, China. The DNA genome consists of 44,180 bp which contain 93 open reading frames, and genes encoding products morphogenesis are located at the end of the genome. The amino acid sequence of vB_AbaM-SHI endolysin is different from those of previously reported A. baumannii phages in NCBI. Phage vB_AbaM-SHI endolysin has two additional ß strands due to the replacement of a lysine (K) (in KU510289.1, NC_041857.1, JX976549.1 and MH853786.1) with an arginine (R) (SHI) at position 21 of A. baumannii phage endolysin. Spot test showed that phage vB_AbaM-SHI is able to lyse some antibiotic-resistant bacteria, such as A. baumannii (SL, SL1, and SG strains) and E. coli BL21 strain. Additionally, phage vB_AbaM-SHI independently killed bacteria and inhibited bacterial biofilm formation, and synergistically exerted strong antibacterial effects with antibiotics. This study provided a new perspective into the potential application value of phage vB_AbaM-SHI as an antimicrobial agent.


Assuntos
Acinetobacter baumannii , Bacteriófagos , Humanos , Bacteriófagos/genética , Escherichia coli , Antibacterianos/farmacologia , Biofilmes
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