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1.
World J Radiol ; 16(6): 211-220, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38983836

RESUMO

BACKGROUND: Solid pseudopapillary neoplasms of the pancreas (SPN) share similar imaging findings with pancreatic ductal adenocarcinoma with cystic changes (PDAC with cystic changes), which may result in unnecessary surgery. AIM: To investigate the value of computed tomography (CT) in differentiation of SPN from PDAC with cystic changes. METHODS: This study retrospectively analyzed the clinical and imaging findings of 32 patients diagnosed with SPN and 14 patients diagnosed with PDAC exhibiting cystic changes, confirmed through pathological diagnosis. Quantitative and qualitative analysis was performed, including assessment of age, sex, tumor size, shape, margin, density, enhancement pattern, CT values of tumors, CT contrast enhancement ratios, "floating cloud sign," calcification, main pancreatic duct dilatation, pancreatic atrophy, and peripancreatic invasion or distal metastasis. Multivariate logistic regression analysis was used to identify relevant features to differentiate between SPN and PDAC with cystic changes, and receiver operating characteristic curves were obtained to evaluate the diagnostic performance of each variable and their combination. RESULTS: When compared to PDAC with cystic changes, SPN had a lower age (32 years vs 64 years, P < 0.05) and a slightly larger size (5.41 cm vs 3.90 cm, P < 0.05). SPN had a higher frequency of "floating cloud sign" and peripancreatic invasion or distal metastasis than PDAC with cystic changes (both P < 0.05). No significant difference was found with respect to sex, tumor location, shape, margin, density, main pancreatic duct dilatation, calcification, pancreatic atrophy, enhancement pattern, CT values of tumors, or CT contrast enhancement ratios between the two groups (all P > 0.05). The area under the receiver operating characteristic curve of the combination was 0.833 (95% confidence interval: 0.708-0.957) with 78.6% sensitivity, 81.3% specificity, and 80.4% accuracy in differentiation of SPN from PDAC with cystic changes. CONCLUSION: A larger tumor size, "floating cloud sign," and peripancreatic invasion or distal metastasis are useful CT imaging features that are more common in SPN and may help discriminate SPN from PDAC with cystic changes.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38970420

RESUMO

SIGNIFICANCE: Herbal medicines demonstrate clinical promise for cancer treatment. Protein post translational modifications (PTMs) regulate tumorigenesis and cancer progression. While PTMs contributing to cancer are well-studied, the precise mechanisms and defined targets of herbal medicines on PTM-associated carcinogenesis remain unclear. Hence, comprehensively understanding how PTMs regulate cancer hallmarks is crucial to elucidate the pharmacological mechanisms of herbal medicines for cancer treatment. RECENT ADVANCES: Advanced development in highly sensitive mass spectrometry (MS)-based techniques has helped utilize PTM-focused studies on cancers. Accumulating evidence has been achieved in laboratory to ascertain the biological mechanism of herbal medicines in cancer therapy. Implication of the strong association between cancer and PTM makes new perspective to comprehend the intricate dialogues between herbal medicines and cellular contexts. CRITICAL ISSUES: Complex components of herbal medicines limit the benefits of herbal-based cancer therapies. In this review, we address that PTMs add a layer of proteomic complexity to the cancer through altering the protein structure, expression, function, and localization. Elaborating PTM implicated in cell signaling, apoptosis and transcriptional regulation function, and the possible cellular signaling, have provided important information about the mechanism of many herbal therapies. Continued optimization of proteomic strategies for PTM analysis in herbal medicines are also discussed. FUTURE DIRECTIONS: Rigorous evaluations of herbal medicines and the chemoproteomic strategies are necessary to explore the aberrant regulation of PTM dynamics contributed to the cancer development and herbal associated pharmacological issues. These efforts will eventually help develop more herbal drugs as modern therapeutic agents.

3.
ACS Sens ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970501

RESUMO

The combination of closed bipolar electrodes (cBPE) with electrochemiluminescence (ECL) imaging has demonstrated remarkable capabilities in the field of bioanalysis. Here, we established a cBPE-ECL platform for ultrasensitive detection of alkaline phosphatase (ALP) and two-dimensional imaging of epidermal growth factor receptor (EGFR). This cBPE-ECL system consists of a high-density gold nanowire array in anodic aluminum oxide (AAO) membrane as the cBPE coupled with ECL of highly luminescent cadmium selenide quantum dots (CdSe QDs) luminophores to achieve cathodic electro-optical conversion. When an enzyme-catalyzed amplification effect of ALP with 4-aminophenyl phosphate monosodium salt hydrate (p-APP) as the substrate and 4-aminophenol (p-AP) as the electroactive probe is introduced, a significant improvement of sensing sensitivity with a detection limit as low as 0.5 fM for ALP on the cBPE-ECL platform can be obtained. In addition, the cBPE-ECL sensing system can also be used to detect cancer cells with an impressive detection limit of 50 cells/mL by labeling ALP onto the EGFR protein on A431 human epidermal cancer cell membranes. Thus, two-dimensional (2D) imaging of the EGFR proteins on the cell surface can be achieved, demonstrating that the established cBPE-ECL sensing system is of high resolution for spatiotemporal cell imaging.

4.
Angew Chem Int Ed Engl ; : e202412651, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39030810

RESUMO

Photonic heterostructures with codable properties have shown great values as versatile information carriers at the micro and nanoscale. These heterostructures are typically prepared by a step-by-step growth or post-functionalization method to achieve varied emission colors among different building blocks. In order to realize high-throughput and multivariate information loading, we report here a strategy to integrate polarization signals into photonic heterojunctions. A U-shaped di-Pt(II) complex is assembled into highly-polarized yellow-phosphorescent crystalline microrods (Y-rod) by strong intermolecular Pt···Pt interaction. Upon end-initiated desorption of the incorporated CH2Cl2 solvents, Y-rod is transformed in a domino fashion into tri-block polarized photonic heterojunctions (PPHs) with alternate red-yellow-red emissions or red-phosphorescent microrods (R-rod). The red emissions of these structures are also highly polarized; however, their polarization directions are just orthogonal to those of the yellow phosphorescence of Y-rod. With the aid of a patterned mask, R-rod is further programmed into multi-block PPHs with precisely-controlled block sizes by side-allowed adsorption of CH2Cl2 vapor. X-ray diffraction analysis and theoretical calculations suggest that the solvent-regulated modulation of intramolecular and intermolecular excited states is critical for the construction of these PPHs.

5.
Nat Microbiol ; 9(7): 1828-1841, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38886583

RESUMO

Bacteriophages have evolved diverse strategies to overcome host defence mechanisms and to redirect host metabolism to ensure successful propagation. Here we identify a phage protein named Dap1 from Pseudomonas aeruginosa phage PaoP5 that both modulates bacterial host behaviour and contributes to phage fitness. We show that expression of Dap1 in P. aeruginosa reduces bacterial motility and promotes biofilm formation through interference with DipA, a c-di-GMP phosphodiesterase, which causes an increase in c-di-GMP levels that trigger phenotypic changes. Results also show that deletion of dap1 in PaoP5 significantly reduces genome packaging. In this case, Dap1 directly binds to phage HNH endonuclease, prohibiting host Lon-mediated HNH degradation and promoting phage genome packaging. Moreover, PaoP5Δdap1 fails to rescue P. aeruginosa-infected mice, implying the significance of dap1 in phage therapy. Overall, these results highlight remarkable dual functionality in a phage protein, enabling the modulation of host behaviours and ensuring phage fitness.


Assuntos
Terapia por Fagos , Infecções por Pseudomonas , Fagos de Pseudomonas , Pseudomonas aeruginosa , Proteínas Virais , Pseudomonas aeruginosa/virologia , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/genética , Animais , Camundongos , Fagos de Pseudomonas/genética , Fagos de Pseudomonas/fisiologia , Infecções por Pseudomonas/terapia , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/imunologia , Virulência , Proteínas Virais/genética , Proteínas Virais/metabolismo , Biofilmes/crescimento & desenvolvimento , GMP Cíclico/metabolismo , GMP Cíclico/análogos & derivados , Feminino , Bacteriófagos/fisiologia , Bacteriófagos/genética
6.
Clin Lab ; 70(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38868873

RESUMO

BACKGROUND: From June 2021 to July 2021, our hospital confirmed 3 cases of Mycobacterium infection in skin abscesses. All 3 patients underwent thread embedding and weight loss surgery at the same informal beauty institution, with a history of silk protein injection. None of the patients had any other underlying diseases or surgical history. Symptoms and signs show that the disease is acute and the course of the disease is short. All patients have found subcutaneous masses in different parts of the body. In most cases, the masses show redness and swelling, and some of the masses are accompanied by tenderness, wave sensation, and rupture. After some of the masses rupture, purulent secretions can be seen. METHODS: The pus secreted by the skin lesions of the three patients were cultured to a single bacterium, which was identified by MALDI-TOF MS. Multiple locus sequence typing (MLST) was performed using three specific genes (hsp65, rpoB, and secA1) and seven housekeeping genes (argH, cya, glpK, gnd, murC, pta, and purH). The results were queried through the MLST database of Mycobacterium abscess. RESULTS: All three strains of bacteria were Mycobacterium abscess type ST279 massiliense subtype. Three antibacterial drugs including cefmetazole, amikacin, and clarithromycin were administered in combination with 5-aminolevulinic acid photodynamic therapy (ALA-PDT). After 3 - 6 months, there was no obvious redness or swelling in the surrounding tissues of the wound, and no obvious purulent secretions were observed. All patients were cured and discharged from the hospital. After a follow-up of six months, there was no recurrence of the lesions. CONCLUSIONS: Medical institutions must strictly follow infection control guidelines and take preventive measures to prevent such incidents from happening again. ALA-PDT as a combination therapy for nontuberculous Mycobacterium (NTM) skin infections can improve treatment efficacy and shorten antibiotic usage time.


Assuntos
Antibacterianos , Surtos de Doenças , Infecções por Mycobacterium não Tuberculosas , Humanos , Feminino , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Adulto , Antibacterianos/uso terapêutico , Dermatopatias Bacterianas/epidemiologia , Dermatopatias Bacterianas/microbiologia , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Abscesso/microbiologia , Abscesso/epidemiologia , Abscesso/diagnóstico , Mycobacterium abscessus/isolamento & purificação , Mycobacterium abscessus/genética , Micobactérias não Tuberculosas/isolamento & purificação , Micobactérias não Tuberculosas/genética , Micobactérias não Tuberculosas/efeitos dos fármacos
7.
Clin Lab ; 70(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38868894

RESUMO

BACKGROUND: In July 2023, our hospital confirmed one case of lumbar spine infected complicated by Mycobacterium tuberculosis and Cryptococcus neoformans. The patient was admitted due to lower back pain for 1 year and a hard lump for 3 months. Symptoms and signs: Dressing can be seen fixed on the lower back, with severe bleeding. When the dressing is removed, a hard and protruding lump with a size of 6 cm x 8 cm, a sinus tract can be seen near the mass, with a slightly red wound and a sinus depth of about 3 cm. Light red fluid can be seen flowing out. There are no symptoms such as redness, swelling, or heat in the rest of the lower back, and the patient has no other underlying diseases or surgical history. METHODS: Lumbar magnetic resonance imaging and lumbar CT examination; Percutaneous puncture lumbar vertebral biopsy was performed, and the biopsy tissue was subjected to pathological examination, mNGS (metagenomic next-generation sequencing), and acid-fast staining; Extract pus from the lump for fungal culture and ink staining, and identify the fungi through MALDI-TOF MS. RESULTS: Bone destruction and bone marrow edema in the L5 vertebral body, compression of the spinal canal at the L5 vertebral body level; The pathological results of the biopsy tissue indicate granulomatous lesions. The acid-fast staining of the tissue is positive, and the mNGS of the tissue indicates infection with Mycobacterium tuberculosis. A single fungus was cultured from pus and identified by MALDI-TOF MS as Cryptococcus neoformans. Clinically, isoniazid 0.3 g ivgtt + rifampicin 0.45 g qd po + ethambutol 0.25 g qd po + pyrazinamide 0.75 g qd po + fluconazole 0.3 g qd po was administered for treatment. After 11 days, there was slight pain at the incision site, and the original symptoms were significantly relieved. The wound dressing was fixed in place, dry and without obvious exudation. Improved and discharged, followed up for 3 months with no recurrence of the lesion. CONCLUSIONS: mNGS is an effective identification technique that can be used to accurately diagnose suspected infection cases. MALDI-TOF MS has significant advantages over traditional detection methods in shortening detection time. This case achieved satisfactory treatment results for patients through a reasonable treatment plan, which is of great significance for exploring the diagnosis and treatment of similar disease infections.


Assuntos
Criptococose , Cryptococcus neoformans , Vértebras Lombares , Mycobacterium tuberculosis , Humanos , Cryptococcus neoformans/isolamento & purificação , Vértebras Lombares/microbiologia , Mycobacterium tuberculosis/isolamento & purificação , Criptococose/diagnóstico , Criptococose/microbiologia , Criptococose/tratamento farmacológico , Masculino , Tuberculose da Coluna Vertebral/diagnóstico , Tuberculose da Coluna Vertebral/microbiologia , Imageamento por Ressonância Magnética , Antituberculosos/uso terapêutico , Antituberculosos/administração & dosagem , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
8.
Angew Chem Int Ed Engl ; : e202405520, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896428

RESUMO

Functionalization of Si-bound methyl group provides an efficient access to diverse organosilanes. However, the asymmetric construction of silicon-stereogenic architectures by functionalization of Si-bound methyl group has not yet been described despite recent significant progress in producing chiral silicon. Herein, we disclosed the enantioselective silylmethyl functionalization involving the aryl to alkyl 1,5-palladium migration to access diverse naphthalenes possessing an enantioenriched stereogenic silicon center, which are inaccessible before. It is worthy to note that the realization of asymmetric induction at the step of metal migration itself remains challenging. Our study constitutes the first enantioselective aryl to alkyl 1,5-palladium migration reaction. The key to the success is the discovery and fine-tuning of the different substituents of α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL)-based phosphoramidites, which ensure the enantioselectivity and desired reactivity.

9.
BMC Cancer ; 24(1): 775, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937687

RESUMO

BACKGROUND: Lung cancer (LC), characterized by high incidence and mortality rates, presents a significant challenge in oncology. Despite advancements in treatments, early detection remains crucial for improving patient outcomes. The accuracy of screening for LC by detecting volatile organic compounds (VOCs) in exhaled breath remains to be determined. METHODS: Our systematic review, following PRISMA guidelines and analyzing data from 25 studies up to October 1, 2023, evaluates the effectiveness of different techniques in detecting VOCs. We registered the review protocol with PROSPERO and performed a systematic search in PubMed, EMBASE and Web of Science. Reviewers screened the studies' titles/abstracts and full texts, and used QUADAS-2 tool for quality assessment. Then performed meta-analysis by adopting a bivariate model for sensitivity and specificity. RESULTS: This study explores the potential of VOCs in exhaled breath as biomarkers for LC screening, offering a non-invasive alternative to traditional methods. In all studies, exhaled VOCs discriminated LC from controls. The meta-analysis indicates an integrated sensitivity and specificity of 85% and 86%, respectively, with an AUC of 0.93 for VOC detection. We also conducted a systematic analysis of the source of the substance with the highest frequency of occurrence in the tested compounds. Despite the promising results, variability in study quality and methodological challenges highlight the need for further research. CONCLUSION: This review emphasizes the potential of VOC analysis as a cost-effective, non-invasive screening tool for early LC detection, which could significantly improve patient management and survival rates.


Assuntos
Testes Respiratórios , Detecção Precoce de Câncer , Neoplasias Pulmonares , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Detecção Precoce de Câncer/métodos , Testes Respiratórios/métodos , Expiração , Sensibilidade e Especificidade , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo
10.
Vet Microbiol ; 295: 110152, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38896938

RESUMO

The intestinal barrier of newborn piglets is vulnerable and underdeveloped, making them susceptible to enteric virus infections. Benzoic acid (BA), employed as a growth promoter, exhibits the potential to enhance the gut health of piglets by modulating intestinal morphometry and tight junction dynamics. However, the extent to which BA regulates the intestinal mucus barrier through its impact on stem cells remains inadequately elucidated. Therefore, this study was conducted to investigate the effects of BA on the intestinal barrier and the differentiation of intestinal stem cells, employing in vivo piglet and in vitro intestinal organoid models. Our investigation revealed a significant increase in the number of goblet cells within the small intestine, as well as the strengthening of the mucus barrier in vivo following oral treatment with BA, providing partial protection against PEDV infection in piglets. Additionally, in vitro cultivation of enteroids with BA led to a notable increase in the number of MUC2+ GCs, indicating the promotion of GC differentiation by BA. Furthermore, transcriptome analysis revealed an upregulation of the number of GCs and the expression of cell vesicle transport-related genes during BA stimulation, accompanied by the downregulation of the Wnt and Notch signaling pathways. Mechanistically, MCT1 facilitated the transport of BA, subsequently activating the MAPK pathway to mediate GC differentiation. Overall, this study highlights a novel function for BA as a feed additive in enhancing the intestinal mucus barrier by promoting intestinal GC differentiation, and further prevents viral infection in piglets.


Assuntos
Ácido Benzoico , Infecções por Coronavirus , Mucosa Intestinal , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Suínos , Ácido Benzoico/farmacologia , Doenças dos Suínos/virologia , Doenças dos Suínos/tratamento farmacológico , Vírus da Diarreia Epidêmica Suína/efeitos dos fármacos , Vírus da Diarreia Epidêmica Suína/fisiologia , Mucosa Intestinal/efeitos dos fármacos , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Infecções por Coronavirus/tratamento farmacológico , Animais Recém-Nascidos , Células Caliciformes/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Organoides/virologia , Organoides/efeitos dos fármacos , Intestinos/virologia , Intestinos/efeitos dos fármacos
11.
Radiother Oncol ; 199: 110390, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38897316

RESUMO

PURPOSE: To evaluate the prognostic value of peripheral lymphocyte count (PLC) in the breast cancer patients after breast-conserving surgery (BCS) with radiotherapy (RT). METHODS AND MATERIALS: This post hoc analysis was performed using data of 628 patients from a phase III, randomized controlled trial comparing hypofractionated RT (HFRT) with conventional fractionated RT (CFRT) after BCS. PLCs were obtained before, during, and after RT until the 1-year follow-up. The optimal cut-off PLCs were determined using the maxstat package in R. Survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: A total of 275 (46.1 %) patients developed lymphopenia during RT, among them, 17 (2.8 %) had grade 3 lymphopenia and no one developed grade 4 lymphopenia. With a median follow-up of 110.8 months, patients with pre-RT PLCs of < 1.77 × 109/L had a significantly lower 10-year breast cancer-specific survival (BCSS) rate (P = 0.013) and overall survival (OS) rate (P = 0.026). Patients with a nadir PLC of < 1.35 × 109/L had a significantly poorer 10-year OS rate (P = 0.048). Multivariate analysis showed that a pre-RT PLC of < 1.77 × 109/L was an independent factor influencing BCSS and OS, while the effect of the nadir PLC did not remain significant. Neither PLC nor lymphopenia recovery at post-RT 1, 3, and 6 months and 1 year was associated with survival. CONCLUSIONS: Radiation-induced lymphopenia in patients with breast cancer after BCS tends to be mild. The lower pre-RT PLC predicted poorer survival.

12.
Nat Commun ; 15(1): 4402, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782924

RESUMO

Endowing the widely-used synthetic polymer nylon with high-performance organic room-temperature phosphorescence would produce advanced materials with a great potential for applications in daily life and industry. One key to achieving this goal is to find a suitable organic luminophore that can access the triplet excited state with the aid of the nylon matrix by controlling the matrix-luminophore interaction. Herein we report highly-efficient room-temperature phosphorescence nylons by doping cyano-substituted benzimidazole derivatives into the nylon 6 matrix. These homogeneously doped materials show ultralong phosphorescence lifetimes of up to 1.5 s and high phosphorescence quantum efficiency of up to 48.3% at the same time. The synergistic effect of the homogeneous dopant distribution via hydrogen bonding interaction, the rigid environment of the matrix polymer, and the potential energy transfer between doped luminophores and nylon is important for achieving the high-performance room-temperature phosphorescence, as supported by combined experimental and theoretical results with control compounds and various polymeric matrices. One-dimensional optical fibers are prepared from these doped room-temperature phosphorescence nylons that can transport both blue fluorescent and green afterglow photonic signals across the millimeter distance without significant optical attenuation. The potential applications of these phosphorescent materials in dual information encryption and rewritable recording are illustrated.

13.
Hum Mol Genet ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776958

RESUMO

The ubiquitin-proteasome system mediates the degradation of a wide variety of proteins. Proteasome dysfunction is associated with neurodegenerative diseases and neurodevelopmental disorders in humans. Here we identified mutations in PSMC5, an AAA ATPase subunit of the proteasome 19S regulatory particle, in individuals with neurodevelopmental disorders, which were initially considered as variants of unknown significance. We have now found heterozygotes with the following mutations: P320R (6 individuals), R325W, Q160A, and one nonsense mutation at Q69. We focused on understanding the functional consequence of PSMC5 insufficiency and the P320R mutation in cells and found that both impair proteasome function and activate apoptosis. Interestingly, the P320R mutation impairs proteasome function by weakening the association between the 19S regulatory particle and the 20S core particle. Our study supports that proteasome dysfunction is the pathogenic cause of neurodevelopmental disorders in individuals carrying PSMC5 variants.

14.
Nat Commun ; 15(1): 4347, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773146

RESUMO

Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.


Assuntos
Homólogo AlkB 5 da RNA Desmetilase , Astrócitos , Transtorno Depressivo Maior , Camundongos Knockout , Animais , Astrócitos/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Camundongos , Humanos , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/patologia , Masculino , Feminino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Estresse Psicológico/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/genética , Comportamento Animal , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Depressão/metabolismo , Depressão/genética , Adulto , Transmissão Sináptica , Pessoa de Meia-Idade
15.
Parasit Vectors ; 17(1): 205, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715092

RESUMO

BACKGROUND: Angiostrongyliasis is a highly dangerous infectious disease. Angiostrongylus cantonensis larvae migrate to the mouse brain and cause symptoms, such as brain swelling and bleeding. Noncoding RNAs (ncRNAs) are novel targets for the control of parasitic infections. However, the role of these molecules in A. cantonensis infection has not been fully clarified. METHODS: In total, 32 BALB/c mice were randomly divided into four groups, and the infection groups were inoculated with 40 A. cantonensis larvae by gavage. Hematoxylin and eosin (H&E) staining and RNA library construction were performed on brain tissues from infected mice. Differential expression of long noncoding RNAs (lncRNAs) and mRNAs in brain tissues was identified by high-throughput sequencing. The pathways and functions of the differentially expressed lncRNAs were determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The functions of the differentially expressed lncRNAs were further characterized by lncRNA‒microRNA (miRNA) target interactions. The potential host lncRNAs involved in larval infection of the brain were validated by quantitative real-time polymerase chain reaction (qRT‒PCR). RESULTS: The pathological results showed that the degree of brain tissue damage increased with the duration of infection. The transcriptome results showed that 859 lncRNAs and 1895 mRNAs were differentially expressed compared with those in the control group, and several lncRNAs were highly expressed in the middle-late stages of mouse infection. GO and KEGG pathway analyses revealed that the differentially expressed target genes were enriched mainly in immune system processes and inflammatory response, among others, and several potential regulatory networks were constructed. CONCLUSIONS: This study revealed the expression profiles of lncRNAs in the brains of mice after infection with A. cantonensis. The lncRNAs H19, F630028O10Rik, Lockd, AI662270, AU020206, and Mexis were shown to play important roles in the infection of mice with A. cantonensis infection.


Assuntos
Angiostrongylus cantonensis , Encéfalo , Camundongos Endogâmicos BALB C , RNA Longo não Codificante , Infecções por Strongylida , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Angiostrongylus cantonensis/genética , Infecções por Strongylida/parasitologia , Infecções por Strongylida/genética , Encéfalo/parasitologia , Encéfalo/metabolismo , Encéfalo/patologia , Camundongos , Larva/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Perfilação da Expressão Gênica , Feminino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
16.
World J Psychiatry ; 14(5): 715-725, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38808090

RESUMO

BACKGROUND: Psychological distress, especially depression, associated with perianal fistulizing Crohn's disease (PFCD) is widespread and refractory. However, there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD. AIM: To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD. METHODS: The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff. Depressive symptoms, life quality, and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9, Inflammatory Bowel Disease Patient Quality of Life Questionnaire (IBDQ), and Inflammatory Bowel Disease (IBD) Fatigue Patient Self-assessment Scale. The basic demographic information, overall disease features, perianal clinical information, and laboratory inflammation indicators were also gathered. Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD. RESULTS: A total of 123 patients with PFCD were involved, and 56.91% were suffering from depression. According to multivariate logistic regression analysis, Perianal Disease Activity Index (PDAI) score [odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50 to 0.95], IBDQ score (OR = 0.93, 95%CI: 0.88 to 0.97), modified Van Assche index (OR = 1.24, 95%CI: 1.01 to 1.53), and IBD Fatigue score (OR = 1.72, 95%CI: 1.23 to 2.42) were independent risk factors of depression-related prevalence among patients with PFCD (P < 0.05). Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index (ß value = 0.166, 95%CI: 0.02 to 0.31) and decreasing IBDQ score (ß value = -0.116, 95%CI: -0.14 to -0.09) were independently associated with the severity of depression (P < 0.05). CONCLUSION: Depressive symptoms in PFCD patients have significantly high prevalence. PDAI score, modified Van Assche index, quality of life, and fatigue severity were the main independent risk factors.

17.
Angew Chem Int Ed Engl ; 63(25): e202402882, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38594208

RESUMO

Circularly polarized luminescence (CPL)-active molecular materials have drawn increasing attention due to their promising applications for next-generation display and optoelectronic technologies. Currently, it is challenging to obtain CPL materials with both large luminescence dissymmetry factor (glum) and high quantum yield (Φ). A pair of enantiomeric N N C-type Pt(II) complexes (L/D)-1 modified with chiral Leucine methyl ester are presented herein. Though the solutions of these complexes are CPL-inactive, the spin-coated thin films of (L/D)-1 exhibit giantly-amplified circularly polarized phosphorescences with |glum| of 0.53 at 560 nm and Φair of ~50 %, as well as appealing circular dichroism (CD) signals with the maximum absorption dissymmetry factor |gabs| of 0.37-0.43 at 480 nm. This superior CPL performance benefits from the hierarchical formation of crystalline fibrillar networks upon spin coating. Comparative studies of another pair of chiral Pt(II) complexes (L/D)-2 with a symmetric N C N coordination mode suggest that the asymmetric N N C coordination of (L/D)-1 are favorable for the efficient exciton delocalization to amplify the CPL performance. Optical applications of the thin films of (L/D)-1 in CPL-contrast imaging and inducing CP light generation from achiral emitters and common light-emitting diode lamps have been successfully realized.

18.
Emerg Infect Dis ; 30(5): 1055-1057, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38666739

RESUMO

We report a clinical isolate of Burkholderia thailandensis 2022DZh obtained from a patient with an infected wound in southwest China. Genomic analysis indicates that this isolate clusters with B. thailandensis BPM, a human isolate from Chongqing, China. We recommend enhancing monitoring and surveillance for B. thailandensis infection in both humans and livestock.


Assuntos
Infecções por Burkholderia , Burkholderia , Filogenia , Infecção dos Ferimentos , Humanos , Masculino , Burkholderia/genética , Burkholderia/isolamento & purificação , Burkholderia/classificação , Infecções por Burkholderia/microbiologia , Infecções por Burkholderia/diagnóstico , China/epidemiologia , Genoma Bacteriano , Infecção dos Ferimentos/microbiologia , Pessoa de Meia-Idade
19.
Proc Natl Acad Sci U S A ; 121(16): e2319790121, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38593079

RESUMO

Bacteriophages (phages) play critical roles in modulating microbial ecology. Within the human microbiome, the factors influencing the long-term coexistence of phages and bacteria remain poorly investigated. Saccharibacteria (formerly TM7) are ubiquitous members of the human oral microbiome. These ultrasmall bacteria form episymbiotic relationships with their host bacteria and impact their physiology. Here, we showed that during surface-associated growth, a human oral Saccharibacteria isolate (named TM7x) protects its host bacterium, a Schaalia odontolytica strain (named XH001) against lytic phage LC001 predation. RNA-Sequencing analysis identified in XH001 a gene cluster with predicted functions involved in the biogenesis of cell wall polysaccharides (CWP), whose expression is significantly down-regulated when forming a symbiosis with TM7x. Through genetic work, we experimentally demonstrated the impact of the expression of this CWP gene cluster on bacterial-phage interaction by affecting phage binding. In vitro coevolution experiments further showed that the heterogeneous populations of TM7x-associated and TM7x-free XH001, which display differential susceptibility to LC001 predation, promote bacteria and phage coexistence. Our study highlights the tripartite interaction between the bacterium, episymbiont, and phage. More importantly, we present a mechanism, i.e., episymbiont-mediated modulation of gene expression in host bacteria, which impacts their susceptibility to phage predation and contributes to the formation of "source-sink" dynamics between phage and bacteria in biofilm, promoting their long-term coexistence within the human microbiome.


Assuntos
Bacteriófagos , Humanos , Bacteriófagos/fisiologia , Simbiose , Bactérias/genética
20.
Heliyon ; 10(8): e29156, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38644822

RESUMO

Background: The occurrence and development of sepsis are related to the excessive production of oxygen free radicals and the weakened natural clearance mechanism. Further dependable evidence is required to clarify the effectiveness of antioxidant therapy, especially its impact on short-term mortality. Objectives: The purpose of this systematic review and meta-analysis was to evaluate the effect of common antioxidant therapy on short-term mortality in patients with sepsis. Methods: According to PRISMA guidelines, a systematic literature search on antioxidants in adults sepsis patients was performed on PubMed/Medline, Embase, and the Cochrane Library from the establishment of the database to November 2023. Antioxidant supplements can be a single-drug or multi-drug combination: HAT (hydrocortisone, ascorbic acid, and thiamine), ascorbic acid, thiamine, N-acetylcysteine and selenium. The primary outcome was the effect of antioxidant treatment on short-term mortality, which included 28-day mortality, in-hospital mortality, intensive care unit mortality, and 30-day mortality. Subgroup analyses of short-term mortality were used to reduce statistical heterogeneity and publication bias. Results: Sixty studies of 130,986 sepsis patients fulfilled the predefined criteria and were quantified and meta-analyzed. Antioxidant therapy reduces the risk of short-term death in sepsis patients by multivariate meta-analysis of current data, including a reduction of in-hospital mortality (OR = 0.81, 95% CI 0.67 to 0.99; P = 0.040) and 28-day mortality (OR = 0.81, 95% CI 0.69 to 0.95]; P = 0.008). Particularly in subgroup analyses, ascorbic acid treatment can reduce in-hospital mortality (OR = 0.66, 95% CI 0.90 to 0.98; P = 0.006) and 28-day mortality (OR = 0.43, 95% CI 0.24 to 0.75; P = 0.003). However, the meta-analysis of RCTs found that antioxidant therapy drugs, especially ascorbic acid, did substantially reduce short-term mortality(OR = 0.78, 95% CI 0.62 to 0.98; P = 0.030; OR = 0.57, 95% CI 0.36 to 0.91; P = 0.020). Conclusions: According to current data of RCTs, antioxidant therapy, especially ascorbic acid, has a trend of improving short-term mortality in patients with sepsis, but the evidence remains to be further demonstrated.

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