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1.
Sci Adv ; 10(27): eadl6428, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38959319

RESUMO

Cyanobacteria use a series of adaptation strategies and a complicated regulatory network to maintain intracellular iron (Fe) homeostasis. Here, a global activator named IutR has been identified through three-dimensional chromosome organization and transcriptome analysis in a model cyanobacterium Synechocystis sp. PCC 6803. Inactivation of all three homologous IutR-encoding genes resulted in an impaired tolerance of Synechocystis to Fe deficiency and loss of the responses of Fe uptake-related genes to Fe-deplete conditions. Protein-promoter interaction assays confirmed the direct binding of IutR with the promoters of genes related to Fe uptake, and chromatin immunoprecipitation sequencing analysis further revealed that in addition to Fe uptake, IutR could regulate many other physiological processes involved in intracellular Fe homeostasis. These results proved that IutR is an important transcriptional activator, which is essential for cyanobacteria to induce Fe-deficiency response genes. This study provides in-depth insights into the complicated Fe-deficient signaling network and the molecular mechanism of cyanobacteria adaptation to Fe-deficient environments.


Assuntos
Regulação Bacteriana da Expressão Gênica , Homeostase , Ferro , Regiões Promotoras Genéticas , Synechocystis , Ferro/metabolismo , Synechocystis/metabolismo , Synechocystis/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Cianobactérias/metabolismo , Cianobactérias/genética , Perfilação da Expressão Gênica
2.
Balkan Med J ; 41(4): 286-297, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38966918

RESUMO

Background: Cannabidiol (CBD), extracted from Cannabis sativa, has anticancer, anti-inflammation, and analgesic effects. Nevertheless, its therapeutic effect and the mechanism by which it alleviates oral mucositis (OM) remain unclear. Aims: To explore the impact of CBD on OM in mice and on human oral keratinocyte (HOK) cells. Study Design: Expiremental study. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, GeneCard, DisGeNET, and Gene Expression Omnibus databases were used to conduct therapeutic target gene screening for drugs against OM. Cytoscape software was used to build networks linking components, targets, and diseases. The STRING database facilitated analysis of intertarget action relationships, and the target genes were analyzed for Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Occurrence of serum inflammation-related factors, hematoxylin and eosin staining, and immunohistochemistry were used to assess OM injury. Cell proliferation, migration, pyroptosis, and apoptosis of HOK cells under different treatments were assessed. Molecular mechanisms were elucidated through western blot and quantitative real-time polymerase chain reaction analyses. Results: A total of 49 overlapping genes were pinpointed as potential targets, with NF-κB1, PIK3R1, NF-κBIA, and AKT1 being recognized as hub genes among them. Additionally, the PI3K/Akt/NF-κB and interleukin-17 signaling pathways were identified as relevant. Our in vivo experiments showed that CBD significantly reduced the proportion of lesion area, mitigated oral mucosal tissue lesions, and downregulated the expression levels of genes and levels of proteins, including NLRP3, P65, AKT, and PI3K. In vitro experiments indicated that CBD enhanced HOK cell proliferation and migration and reduced apoptosis through inhibition of the PI3K/Akt/NF-κB signaling pathway and pyroptosis. Conclusion: Our findings suggest a novel mechanism for controlling OM, in which CBD suppresses the PI3K/Akt/NF-κB signaling pathway and pyroptosis, thereby mitigating OM symptoms.


Assuntos
Canabidiol , NF-kappa B , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Piroptose , Estomatite , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Animais , Piroptose/efeitos dos fármacos , Camundongos , Estomatite/tratamento farmacológico , NF-kappa B/efeitos dos fármacos , NF-kappa B/análise , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Modelos Animais de Doenças
3.
ACS Sens ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967239

RESUMO

Limited by insufficient active sites and restricted mechanical strength, designing reliable and wearable gas sensors with high activity and ductility remains a challenge for detecting hazardous gases. In this work, a thermally induced and solvent-assisted oxyanion etching strategy was implemented for selective pore opening in a rigid microporous Cu-based metal-organic framework (referred to as CuM). A conductive CuM/MXene aerogel was then self-assembled through cooperative hydrogen bonding interactions between the carbonyl oxygen atom in PVP grafted on the surface of defect-rich Cu-BTC and the surface functional hydroxyl group on MXene. A flexible NO2 sensing performance using the CuM/MXene aerogel hybridized sodium alginate hydrogel is finally achieved, demonstrating extraordinary sensitivity (S = 52.47 toward 50 ppm of NO2), good selectivity, and rapid response/recovery time (0.9/4.5 s) at room temperature. Compared with commercial sensors, the relative error is less than 7.7%, thereby exhibiting significant potential for application in monitoring toxic and harmful gases. This work not only provides insights for guiding rational synthesis of ideal structure models from MOF composites but also inspires the development of high-performance flexible gas sensors for potential multiscenario applications.

4.
Stem Cell Res ; 79: 103486, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38968760

RESUMO

Pluripotent stem cells were generated through the electroporation of episomal plasmids, containing crucial reprogramming factors, into skin fibroblasts extracted from a female Alzheimer's patient harboring the PSEN1 709 T > C (p.Phe237Leu) heterozygous mutation. The pluripotent stem cells exhibit a normal karyotype and express pivotal stem cell markers including TRA-1-60, Nanog, SOX2, and OCT4. Furthermore, their capacity to differentiate into the three germ layers in in vivo teratoma experiments has been substantiated. The pluripotent stem cell line can serve as a cellular model for Alzheimer's disease, offering significant value in elucidating the pathogenesis and therapeutic strategies of the disease.

5.
BMC Musculoskelet Disord ; 25(1): 515, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961403

RESUMO

OBJECTIVE: The purpose of this study is to compare radiological and clinical outcomes between alternate levels (C4 and C6) and all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. METHODS: Ninety-six patients who underwent C3-6 unilateral open-door laminoplasty with alternate levels mini-plate fixation (54 patients in group A) or all levels mini-plate fixation (42 patients in group B) between September 2014 and September 2019 were reviewed in this study. Radiologic and clinical outcomes were assessed. Clinical results included Visual Analogue Scale (VAS) of axial neck pain and Japanese Orthopedic Association (JOA) score. Radiographic results included cervical range of motion (ROM), cervical curvature index (CCI), and the spinal canal expansive parameters including open angle, anteroposterior diameter (APD), and Pavlov`s ratio. RESULTS: There was no significant difference in VAS, JOA score, ROM, and CCI between two groups. There was no significant difference in canal expansion postoperatively between two groups. However, open angle, APD, and Pavlov`s ratio in group A decreased significantly during the follow-up. In group B, APD, Pavlov`s ratio, and open angle were maintained until the final follow-up. There was no hardware failure or lamina reclosure occurred in both groups during the follow-up. The mean cost of group B was higher than that of group A. CONCLUSIONS: Despite the differences in the maintenance of canal expansion, alternate levels mini-plate fixation can achieve similar clinical outcomes as all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. As evidenced in this study, we believe C3-6 laminoplasty with alternate levels (C4 and C6) mini-plate fixation is an economical, effective, and safe treatment method.


Assuntos
Placas Ósseas , Vértebras Cervicais , Laminoplastia , Humanos , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Laminoplastia/métodos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Masculino , Idoso , Resultado do Tratamento , Amplitude de Movimento Articular , Adulto , Cervicalgia/etiologia , Cervicalgia/cirurgia
6.
Biopreserv Biobank ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959173

RESUMO

The emergence of organoids is considered a revolutionary model, changing the landscape of traditional translational research. These three-dimensional miniatures of human organs or tissues, cultivated from stem cells or biospecimens obtained from patients, faithfully replicate the structural and functional characteristics of specific target organs or tissues. In this extensive review, we explore the profound impact of organoids and assess the current state of living organoid biobanks, which are essential repositories for cryopreserving organoids derived from a variety of diseases. These resources hold significant value for translational research. We delve into the diverse origins of organoids, the underlying technologies, and their roles in recapitulating human development, disease modeling, as well as their potential applications in the pharmaceutical field. With a particular emphasis on biobanking organoids for prospective applications, we discuss how these advancements expedite the transition from bench to bedside translational research, thereby fostering personalized medicine and enriching our comprehension of human health.

7.
FASEB J ; 38(13): e23791, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38963340

RESUMO

Inflammatory bowel disease (IBD) is a kind of recurrent inflammatory disorder of the intestinal tract. The purpose of this study was to investigate the effects of Weissella paramesenteroides NRIC1542 on colitis in mice. A colitis model was induced by adding 1.5% DSS to sterile distilled water for seven consecutive days. During this process, mice were administered different concentrations of W. paramesenteroides NRIC1542. Colitis was assessed by DAI, colon length and hematoxylin-eosin staining of colon sections. The expressions of NF-κB signaling proteins and the tight junction proteins ZO-1 and occludin were detected by western blotting, and the gut microbiota was analyzed by 16S rDNA. The results showed that W. paramesenteroides NRIC1542 significantly reduced the degree of pathological tissue damage and the levels of TNF-α and IL-1ß in colonic tissue, inhibiting the NF-κB signaling pathway and increasing the expression of SIRT1, ZO-1 and occludin. In addition, W. paramesenteroides NRIC1542 can modulate the structure of the gut microbiota, characterized by increased relative abundance of Muribaculaceae_unclassified, Paraprevotella, Prevotellaceae_UCG_001 and Roseburia, and decrease the relative abundance of Akkermansia and Alloprevotella induced by DSS. The above results suggested that W. paramesenteroides NRIC1542 can protect against DSS-induced colitis in mice through anti-inflammatory, intestinal barrier maintenance and flora modulation.


Assuntos
Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , NF-kappa B , Transdução de Sinais , Sirtuína 1 , Weissella , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Sirtuína 1/metabolismo , Camundongos , Colite/induzido quimicamente , Colite/metabolismo , Colite/microbiologia , Sulfato de Dextrana/toxicidade , Transdução de Sinais/efeitos dos fármacos , NF-kappa B/metabolismo , Weissella/metabolismo , Masculino , Probióticos/farmacologia
8.
Biomed Environ Sci ; 37(6): 617-627, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38988112

RESUMO

Objective: The aim of this study was to explore the role and mechanism of ferroptosis in SiO 2-induced cardiac injury using a mouse model. Methods: Male C57BL/6 mice were intratracheally instilled with SiO 2 to create a silicosis model. Ferrostatin-1 (Fer-1) and deferoxamine (DFO) were used to suppress ferroptosis. Serum biomarkers, oxidative stress markers, histopathology, iron content, and the expression of ferroptosis-related proteins were assessed. Results: SiO 2 altered serum cardiac injury biomarkers, oxidative stress, iron accumulation, and ferroptosis markers in myocardial tissue. Fer-1 and DFO reduced lipid peroxidation and iron overload, and alleviated SiO 2-induced mitochondrial damage and myocardial injury. SiO 2 inhibited Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes, while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion: Iron overload-induced ferroptosis contributes to SiO 2-induced cardiac injury. Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO 2 cardiotoxicity, potentially via modulation of the Nrf2 pathway.


Assuntos
Modelos Animais de Doenças , Ferroptose , Sobrecarga de Ferro , Camundongos Endogâmicos C57BL , Miócitos Cardíacos , Dióxido de Silício , Silicose , Animais , Ferroptose/efeitos dos fármacos , Masculino , Camundongos , Sobrecarga de Ferro/metabolismo , Dióxido de Silício/toxicidade , Silicose/metabolismo , Silicose/tratamento farmacológico , Silicose/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Desferroxamina/farmacologia , Fenilenodiaminas/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Ferro/metabolismo , Cicloexilaminas/farmacologia
9.
Oncologist ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990195

RESUMO

BACKGROUND: Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC). METHODS: In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Between July 16, 2019, and September 9, 2022, 62 patients (AS, n = 32; AG, n = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group. CONCLUSION: The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308).

10.
Clin Neurophysiol ; 165: 97-106, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38996613

RESUMO

OBJECTIVE: As a prodromal stage to major depressive disorder (MDD), subthreshold depression (StD) has a higher prevalence in the population, resulting in a greater healthcare burden. StD individuals' current negative emotion could be moderated by attentional deployment. However, it remains unclear whether attentional deployment training can mitigate subsequent negative emotion in StD individuals. METHODS: Based on 160 participants, we combined decision task (Experiment 1, N = 69), eye-tracking (Experiment 2, N = 40), and EEG (Experiment 3, N = 51) techniques to investigate how one-week attentional deployment (gain-focus, GF) training modulated the emotional processing of negative stimulus and its underlying neural correlates in StD individuals. RESULTS: After one-week GF training, StD individuals significantly reduced the first fixation time and total fixation time on the negative part (missed opportunities) of decision outcome and showed a decrease in emotional sensitivity to missed opportunities. An increase in N1 and decrease in P3 and LPP (late positive potentials) amplitudes, as well as a decrease in alpha oscillation, were observed when StD individuals faced missed opportunities after training. Additionally, the extent of reduction in StD individuals' emotional sensitivity to missed opportunities could be significantly predicted by the degree of decrease in alpha oscillation. CONCLUSION: One-week attentional deployment training could modulate negative emotion in StD individuals and the degree of change in alpha oscillation might act as an objective indicator for the effectiveness of training. SIGNIFICANCE: Our study provides a convenient and effective approach to alleviate the negative emotion of StD individuals.

11.
Mol Ther Nucleic Acids ; 35(3): 102238, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38983242
12.
Mol Neurobiol ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39017976

RESUMO

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies. The important roles of circRNAs modified by m6A methylation have been reported in the pathogenesis of other autoimmune diseases, but remain unclear in MG. To address this point, we collected peripheral blood mononuclear cells from six MG patients and six healthy controls and performed m6A­circRNA epitranscriptomic microarray and RNA sequencing. Differentially m6A-modified circRNAs and differentially expressed genes (DEGs) were analyzed. A network was constructed containing 17 circRNAs, 30 miRNAs, and 34 DEGs. The GSE85452 dataset was downloaded. DEGs that were differentially expressed in the GSE85452 dataset were selected as seed genes. Finally, four candidate m6A-modified circRNAs (hsa_circ_0084735, hsa_circ_0018652, hsa_circ_0025731, and hsa_circ_0030997) were identified through a random walk with restart. We found that they had different degree correlations with different immune cells. The results of MeRIP-qPCR showed that the m6A methylated levels of hsa_circ_0084735 and hsa_circ_0025731 were downregulated in MG patients, while the other two circRNAs were not significantly different between MG and control group. For the first time, we explored the pathogenesis of MG at the epigenetic transcriptome level. Our results will open new perspectives for MG research and identify potential biomarkers and therapeutic targets for MG.

13.
Food Chem ; 459: 140403, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39024873

RESUMO

Ionic strength plays a significant role in the aggregation behavior of myofibrillar proteins. The study investigated the effects of KCl or CaCl2 as substitutes for NaCl on the gel properties and taste of shrimp surimi at a constant ionic strength (IS = 0.51). Increased KCl substitution ratio resulted in a reduction in α-helix content and an increase in ß-sheet content of myofibrillar proteins, thereby enhancing water holding capacity. Optimal KCl substitutions (1.5% NaCl +1.94% KCl) contributed to maintaining the desired taste and improving gel properties. CaCl2 facilitates the extraction and dissolution of myofibrillar proteins, resulting in an organized and dense gel network with significant water-holding capacity. However, excessive additions (>1.27%) resulted in a notable decrease in taste and gel strength due to excessive aggregation and precipitation of myofibrillar proteins. These findings provide a solid theoretical foundation for production of high-quality, low-salt shrimp surimi.

14.
ChemSusChem ; : e202401138, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020482

RESUMO

With the rapid development of non-fullerene acceptors (NFAs), the power conversion efficiency (PCE) of organic solar cells (OSCs) is increasing. According to their different chemical structures, NFAs can initially be divided into two categories: small molecule acceptors (SMAs) and polymerized small molecule acceptors (PSMAs). Due to the strong absorption capacity and controllable energy levels, the PCE of devices based on SMAs has approached 20%. Compared with SMAs, PSMAs have advantages in stability and flexibility, and the PCE of PSMA-based devices has exceeded 18%. However, the higher synthesis cost and lower batch repeatability hinder its further development. Recently, the concept of giant molecule acceptors (GMAs) has been proposed. These materials have a clear molecular structure and are considered novel acceptor materials that combine the advantages of SMAs and PSMAs. Currently, the PCE of devices based on GMAs has exceeded 19%. In this review, we will introduce the latest developments in SMAs, PSMAs, and GMAs. Then, the advantages of GMAs and the relationship between their structure and performance will be analyzed. In the end, perspectives on the opportunities and challenges of these materials are provided, which could inspire further development of NFAs for advanced OSCs.

15.
Plant Physiol Biochem ; 214: 108944, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39033651

RESUMO

Anoplophora glabripennis (ALB) is one of the most devastating wood boring insects of poplars. Populus deltoides 'Shalinyang (PdS), a new poplar variety, shows strong resistance to ALB infestation. However, the molecular mechanism of insect resistance in PdS is unclear. Here, we found that lignan content was much higher in PdS phloem after ALB infestation than in healthy trees, and that adding lignan to artificial diet significantly reduced: larval weight; digestive enzyme activity (cellulase [CL], polygalacturonase [PG]); detoxification enzyme activity (carboxylesterase [CarE], glutathione S-transferase [GSH-ST]); and defense enzyme activity (Catalase [CAT]). We further identified the lignan biosynthesis-related PdPLR1 gene (Pinoresinol-lariciresinol reductase, PLR) based on transcriptome analysis, and it was significantly up-regulated in the PdS phloem attacked by ALB. Overexpression of PdPLR1 in Arabidopsis increased th lignan content. In contrast, silencing PdPLR1 in PdS significantly decreased expression levels of PdPLR1 and lignan content by 82.45% and 56.85%. However, silencing PdPLR1 increased the number of adults ovipositions and eggs hatching. The activity of CL, PG, CarE, GSH-ST and CAT and the biomass of larvae fed on phloem of PdS with silenced PdPLR1 were significantly higher than in the control. Taken together, up regulation of PdPLR1 enhanced PdS resistance to ALB by regulating lignan synthesis. Our findings provide in-depth insights into the molecular mechanisms of PdS-ALB interactions, which lay the foundation for understanding of defense in poplars to pest infection.

16.
Nat Commun ; 15(1): 6149, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39034317

RESUMO

Surface passivation, a desirable natural consequence during initial oxidation of alloys, is the foundation for functioning of corrosion and oxidation resistant alloys ranging from industrial stainless steel to kitchen utensils. This initial oxidation has been long perceived to vary with crystal facet, however, the underlying mechanism remains elusive. Here, using in situ environmental transmission electron microscopy, we gain atomic details on crystal facet dependent initial oxidation behavior in a model Ni-5Cr alloy. We find the (001) surface shows higher initial oxidation resistance as compared to the (111) surface. We reveal the crystal facet dependent oxidation is related to an interfacial atomic sieving effect, wherein the oxide/metal interface selectively promotes diffusion of certain atomic species. Density functional theory calculations rationalize the oxygen diffusion across Ni(111)/NiO(111) interface, as contrasted with Ni(001)/NiO(111), is enhanced. We unveil that crystal facet with initial fast oxidation rate could conversely switch to a slow steady state oxidation.

17.
Biosens Bioelectron ; 263: 116558, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39029277

RESUMO

Organophosphorus compounds are widely distributed and highly toxic to the environment and living organisms. The current detection of organophosphorus compounds is based on a single-mode method, which makes it challenging to achieve good portability, accuracy, and sensitivity simultaneously. This study designed a multifunctional microfluidic chip to develop a dual-mode biosensor employing a DNA hydrogel as a carrier and aptamers as recognition probes for the colorimetric/electrochemical detection of malathion, an organophosphorus compound. The biosensor balanced portability and stability by combining a microfluidic chip and target-triggered DNA hydrogel-sensing technologies. Moreover, the biosensor based on target-triggered DNA hydrogel modified microfluidic developed in this study exhibited a dual-mode response to malathion, providing both colorimetric and electrochemical signals. The colorimetric mode enables rapid visualization and qualitative detection and, when combined with a smartphone, allows on-site quantitative analysis with a detection limit of 56 nM. The electrochemical mode offers a broad linear range (0.01-3000 µM) and high sensitivity (a limit of detection of 5 nM). The two modes could validate each other and improve the accuracy of detection. The colorimetric/electrochemical dual-mode biosensor based on target-triggered DNA hydrogel modified microfluidic chip offers a portable, simple, accurate, and sensitive strategy for detecting harmful environmental and food substances.

18.
Oncogenesis ; 13(1): 27, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030175

RESUMO

The regulatory significance of ubiquitin-specific peptidase 32 (USP32) in tumor is significant, nevertheless, the biological roles and regulatory mechanisms of USP32 in non-small cell lung cancer (NSCLC) remain unclear. According to our research, USP32 was strongly expressed in NSCLC cell lines and tissues and was linked to a bad prognosis for NSCLC patients. Interference with USP32 resulted in a significant inhibition of NSCLC cell proliferation, migration potential, and EMT development; on the other hand, USP32 overexpression had the opposite effect. To further elucidate the mechanism of action of USP32 in NSCLC, we screened H1299 cells for interacting proteins and found that USP32 interacts with BAG3 (Bcl2-associated athanogene 3) and deubiquitinates and stabilizes BAG3 in a deubiquitinating activity-dependent manner. Functionally, restoration of BAG3 expression abrogated the antitumor effects of USP32 silencing. Furthermore, USP32 increased the phosphorylation level of the RAF/MEK/ERK signaling pathway in NSCLC cells by stabilizing BAG3. In summary, these findings imply that USP32 is critical to the development of NSCLC and could offer a theoretical framework for the clinical diagnosis and management of NSCLC patients in the future.

19.
bioRxiv ; 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38979320

RESUMO

m 6 A RNA methylation suppresses the immunostimulatory potential of endogenous RNA. Deficiency of m 6 A provokes inflammatory responses and cell death, but the underlying mechanisms remain elusive. Here we showed that the noncoding RNA 7SK gains immunostimulatory potential upon m 6 A depletion and subsequently activates the RIG-I/MAVS axis to spark interferon (IFN) signaling cascades. Concomitant excess of IFN and m 6 A deficiency synergistically facilitate the formation of RNA G-quadruplexes (rG4) to promote ZBP1-mediated necroptotic cell death. Collectively, our findings delineate a hitherto uncharacterized mechanism that links m 6 A dysregulation with ZBP1 activity in triggering inflammatory cell death.

20.
J Phycol ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016211

RESUMO

Neoporphyra haitanensis, a red alga harvested for food, thrives in the intertidal zone amid dynamic and harsh environments. High irradiance represents a major stressor in this habitat, posing a threat to the alga's photosynthetic apparatus. Interestingly, N. haitanensis has adapted to excessive light despite the absence of a crucial xanthophyll cycle-dependent photoprotection pathway. Thus, it is valuable to investigate the mechanisms by which N. haitanensis copes with excessive light and to understand the photoprotective roles of carotenoids. Under high light intensities and prolonged irradiation time, N. haitanensis displayed reduction in photosynthetic efficiency and phycobiliproteins levels, as well as different responses in carotenoids. The decreased carotene contents suggested their involvement in the synthesis of xanthophylls, as evidenced by the up-regulation of lycopene-ß-cyclase (lcyb) and zeaxanthin epoxidase (zep) genes. Downstream xanthophylls such as lutein, zeaxanthin, and antheraxanthin increased proportionally to light stress, potentially participating in scavenging reactive oxygen species (ROS). When accompanied by the enhanced activity of ascorbate peroxidase (APX), these factors resulted in a reduction in ROS production. The responses of intermediates α-cryptoxanthin and ß-cryptoxanthin were felt somewhere between carotenes and zeaxanthin/lutein. Furthermore, these changes were ameliorated when the organism was placed in darkness. In summary, down-regulation of the organism's photosynthetic capacity, coupled with heightened xanthophylls and APX activity, activates photoinhibition quenching (qI) and antioxidant activity, helping N. haitanensis to protect the organism from the damaging effects of excessive light exposure. These findings provide insights into how red algae adapt to intertidal lifestyles.

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