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1.
J Biol Chem ; : 107667, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39128721

RESUMO

Isochorismate-derived metabolism enables biosynthesis of the plant defence hormone salicylic acid (SA) and its derivatives. In Arabidopsis thaliana, the stress-induced accumulation of SA depends on ISOCHORISMATE SYNTHASE1 (ICS1), and also requires the presumed isochorismate transporter ENHANCED DISEASE SUSCEPTIBILITY5 (EDS5) and the GH3 enzyme avrPphB SUSCEPTIBLE3 (PBS3). By comparative metabolite and structural analyses, we identified several hitherto unreported ICS1- and EDS5-dependent, biotic stress-inducible Arabidopsis metabolites. These involve meta-substituted SA derivatives (5-formyl-SA, 5-carboxy-SA, 5-carboxymethyl-SA), their benzoic acid (BA) analogues (3-formyl-BA, 3-carboxy-BA, 3-carboxymethyl-BA) and, besides the previously detected salicyloyl-aspartate (SA-Asp), the ester conjugate salicyloyl-malate (SA-Mal). SA functions as a biosynthetic precursor for SA-Mal and SA-Asp, but not for the meta-substituted SA- and BA-derivatives, which accumulate to moderate levels at later stages of bacterial infection. Interestingly, Arabidopsis leaves possess oxidising activity to effectively convert meta-formyl- into meta-carboxy-SA/BAs. In contrast to SA, exogenously applied meta-substituted SA/BA-derivatives and SA-Mal exert moderate impact on plant immunity and defence-related gene expression. While the isochorismate-derived metabolites are negatively regulated by the SA receptor NON-EXPRESSOR OF PR GENES1, SA conjugates (SA-Mal, SA-Asp, SA-glucose conjugates) and meta-substituted SA/BA-derivatives are oppositely affected by PBS3. Notably, our data indicate a PBS3-independent path to isochorismate-derived SA at later stages of bacterial infection, which does not considerably impact immune-related characteristics. Moreover, our results argue against a previously proposed role of EDS5 in the biosynthesis of the immune signal N-hydroxypipecolic acid and associated transport processes. We propose a significantly extended biochemical scheme of plant isochorismate metabolism that involves an alternative generation mode for benzoate- and salicylate-derivatives.

2.
Proc Natl Acad Sci U S A ; 119(11): e2119415119, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35259018

RESUMO

SignificanceHosts often target the relatively conserved regions in rapidly mutating retroviruses to inhibit their replication. One of these regions is called a primer binding site (PBS), which has to be complementary to the host tRNA to initiate reverse transcription. By analyzing endogenous retroviral elements, we found that host cells use this sequence as a target in efforts to block the expression of viral elements. A specific type of zinc finger protein targets the PBS in a host genome, which not only inhibits the transcription of endogenous viruses but also inhibits the replication of exogenous retroviruses with the same PBS. Thus, our study sheds light on a strategy for searching for host restriction factors targeting retroviruses.


Assuntos
Regulação Viral da Expressão Gênica , Interações Hospedeiro-Patógeno , RNA Viral/genética , RNA Viral/metabolismo , Proteínas Repressoras/metabolismo , Retroviridae/fisiologia , Dedos de Zinco , Sequência de Bases , Sítios de Ligação , Mapeamento Cromossômico , Retrovirus Endógenos , Estudo de Associação Genômica Ampla , Humanos , Motivos de Nucleotídeos , Retroviridae/classificação , Transcrição Gênica , Replicação Viral
3.
Proc Natl Acad Sci U S A ; 119(12): e2118675119, 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35286210

RESUMO

SignificanceBased on the analysis of three thermodynamic parameters of various M-S systems (solubility of metal sulfides [MxSy] in aqueous solution, volume change of the metal-sulfur [M-S] battery system, and the potential of S/MxSy cathode redox couple), an aqueous Pb-S battery operated by synergistic dual conversion reactions (cathode: S⇄PbS, anode: Pb2+⇄PbO2) has been officially reported. Benefitting from the inherent insolubility of PbS and a conversion-type counter electrode, the aqueous Pb-S battery exhibited two advantages: it is shuttle effect free and has a dendrite-free nature. Moreover, the practical value of the Pb-S battery was further certified by the prototype S|Pb(NO3)2ǁZn(NO3)2|Zn hybrid cell, which afforded an energy density of 930.9 Wh kg-1sulfur.

4.
J Biol Chem ; 299(4): 104569, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36870684

RESUMO

To cope with an increased external osmolarity, the budding yeast Saccharomyces cerevisiae activates the Hog1 mitogen-activated protein kinase (MAPK) through the high-osmolarity glycerol (HOG) pathway, which governs adaptive responses to osmostress. In the HOG pathway, two apparently redundant upstream branches, termed SLN1 and SHO1, activate cognate MAP3Ks (MAPKK kinase) Ssk2/22 and Ste11, respectively. These MAP3Ks, when activated, phosphorylate and thus activate the Pbs2 MAP2K (MAPK kinase), which in turn phosphorylates and activates Hog1. Previous studies have shown that protein tyrosine phosphatases and the serine/threonine protein phosphatases type 2C negatively regulate the HOG pathway to prevent its excessive and inappropriate activation, which is detrimental to cell growth. The tyrosine phosphatases Ptp2 and Ptp3 dephosphorylate Hog1 at Tyr-176, whereas the protein phosphatase type 2Cs Ptc1 and Ptc2 dephosphorylate Hog1 at Thr-174. In contrast, the identities of phosphatases that dephosphorylate Pbs2 remained less clear. Here, we examined the phosphorylation status of Pbs2 at the activating phosphorylation sites Ser-514 and Thr-518 (S514 and T518) in various mutants, both in the unstimulated and osmostressed conditions. Thus, we found that Ptc1-Ptc4 collectively regulate Pbs2 negatively, but each Ptc acts differently to the two phosphorylation sites in Pbs2. T518 is predominantly dephosphorylated by Ptc1, while S514 can be dephosphorylated by any of Ptc1-4 to an appreciable extent. We also show that Pbs2 dephosphorylation by Ptc1 requires the adaptor protein Nbp2 that recruits Ptc1 to Pbs2, thus highlighting the complex processes involved in regulating adaptive responses to osmostress.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Glicerol/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Concentração Osmolar , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Fosforilação , Proteínas Quinases/metabolismo , Proteína Fosfatase 2C/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Transdução de Sinais/fisiologia
5.
Small ; : e2400380, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564784

RESUMO

Thermal annealing (TA) of colloidal quantum dot (CQD) films is considered an important process for recent high-performing CQD solar cells (SCs) due to its beneficial effects on CQD solids, including enhanced electrical conductivity, denser packing of CQD films, and the removal of organic residues and solvents. However, the conventional TA for CQDs, which requires several  minutes, leads to hydroxylation and oxidation on the CQD surface, resulting in the formation of trap states and a subsequent decline in SC performance. To address these challenges, this study introduces a flashlight annealing (FLA) technique that significantly reduces the annealing time to the millisecond scale. Through the FLA approach, it successfully suppressed hydroxylation and oxidation, resulting in decreased trap states within the CQD solids while simultaneously preserving their charge transport properties. As a result, CQD SCs treated with FLA exhibited a notable improvement, achieving an open-circuit voltage of 0.66 V compared to 0.63 V in TA-treated devices, leading to an increase in power conversion efficiency from 12.71% to 13.50%.

6.
Mycoses ; 67(1): e13667, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37914666

RESUMO

BACKGROUND: Clinical severity scores, such as acute physiology, age, chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), Pitt Bacteremia Score (PBS), and European Confederation of Medical Mycology Quality (EQUAL) score, may not reliably predict candidemia prognosis owing to their prespecified scorings that can limit their adaptability and applicability. OBJECTIVES: Unlike those fixed and prespecified scorings, we aim to develop and validate a machine learning (ML) approach that is able to learn predictive models adaptively from available patient data to increase adaptability and applicability. METHODS: Different ML algorithms follow different design philosophies and consequently, they carry different learning biases. We have designed an ensemble meta-learner based on stacked generalisation to integrate multiple learners as a team to work at its best in a synergy to improve predictive performances. RESULTS: In the multicenter retrospective study, we analysed 512 patients with candidemia from January 2014 to July 2019 and compared a stacked generalisation model (SGM) with APACHE II, SOFA, PBS and EQUAL score to predict the 14-day mortality. The cross-validation results showed that the SGM significantly outperformed APACHE II, SOFA, PBS, and EQUAL score across several metrics, including F1-score (0.68, p < .005), Matthews correlation coefficient (0.54, p < .05 vs. SOFA, p < .005 vs. the others) and the area under the curve (AUC; 0.87, p < .005). In addition, in an independent external test, the model effectively predicted patients' mortality in the external validation cohort, with an AUC of 0.77. CONCLUSIONS: ML models show potential for improving mortality prediction amongst patients with candidemia compared to clinical severity scores.


Assuntos
Bacteriemia , Candidemia , Humanos , Escores de Disfunção Orgânica , APACHE , Estudos Retrospectivos , Candidemia/diagnóstico , Estudos de Viabilidade , Prognóstico , Aprendizado de Máquina , Curva ROC , Unidades de Terapia Intensiva
7.
J Appl Clin Med Phys ; 25(7): e14362, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38669175

RESUMO

PURPOSE: Proton stereotactic radiosurgery (PSRS) has emerged as an innovative proton therapy modality aimed at achieving precise dose delivery with minimal impact on healthy tissues. This study explores the dosimetric outcomes of PSRS in comparison to traditional intensity-modulated proton therapy (IMPT) by focusing on cases with small target volumes. A custom-made aperture system designed for proton therapy, specifically tailored to small target volumes, was developed and implemented for this investigation. METHODS: A prerequisite mechanical validation through an isocentricity test precedes dosimetric assessments, ensuring the seamless integration of mechanical and dosimetry analyses. Five patients were enrolled in the study, including two with choroid melanoma and three with arteriovenous malformations (AVM). Two treatment plans were meticulously executed for each patient, one utilizing a collimated aperture and the other without. Both plans were subjected to robust optimization, maintaining identical beam arrangements and consistent optimization parameters to account for setup errors of 2 mm and range uncertainties of 3.5%. Plan evaluation metrics encompassing the Heterogeneity Index (HI), Paddick Conformity Index (CIPaddick), Gradient Index (GI), and the R50% index to evaluate alterations in low-dose volume distribution. RESULTS: The comparative analysis between PSRS and traditional PBS treatment revealed no significant differences in plan outcomes, with both modalities demonstrating comparable target coverage. However, collimated apertures resulted in discernible improvements in dose conformity, dose fall-off, and reduced low-dose volume. CONCLUSIONS: This study underscores the advantageous impact of the aperture system on proton therapy, particularly in cases involving small target volumes.


Assuntos
Órgãos em Risco , Terapia com Prótons , Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Radiocirurgia/métodos , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Órgãos em Risco/efeitos da radiação , Melanoma/radioterapia , Melanoma/cirurgia
8.
J Appl Clin Med Phys ; 25(2): e14186, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37974385

RESUMO

PURPOSE: Noncoplanar plans (NCPs) are commonly used for proton treatment of bilateral head and neck (HN) malignancies. NCP requires additional verification setup imaging between beams to correct residual errors of robotic couch motion, which increases imaging dose and total treatment time. This study compared the quality and robustness of NCPs with those of coplanar plans (CPs). METHODS AND MATERIALS: Under an IRB-approved study, CPs were created retrospectively for 10 bilateral HN patients previously treated with NCPs maintaining identical beam geometry of the original plan but excluding couch rotations. Plan robustness to the inter-fractional variation (IV) of both plans was evaluated through the Dose Volume Histograms (DVH) of weekly quality assurance CT (QACT) sets (39 total). In addition, delivery efficiency for both plans was compared using total treatment time (TTT) and beam-on time (BOT). RESULTS: No significant differences in plan quality were observed in terms of clinical target volume (CTV) coverage (D95) or organ-at-risk (OAR) doses (p > 0.4 for all CTVs and OARs). No significant advantage of NCPs in the robustness to IV was found over CP, either. Changes in D95 of QA plans showed a linear correlation (slope = 1.006, R2  > 0.99) between NCP and CP for three CTV data points (CTV1, CTV2, and CTV3) in each QA plan (117 data points for 39 QA plans). NCPs showed significantly higher beam delivery time than CPs for TTT (539 ± 50 vs. 897 ± 142 s; p < 0.001); however, no significant differences were observed for BOT. CONCLUSION: NCPs are not more robust to IV than CPs when treating bilateral HN tumors with pencil-beam scanning proton beams. CPs showed plan quality and robustness similar to NCPs while reduced treatment time (∼6 min). This suggests that CPs may be a more efficient planning technique for bilateral HN cancer proton therapy.


Assuntos
Neoplasias de Cabeça e Pescoço , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Prótons , Terapia com Prótons/métodos , Estudos Retrospectivos , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Órgãos em Risco
9.
J Appl Clin Med Phys ; 25(7): e14342, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38590112

RESUMO

BACKGROUND: Rescanning is a common technique used in proton pencil beam scanning to mitigate the interplay effect. Advances in machine operating parameters across different generations of particle therapy systems have led to improvements in beam delivery time (BDT). However, the potential impact of these improvements on the effectiveness of rescanning remains an underexplored area in the existing research. METHODS: We systematically investigated the impact of proton machine operating parameters on the effectiveness of layer rescanning in mitigating interplay effect during lung SBRT treatment, using the CIRS phantom. Focused on the Hitachi synchrotron particle therapy system, we explored machine operating parameters from our institution's current (2015) and upcoming systems (2025A and 2025B). Accumulated dynamic 4D dose were reconstructed to assess the interplay effect and layer rescanning effectiveness. RESULTS: Achieving target coverage and dose homogeneity within 2% deviation required 6, 6, and 20 times layer rescanning for the 2015, 2025A, and 2025B machine parameters, respectively. Beyond this point, further increasing the number of layer rescanning did not further improve the dose distribution. BDTs without rescanning were 50.4, 24.4, and 11.4 s for 2015, 2025A, and 2025B, respectively. However, after incorporating proper number of layer rescanning (six for 2015 and 2025A, 20 for 2025B), BDTs increased to 67.0, 39.6, and 42.3 s for 2015, 2025A, and 2025B machine parameters. Our data also demonstrated the potential problem of false negative and false positive if the randomness of the respiratory phase at which the beam is initiated is not considered in the evaluation of interplay effect. CONCLUSION: The effectiveness of layer rescanning for mitigating interplay effect is affected by machine operating parameters. Therefore, past clinical experiences may not be applicable to modern machines.


Assuntos
Neoplasias Pulmonares , Imagens de Fantasmas , Terapia com Prótons , Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Órgãos em Risco/efeitos da radiação
10.
Sensors (Basel) ; 24(15)2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39123934

RESUMO

The response of a DPbS3200 infrared detector irradiated by a nanosecond pulsed laser and CW laser has been investigated to study laser-induced interference. A laser interference experiment system was constructed to measure the time-varying response signal. A nanosecond pulsed laser and a CW laser of 10 Hz were used, with a 1064 nm wavelength and a millimeter-scale irradiation spot diameter. Firstly, the characteristics of transient interference signals induced by pulsed lasers were analyzed. Then, the characteristics of response signal interference by both CW laser and pulsed laser irradiation were further investigated. The results showed that the pulsed laser only produced transient interference. However, the CW laser led to a significant amplitude reduction of the response signal, which could continuously interfere in the operating time. For transient interferences, the amplitude of the interference signal increased linearly with the laser fluence. The relation between the pulse repetition rate of the incident laser and the operating frequency of the detector determined the numbers of transient interference signals in one response period; for the interference induced by both the CW laser and pulsed laser, CW laser interference played a leading role when CW laser power density increased to 4.1 W/cm2 or more. As the CW laser fluence reached 6.1 W/cm2, the PbS infrared detector was no longer able to detect any signal, which caused temporary blindness. In the end, a probit model was used to determine the interference threshold.

11.
Nano Lett ; 23(21): 9943-9952, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37874973

RESUMO

Colloidal quantum dots (CQDs) are finding increasing applications in optoelectronic devices, such as photodetectors and solar cells, because of their high material quality, unique and attractive properties, and process flexibility without the constraints of lattice match and thermal budget. However, there is no adequate device model for colloidal quantum dot heterojunctions, and the popular Shockley-Quiesser diode model does not capture the underlying physics of CQD junctions. Here, we develop a compact, easy-to-use model for CQD devices rooted in physics. We show how quantum dot properties, QD ligand binding, and the heterointerface between quantum dots and the electron transport layer (ETL) affect device behaviors. We also show that the model can be simplified to a Shockley-like equation with analytical approximate expressions for reverse saturation current, ideality factor, and quantum efficiency. Our model agrees well with the experiment and can be used to describe and optimize CQD device performance.

12.
Molecules ; 29(6)2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38542869

RESUMO

Huperzine A (HUP) plays a crucial role in Alzheimer's therapy by enhancing cognitive function through increased cholinergic activity as a reversible acetylcholinesterase (AChE) inhibitor. Despite some limitations being seen in AChE inhibitors, ongoing research remains dedicated to finding innovative and more effective treatments for Alzheimer's disease. To achieve the goal of the discovery of potential HUP analogues with improved physicochemical properties, less toxic properties, and high biological activity, many in silico methods were applied. Based on the acetylcholinesterase-ligand complex, an e-pharmacophore model was developed. Subsequently, a virtual screening involving a collection of 1762 natural compounds, sourced from the PubChem database, was performed. This screening yielded 131 compounds that exhibited compatibility with the established pharmacophoric hypothesis. These selected ligands were then subjected to molecular docking within the active site of the 4EY5 receptor. As a result, we identified four compounds that displayed remarkable docking scores and exhibited low free binding energy to the target. These top four compounds, CID_162895946, CID_44461278, CID_44285285, and CID_81108419, were submitted to ADMET prediction and molecular dynamic simulations, yielding encouraging findings in terms of their pharmacokinetic characteristics and stability. Finally, the molecular dynamic simulation, cross-dynamic correlation matrix, free energy landscape, and MM-PBSA calculations demonstrated that two ligands from the selected ligands formed very resilient complexes with the enzyme acetylcholinesterase, with significant binding affinity. Therefore, these two compounds are recommended for further experimental research as possible (AChE) inhibitors.


Assuntos
Alcaloides , Doença de Alzheimer , Inibidores da Colinesterase , Sesquiterpenos , Humanos , Inibidores da Colinesterase/química , Doença de Alzheimer/tratamento farmacológico , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Acetilcolinesterase/metabolismo , Ligantes
13.
Angew Chem Int Ed Engl ; : e202411502, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39072890

RESUMO

Plastic pollution, an increasingly serious global problem, can be addressed through the full lifecycle management of plastics, including plastics recycling as one of the most promising approaches. System design, catalyst development, and product separation are the keys in improving the economics of electrocatalytic plastics recycling. Here, a membrane-free co-production system was devised to produce succinic acid (SA) at both anode and cathode respectively by the co-electrolysis of polybutylene succinate (PBS) waste plastics and biomass-derived maleic acid (MA) for the first time. To this end, Cr3+-Ni(OH)2 electrocatalyst featuring much enhanced 1,4-butanediol (BDO) oxidation reaction (BOR) activity has been synthesized and the role of doped Cr has been revealed as an "electron puller" to accelerate the rate-determining step (RDS) in the Ni2+/Ni3+ cycling. Impressively, an extra-high SA production rate of 3.02 g h-1 and ultra-high apparent Faraday efficiency towards SA (FEapparent=181.5%) have been obtained. A carbon dioxide-assisted sequential precipitation approach has been developed to produce high-purity SA and byproduct NaHCO3 solids. Preliminary techno-economic analysis demonstrates that the reported system is economically profitable and promising for future industrial applications.

14.
J Bacteriol ; 205(10): e0011223, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37728605

RESUMO

Sigma factors bind and direct the RNA polymerase core to specific promoter sequences, and alternative sigma factors direct transcription of different regulons of genes. Here, we study the pBS32 plasmid-encoded sigma factor SigN of Bacillus subtilis to determine how it contributes to DNA damage-induced cell death. We find that SigN causes cell death when expressed at high levels and does so in the absence of its regulon suggesting it is intrinsically toxic. One way toxicity was relieved was by curing the pBS32 plasmid, which eliminated a positive feedback loop that led to SigN hyper-accumulation. Another way toxicity was relieved was through mutating the chromosomally encoded transcriptional repressor protein AbrB, thereby derepressing a potent antisense transcript that antagonized SigN expression. SigN efficiently competed with the vegetative sigma factor SigA in vitro, and SigN accumulation in the absence of positive feedback reduced SigA-dependent transcription suggesting that toxicity may be due to competitive inhibition of one or more essential transcripts. Why B. subtilis encodes a toxic sigma factor is unclear but SigN may function in host-inhibition during lytic conversion, as phage lysogen genes are also encoded on pBS32. IMPORTANCE Alternative sigma factors activate entire regulons of genes to improve viability in response to environmental stimuli. The pBS32 plasmid-encoded alternative sigma factor SigN of Bacillus subtilis however, is activated by the DNA damage response and leads to cellular demise. Here we find that SigN impairs viability by hyper-accumulating and outcompeting the vegetative sigma factor for the RNA polymerase core. Why B. subtilis retains a plasmid with a deleterious alternative sigma factor is unknown.


Assuntos
Bacillus subtilis , Fator sigma , Fator sigma/metabolismo , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Imunoglobulina A Secretora/genética , Transcrição Gênica , Regulação Bacteriana da Expressão Gênica
15.
J Bacteriol ; 205(10): e0020323, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37795990

RESUMO

A rogue, plasmid-encoded sigma factor that kills Bacillus subtilis is the focus of a new study by A. T. Burton, D. Pospísilová, P. Sudzinová, E. V. Snider, A. M. Burrage, L. Krásný, and D. B. Kearns (J Bacteriol 205:e00112-23, 2023, https://doi.org/10.1128/jb.00112-23). The authors demonstrate that SigN is toxic in its own right, causing cell death by potently outcompeting the housekeeping sigma factor for access to RNA polymerase.


Assuntos
Bacillus subtilis , Fator sigma , Fator sigma/genética , Fator sigma/metabolismo , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Plasmídeos , Morte Celular
16.
New Phytol ; 237(2): 414-422, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36263689

RESUMO

AVRPPHB SUSCEPTIBLE 3 (PBS3) belongs to the GH3 family of acyl acid amido synthetases, which conjugates amino acids to diverse acyl acid substrates. Recent studies demonstrate that PBS3 in Arabidopsis plays a key role in the biosynthesis of plant defense hormone salicylic acid (SA) by catalyzing the conjugation of glutamate to isochorismate to form isochorismate-9-glutamate, which is then used to produce SA through spontaneous decay or ENHANCED PSEUDOMONAS SUSCEPTIBILITY (EPS1) catalysis. Consistent with its function as an essential enzyme for SA biosynthesis, PBS3 is well known to be a positive regulator of plant immunity in Arabidopsis. Additionally, PBS3 is also involved in the trade-off between abiotic and biotic stress responses in Arabidopsis by suppressing the inhibitory effect of abscisic acid on SA-mediated plant immunity. Besides stress responses, PBS3 also plays a role in plant development. Under long-day conditions, PBS3 influences Arabidopsis flowering time by regulating the expression of flowering regulators FLOWERING LOCUS C and FLOWERING LOCUS T. Taken together, PBS3 functions in the signaling network of plant development and responses to biotic and/or abiotic stresses, but the molecular mechanisms underlying its diverse roles remain obscure.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Ácido Corísmico/metabolismo , Ácido Salicílico/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Doenças das Plantas
17.
Gynecol Oncol ; 172: 92-97, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37003073

RESUMO

OBJECTIVE: To characterize long-term toxicity and disease outcomes with whole pelvis (WP) pencil beam scanning proton radiation therapy (PBS PRT) for gynecologic malignancies. METHODS: We reviewed 23 patients treated from 2013 to 2019 with WP PBS PRT for endometrial, cervical, and vaginal cancer. We report acute and late Grade (G)2+ toxicities, graded by Common Terminology Criteria for Adverse Events, Version 5. Disease outcomes were assessed by Kaplan-Meier method. RESULTS: Median age was 59 years. Median follow up was 4.8 years. 12 (52.2%) had uterine cancer, 10 (43.5%) cervical, 1 (4.3%) vaginal. 20 (86.9%) were treated post-hysterectomy. 22 (95.7%) received chemotherapy, 12 concurrently (52.2%). The median PBS PRT dose was 50.4GyRBE (range, 45-62.5). 8 (34.8% had para-aortic/extended fields. 10 (43.5%) received brachytherapy boost. Median follow up was 4.8 years. 5-year actuarial local control was 95.2%, regional control 90.9%, distant control 74.7%, both disease control and progression-free survival 71.2%. Overall survival was 91.3%. In the acute period, 2 patients (8.7%) had G2 genitourinary (GU) toxicity, 6 (26.1%) had gastrointestinal (GI) G2-3 toxicity, 17 (73.9%) had G2-4 hematologic (H) toxicity. In the late period, 3 (13.0%) had G2 GU toxicity, 1 (4.3%) had G2 GI toxicity, 2 (8.7%) had G2-3H toxicity. The mean small bowel V15Gy was 213.4 cc. Mean large bowel V15 Gy was 131.9 cc. CONCLUSIONS: WP PBS PRT for gynecologic malignancies delivers favorable locoregional control. Rates of GU and GI toxicity are low. Acute hematologic toxicity was most common, which may be related to the large proportion of patients receiving chemotherapy.


Assuntos
Braquiterapia , Gastroenteropatias , Neoplasias dos Genitais Femininos , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias dos Genitais Femininos/radioterapia , Neoplasias dos Genitais Femininos/etiologia , Prótons , Radioterapia de Intensidade Modulada/efeitos adversos , Pelve , Terapia com Prótons/efeitos adversos , Gastroenteropatias/etiologia , Braquiterapia/efeitos adversos , Dosagem Radioterapêutica
18.
Environ Res ; 226: 115651, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36894113

RESUMO

Gamma-irradiation effects on photocatalytic action of PbS nanocrystallites codoped with Cu and Sr ions were performed for organic dye degradation. The physical and chemical characterizations of these nanocrystallites were examined employing X-ray diffraction, Raman, and field emission electron microscopic analysis. The optical bandgaps of gamma-irradiated PbS with co-dopants have shifted from 1.95 eV (pristine PbS) to 2.45 eV in the visible spectrum. Under direct sunlight, the photocatalytic action of these compounds against methylene blue (MB) was investigated. Observations indicated that gamma-irradiated Pb(0.98)Cu0.01Sr0.01S nanocrystallite sample exhibits a higher photocatalytic degradation activity of 74.02% in 160 min and stability of 69.4% after three cycles, suggesting that gamma irradiation could potentially influence organic MB degradation. This is due to combined action of high-energy gamma irradiation (at an optimzed dose), which causes sulphur vacancies, and defects created by dopant ions, which alter the crystal structure by inducing strain in the crystal lattice, hence altering the crystallinity of PbS.


Assuntos
Corantes , Luz Solar , Difração de Raios X , Corantes/química , Azul de Metileno/química
19.
Sens Actuators A Phys ; 349: 114052, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36447950

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been garnered increasing for its rapid worldwide spread. Each country had implemented city-wide lockdowns and immigration regulations to prevent the spread of the infection, resulting in severe economic consequences. Materials and technologies that monitor environmental conditions and wirelessly communicate such information to people are thus gaining considerable attention as a countermeasure. This study investigated the dynamic characteristics of batteryless magnetostrictive alloys for energy harvesting to detect human coronavirus 229E (HCoV-229E). Light and thin magnetostrictive Fe-Co/Ni clad plate with rectification, direct current (DC) voltage storage capacitor, and wireless information transmission circuits were developed for this purpose. The power consumption was reduced by improving the energy storage circuit, and the magnetostrictive clad plate under bending vibration stored a DC voltage of 1.9 V and wirelessly transmitted a signal to a personal computer once every 5 min and 10 s under bias magnetic fields of 0 and 10 mT, respectively. Then, on the clad plate surface, a novel CD13 biorecognition layer was immobilized using a self-assembled monolayer of -COOH groups, thus forming an amide bond with -NH2 groups for the detection of HCoV-229E. A bending vibration test demonstrated the resonance frequency changes because of HCoV-229E binding. The fluorescence signal demonstrated that HCoV-229E could be successfully detected. Thus, because HCoV-229E changed the dynamic characteristics of this plate, the CD13-modified magnetostrictive clad plate could detect HCoV-229E from the interval of wireless communication time. Therefore, a monitoring system that transmits/detects the presence of human coronavirus without batteries will be realized soon.

20.
Lasers Med Sci ; 38(1): 135, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37300640

RESUMO

Pulsed laser ablation in liquids (PLAL) is considered as green, cost effective, and facile method to produce nanocolloids which exhibit anticancer effect. When comparing breast cancer with other types of cancers, breast cancer is considered as the second cause of death in women. The objective of this article is to test the cytotoxicity of carbon-based materials prepared by PLAL on both the normal (REF) cell line and the human breast cancer (MCF7) cell line. In this study, PLAL is used to prepare nanocolloids of asphalt and coal in different solvents (ethanol, dimethyl sulfoxide (DMSO), phosphate buffer saline (PBS), and distilled water (DW)). A fiber laser of wavelength of 1.06 µm and an average power of 10 watts was used to prepare different nanocolloids in different solvents from asphalt and coal. The cytotoxic effect of the prepared materials was tested against breast cancer MCF7 cell line in vitro. The asphalt in both ethanol and DMSO was found to have a significant cytotoxic effect and the growth inhibition (GI) was found to be 62.1% and 50.5% at concentrations of 620 and 80 ppm respectively, unlike the coal in DMSO which showed G.I. of 59.5%. Both the prepared materials in the mentioned solvents showed low cytotoxicity against the normal cell line (REF). We can conclude that the organic materials prepared in organic solvents using the PLAL had shown a low cytotoxicity against the (REF) cell line while they exhibited a significant cytotoxic effect against the MCF7 cell line. Further studies are recommended to test these prepared materials in vivo.


Assuntos
Neoplasias da Mama , Terapia a Laser , Feminino , Humanos , Solventes/farmacologia , Dimetil Sulfóxido/farmacologia , Carvão Mineral , Etanol/farmacologia , Células MCF-7
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