Search Results (487)

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly threatening foodborne pathogen capable of causing severe organ and life-threatening diseases. Over the past years, various commercial antibiotics have been used to treat MRSA infections. However, these commercial antibiotics have not yielded efficient results and also cause other side effects; therefore, there is a need for the development of effective alternatives to replace these commercial antibiotics. Suberanilic acid, an amide alkaloid obtained from the endophytic fungus Pestalotiopsis trachycarpicola DCL44, has been identified as a significant antimicrobial agent. However, its antibiotic properties on multi-drug-resistant bacteria such as MRSA have not been fully explored. Therefore, to investigate the potential antimicrobial mechanism of suberanilic acid against MRSA, a quantitative proteomics approach using tandem mass tagging (TMT) was used. The results obtained in the study revealed that suberanilic acid targets multiple pathways in MRSA, including disruption of ribosome synthesis, inhibition of membrane translocation for nutrient uptake (ABC transporter system), and causing dysregulation of carbohydrate and amino acid energy metabolism. These results provide new insights into the mechanism of action of suberanilic acid against MRSA and offer technical support and a theoretical basis for the development of novel food antimicrobial agents derived from endophytic fungal origin. Full article

The pursuit of innovation and the motivation of personnel have long been crucial considerations for sustainable development of organizations. However, an insufficiently addressed issue lies in the optimization of managerial and employee motivation through compensation structures. Drawing on tournament theory and social comparison theory, this research investigates the influence of both the top management team (TMT) pay gap and the TMT-employee pay gap on firms’ innovation performance. Leveraging an empirical analysis of a longitudinal dataset comprising 2517 firms with 12,052 observations spanning from 2004 to 2020, this study reveals an inverted U-shaped relationship between the TMT team pay gap and firm innovation performance. Additionally, this effect is found to be significantly mitigated in firms characterized by highly homogeneous management teams. Furthermore, our investigation indicates that a wider pay gap between executives and employees positively correlates with improved firm innovation performance. The findings from this study contribute novel theoretical explanations and empirical evidence, offering valuable insights into the nuanced ways in which pay gaps impact innovation performance within distinct organizational contexts. A better system of incentives within organizations directly promotes the development of technological innovation, contributing to social progress, human harmony, and sustainable development. Full article

Insufficient dietary vitamin intake can lead to severe health conditions in humans. Improving the vitamin E (VE) content of food crops such as rice through breeding is an economical and effective means to alleviate this problem. In this study, Homogentisate phytyltransferase (HPT) and γ-tocopherol methyltransferase (γ-TMT), two genes derived from sunflower (Helianthus annuus L., a high VE species), were introduced into an elite rice (Oryza sativa L.) cultivar “Ningjing 7” for biofortification. We verified the successful expression of the two genes in multiple transformation events. High-performance liquid chromatography revealed that transgenic plants expressing either HaHPT alone or HaHPT and HaTMT accumulate more VE compared with the wild type. We also revealed that the level of α-tocopherol, the form of VE with the highest biological activity, had increased to 2.33 times in transgenic HaTMT plants compared with the wild type. Transcriptome analysis revealed that the expression levels of some chlorophyll synthesis pathway genes related to VE precursor synthesis significantly increased during grain filling in transgenic rice grains. No difference in agronomic traits was observed between the transgenic plants and their wild type except for a slightly reduced plant height associated with the transgenic plants. These data demonstrate that the heterologous expression of HaHPT gene is effective in increasing the total VE content, while HaTMT plays an important role in the relative abundance of α-tocopherol in rice grains. This study demonstrates a promising strategy for breeding rice with elevated VE content via metabolic engineering. Full article

The Tsinghua University–Ma Huateng Telescopes for Survey (TMTS) started to monitor the LAMOST plates in 2020, leading to the discovery of numerous short-period eclipsing binaries, peculiar pulsators, flare stars, and other variable objects. Here, we present the uninterrupted light curves for a sample of 64 cataclysmic variables (CVs) observed/discovered using the TMTS during its first three-year observations, and we introduce new CVs and new light-variation periods (from known CVs) revealed through the TMTS observations. Thanks to the high-cadence observations of TMTS, diverse light variations, including superhumps, quasi-periodic oscillations, large-amplitude orbital modulations, and rotational modulations, are able to be detected in our CV samples, providing key observational clues for understanding the fast-developing physical processes in various CVs. All of these short-timescale light-curve features help further classify the subtypes of CV systems. We highlight the light-curve features observed in our CV sample and discuss further implications of minute-cadence light curves for CV identifications and classifications. Moreover, we examine the Hα emission lines in the spectra from our nonmagnetic CV samples (i.e., dwarf novae and nova-like subclasses) and find that the distribution of Hα emission strength shows significant differences between the sources with orbital periods above and below the period gap, which agrees with the trend seen from the SDSS nonmagnetic CV sample. Full article

HIV-1 infects monocyte-derived macrophages (MDM) that migrate into the brain and secrete virus and neurotoxic molecules, including cathepsin B (CATB), causing cognitive dysfunction. Cocaine potentiates CATB secretion and neurotoxicity in HIV-infected MDM. Pretreatment with BD1047, a sigma-1 receptor antagonist, before cocaine exposure reduces HIV-1, CATB secretion, and neuronal apoptosis. We aimed to elucidate the intracellular pathways modulated by BD1047 in HIV-infected MDM exposed to cocaine. We hypothesized that the Sig1R antagonist BD1047, prior to cocaine, significantly deregulates proteins and pathways involved in HIV-1 replication and CATB secretion that lead to neurotoxicity. MDM culture lysates from HIV-1-infected women treated with BD1047 before cocaine were compared with untreated controls using TMT quantitative proteomics, bioinformatics, Lima statistics, and pathway analyses. Results demonstrate that pretreatment with BD1047 before cocaine dysregulated eighty (80) proteins when compared with the infected cocaine group. We found fifteen (15) proteins related to HIV-1 infection, CATB, and mitochondrial function. Upregulated proteins were related to oxidative phosphorylation (SLC25A-31), mitochondria (ATP5PD), ion transport (VDAC2–3), endoplasmic reticulum transport (PHB, TMED10, CANX), and cytoskeleton remodeling (TUB1A-C, ANXA1). BD1047 treatment protects HIV-1-infected MDM exposed to cocaine by upregulating proteins that reduce mitochondrial damage, ER transport, and exocytosis associated with CATB-induced neurotoxicity. Full article

A wide range of outcomes makes identifying clinical and functional features distinguishing older persons who fall from non-fallers challenging, especially for professionals with less clinical experience. Thus, this study aimed to map a high-dimensional and complex clinical and functional dataset and determine which outcomes better discriminate older adults with and without self-reported falls. For this, clinical, functional, and cognitive outcomes of 60 community-dwelling older adults classified as fallers and non-fallers were selected based on self-report of a single fall in the last 12 months. An unsupervised intelligent algorithm (Self-Organizing Maps—SOM) was used to cluster and topographically represent the data studied. The SOM model mapped and identified two different groups (topographic error: 0.00; sensitivity: 0.77; precision: 0.42; accuracy: 0.53; F1-score: 0.55) based on self-report of a single fall. We concluded that although two distinct groups were mapped and clustered by the SOM, participants were not necessarily fallers or non-fallers. The increased cost of cognitive demands regarding a motor task (Timed Up and Go Test) and the effect of the Trail Making Test (TMT) Part B regarding TMT Part A could discriminate the functional and cognitive patterns in community-dwelling older adults. Therefore, in clinical practice, identifying patterns involving the interaction between cognition and motor skills, even in once-only faller older adults, can be an efficient approach to assessment and, consequently, to compound intervention programs to prevent falls in this population. Full article

Capsular contracture (CC) is one of the most common postoperative complications associated with breast implant-associated infections. The mechanisms that lead to CC remain poorly understood. Plasma is an ideal biospecimen for early proteomics biomarker discovery. However, as high-abundance proteins mask signals from low-abundance proteins, identifying novel or specific proteins as biomarkers for a particular disease has been hampered. Here, we employed depletion of high-abundance plasma proteins followed by Tandem Mass Tag (TMT)-based quantitative proteomics to compare 10 healthy control patients against 10 breast implant CC patients. A total of 450 proteins were identified from these samples. Among them, 16 proteins were significantly differentially expressed in which 5 proteins were upregulated and 11 downregulated in breast implant CC patients compared to healthy controls. Gene Ontology enrichment analysis revealed that proteins related to cell, cellular processes and catalytic activity were highest in the cellular component, biological process, and molecular function categories, respectively. Further, pathway analysis revealed that inflammatory responses, focal adhesion, platelet activation, and complement and coagulation cascades were enriched pathways. The differentially abundant proteins from TMT-based quantitative proteomics have the potential to provide important information for future mechanistic studies and in the development of breast implant CC biomarkers. Full article

There is a limited number of studies analyzing the molecular and biochemical processes regulating the metabolism of the maturation of Cocos nucifera L. zygotic embryos. Our research focused on the regulation of carbohydrate and lipid metabolic pathways occurring at three developmental stages of embryos from the Mexican Pacific tall (MPT) and the Yucatan green dwarf (YGD) cultivars. We used the TMT-synchronous precursor selection (SPS)-MS3 strategy to analyze the dynamics of proteomes from both embryos; 1044 and 540 proteins were determined for the MPT and YGD, respectively. A comparison of the differentially accumulated proteins (DAPs) revealed that the biological processes (BP) enriched in the MPT embryo included the glyoxylate and dicarboxylate metabolism along with fatty acid degradation, while in YGD, the nitrogen metabolism and pentose phosphate pathway were the most enriched BPs. Findings suggest that the MPT embryos use fatty acids to sustain a higher glycolytic/gluconeogenic metabolism than the YGD embryos. Moreover, the YGD proteome was enriched with proteins associated with biotic or abiotic stresses, e.g., peroxidase and catalase. The goal of this study was to highlight the differences in the regulation of carbohydrate and lipid metabolic pathways during the maturation of coconut YGD and MPT zygotic embryos. Full article

Wood extractives have proven strong anti-oxidative properties which may be used to mitigate surface deterioration caused by photolytic effects and free radical formations. An interesting challenge regarding wood extractives is understanding how they behave in terms of treating natural wood surfaces to reduce anti-oxidative processes that arise from exposure to the main environmental factors. In this study, the possible efficacy of chestnut (Castanea sativa Mill.) extractives derived from native (CH) and thermally modified wood (TMT CH), as a means of protecting against UV exposure in poplar (Populus spp.) and spruce (Picea abies Karst.) wood, was evaluated. Chestnut wood was first thermally modified at 180 °C for 3 h, and the extractives were obtained by the accelerated solvent extraction technique (ASE) and subsequently used to treat wood surfaces. Samples were immersed in extractive solutions and exposed to artificial UV-weathering exposure, then contact angle and colour stability were monitored during the process. An FTIR analysis of the photo-degradation process of poplar and spruce surfaces was also executed. Extractives of TMT chestnut changed the total colour variation in both poplar and spruce wood. A much darker colour compared to the extractives of native wood was observed and an increase in ∆E* from 9.75 to 30.76 and 6.24 to 22.97 in poplar and spruce was calculated. The stability of the colour depended both on the surface wood and the type of extractive. The initial contact angle remained almost unchanged in the poplar wood surface and only slightly increased in spruce regardless of whether they were treated with extractives from native or TMT chestnut wood. A strong reduction in contact angle after the accelerated UV exposure test was observed, especially in spruce treated with CH extractives. FTIR analysis confirmed the lower levels of chemical degradation of surfaces observed by colorimetry, where TMT CH extractives formed more stable chemical bonds than native extractives. The comparative analysis in this study clarified the complex relationships between the effects of high-temperature modification of wood and the potential protective role of TMT extractives on some wood surfaces. Full article

Male reproductive health is largely determined already in the early development of the testis. Although much work has been carried out to study the mechanisms of testicular development and spermatogenesis, there was previously no information on the differences in the protein composition of yak testicles during early development. In this study, the protein profiles in the testicles of 6- (M6), 18- (M18), and 30-month-old (M30) yaks were comparatively analyzed using TMT proteomics. A total of 5521 proteins were identified, with 13, 1295, and 1397 differentially expressed proteins (DEPs) in 30- vs. 18-, 18- vs. 6-, and 30- vs. 6-month-old testes, respectively. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that DEPs were mainly involved in signaling pathways related to testicular development and spermatogenesis, including the MAPK, PI3K–Akt, Wnt, mTOR, TGF-β, and AMPK signaling pathways. Furthermore, we also identified eight potential proteins (TEX101, PDCL2, SYCP2, SYCP3, COL1A1, COL1A2, ADAM10, and ATF1) that may be related to the testicular development and spermatogenesis of yaks. This study may provide new insights into the molecular mechanisms of the testicular development and spermatogenesis of yaks. Full article

Fermentation with Bacillus subtilis significantly enhances the physiological activity and bioavailability of soymilk, but the resulting characteristic flavor seriously affects its industrial promotion. The objective of this study was to identify key proteins associated with characteristic flavors in B. subtilis BSNK-5-fermented soymilk using tandem mass tag (TMT) proteomics. The results showed that a total of 765 differentially expressed proteins were identified. Seventy differentially expressed proteins related to characteristic flavor were screened through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. After integrating metabolomics data, fifteen key proteases of characteristic flavor components in BSNK-5-fermented soymilk were further identified, and free ammonia was added. In addition, there were five main formation mechanisms, including the decomposition of urea to produce ammonia; the degradation of glutamate by glutamate dehydrogenase to produce ammonia; the degradation of threonine and non-enzymatic changes to form the derivative 2,5-dimethylpyrazine; the degradation of valine, leucine, and isoleucine to synthesize isovalerate and 2-methylbutyrate; and the metabolism of pyruvate and lactate to synthesize acetate. These results provide a theoretical foundation for the improvement of undesirable flavor in B. subtilis BSNK-5-fermented soy foods. Full article

Bladder cancer (BC) is the tenth most commonly diagnosed malignancy worldwide. In approximately 25% of cases, it presents as a muscle-invasive disease, requiring a radical treatment. Traditionally, the mainstay of treatment has been radical cystectomy (RC), but in the last decade, bladder-sparing treatments have been gaining growing interest. In particular, trimodal therapy (TMT) seems to yield survival results comparable to RC with less morbidity and better quality of life (QoL) outcomes. In this scenario, we aimed at shedding light on the role of the histological subtypes (HS) of BC and their prognostic significance in muscle-invasive BC (MIBC), treated either surgically or with TMT. We performed a narrative review to provide an overview of the current literature on this topic. When compared with patients diagnosed with conventional urothelial carcinoma (UC) of the same disease stage, survival did not appear to be significantly worse across the reports. But when sub-analyzed for separate subtype, some appeared to be independently associated with adverse survival outcomes such as the micropapillary, plasmacytoid, small-cell, and sarcomatoid subtypes, whereas others did not. Moreover, the optimal management remains to be defined, also depending on the therapeutic susceptibility of each histology. From this perspective, multi-disciplinary assessment alongside the routine inclusion of such entities in randomized clinical trials appears to be essential. Full article

Histone acetylation is an important epigenetic mechanism that has been shown to play a role in diapause regulation. To explore the physiological and molecular mechanisms of histone deacetylase in the diapause process, LC-MS/MS analysis was used to perform TMT proteomic and metabolomic analysis on non-diapause (ND), pre-diapause (PreD), diapause (D), cold treatment (CT), and post-diapause (RD) stages of the meadow moth. A total of 5367 proteins were identified by proteomics, including 1179 differentially expressed proteins. We found 975 (602 up-regulated and 373 down-regulated), 997 (608 up-regulated and 389 down-regulated), 1119 (726 up-regulated and 393 down-regulated), 1179 (630 up-regulated and 549 down-regulated), 94 (51 up-regulated and 43 down-regulated), 111 (63 up-regulated and 48 down-regulated), 533 (243 up-regulated and 290 down-regulated), 58 (31 up-regulated and 27 down-regulated), and 516 (228 up-regulated and 288 down-regulated) proteins in ND and PreD, ND and D, ND and CT, ND and RD, PreD and D, PreD and CT, PreD and RD, D and CT, D and RD, and CT and RD stages, respectively. A total of 1255 differentially expressed metabolites were annotated by metabolomics. Through KEGG analysis and time series analysis of differentially expressed metabolites, we found that phospholipids were annotated in significantly different modules, demonstrating their important role in the diapause process of the meadow moth. Using phospholipids as an indicator for weighted gene co-expression network analysis, we analyzed the most relevant differentially expressed proteins in the module and found that ribosomal 40s and 60s subunits were the most relevant proteins for diapause. Because there have been studies that have shown that histone deacetylase is associated with the diapause of meadow moths, we believe that histone deacetylase regulates the 40s and 60s subunits of ribosomes, which in turn affects the diapause of meadow moths. This finding expands our understanding of the regulation of meadow moth diapause and provides new insights into its control mechanism. Full article

Exposure to the neurotoxin trimethyltin (TMT) selectively induces hippocampal neuronal injury and astrocyte activation accompanied with resultant neuroinflammation, which causes severe behavioral, cognitive, and memory impairment. A large body of evidence suggests that flaxseed oil (FSO), as one of the richest sources of essential omega-3 fatty acids, i.e., α-linolenic acids (ALA), displays neuroprotective properties. Here, we report the preventive effects of dietary FSO treatment in a rat model of TMT intoxication. The administration of FSO (1 mL/kg, orally) before and over the course of TMT intoxication (a single dose, 8 mg/kg, i.p.) reduced hippocampal cell death, prevented the activation of astrocytes, and inhibited their polarization toward a pro-inflammatory/neurotoxic phenotype. The underlying protective mechanism was delineated through the selective upregulation of BDNF and PI3K/Akt and the suppression of ERK activation in the hippocampus. Pretreatment with FSO reduced cell death and efficiently suppressed the expression of inflammatory molecules. These beneficial effects were accompanied by an increased intrahippocampal content of n-3 fatty acids. In vitro, ALA pretreatment prevented the TMT-induced polarization of cultured astrocytes towards the pro-inflammatory spectrum. Together, these findings support the beneficial neuroprotective properties of FSO/ALA against TMT-induced neurodegeneration and accompanied inflammation and hint at a promising preventive use of FSO in hippocampal degeneration and dysfunction. Full article

This paper presents the state-of-the-art techniques employed in aerothermal modeling to respond to the current observatory design challenges, particularly those of the next generation of extremely large telescopes (ELTs), such as the European ELT, the Thirty Meter Telescope International Observatory (TIO), and the Giant Magellan Telescope (GMT). It reviews the various aerothermal simulation techniques, the synergy between modeling outputs and observatory integrating modeling, and recent applications. The suite of aerothermal modeling presented includes thermal network models, Computational Fluid Dynamics (CFD) models, solid thermal and deformation models, and conjugate heat transfer models (concurrent fluid/solid simulations). The aerothermal suite is part of the overall observatory integrated modeling (IM) framework, which also includes optics, dynamics, and controls. The outputs of the IM framework, nominally image quality (IQ) metrics for a specific telescope state, are fed into a stochastic framework in the form of a multidimensional array that covers the range of influencing operational parameters, thus providing a statistical representation of observatory performance. The applications of the framework range from site selection, ground layer characterization, and site development to observatory performance current best estimate and optimization, active thermal control design, structural analysis, and an assortment of cost–performance trade studies. Finally, this paper addresses planned improvements, the development of new ideas, attacking new challenges, and how it all ties to the “Computational Fluid Dynamics Vision 2030” initiative. Full article