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1.
Int J Biol Macromol ; 269(Pt 2): 132131, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719017

RESUMO

Chitosan oligosaccharide (COS) modification is a feasible way to develop novel green nematicides. This study involved the synthesis of various COS sulfonamide derivatives via hydroxylated protection and deprotection, which were then characterized using NMR, FTIR, MS, elemental analysis, XRD, and TG/DTG. In vitro experiments found that COS-alkyl sulfonamide derivatives (S6 and S11-S13) exhibited high mortality (>98 % at 1 mg/mL) against Meloidogyne incognita second-instar larvaes (J2s) among the derivatives. S6 can cause vacuole-like structures in the middle and tail regions of the nematode body and effectively inhibit egg hatching. In vivo tests have found that S6 has well control effects and low plant toxicity. Additionally, the structure-activity studies revealed that S6 with a high degree of substitution, a low molecular weight, and a sulfonyl bond on the amino group of the COS backbone exhibited increased nematicidal activity. The sulfonamide group is a potential active group for developing COS-based nematicides.

2.
Traffic Inj Prev ; : 1-9, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709142

RESUMO

OBJECTIVE: Road familiarity is an important factor affecting drivers' visual features. Analyzing the quantitative correlation between drivers' road familiarity and visual features in complex environment is of great help to improve driving safety. However, there are few relevant studies. This paper takes urban plane intersection as the environmental object to explore the correlation between drivers' glance behavior and road familiarity, and conducts research on the quantitative evaluation model of road familiarity based on this correlation. METHOD: First, a real vehicle experiment was carried out to record the eye movement data of 24 drivers with different road familiarity. The driver's visual field plane was divided into 10 areas of interest (AOIs) based on the driver's perspective. Three measures, including average glance duration, number of glances, and fixation transition probabilities between AOIs at urban plane intersections, were extracted. Finally, based on the experimental results, the driver road familiarity evaluation model was constructed using the factor analysis method. RESULTS: There are significant differences between unfamiliar and familiar drivers regarding the average glance duration toward the forward (FW) area, the left window (LW) area, the left rearview mirror (LVM) area and the left forward (LF) area, the number of glances toward the other (OT) area, and the fixation transition probabilities of LW→RF (right forward), LF→LF, LF→FW, FW→LW, FW→FW, FW→RVM (right rearview mirror). The comprehensive evaluation results show that the accuracy rate of the driver road familiarity evaluation model reached 83%. CONCLUSIONS: This paper revealed that there is a strong correlation between drivers' road familiarity and drivers' glance behavior. Based on this correlation, we can include road familiarity as a part of drivers' working status and establish a high accuracy evaluation model of driver road familiarity. The conclusion of this paper can provide some reference for the humanized design and improvement of advanced driving assistance system, which is of great significance for reducing the driving workload of drivers and improving the driving safety.

3.
Heliyon ; 10(10): e30828, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38770333

RESUMO

Modified Jiawei Juanbi decoction (MJD) is used for the treatment of early-stage knee osteoarthritis (KOA). Here, modified Jiawei Juanbi decoction (MJD) was employed for the treatment of early-stage knee osteoarthritis (KOA) and its mechanisms were assessed via metabonomics and network pharmacology. A total of 24 male Sprague-Dawley rats were randomly allocated into a normal control group, a model group, and an MJD group (n = 8 rats per group). Each rat group was further equally divided into two subgroups for investigation for either 14 or 28 days. A rat model of early-stage KOA was constructed and rats were treated with MJD. Effects were evaluated based on changes in knee circumference, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). We also analyzed histopathological changes in articular cartilage. High-resolution mass spectrometry was used to analyze the chemical profile of MJD, identifying 228 components. Using an LC-Q-TOF-MS metabonomics approach, 33 differential metabolites were identified. The relevant pathways significantly associated with MJD include arginine and proline metabolism, vitamin B6 metabolism, as well as the biosynthesis of phenylalanine, tyrosine and tryptophan. The system pharmacology paradigm revealed that MJD contains 1027 components and associates with 1637 genes, of which 862 disease genes are related to osteoarthritis. The construction of the MJD composition-target-KOA network revealed a total of 140 intersection genes. A total of 39 hub genes were identified via integration of betweenness centrality values greater than 100 using CytoHubba. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed several significantly affected signaling pathways including the HIF-1, AGE-RAGE (in diabetic complications), IL-17, rheumatoid arthritis and TNF pathways. Integrated-omics and network pharmacology approaches revealed a necessity for further detailed investigation focusing on two major targets, namely NOS2 and NOS3, along with their essential metabolite (arginine) and associated pathways (HIF-1 signaling and arginine and proline metabolism). Real-time PCR validated significantly greater downregulation of NOS2 and HIF-1ɑ in the MJD as compared to the model group. Molecular docking analysis further confirmed the binding of active MJD with key active components. Our findings elucidate the impact of MJD on relevant pathophysiological and metabolic networks relevant to KOA and assess the drug efficacy of MJD and its underlying mechanisms of action.

4.
J Hazard Mater ; 473: 134434, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38762983

RESUMO

The behavior of As is closely related to trans(formation) of ferrihydrite, which often coprecipitates with extracellular polymeric substances (EPS), forming EPS-mineral aggregates in natural environments. While the effect of EPS on ferrihydrite properity, mineralogy reductive transformation, and associated As fate in sulfate-reducing bacteria (SRB)-rich environments remains unclear. In this research, ferrihydrite-EPS aggregates were synthesized and batch experiments combined with spectroscopic, microscopic, and geochemical analyses were conducted to address these knowledge gaps. Results indicated that EPS blocked micropores in ferrihydrite, and altered mineral surface area and susceptibility. Although EPS enhanced Fe(III) reduction, it retarded ferrihydrite transformation to magnetite by inhibiting Fe atom exchange in systems with low SO42-. As a result, 16% of the ferrihydrite was converted into magnetite in the Fh-0.3 treatment, and no ferrihydrite transformation occurred in the Fh-EPS-0.3 treatment. In systems with high SO42-, however, EPS promoted mackinawite formation and increased As mobilization into the solution. Additionally, the coprecipitated EPS facilitated As(V) reduction to more mobilized As(III) and decreased conversion of As into the residual phase, enhancing the potential risk of As contamination. These findings advance our understanding on biogeochemistry of elements Fe, S, and As and are helpful for accurate prediction of As behavior.

5.
Elife ; 122024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738857

RESUMO

Enhanced protein synthesis is a crucial molecular mechanism that allows cancer cells to survive, proliferate, metastasize, and develop resistance to anti-cancer treatments, and often arises as a consequence of increased signaling flux channeled to mRNA-bearing eukaryotic initiation factor 4F (eIF4F). However, the post-translational regulation of eIF4A1, an ATP-dependent RNA helicase and subunit of the eIF4F complex, is still poorly understood. Here, we demonstrate that IBTK, a substrate-binding adaptor of the Cullin 3-RING ubiquitin ligase (CRL3) complex, interacts with eIF4A1. The non-degradative ubiquitination of eIF4A1 catalyzed by the CRL3IBTK complex promotes cap-dependent translational initiation, nascent protein synthesis, oncogene expression, and cervical tumor cell growth both in vivo and in vitro. Moreover, we show that mTORC1 and S6K1, two key regulators of protein synthesis, directly phosphorylate IBTK to augment eIF4A1 ubiquitination and sustained oncogenic translation. This link between the CRL3IBTK complex and the mTORC1/S6K1 signaling pathway, which is frequently dysregulated in cancer, represents a promising target for anti-cancer therapies.


Assuntos
Fator de Iniciação 4A em Eucariotos , Alvo Mecanístico do Complexo 1 de Rapamicina , Transdução de Sinais , Ubiquitinação , Humanos , Fator de Iniciação 4A em Eucariotos/metabolismo , Fator de Iniciação 4A em Eucariotos/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Animais , Biossíntese de Proteínas , Linhagem Celular Tumoral , Camundongos , Receptores de Interleucina-17
6.
Artigo em Inglês | MEDLINE | ID: mdl-38757708

RESUMO

Electro-optical synergy has recently been targeted to improve the separation of hot carriers and thereby further improve the efficiency of plasmon-mediated chemical reactions (PMCRs). However, the electro-optical synergy in PMCRs needs to be more deeply understood, and its contribution to bond dissociation and product selectivity needs to be clarified. Herein, the electro-optical synergy in plasmon-mediated reduction of p-bromothiophenol (PBTP) was studied on a plasmonic nanostructured silver electrode using in situ Raman spectroscopy and theoretical calculations. It was found that the electro-optical synergy-induced enhancements in the cleavage of carbon-bromine bonds, reaction rate, and product selectivity (4,4'-biphenyl dithiol vs thiophenol) were largely affected by the applied bias, laser wavelength, and laser power. The theoretical simulation further clarified that the strong electro-optical synergy is attributed to the matching of energy band diagrams of the plasmonic silver with those of the adsorbed PBTP molecules. A deep understanding of the electro-optical synergy in PBTP reduction and the clarification of the mechanism will be highly beneficial for the development of other highly efficient PMCRs.

7.
Mar Drugs ; 22(5)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38786596

RESUMO

The escalation of jellyfish stings has drawn attention to severe skin reactions, underscoring the necessity for novel treatments. This investigation assesses the potential of hydroxybenzoic acid derivatives, specifically protocatechuic acid (PCA) and gentisic acid (DHB), for alleviating Nemopilema nomurai Nematocyst Venom (NnNV)-induced injuries. By employing an in vivo mouse model, the study delves into the therapeutic efficacy of these compounds. Through a combination of ELISA and Western blot analyses, histological examinations, and molecular assays, the study scrutinizes the inflammatory response, assesses skin damage and repair mechanisms, and investigates the compounds' ability to counteract venom effects. Our findings indicate that PCA and DHB significantly mitigate inflammation by modulating critical cytokines and pathways, altering collagen ratios through topical application, and enhancing VEGF and bFGF levels. Furthermore, both compounds demonstrate potential in neutralizing NnNV toxicity by inhibiting metalloproteinases and phospholipase-A2, showcasing the viability of small-molecule compounds in managing toxin-induced injuries.


Assuntos
Venenos de Cnidários , Hidroxibenzoatos , Pele , Animais , Hidroxibenzoatos/farmacologia , Camundongos , Venenos de Cnidários/farmacologia , Pele/efeitos dos fármacos , Pele/patologia , Pele/metabolismo , Gentisatos/farmacologia , Nematocisto/efeitos dos fármacos , Modelos Animais de Doenças , Citocinas/metabolismo
8.
Heliyon ; 10(7): e28112, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586392

RESUMO

The Long Short-Term Memory neural network is a specialized architecture designed for handling time series data, extensively applied in the field of predicting gas concentrations. In the harsh conditions prevalent in coal mines, the time series data of gas concentrations collected by sensors are susceptible to noise interference. Directly inputting such noisy data into a neural network for training would significantly reduce predictive accuracy and lead to deviations from the actual values. The Empirical Mode Decomposition method, commonly employed in gas concentration prediction, faces challenges in practical engineering applications due to the substantial influence of newly acquired data on the initial decomposition subsequence values. Consequently, it is difficult to use this method as intended. Conversely, the Wavelet Threshold Denoising method does not encounter this issue. Furthermore, gas concentration sequences exhibit chaotic characteristics. Performing phase space reconstruction allows for the extraction of additional valuable hidden information. In light of these factors, a prediction model is proposed, integrating WTD, Phase Space Reconstruction, and LSTM neural networks. Initially, the gas concentration sequence itself is subjected to wavelet threshold denoising. Subsequently, phase space reconstruction is performed, and the resulting reconstructed phase space matrix serves as the input for the LSTM neural network. The outcomes from the final LSTM neural network reveal that the PS method indeed extracts more valuable information. The Mean Absolute Error and Root Mean Square Error are reduced by 35.1% and 25%, respectively. Additionally, when compared to the PS-LSTM model without utilizing the WTD method, the WTD-PS-LSTM predictive model showcases reductions of 77.1% and 80% in MAE and RMSE, respectively. Compared with the LSTM model, the MAE and RMSE of the WTD-PS-LSTM prediction model were reduced by 81.4% and 82.6%, respectively. This greatly improves the credibility of whether or not a response related to coal mine safety management is implemented.

9.
Sci Rep ; 14(1): 7662, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561397

RESUMO

The disintegration of red-bed soft rock exhibits a strong correlation with various geological disasters. However, the investigation into the evolutionary mechanisms underlying disintegration breakage has not yet received extensive exploration. In order to comprehensively examine the disintegration characteristics of red-bed soft rock, the slake durability tests were conducted to red-bed soft rocks of varying burial depths. Subsequently, an investigation was carried out to examine the disintegration characteristics and the evolution of disintegration parameters, including the coefficient of uniformity (Cu), coefficient of curvature (Cc), disintegration rate (DRE), disintegration ratio (Dr), and fractal dimension (D), throughout the disintegration process. Finally, employing the energy dissipation theory, an energy dissipation model was developed to predicate the disintegration process of samples at various burial depths. The findings demonstrate a decrease in the abundance of large particles and a concurrent increase in the abundance of small particles as the number of drying-wetting cycles increases. Furthermore, as the number of drying-wetting cycles increases, a significant alteration is observed in the content of particles larger than 10 mm, whereas the content of particles smaller than 10 mm undergoes only minor changes. The disintegration parameters, including the curvature coefficient, non-uniformity coefficient, disintegration rate, and fractal dimension, exhibit a positive correlation with the number of drying-wetting cycles. Conversely, the disintegration index demonstrates a decreasing trend with the increasing number of cycles. Nevertheless, as the burial depth increases, a notable trend emerges in the disintegration process, characterized by a gradual increase in the content of large particles alongside a progressive decrease in the content of small particles. Concurrently, the curvature coefficient, non-uniformity coefficient, disintegration rate, and fractal dimension exhibit a gradual decline, while the durability index experiences a gradual increase. In addition, based on the principle of energy dissipation, it is revealed that the surface energy increment of red-bed soft rock increases with the increase of the number of drying-wetting cycles, but decreases with the increase of burial depth. Ultimately, by leveraging the outcomes of energy dissipation analyses, a theoretical model is constructed to elucidate the correlation between surface energy and both the number of drying-wetting cycles and burial depth. This model serves as a theoretical reference for predicting the disintegration behavior of samples, offering valuable insights for future research endeavors.

10.
Diab Vasc Dis Res ; 21(2): 14791641241244658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38597578

RESUMO

BACKGROUND: The intricate interaction between oxidative stress and atherosclerotic cardiovascular disease (ASCVD) is an essential area of research because of the potential role of oxidative homeostasis in regulating ASCVD risk. This study aimed to investigate the relationship between the oxidative balance score (OBS) and the 10-years risk of ASCVD to gain insight into how oxidative balance affects cardiovascular health. METHODS: This cross-sectional study analyzed National Health and Nutrition Examination Survey (NHANES) 2011-2020 data (40-79 age group), exploring OBS's link to 10-years ASCVD risk. OBS categorized dietary and lifestyle factors. Multivariate logistic regression controlled for age, sex, race, and demographics. A restricted cubic spline examined linear relationships; robustness was ensured through subgroup analyses. RESULTS: Analysis of 4955 participants reveals a negative association between OBS and 10-years ASCVD risk. Continuous OBS adjusted OR: 0.97 (95% CI: 0.95∼0.99, p < .001). Quartile analysis shows reduced risk in Q2 0.88 (95% CI: 0.63∼1.22, p = .43), Q3 0.92 (95% CI: 0.66∼1.28, p = .614), and Q4 0.59 (95% CI: 0.42∼0.83, p = .002) compare Q1. Quartile analysis indicated decreasing risk in higher OBS quartiles. Lifestyle OBS and Dietary OBS demonstrated similar trends. Stratified analyses highlight race and hypertension as effect modifiers (p < .05). CONCLUSION: Our study suggests an association between higher OBS and a reduced 10-years ASCVD risk. However, causation should not be inferred, and in the future, more extensive clinical and fundamental research is required to delve deeper into this association.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Humanos , Inquéritos Nutricionais , Estudos Transversais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Estresse Oxidativo
11.
J Med Chem ; 67(6): 4560-4582, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38502936

RESUMO

Inspired by the structure of dysoxylactam A (DLA) that has been demonstrated to reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) effectively, 61 structurally simplified cyclolipopeptides were thus designed and synthesized via an effective method, and their reversing P-gp-mediated MDR potentials were evaluated, which provided a series of more potent analogues and allowed us to explore their structure-activity relationship (SAR). Among them, a well-simplified compound, 56, with only two chiral centers that all derived from amino acids dramatically reversed drug resistance in KBV200 cells at 10 µM in combination with vinorelbine (VNR), paclitaxel (PTX), and adriamycin (ADR), respectively, which is more promising than DLA. The mechanism study showed that 56 reversed the MDR of tumor cells by inhibiting the transport function of P-gp rather than reducing its expression. Notably, compound 56 effectively restored the sensitivity of MDR tumors to VNR in vivo at a dosage without obvious toxicity.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Resistencia a Medicamentos Antineoplásicos , Lipopeptídeos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Resistência a Múltiplos Medicamentos , Subfamília B de Transportador de Cassetes de Ligação de ATP , Doxorrubicina/farmacologia , Linhagem Celular Tumoral
12.
Int Urol Nephrol ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466510

RESUMO

BACKGROUND: At present, estimated glomerular filtration rate (eGFR) remains the most frequently utilized parameter in the evaluation of kidney injury severity. Numerous equations have been formulated based on serum creatinine (Scr) or serum cystatin C (Cysc) levels. However, there is a lack of consensus regarding the efficacy of these equations in assessing eGFR, particularly for elderly individuals in China. This study aimed to evaluate the applicability of the MDRD, MDRDc, CKD-EPI series, BIS1, and FAS equations within the Chinese elderly population. METHODS: A cohort of 298 elderly patients with measured GFR (mGFR) was enrolled. The patients were categorized into three subgroups based on their mGFR levels. The eGFR performance was examined, taking into account bias, interquartile range (IQR), accuracy P30, and root-mean-square error (RMSE). Bland-Altman plots were employed to verify the validity of eGFR. RESULTS: The participants had a median age of 71 years, with 167 (56.0%) being male. Overall, no significant differences in bias were observed among the seven equations (P > 0.05). In terms of IQR, P30, and RMSE, the BIS1 equation demonstrated superior accuracy (14.61, 72.1%, and 13.53, respectively). When mGFR < 30 ml/min/1.73 m2, all equations underestimated the true GFR, with the highest accuracy reaching only 59%. Bland-Altman plots indicated that the BIS1 equation exhibited the highest accuracy, featuring a 95% confidence interval (CI) width of 52.37. CONCLUSIONS: This study suggested that the BIS1 equation stands out as the most applicable for estimating GFR in Chinese elderly patients with normal renal function or only moderate decline. 2020NL-085-03, 2020.08.10, retrospectively registered.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38486386

RESUMO

OBJECTIVE: The objective of this study is to investigate Gegen Qinlian decoction (GQD) effects on lipid metabolism and explore its mechanism for preventing and treating atherosclerosis. METHODS: An atherosclerotic rat model was established;, and after an 8-week high-fat diet, atherosclerosis and non-alcoholic fatty liver disease were assessed. Subsequently, GQD was administered at low and high doses. Histopathological aortic wall changes, hepatic lipid deposition, and blood lipid changes were evaluated. ELISA indicated the influence of TNF-α and IL-13, and Western blotting revealed MerTK, ABCA1, and LXR-α expression. A foam macrophage model was established, and Cell activity was detected by the MTT method. ELISA indicated the influence of PPAR-γ. The expression of ABCA1, ABCA7, ABCG1, GAS6, MerTK, SCARB1, LXR- α and LXR-ß mRNA were detected by qPCR, and Western blotting revealed MerTK and LXR-α expression. The impact of drug-containing serum of GQD on efferocytosis-related factors was studied. RESULTS: GQD improved atherosclerosis and non-alcoholic fatty liver disease and reduced serum low-density lipoprotein levels in the high-dose group. The high- and low-dose groups showed upregulated ABCA1, MerTK, and LXR-α expression in blood vessels and the liver, respectively. GQD decreased serum TNF-α and increased IL-13 levels. PPAR-γ expression was elevated in the high-, and low-dose groups. In the high-and low-dose groups, ABCA7, GAS6, SCARB1, and LXR-α, ABCA1 and MerTK, and ABCG1 gene expression were upregulated, respectively. Both low- and high-dose serum-containing drugs promoted LXR-ß gene expression, and LXR-α protein expression was improved in the high-dose group. CONCLUSION: GQD improves rat atherosclerosis and hepatic lipid metabolism by regulating PPAR-γ, LXR-α, LXR-ß, ABCA1, ABCA7, and ABCG1 expression and augmenting cellular intercalation through the GAS6/TAM pathway.

14.
Accid Anal Prev ; 199: 107528, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38447355

RESUMO

Spatial analyses of traffic crashes have drawn much interest due to the nature of the spatial dependence and spatial heterogeneity in the crash data. This study makes the best of Geographically Weighted Random Forest (GW-RF) model to explore the local associations between crash frequency and various influencing factors in the US, including road network attributes, socio-economic characteristics, and land use factors collected from multiple data sources. Special emphasis is put on modeling the spatial heterogeneity in the effects of a factor on crash frequency in different geographical areas in a data-driven way. The GW-RF model outperforms global models (e.g. Random Forest) and conventional geographically weighted regression, demonstrating superior predictive accuracy and elucidating spatial variations. The GW-RF model reveals spatial distinctions in the effects of certain factors on crash frequency. For example, the importance of intersection density varies significantly across regions, with high significance in the southern and northeastern areas. Low-grade road density emerges as influential in specific cities. The findings highlight the significance of different factors in influencing crash frequency across zones. Road network factors, particularly intersection density, exhibit high importance universally, while socioeconomic variables demonstrate moderate effects. Interestingly, land use variables show relatively lower importance. The outcomes could help to allocate resources and implement tailored interventions to reduce the likelihood of crashes.


Assuntos
Acidentes de Trânsito , Regressão Espacial , Humanos , Análise Espacial , Cidades , Aprendizado de Máquina
15.
Appl Environ Microbiol ; 90(3): e0211023, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38391210

RESUMO

Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides. Exposures to 5-15 W m-2 (15-46 µmol photons m-2 s-1) UV-A and 4.35 W m-2 (20 µmol photons m-2 s-1) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), QA re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides.IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides, which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO2 sequestration in the frame of a future CO2 neutral, circular, and sustainable bioeconomy.


Assuntos
Nostoc , Raios Ultravioleta , Humanos , Biomassa , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Nostoc/metabolismo , Fotossíntese/fisiologia
16.
J Nat Prod ; 87(4): 893-905, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38417166

RESUMO

The bridged polycyclic sesquiterpenoids derived from sativene, isosativene, and longifolene have unique structures, and many chemical synthesis approaches with at least 10 steps have been reported. However, their biosynthetic pathway remains undescribed. A minimal biosynthetic gene cluster (BGC), named bip, encoding a sesquiterpene cyclase (BipA) and a cytochrome P450 (BipB) is characterized to produce such complex sesquiterpenoids with multiple carbon skeletons based on enzymatic assays, heterologous expression, and precursor experiments. BipA is demonstrated as a versatile cyclase with (-)-sativene as the dominant product and (-)-isosativene and (-)-longifolene as minor ones. BipB is capable of hydroxylating different enantiomeric sesquiterpenes, such as (-)-longifolene and (+)-longifolene, at C-15 and C-14 in turn. The C-15- or both C-15- and C-14-hydroxylated products are then further oxidized by unclustered oxidases, resulting in a structurally diverse array of sesquiterpenoids. Bioinformatic analysis reveals the BipB homologues as a discrete clade of fungal sesquiterpene P450s. These findings elucidate the concise and divergent biosynthesis of such intricate bridged polycyclic sesquiterpenoids, offer valuable biocatalysts for biotransformation, and highlight the distinct biosynthetic strategy employed by nature compared to chemical synthesis.


Assuntos
Sistema Enzimático do Citocromo P-450 , Família Multigênica , Estrutura Molecular , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sesquiterpenos/metabolismo , Sesquiterpenos/química , Vias Biossintéticas/genética , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/metabolismo , Estereoisomerismo
17.
J Exp Clin Cancer Res ; 43(1): 54, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383447

RESUMO

BACKGROUND: LATS1/2 are frequently mutated and down-regulated in endometrial cancer (EC), but the contributions of LATS1/2 in EC progression remains unclear. Impaired antigen presentation due to mutations or downregulation of the major histocompatibility complex class I (MHC-I) has been implicated in tumor immune evasion. Herein, we elucidate the oncogenic role that dysregulation of LATS1/2 in EC leads to immune evasion through the down-regulation of MHC-I. METHODS: The mutation and expression as well as the clinical significance of LATS1/2 in EC was assessed in the TCGA cohort and our sample cohort. CRISPR-Cas9 was used to construct knockout cell lines of LATS1/2 in EC. Differentially expressed genes were analyzed by RNA-seq. The interaction between LATS1/2 and STAT1 was verified using co-immunoprecipitation and GST pull-down assays. Mass spectrometry, in vitro kinase assays, ChIP-qPCR, flow cytometry, immunohistochemistry, immunofluorescence and confocal microscopy were performed to investigate the regulation of LATS1/2 on MHC-I through interaction with and phosphorylate STAT1. The killing effect of activated PBMCs on EC cells were used to monitor anti-tumor activity. RESULTS: Here, we demonstrate that LATS1/2 are frequently mutated and down-regulated in EC. Moreover, LATS1/2 loss was found to be associated with a significant down-regulation of MHC-I, independently of the Hippo-YAP pathway. Instead, LATS1/2 were found to directly interact with and phosphorylate STAT1 at Ser727, a crucial transcription factor for MHC-I upregulation in response to interferon-gamma (IFN-γ) signaling, to promote STAT1 accumulating and moving into the nucleus to enhance the transcriptional activation of IRF1/NLRC5 on MHC-I. Additionally, the loss of LATS1/2 was observed to confer increased resistance of EC cells to immune cell-mediated killing and this resistance could be reversed by over-expression of MHC-I. CONCLUSION: Our findings indicate that dysregulation of LATS1/2 in EC leads to immune evasion through the down-regulation of MHC-I, leading to the suppression of infiltrating activated CD8 + T cells and highlight the importance of LATS1/2 in IFN-γ signaling-mediated tumor immune response, suggesting that LATS1/2 is a promising target for immune checkpoint blockade therapy in EC.


Assuntos
Neoplasias do Endométrio , Evasão Tumoral , Feminino , Humanos , Antígenos de Histocompatibilidade Classe I , Apresentação de Antígeno , Proteínas Serina-Treonina Quinases/genética , Neoplasias do Endométrio/genética , Peptídeos e Proteínas de Sinalização Intracelular
18.
Small ; : e2310352, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368257

RESUMO

Extensive research has focused on developing wide-bandgap metal compound-based passivating contacts as alternatives to conventional doped-silicon-layer-based passivating contacts to mitigate parasitic absorption losses in crystalline silicon (c-Si) solar cells. Herein, thermally-evaporated aluminum halides (AlX)-based electron-selective passivating contacts for c-Si solar cells are investigated. A low contact resistivity of 60.5 and 38.4 mΩ cm2 is obtained on the AlClx /n-type c-Si (n-Si) and AlFx /n-Si heterocontacts, respectively, thanks to the low work function of AlX. Power conversion efficiencies (PCEs) of 19.1% and 19.6% are achieved on proof-of-concept n-Si solar cells featuring a full-area AlClx /Al and AlFx /Al passivating contact, respectively. By further implementing an ultrathin SiO2 passivation interlayer and a pre-annealing treatment, the electron selectivity (especially the surface passivation) of AlX is significantly enhanced. Accordingly, a remarkable PCE of 21% is achieved on n-Si solar cells featuring a full-area SiO2 /AlFx /Al rear contact. AlFx -based electron-selective passivating contacts exhibit good thermal stability up to ≈400 °C and better long-term environmental stability. This work demonstrates the potential of AlFx -based electron-selective passivating contact for solar cells.

19.
Compr Rev Food Sci Food Saf ; 23(1): e13269, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38284590

RESUMO

Plant proteins are expected to become a major protein source to replace currently used animal-derived proteins in the coming years. However, there are always challenges when using these proteins due to their low water solubility induced by the high molecular weight storage proteins. One approach to address this challenge is to modify proteins through Maillard glycation, which involves the reaction between proteins and carbohydrates. In this review, we discuss various chemical methods currently available for determining the indicators of the Maillard reaction in the early stage, including the graft degree of glycation and the available lysine or sugar, which are involved in the very beginning of the reaction. We also provide a detailed description of the most popular methods for determining graft sites and assessing different plant protein structures and functionalities upon non-enzymatic glycation. This review offers valuable insights for researchers and food scientists in order to develop plant-based protein ingredients with improved functionality.


Assuntos
Reação de Maillard , Proteínas de Plantas , Animais , Alimentos
20.
Compr Rev Food Sci Food Saf ; 23(1): e13291, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38284592

RESUMO

Fruit and vegetable processing can effectively maintain the quality and safety of fruit and vegetable-based products while extending the shelf life of products and saving transportation costs. Infrared (IR) technology has been widely used in many operating units of fruit and vegetable processing because of its versatility of uniform heating, high heat transfer efficiency, and minimized damage to fruit and vegetable tissues. Catalytic IR (CIR), compared to traditional electric IR, is powered by natural gas or liquefied gas, which can improve thermal efficiency while significantly saving energy. However, there is no comprehensive overview discussing and summarizing the utilization and application of the CIR technology in fruit and vegetable processing. Therefore, this review aims to highlight recent advances in the application of CIR technology in fruit and vegetable processing. Specifically, a comprehensive discussion of the physicochemical properties and underlying mechanisms of CIR is provided, and its applications as a single method or in combination with other technologies in fruit and vegetable processes, such as blanching, peeling, microbial population reduction, and drying, are also presented. Besides, the currently used laboratory and pilot-scale equipment of CIR has also been summarized.


Assuntos
Frutas , Verduras , Verduras/química , Frutas/química , Temperatura Alta , Controle de Qualidade
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