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1.
Plants (Basel) ; 13(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38794428

RESUMO

Leguminous green manure (LGM) has a reputation for improving crop productivity. However, little is known about the beneficial interactions with straw on crop yield and nutrient (N, P, K) use efficiency. Herein, a 9-year field experiment (from 2015 to 2023) containing three treatments-(1) chemical fertilizer as the control (CK), (2) NPK + straw return (Straw) and (3) NPK + straw return with LGM (Straw + LGM)-was conducted to investigate whether the combined application of LGM and straw can increase productivity and nutrient use efficiency in the wheat-maize-sunflower diversified cropping rotation. The results showed that in the third rotation (2021-2023), Straw + LGM significantly increased wheat yield by 10.2% and maize yield by 19.9% compared to CK. The total equivalent yield under Straw + LGM was the highest (26.09 Mg ha-1), exceeding Straw and CK treatments by 2.7% and 12.3%, respectively. For each 2 Mg ha-1 increase in straw returned to the field, sunflower yield increased by 0.2 Mg ha-1, whereas for each 1 Mg ha-1 increase in LGM yield from the previous crop, sunflower yield increased by 0.45 Mg ha-1. Compared to CK, the co-application of LGM and straw increased the N use efficiency of maize in the first and third rotation cycle by 70.6% and 55.8%, respectively, and the P use efficiency by 147.8% in the third rotation cycle. Moreover, Straw treatment led to an increase of net income from wheat and sunflower by 14.5% and 44.6%, while Straw + LGM increased the net income from maize by 15.8% in the third rotation cycle. Combining leguminous green manure with a diversified cropping rotation has greater potential to improve nutrient use efficiency, crop productivity and net income, which can be recommended as a sustainable agronomic practice in the Hetao District, Northwest China.

2.
Front Immunol ; 15: 1383503, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756780

RESUMO

With the development of global social economy and the deepening of the aging population, diseases related to aging have received increasing attention. The pathogenesis of many respiratory diseases remains unclear, and lung aging is an independent risk factor for respiratory diseases. The aging mechanism of the lung may be involved in the occurrence and development of respiratory diseases. Aging-induced immune, oxidative stress, inflammation, and telomere changes can directly induce and promote the occurrence and development of lung aging. Meanwhile, the occurrence of lung aging also further aggravates the immune stress and inflammatory response of respiratory diseases; the two mutually affect each other and promote the development of respiratory diseases. Explaining the mechanism and treatment direction of these respiratory diseases from the perspective of lung aging will be a new idea and research field. This review summarizes the changes in pulmonary microenvironment, metabolic mechanisms, and the progression of respiratory diseases associated with aging.


Assuntos
Envelhecimento , Microambiente Celular , Pulmão , Estresse Oxidativo , Humanos , Envelhecimento/imunologia , Pulmão/imunologia , Animais , Pneumopatias/imunologia , Pneumopatias/etiologia , Inflamação/imunologia
3.
Int J Biol Macromol ; 271(Pt 1): 132565, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38782327

RESUMO

There is a growing demand for the development of epoxy resin modified with biomaterials, aiming to achieve high toughness. Herein, chitosan crosslinked epoxy resin (CE) was synthesized by diisocyanate as a bridge. With 4,4'-diamino-diphenylmethane (DDM) as the curing agent, thanks to the unique cross-linking structure of the CE resin and the presence of carbamate groups, the cured CE/DDM exhibited superior properties compared to commercially available epoxy resin (E51). The tensile strength of the cured CE-3/DDM reached 90.17 MPa, the elongation at break was 11.2 %, and the critical stress intensity factor (KIC) measured 1.78 MPa m1/2. These values were 21.4 %, 151.6 %, and 81.6 % higher than those of the cured E51/DDM, respectively. It is worth noting that the addition of biomass material chitosan did not reduce the thermal stability of the resin. Additionally, the CE coatings on the metal substrate exhibited exceptional corrosion resistance, as evidenced by higher impedance values in electrochemical impedance spectroscopy (EIS) and polarization voltages in the Tafel curve compared to those of the E51 coating. This study opens up a novel approach to modifying epoxy resin with biomass materials with high toughness and corrosion resistance, without sacrificing other performance.

4.
Nat Commun ; 15(1): 4394, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782957

RESUMO

Manipulating dynamic behaviours of charge carriers and excitons in organic light-emitting diodes (OLEDs) is essential to simultaneously achieve high colour purity and superior operational lifetime. In this work, a comprehensive transient electroluminescence investigation reveals that incorporating a thermally activated delayed fluorescence assistant molecule with a deep lowest unoccupied molecular orbital into a bipolar host matrix effectively traps the injected electrons. Meanwhile, the behaviours of hole injection and transport are still dominantly governed by host molecules. Thus, the recombination zone notably shifts toward the interface between the emissive layer (EML) and the electron-transporting layer (ETL). To mitigate the interfacial carrier accumulation and exciton quenching, this bipolar host matrix could serve as a non-barrier functional spacer between EML/ETL, enabling the distribution of recombination zone away from this interface. Consequently, the optimized OLED exhibits a low driving voltage, promising device stability (95% of the initial luminance of 1000 cd m-2, LT95 > 430 h), and a high Commission Internationale de L'Éclairage y coordinate of 0.69. This indicates that managing the excitons through rational energy level alignment holds the potential for simultaneously satisfying Rec.2020 standard and achieving commercial-level stability.

5.
Org Lett ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802298

RESUMO

To realize strong donor-acceptor face-to-face stacking for efficient through-space charge transfer-type thermally activated delayed fluorescence, a conceptually new design strategy is proposed to couple flexible bridges with adequate rigidity via built-in intramolecular hydrogen bonds (IHBs). The resulting emitter ACE-CN has a planarized benzyl methyl ether bridge self-anchored by the C-H···O IHB and shows a high photoluminescence quantum efficiency of 93%. The solution- and vacuum-processed devices exhibited high external quantum efficiencies of 11.8% and 24.7%, respectively.

6.
World J Gastrointest Oncol ; 16(5): 1925-1946, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38764837

RESUMO

BACKGROUND: The treatment of gastric cancer (GC) has caused an enormous social burden worldwide. Accumulating studies have reported that N6-methyladenosine (m6A) is closely related to tumor progression. METTL5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of cells. However, its aberrant regulation in GC has not been fully elucidated. AIM: To excavate the role of METTL5 in the development of GC. METHODS: METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical samples. The tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays, colony formation assays, scratch healing assays, transwell assays and flow cytometry. The tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor model. The EpiQuik m6A RNA Methylation Quantification Kit was used for m6A quantification. Next, liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism, which was confirmed by Enzyme-linked immunosorbent assay and rescue tests. In addition, we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell experiments. RESULTS: Our research revealed substantial upregulation of METTL5, which suggested a poor prognosis of GC patients. Increased METTL5 expression indicated distant lymph node metastasis, advanced cancer stage and pathological grade. An increased level of METTL5 correlated with a high degree of m6A methylation. METTL5 markedly promotes the proliferation, migration, and invasion of GC cells in vitro. METTL5 also promotes the growth of GC in animal models. METTL5 knockdown resulted in significant changes in sphingomyelin metabolism, which implies that METTL5 may impact the development of GC via sphingomyelin metabolism. In addition, high METTL5 expression led to cisplatin resistance. CONCLUSION: METTL5 was found to be an oncogenic driver of GC and may be a new target for therapy since it facilitates GC carcinogenesis through sphingomyelin metabolism and cisplatin resistance.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38768497

RESUMO

Developing thermally activated delayed fluorescence (TADF) near-infrared (NIR) organic light-emitting diodes (OLEDs) based on nondoped emitting layers is intriguing yet challenging, limited by low exciton utilization and notorious concentration quenching. Herein, a facile strategy is proposed to address this issue by incorporating an internal host component onto a traditional donor (D)-acceptor (A)-type red TADF molecule. A proof-of-concept emitter with an internal host is accordingly developed as well as a control one without an internal host. In the case of their monomer states, both emitters exhibit similar emission spectra due to their identical D-A pairs. However, under nondoped conditions, significant improvement in exciton utilization and quenching-resistant features are observed for the molecule with the internal host. The corresponding nondoped OLED yielded a maximum external quantum efficiency of 2.4%, with NIR emission peaking at 765 nm, which was a nearly 10-fold improvement relative to the efficiency based on the control molecule without an internal host. To the best of our knowledge, this result is on par with those of state-of-the art nondoped NIR TADF OLEDs in a similar emission region. These results offer a feasible pathway for the design and development of high-efficiency NIR nondoped OLEDs.

9.
Front Oncol ; 14: 1387735, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720807

RESUMO

Background: Rhabdomyosarcoma(RMS) is the most common soft tissue sarcoma in children and single nucleotide polymorphisms(SNPs) in certain genes influence risk of RMS. Although FOXO3 had been reported in multiple cancers including RMS, the role of FOXO3 polymorphisms in RMS remains unclear. In this case-control study, we evaluated the association of FOXO3 SNPs with RMS risk and prognosis in children. Methods: Four FOXO3 SNPs(rs17069665 A>G, rs4946936 T>C, rs4945816 C>T and rs9400241 C>A) were genotyped in 110 RMS cases and 359 controls. The associations between FOXO3 polymorphisms and RMS risk were determined by odds ratios(ORs) with 95% confidence intervals(CIs). The associations of rs17069665 and rs4946936 with overall survival in RMS children were estimated using the Kaplan-Meier method and log-rank test. Functional analysis in silico was performed to estimate the probability that rs17069665 and rs4946936 might influence the regulation of FOXO3. Results: We found that rs17069665 (GG vs. AA+AG, adjusted OR=2.96; 95%CI [1.10-3.32]; P=0.010) and rs4946936 (TC+CC vs. TT, adjusted OR=0.48; 95%CI [0.25-0.90]; P=0.023) were related to the increased and decreased RMS risk, respectively. Besides, rs17069665(P<0.001) and rs4946936(P<0.001) were associated with decreased and increased overall survival in RMS patients, respectively. Functional analysis showed that rs17069665 and rs4946936 might influence the transcription and expression of FOXO3 via altering the bindings to MYC, CTCF, and/or RELA. Conclusions: This study revealed that FOXO3 polymorphisms influence the RMS susceptibility and prognosis in children, and might altered the expression of FOXO3. FOXO3 polymorphism was suggested as a biomarker for RMS susceptibility and prognosis.

10.
J Stroke Cerebrovasc Dis ; : 107763, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38723921

RESUMO

OBJECTIVE: To assess the utility of combined neutrophil-to-lymphocyte ratio (NLR) and D-dimer detection in determining the severity and short-term prognosis of acute cardiogenic cerebral embolism in older adults. METHODS: A total of 202 elderly patients with NVAF who were hospitalized in the Third Affiliated Hospital of Anhui Medical University from April 1, 2020, to April 1, 2023, were selected and divided into the observation group (69 patients with NVAF combined with ACCE) and the control group (133 patients with NVAF alone) according to whether they had acute cardiogenic cerebral embolism. According to the National Institutes of Health Stroke Scale (NIHSS), the observation group was divided into mild, moderate, and severe cerebral infarction groups: 26 cases (MICI group), 29 cases (MOCI group) and 14 cases (SCI group), respectively. According to the modified Rankin scale (mRS) after 3 months, 30 cases were divided into the good prognosis group and 39 cases were divided into the poor prognosis group. The D-dimer and NLR levels were detected in the two groups. Logistic regression was used to analyze whether the two factors were factors affecting the short-term prognosis of patients with acute cardiogenic cerebral embolism, and the ROC curve was drawn to evaluate the value of the two combined tests on the short-term prognosis of patients with acute cardiogenic cerebral embolism RESULTS: The levels of D-dimer and NLR in peripheral blood in SCI group [1.82 (0.68-6.71) mg/l, 4.55 (2.31-6.68)] were higher than those in MOCI group [1.16 (0.65-1.90) mg/l, 3.84 (3.14-6.87)] and MICI group [0.53(0.32-0.90) mg/l, 2.46(2.09-3.79)]; The difference between groups was statistically significant (P<0.05). Logistic regression analysis showed that D-dimer and NLR were independent risk factors for poor prognosis in patients with acute cardiogenic cerebral embolism (OR values were 1.772 and 1.603, and 95%CI were 1.060-2.963 and 1.100-2.338, respectively, both P<0.05). The AUC of D-dimer combined with NLR for predicting poor prognosis of acute cardiogenic cerebral embolism was 0.812, which is better than D-dimer and NLR alone. CONCLUSION: Peripheral blood D-dimer combined with NLR detection is helpful for the risk stratification and short-term prognosis assessment of patients with acute cardiogenic cerebral embolism. Clinical detection is of great significance for the prevention and monitoring of disease development.

11.
Sci Rep ; 14(1): 10642, 2024 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724565

RESUMO

Colorectal cancer (CRC) often necessitates cetuximab (an EGFR-targeting monoclonal antibody) for treatment. Despite its clinical utility, the specific operative mechanism of cetuximab remains elusive. This research investigated the influence of PLCB3, a potential CRC oncogene, on cetuximab treatment. We extracted differentially expressed genes from the GSE140973, the overlapping genes combined with 151 Wnt/ß-Catenin signaling pathway-related genes were identified. Then, we conducted bioinformatics analysis to pinpoint the hub gene. Subsequently, we investigated the clinical expression characteristics of this hub gene, through cell experimental, scrutinized the impact of cetuximab and PLCB3 on CRC cellular progression. The study identified 26 overlapping genes. High expression of PLCB3, correlated with poorer prognosis. PLCB3 emerged as a significant oncogene associated with patient prognosis. In vitro tests revealed that cetuximab exerted a cytotoxic effect on CRC cells, with PLCB3 knockdown inhibiting CRC cell progression. Furthermore, cetuximab treatment led to a reduction in both ß-catenin and PLCB3 expression, while simultaneously augmenting E-cadherin expression. These findings revealed PLCB3 promoted cetuximab inhibition on Wnt/ß-catenin signaling. Finally, simultaneous application of cetuximab with a Wnt activator (IM12) and PLCB3 demonstrated inhibited CRC proliferation, migration, and invasion. The study emphasized the pivotal role of PLCB3 in CRC and its potential to enhance the efficacy of cetuximab treatment. Furthermore, cetuximab suppressed Wnt/ß-catenin pathway to modulate PLCB3 expression, thus inhibiting colorectal cancer progression. This study offered fresh perspectives on cetuximab mechanism in CRC.


Assuntos
Proliferação de Células , Cetuximab , Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Wnt , beta Catenina , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Cetuximab/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , beta Catenina/metabolismo , beta Catenina/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Prognóstico , Antineoplásicos Imunológicos/farmacologia
12.
Nurs Crit Care ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639246

RESUMO

BACKGROUND: Pneumonia has a high incidence in traumatic brain injury (TBI) patients and lacks effective treatments. Early mobilization (EM) may be a potentially effective treatment. AIM: To explore the impact of EM on TBI-related pneumonia in the neurosurgical intensive care unit (NICU). METHOD: This study was a historical control study. 100 TBI patients who received EM intervention were prospectively included as the experimental group (EM cohort), and 250 TBI patients were retrospectively included as the control group. The propensity score matching (PSM) method was employed to balance baseline and minimize potential bias. The relationship between EM and TBI-related pneumonia was investigated by univariate and multivariate logistic regression, then further determined by subgroup analysis. The influence of other variables was excluded by interaction analyses. Finally, the effect of EM on the prognosis of TBI patients was analysed by comparing the Glasgow Coma Scale (GCS) and the hospital stay. RESULTS: After screening, 86 patients were included in the EM cohort and 199 patients were included in the control cohort. There were obvious differences between the two cohorts at baseline, and these differences were eliminated after PSM, when the incidence of pneumonia was significantly lower in the EM cohort than in the control cohort (35.0% vs. 61.9%, p < .001). Multivariate logistic regression showed that EM was an independent risk factor for TBI-related pneumonia and was significantly associated with a decreased incidence of pneumonia. This correlation was present in most subgroups and was not affected by other variables (p for interaction >.05). Patients in the EM cohort had shorter length of ICU stay (6 vs. 7 days, p = .017) and higher GCS at discharge (12 vs. 11, p = .010). CONCLUSION: EM is a safe and effective treatment for TBI patients in NICU, which can reduce the incidence of pneumonia, help to improve prognosis and shorten the length of ICU stay. RELEVANCE TO CLINICAL PRACTICE: Although the utilization rate of EM is low in TBI patients for various reasons, EM is still an effective method to prevent complications. Our study confirms that a scientific and detailed EM strategy can effectively reduce the incidence of pneumonia while ensuring the safety of TBI patients, which is worthy of further research and clinical application.

13.
Cancer Sci ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623968

RESUMO

Enhancing sensitivity to sorafenib can significantly extend the duration of resistance to it, offering substantial benefits for treating patients with hepatocellular carcinoma (HCC). However, the role of ferroptosis in influencing sorafenib sensitivity within HCC remains pivotal. The enhancer of zeste homolog 2 (EZH2) plays a significant role in promoting malignant progression in HCC, yet the relationship between ferroptosis, sorafenib sensitivity, and EZH2 is not entirely clear. Bioinformatic analysis indicates elevated EZH2 expression in HCC, predicting an unfavorable prognosis. Overexpressing EZH2 can drive HCC cell proliferation while simultaneously reducing ferroptosis. Further analysis reveals that EZH2 amplifies the modification of H3K27 me3, thereby influencing TFR2 expression. This results in decreased RNA polymerase II binding within the TFR2 promoter region, leading to reduced TFR2 expression. Knocking down EZH2 amplifies sorafenib sensitivity in HCC cells. In sorafenib-resistant HepG2(HepG2-SR) cells, the expression of EZH2 is increased. Moreover, combining tazemetostat-an EZH2 inhibitor-with sorafenib demonstrates significant synergistic ferroptosis-promoting effects in HepG2-SR cells. In conclusion, our study illustrates how EZH2 epigenetically regulates TFR2 expression through H3K27 me3, thereby suppressing ferroptosis. The combination of the tazemetostat with sorafenib exhibits superior synergistic effects in anticancer therapy and sensitizes the HepG2-SR cells to sorafenib, shedding new light on delaying and ameliorating sorafenib resistance.

14.
Materials (Basel) ; 17(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612050

RESUMO

As the central component in friction stir welding, the design and manufacture of welding tools for aluminum alloys have garnered substantial attention. However, the understanding of tool reliability during the welding process, especially in terms of fatigue performance, remains unclear. This paper focuses on the welding of AA2219-T4 as a case study to elucidate the predominant failure mode of the tool during the friction stir welding (FSW) of aluminum alloys. Experimental methods, including FSW welding and fracture morphology analysis of the failed tool, coupled with numerical simulation, confirm that high-cycle mechanical fatigue fracture is the primary mode of the tool failure. Failures predominantly occur at the tool pin's root and the shoulder end face with scroll concave grooves. The experimental and simulation results exhibit a noteworthy agreement, validating the reliability of the simulation model. The FSW Arbitrary Lagrangian-Eulerian (ALE) model developed in this study analyzes stress distribution and variation under the thermo-mechanical coupling effect of the tool. It reveals that stress concentration resulting from structural changes in the tool is the primary driver of fatigue crack initiation. This is attributed to exposure to alternating cyclic stresses such as bending, tension, and torsion at the tool pin's root, manifesting as multiaxial composite mechanical fatigue. Among these stresses, bending alternating cyclic stress exerts the most significant influence. The paper employs the Tool Life module in DEFORM software to predict the fatigue life of the tool. Results indicate that reducing welding speed or increasing rotation speed can enhance the tool's fatigue life to some extent. The methodology proposed in this paper serves as a valuable reference for optimizing FSW structures or processes to enhance the fatigue performance of welding tools.

15.
Anal Chim Acta ; 1304: 342572, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38637042

RESUMO

BACKGROUND: Adenosine 5'-triphosphate (ATP) plays an important role in cell metabolism and has been regarded as an indicator of cell survival and damage. Golgi apparatus participates in the signal transduction processes of substance transport, ion homeostasis and stress when extracellular substances enter cells. Till now, there is no fluorescent probe for monitoring Golgi ATP level fluctuation and visualizing the configuration change of the Golgi apparatus during the inhibition of glycolysis. RESULTS: Herein, we report the synthesis of a novel water-soluble cationic polythiophene derivative (PEMTEA) that can be employed as a fluorescent sensor for measuring ATP in the Golgi apparatus. PEMTEA self-assembles into PT-NP nanoparticles in aqueous solution with a diameter of approximately 2 nm. PT-NP displays high sensitivity and superb selectivity towards ATP with a detection limit of 90 nM and a linear detection range from 0 to 3.0 µM. The nanoparticles show low toxicity to HepG2 cells and good photostability in the Golgi apparatus. With the stimulation of Ca2+, PT-NP was practically applied to real-time monitor of endogenous ATP levels in the Golgi apparatus through fluorescence microscopy. Finally, we studied the relationship between the concentration of ATP and configuration of the Golgi apparatus during the inhibition of glycolysis using PT-NP. SIGNIFICANCE: We have demonstrated that PT-NP can not only indicate the fluctuation and distribution of ATP in the Golgi apparatus, but also give the information of the configuration change of the Golgi apparatus at the single-cell level during the inhibition of glycolysis.


Assuntos
Corantes Fluorescentes , Nanopartículas , Corantes Fluorescentes/metabolismo , Água/metabolismo , Complexo de Golgi/metabolismo , Trifosfato de Adenosina/metabolismo , Polímeros , Glicólise
17.
BMC Genomics ; 25(1): 394, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649832

RESUMO

BACKGROUND: Untargeted metabolomics and proteomics were employed to investigate the intracellular response of yak rumen epithelial cells (YRECs) to conditions mimicking subacute rumen acidosis (SARA) etiology, including exposure to short-chain fatty acids (SCFA), low pH5.5 (Acid), and lipopolysaccharide (LPS) exposure for 24 h. RESULTS: These treatments significantly altered the cellular morphology of YRECs. Metabolomic analysis identified significant perturbations with SCFA, Acid and LPS treatment affecting 259, 245 and 196 metabolites (VIP > 1, P < 0.05, and fold change (FC) ≥ 1.5 or FC ≤ 0.667). Proteomic analysis revealed that treatment with SCFA, Acid, and LPS resulted in differential expression of 1251, 1396, and 242 proteins, respectively (FC ≥ 1.2 or ≤ 0.83, P < 0.05, FDR < 1%). Treatment with SCFA induced elevated levels of metabolites involved in purine metabolism, glutathione metabolism, and arginine biosynthesis, and dysregulated proteins associated with actin cytoskeleton organization and ribosome pathways. Furthermore, SCFA reduced the number, morphology, and functionality of mitochondria, leading to oxidative damage and inhibition of cell survival. Gene expression analysis revealed a decrease the genes expression of the cytoskeleton and cell cycle, while the genes expression associated with inflammation and autophagy increased (P < 0.05). Acid exposure altered metabolites related to purine metabolism, and affected proteins associated with complement and coagulation cascades and RNA degradation. Acid also leads to mitochondrial dysfunction, alterations in mitochondrial integrity, and reduced ATP generation. It also causes actin filaments to change from filamentous to punctate, affecting cellular cytoskeletal function, and increases inflammation-related molecules, indicating the promotion of inflammatory responses and cellular damage (P < 0.05). LPS treatment induced differential expression of proteins involved in the TNF signaling pathway and cytokine-cytokine receptor interaction, accompanied by alterations in metabolites associated with arachidonic acid metabolism and MAPK signaling (P < 0.05). The inflammatory response and activation of signaling pathways induced by LPS treatment were also confirmed through protein interaction network analysis. The integrated analysis reveals co-enrichment of proteins and metabolites in cellular signaling and metabolic pathways. CONCLUSIONS: In summary, this study contributes to a comprehensive understanding of the detrimental effects of SARA-associated factors on YRECs, elucidating their molecular mechanisms and providing potential therapeutic targets for mitigating SARA.


Assuntos
Acidose , Proliferação de Células , Células Epiteliais , Metabolômica , Proteômica , Rúmen , Animais , Rúmen/metabolismo , Rúmen/efeitos dos fármacos , Acidose/veterinária , Acidose/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Bovinos , Proliferação de Células/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Lipopolissacarídeos , Doenças dos Bovinos/metabolismo , Proteoma/metabolismo
18.
J Pharmacol Exp Ther ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627096

RESUMO

Organic anions (OA) are compounds including drugs or toxicants that are negatively charged at physiological pH and are typically transported by Organic Anion Transporters (OATs). Human OAT4 (SLC22A11) is expressed in the apical membrane of renal proximal tubules. Although there is no rodent ortholog of hOAT4, rodents express Oat5 (Slc22a19), an anion exchanger that is also localized to the apical membrane of renal proximal tubule cells. The purpose of this study was to determine the functional similarity between mouse Oat5 and human OAT4. Chinese hamster ovary (CHO) cells expressing SLC22A11 or Slc22a19 were used to assess the transport characteristics of radiolabeled ochratoxin (OTA). We determined the kinetics of OTA transport; the resulting Kt and Jmax values were very similar for both hOAT4 and mOat5: Kt 3.9 and 7.2 µM, respectively, & Jmax 4.4 and 3.9 pmol/cm2, respectively. For the profile of OTA inhibition by OAs, IC50 values were determined for several clinically important drugs and toxicants. The resulting IC50 values ranged from 9 µM for indomethacin to ~600 µM for the diuretic hydrochlorothiazide. We measured the efflux of OTA from preloaded cells; both hOAT4 and mOat5 supported the efflux of OTA. These data support the hypothesis that OAT4 and Oat5 are functional orthologs and share selectivity for OTA both for reabsorption and secretion. Significance Statement This study compares the selectivity profile between human OAT4 and mouse Oat5. Our data revealed a similar selectivity profile for OTA reabsorption and secretion by these two transporters, thereby supporting the hypothesis that hOAT4 and mOat5, while not genetic orthologs, behave as functional orthologs for both uptake and efflux. These data will be instrumental in selecting an appropriate animal model when studying the renal disposition of anionic drugs and toxicants.

19.
ACS Appl Mater Interfaces ; 16(17): 21987-21996, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636167

RESUMO

The interest in introducing light into heterogeneous catalysis is driven not only by the urgent need of replacing fossil energy but also by the promise of controlling product selectivity by light. The product selectivity differences observed in recent studies between light and dark reactions are often attributed to photochemical effects. Here, we report the discovery of a non-photochemical origin of selectivity difference, at essentially the same CO2 conversion rate, between photothermal and thermal CO2 hydrogenation reactions over a Ru/TiO2-x catalyst. While the presence of the photochemical effect from ultraviolet light is confirmed, it merely enhances the catalytic activity. Systematic investigation reveals that the gradual formation of an adsorbate-mediated strong metal-support interaction under catalytic conditions is responsible for the variation in the catalytic selectivity. We demonstrate that differences in product selectivity under light/dark reactions do not necessarily originate from photochemical effects. Our study refines the basis for determining photochemical effects and highlights the importance of excluding non-photochemical effects in mechanistic studies of light-controlled product selectivity.

20.
J Phys Chem Lett ; 15(17): 4647-4654, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38647524

RESUMO

Ultraviolet (UV) light plays a crucial role in various applications, but currently, the efficiency of generating artificial UV light is low. The visible-to-ultraviolet (Vis-to-UV) system based on the triplet-triplet annihilation upconversion (TTA-UC) mechanism can be a viable solution. Metal-free multiple resonance thermally activated delayed fluorescence (MR-TADF) materials are ideal photosensitizers (PSs) apart from the drawback of high photoluminescence quantum yields (PLQYs). Herein, we systematically investigated the impact of the heavy-atom effect (HAE) on the MR-TADF sensitizers. BNCzBr was then synthesized by incorporating a bromine atom into the skeleton of the precursor BNCz. Impressively, the internal HAE (iHAE) leads to a significantly decreased PLQY and a remarkably increased intersystem crossing quantum yield (ΦISC). Consequently, a higher upconversion quantum efficiency of 12.5% was realized. While the external HAE (eHAE) harms the UC performance. This work guides the further development of MR-TADF sensitizers for high-performance Vis-to-UV TTA-UC systems.

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