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1.
J Hazard Mater ; 474: 134787, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38823101

ABSTRACT

The developmental toxicity effects of neonicotinoid pesticides such as clothianidin have not been fully explored in agricultural applications. This is particularly noteworthy because such pesticides significantly impact the survival rates of invertebrates, with arthropod larvae being particularly vulnerable. This study aimed to address this research gap by specifically investigating the toxicological effects of clothianidin on the developmental stages of the larvae of the economically important aquaculture species Penaeus vannamei. In these experiments, shrimp eggs were exposed to seawater containing different concentrations of clothianidin beginning at N1, and each phase was observed and analyzed to determine its toxic impact on larval development. These results revealed that clothianidin induces an increase in deformity rates and triggers abnormal cell apoptosis. It also significantly reduced survival rates and markedly decreased body length and heart rate in the later stages of larval development (P3). Transcriptomic analysis revealed disruptions in larval DNA integrity, protein synthesis, and signal transduction caused by clothianidin. To survive prolonged exposure, larvae may attempt to maintain their viability by repairing cell structures and enhancing signal transduction mechanisms. This study offers the first empirical evidence of the toxicity of clothianidin to arthropod larvae, underscoring the impact of environmental pollution on aquatic health.

2.
Food Res Int ; 188: 114525, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823888

ABSTRACT

As a kind of green tea with unique multiple baking processes, the flavor code of Lu'an Guapian (LAGP) has recently been revealed. To improve and stabilize the quality of LAGP, further insight into the dynamic changes in odorants during the whole processing is required. In this study, 50 odorants were identified in processing tea leaves, 14 of which were selected for absolute quantification to profile the effect of processes. The results showed that spreading is crucial for key aroma generation and accumulation, while these odorants undergo significant changes at the deep baking stage. By adjusting the conditions of the spreading and deep baking, it was found that low-temperature (4 °C) spreading for 6 h and low-temperature with long-time baking (final leaf temperature: 102 °C, 45 min) could improve the overall aroma quality. These results provide a new direction for enhancing the quality of LAGP green tea.


Subject(s)
Odorants , Tea , Volatile Organic Compounds , Odorants/analysis , Tea/chemistry , Volatile Organic Compounds/analysis , Plant Leaves/chemistry , Food Handling/methods , Cooking/methods , Camellia sinensis/chemistry , Gas Chromatography-Mass Spectrometry , Hot Temperature
3.
Nat Commun ; 15(1): 3901, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724505

ABSTRACT

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.


Subject(s)
Cytoplasm , NF-KappaB Inhibitor alpha , NF-kappa B , Protein-Tyrosine Kinases , Transcription Factor RelA , Animals , Phosphorylation , NF-KappaB Inhibitor alpha/metabolism , NF-KappaB Inhibitor alpha/genetics , Mice , Transcription Factor RelA/metabolism , Humans , Protein-Tyrosine Kinases/metabolism , Protein-Tyrosine Kinases/genetics , NF-kappa B/metabolism , Cytoplasm/metabolism , Proteolysis , Cell Nucleus/metabolism , Virus Replication , HEK293 Cells , Signal Transduction , Mice, Inbred C57BL , Cytokines/metabolism , Active Transport, Cell Nucleus , Protein Serine-Threonine Kinases
4.
Adv Sci (Weinh) ; : e2401664, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38704673

ABSTRACT

Deep-blue multi-resonance (MR) emitters with stable and narrow full-width-at-half-maximum (FWHM) are of great importance for widening the color gamut of organic light-emitting diodes (OLEDs). However, most planar MR emitters are vulnerable to intermolecular interactions from both the host and guest, causing spectral broadening and exciton quenching in thin films. Their emission in the solid state is environmentally sensitive, and the color purity is often inferior to that in solutions. Herein, a molecular design strategy is presented that simultaneously narrows the FWHM and suppresses intermolecular interactions by combining intramolecular locking and peripheral shielding within a carbonyl/nitrogen-based MR core. Intramolecularly locking carbonyl/nitrogen-based bears narrower emission of 2,10-dimethyl-12,12-diphenyl-4H-benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine-4,8(12H)-dione in solution and further with peripheral-shielding groups, deep-blue emitter (12,12-diphenyl-2,10-bis(9-phenyl-9H-fluoren-9-yl)-4H-benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine-4,8(12H)-dione, DPQAO-F) exhibits ultra-pure emission with narrow FWHM (c.a., 24 nm) with minimal variations (∆FWHM ≤ 3 nm) from solution to thin films over a wide doping range. An OLED based on DPQAO-F presents a maximum external quantum efficiency (EQEmax) of 19.9% and color index of (0.134, 0.118). Furthermore, the hyper-device of DPQAO-F exhibits a record-high EQEmax of 32.7% in the deep-blue region, representing the first example of carbonyl/nitrogen-based OLED that can concurrently achieve narrow bandwidth in the deep-blue region and a high electroluminescent efficiency surpassing 30%.

5.
J Cancer Res Clin Oncol ; 150(5): 231, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703241

ABSTRACT

PURPOSE: Acute myeloid leukemia (AML) is a refractory hematologic malignancy that poses a serious threat to human health. Exploring alternative therapeutic strategies capable of inducing alternative modes of cell death, such as ferroptosis, holds great promise as a viable and effective intervention. METHODS: We analyzed online database data and collected clinical samples to verify the expression and function of BMAL1 in AML. We conducted experiments on AML cell proliferation, cell cycle, ferroptosis, and chemotherapy resistance by overexpressing/knocking down BMAL1 and using assays such as MDA detection and BODIPY 581/591 C11 staining. We validated the transcriptional regulation of HMGB1 by BMAL1 through ChIP assay, luciferase assay, RNA level detection, and western blotting. Finally, we confirmed the results of our cell experiments at the animal level. RESULTS: BMAL1 up-regulation is an observed phenomenon in AML patients. Furthermore, there existed a strong correlation between elevated levels of BMAL1 expression and inferior prognosis in individuals with AML. We found that knocking down BMAL1 inhibited AML cell growth by blocking the cell cycle. Conversely, overexpressing BMAL1 promoted AML cell proliferation. Moreover, our research results revealed that BMAL1 inhibited ferroptosis in AML cells through BMAL1-HMGB1-GPX4 pathway. Finally, knocking down BMAL1 can enhance the efficacy of certain first-line cancer therapeutic drugs, including venetoclax, dasatinib, and sorafenib. CONCLUSION: Our research results suggest that BMAL1 plays a crucial regulatory role in AML cell proliferation, drug resistance, and ferroptosis. BMAL1 could be a potential important therapeutic target for AML.


Subject(s)
ARNTL Transcription Factors , Drug Resistance, Neoplasm , Ferroptosis , HMGB1 Protein , Leukemia, Myeloid, Acute , Phospholipid Hydroperoxide Glutathione Peroxidase , Signal Transduction , Animals , Female , Humans , Male , Mice , ARNTL Transcription Factors/genetics , ARNTL Transcription Factors/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Ferroptosis/drug effects , HMGB1 Protein/metabolism , HMGB1 Protein/genetics , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/genetics , Mice, Nude , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Prognosis , Sulfonamides/pharmacology , Xenograft Model Antitumor Assays
6.
Food Res Int ; 187: 114392, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38763654

ABSTRACT

Variations in cultivars and cultivation altitudes have significant impacts on tea flavour compounds however lack of comprehensive understanding. This study provided insights into differential accumulation of crucial flavour compounds in response to cultivars, cultivation altitudes, and processing. Twelve flavonoids (262.4 âˆ¼ 275.4 mg•g-1) and 20 amino acids (AAs) (56.5 âˆ¼ 64.8 mg•g-1) were comparative analyzed in 'Longjing 43' and 'Qunti' fresh leaves harvested at low (80 m, LA) and high (500 m, HA) altitudes. Additionally, an in-depth correlation unravelling of 31 alkaloids, 25 fatty acids, 31 saccharides, 8 organic acids, and 7 vitamins and flavonoids/AAs during green tea (GT) and black tea (BT) processing was performed. Enhenced flavonoid accumulation alongside higher AAs and saccharides in HA GT promoted a sweet/mellow flavour. Abundant flavonoids, AAs, and saccharides derivates in LA BT gave rise to a sweet aftertaste. The study presents an integrated illustration of major flavour compounds' differential accumulation patterns and their interrelations, providing new insights into the influence of cultivation conditions on tea flavour.


Subject(s)
Altitude , Camellia sinensis , Flavonoids , Plant Leaves , Tea , Plant Leaves/chemistry , Plant Leaves/metabolism , Flavonoids/analysis , Tea/chemistry , Camellia sinensis/chemistry , Camellia sinensis/growth & development , Camellia sinensis/metabolism , Taste , Amino Acids/analysis , Amino Acids/metabolism , Food Handling/methods , Flavoring Agents/analysis , Alkaloids/analysis , Alkaloids/metabolism
7.
Environ Int ; 187: 108719, 2024 May.
Article in English | MEDLINE | ID: mdl-38718677

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) have been shown to penetrate the blood-brain barrier (BBB) and accumulate in human brain. The BBB transmission and accumulation efficiency of PFAS, as well as the potential health risks from human co-exposure to legacy and emerging PFAS due to differences in transport efficiency, need to be further elucidated. In the present pilot study, 23 plasma samples from glioma patients were analyzed for 17 PFAS. The concentrations of PFAS in six paired brain tissue and plasma samples were used to calculate the BBB transmission efficiency of PFAS (RPFAS). This RPFAS analysis was conducted with utmost care and consideration amid the limited availability of valuable paired samples. The results indicated that low molecular weight PFAS, including short-chain and emerging PFAS, may have a greater potential for accumulation in brain tissue than long-chain PFAS. As an alternative to perfluorooctane sulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) exhibited brain accumulation potential similar to that of PFOS, suggesting it may not be a suitable substitute concerning health risk in brain. The BBB transmission efficiencies of perfluorooctanoic acid, PFOS, and 6:2 Cl-PFESA showed similar trends with age, which may be an important factor influencing the entry of exogenous compounds into the brain. A favorable link between perfluorooctane sulfonamide (FOSA) and the development and/or progression of glioma may be implicated by a strong positive correlation (r2 = 0.94; p < 0.01) between RFOSA and Ki-67 (a molecular marker of glioma). However, a causal relationship between RFOSA and glioma incidence were not established in the present study. The present pilot study conducted the first examination of BBB transmission efficiency of PFAS from plasma to brain tissue and highlighted the importance of reducing and/or controlling exposure to PFAS.


Subject(s)
Blood-Brain Barrier , Fluorocarbons , Humans , Blood-Brain Barrier/metabolism , Pilot Projects , Fluorocarbons/blood , Middle Aged , Female , Adult , Male , Glioma , Aged , Environmental Pollutants/blood , Environmental Exposure , Alkanesulfonic Acids/blood , Brain/metabolism
8.
Sci Rep ; 14(1): 12251, 2024 05 28.
Article in English | MEDLINE | ID: mdl-38806615

ABSTRACT

Mesenchymal stem cells (MSCs) have demonstrated promising advantages in the therapies of many diseases, while its multi-directional differentiation potential and immunotoxicity are the major concerns hindered their clinical translation. In this study, human umbilical Mesenchymal stem cell (hUC-MSCs) were labeled with a near-infrared fluorescent dye DiR before infused into cynomolgus monkeys, and the amount of hUC-MSCs in the peripheral blood were dynamically estimated from 5 min to 28 days post a single administration at 3 × 106 cells/kg and 2 × 107 cells/kg intravenously. As results, some hUC-MSCs distributed to the whole body within 5 min, while most of the cells accumulate in the lungs along with the systemic blood circulation, and subsequently released into the blood. The toxicity potentials of hUC-MSCs were investigated in another 30 cynomolgus monkeys, and the cells were repeatedly administrated at doses of 3 × 106 cells/kg and 2 × 107 cells/kg for 5 times on a weekly basis, with a recovery period of 1 months. hUC-MSCs showed no obvious toxic effects in cynomolgus monkeys, except xenogeneic immune rejection to human stem cells. Low levels of the hUC-MSC gene were detected in the peripheral blood of a few animals administered 2 × 107 cells/kg at 30 min subsequent to the first and last administration, and there was no significant difference in the copy number of the hUC-MSC gene in the blood samples compared with the first and last administration, indicating that the hUC-MSC was not significantly amplified in vivo, and it its safe in non-human primates. Our study for the first time verified the safety of long-term use of hUC-MSCs in primates. We have pioneered a technology for the real-time detection of hUC-MSCs in peripheral blood and provide dynamicand rapid monitoring of the distribution characteristics of hUC-MSCs in vivo. Here, we provide data supporting the application of such products for clinical treatment and the application of stem cells in major refractory diseases and regenerative medicine.


Subject(s)
Macaca fascicularis , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Umbilical Cord , Animals , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Humans , Umbilical Cord/cytology , Mesenchymal Stem Cell Transplantation/methods , Male , Cell Differentiation , Female
9.
Comp Biochem Physiol C Toxicol Pharmacol ; 283: 109943, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38810897

ABSTRACT

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents.

10.
World J Gastroenterol ; 30(17): 2321-2331, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38813052

ABSTRACT

BACKGROUND: The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated. AIM: To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC. METHODS: We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen. RESULTS: The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs). CONCLUSION: The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Hepatocellular , Fluorouracil , Hepatic Artery , Infusions, Intra-Arterial , Leucovorin , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/therapy , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/drug therapy , Male , Female , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Middle Aged , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Leucovorin/administration & dosage , Leucovorin/adverse effects , Leucovorin/therapeutic use , Aged , Adult , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , Treatment Outcome , Molecular Targeted Therapy/methods , Progression-Free Survival , Retrospective Studies , Immunotherapy/methods , Immunotherapy/adverse effects , Combined Modality Therapy/methods
11.
Sensors (Basel) ; 24(9)2024 May 01.
Article in English | MEDLINE | ID: mdl-38733003

ABSTRACT

In the context of the rapid development of the Internet of Vehicles, virtual reality, automatic driving and the industrial Internet, the terminal devices in the network show explosive growth. As a result, more and more information is generated from the edge of the network, which makes the data throughput increase dramatically in the mobile communication network. As the key technology of the fifth-generation mobile communication network, mobile edge caching technology which caches popular data to the edge server deployed at the edge of the network avoids the data transmission delay of the backhaul link and the occurrence of network congestion. With the growing scale of the network, distributing hot data from cloud servers to edge servers will generate huge energy consumption. To realize the green and sustainable development of the communication industry and reduce the energy consumption of distribution of data that needs to be cached in edge servers, we make the first attempt to propose and solve the problem of edge caching data distribution with minimum energy consumption (ECDDMEC) in this paper. First, we model and formulate the problem as a constrained optimization problem and then prove its NP-hardness. Subsequently, we design a greedy algorithm with computational complexity of O(n2) to solve the problem approximately. Experimental results show that compared with the distribution strategy of each edge server directly requesting data from the cloud server, the strategy obtained by the algorithm can significantly reduce the energy consumption of data distribution.

12.
Chin Med ; 19(1): 75, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816815

ABSTRACT

BACKGROUND: Myocardial infarction (MI) poses a global public health challenge, often associated with elevated mortality rates and a grim prognosis. A crucial aspect of the inflammatory injury and healing process post-MI involves the dynamic differentiation of macrophages. A promising strategy to alleviate myocardial damage after MI is by modulating the inflammatory response and orchestrating the shift from pro-inflammatory (M1) to anti-inflammatory (M2) macrophages, aiming to achieve a reduced M1/M2 ratio. Nuanxinkang (NXK), a simplified herbal decoction, has demonstrated noteworthy cardioprotective, inflammation-regulating, and myocardial energy metabolism-regulating properties. METHODS: In this study, we constructed an MI model by ligating coronary arteries to investigate the efficacy of NXK in improving ventricular remodeling and cardiac function. Mice were administered NXK (1.65 g/kg/d) or an equivalent volume of regular saline via gavage for 28 consecutive days, commencing the day after surgery. Then, we conducted echocardiography to assess the cardiac function, Masson staining to illustrate the extent of myocardial fibrosis, TUNEL staining to reveal myocardial apoptosis, and flow cytometry to analyze the polarization of M1 and M2 macrophages in the hearts. Besides, a lipopolysaccharide (LPS)-induced pro-inflammatory macrophage (M1) polarization model was implemented in RAW264.7 cells to elucidate the underlying mechanism of NXK in regulating macrophage polarization. RAW264.7 cells were pre-treated with or without NXK-containing serum. Oxidative stress was detected by MitoSox staining, followed by Seahorse energy metabolism assay to evaluate alterations in mitochondrial metabolic patterns and ATP production. Both In vivo and in vitro, HIF-1α and PDK1 were detected by fluorescent quantitative PCR and Western blotting. RESULTS: In vivo, MI mice exhibited a decline in cardiac function, adverse ventricular remodeling, and an increase in glycolysis, coupled with M1-dominant polarization mediated by the HIF-1α/PDK1 axis. Notably, robust responses were evident with high-dose NXK treatment (1.65 g/kg/day), leading to a significant enhancement in cardiac function, inhibition of cardiac remodeling, and partial suppression of macrophage glycolysis and the inflammatory phenotype in MI mice. This effect was achieved through the modulation of the HIF-1α/PDK1 axis. In vitro, elevated levels of mitochondrial ROS production and glycolysis were observed in LPS-induced macrophages. Conversely, treatment with NXK notably reduced the oxidative stress damage induced by LPS and enhanced oxidative phosphorylation (OXPHOS). Furthermore, NXK demonstrated the ability to modify the energy metabolism and inflammatory characteristics of macrophages by modulating the HIF-1α/PDK1 axis. The influence of NXK on this axis was partially counteracted by the HIF-1α agonist DMOG. And NXK downregulated PDK1 expression, curtailed glycolysis, and reversed LPS-induced M1 polarization in macrophages, similar to the PDK1 inhibitor DCA. CONCLUSION: In conclusion, NXK protects against MI-induced cardiac remodeling by inducing metabolic reprogramming and phenotypic differentiation of macrophages, achieved through the modulation of the HIF-1α/PDK1 axis. This provides a novel and promising strategy for the treatment of MI.

13.
FASEB J ; 38(10): e23677, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38775792

ABSTRACT

Although the use of Doxorubicin (Dox) is extensive in the treatment of malignant tumor, the toxic effects of Dox on the heart can cause myocardial injury. Therefore, it is necessary to find an alternative drug to alleviate the Dox-induced cardiotoxicity. Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin, which is an active ingredient of Artemisia annua. The study investigates the effects of DHA on doxorubicin-induced cardiotoxicity and ferroptosis, which are related to the activation of Nrf2 and the regulation of autophagy. Different concentrations of DHA were administered by gavage for 4 weeks in mice. H9c2 cells were pretreated with different concentrations of DHA for 24 h in vitro. The mechanism of DHA treatment was explored through echocardiography, biochemical analysis, real-time quantitative PCR, western blotting analysis, ROS/DHE staining, immunohistochemistry, and immunofluorescence. In vivo, DHA markedly relieved Dox-induced cardiac dysfunction, attenuated oxidative stress, alleviated cardiomyocyte ferroptosis, activated Nrf2, promoted autophagy, and improved the function of lysosomes. In vitro, DHA attenuated oxidative stress and cardiomyocyte ferroptosis, activated Nrf2, promoted clearance of autophagosomes, and reduced lysosomal destruction. The changes of ferroptosis and Nrf2 depend on selective degradation of keap1 and recovery of lysosome. We found for the first time that DHA could protect the heart from the toxic effects of Dox-induced cardiotoxicity. In addition, DHA significantly alleviates Dox-induced ferroptosis through the clearance of autophagosomes, including the selective degradation of keap1 and the recovery of lysosomes.


Subject(s)
Artemisinins , Autophagy , Cardiotoxicity , Doxorubicin , Ferroptosis , Myocytes, Cardiac , NF-E2-Related Factor 2 , Artemisinins/pharmacology , Animals , NF-E2-Related Factor 2/metabolism , Autophagy/drug effects , Doxorubicin/adverse effects , Doxorubicin/toxicity , Mice , Ferroptosis/drug effects , Cardiotoxicity/etiology , Cardiotoxicity/prevention & control , Cardiotoxicity/metabolism , Male , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Oxidative Stress/drug effects , Mice, Inbred C57BL , Cell Line , Rats
14.
Int J Ophthalmol ; 17(3): 466-472, 2024.
Article in English | MEDLINE | ID: mdl-38721508

ABSTRACT

AIM: To investigate the molecular diagnosis of a three-generation Chinese family affected with aniridia, and further to identify clinically a PAX6 missense mutation in members with atypical aniridia. METHODS: Eleven family members with and without atypical aniridia were recruited. All family members underwent comprehensive ophthalmic examinations. A combination of whole exome sequencing (WES) and direct Sanger sequencing were performed to uncover the causative mutation. RESULTS: Among the 11 family members, 8 were clinically diagnosed with congenital aniridia (atypical aniridia phenotype). A rare heterozygous mutation c.622C>T (p.Arg208Trp) in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects. CONCLUSION: A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia. This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia, which may also contribute to genetic counselling and family planning.

15.
Int J Ophthalmol ; 17(3): 401-407, 2024.
Article in English | MEDLINE | ID: mdl-38721512

ABSTRACT

AIM: To investigate a pioneering framework for the segmentation of meibomian glands (MGs), using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis. METHODS: Totally 203 infrared meibomian images from 138 patients with dry eye disease, accompanied by corresponding annotations, were gathered for the study. A rectified scribble-supervised gland segmentation (RSSGS) model, incorporating temporal ensemble prediction, uncertainty estimation, and a transformation equivariance constraint, was introduced to address constraints imposed by limited supervision information inherent in scribble annotations. The viability and efficacy of the proposed model were assessed based on accuracy, intersection over union (IoU), and dice coefficient. RESULTS: Using manual labels as the gold standard, RSSGS demonstrated outcomes with an accuracy of 93.54%, a dice coefficient of 78.02%, and an IoU of 64.18%. Notably, these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%, 2.06%, and 2.69%, respectively. Furthermore, despite achieving a substantial 80% reduction in annotation costs, it only lags behind fully annotated methods by 0.72%, 1.51%, and 2.04%. CONCLUSION: An innovative automatic segmentation model is developed for MGs in infrared eyelid images, using scribble annotation for training. This model maintains an exceptionally high level of segmentation accuracy while substantially reducing training costs. It holds substantial utility for calculating clinical parameters, thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

16.
ACS Appl Mater Interfaces ; 16(22): 28409-28422, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38768313

ABSTRACT

Cross-linked ß-cyclodextrin (ß-CD) polymers are promising adsorbents for the removal of per- and polyfluoroalkyl substances (PFAS) from contaminated water sources, including contaminated groundwater, drinking water, and wastewater. We previously reported porous, styrene-functionalized ß-cyclodextrin (StyDex) polymers derived from radical polymerization with vinyl comonomers. Because of the versatility of these polymerizations, StyDex polymer compositions are tunable, which facilitates efforts to establish structure-adsorption relationships and to discover improved materials. Here, we evaluate the material properties and PFAS adsorption of 20 StyDex derivatives with varied comonomer structure and loading, regiochemistry of styrene placement on the CD monomer, and CD size. A StyDex polymer containing N,N'-dimethylbutyl ammonium ions exhibited the most effective PFAS adsorption in batch experiments. Furthermore, a StyDex polymer containing ß-CD exhibited size-selective host-guest interactions with perfluoroalkyl acids (PFAAs) and neutral contaminants in aqueous electrolyte when compared to similar polymers containing either α-CD or γ-CD. Polymers based on ß-CD monomers with an average of seven styrene groups randomly positioned over the 21 available hydroxyl groups performed similarly to those based on a ß-CD monomer functionalized regiospecifically at each of the seven 6' positions. The former ß-CD monomer is prepared in a single step from unmodified ß-CD, so the ability to use it without compromising performance demonstrates promise for developing economically competitive adsorbents. These results offered important insights into structure-adsorption properties of StyDex polymers and will inform the design of improved StyDex formulations.

17.
PNAS Nexus ; 3(4): pgae128, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38562581

ABSTRACT

Genetically engineered silkworms have been widely used to obtain silk with modified characteristics especially by introducing spider silk genes. However, these attempts are still challenging due to limitations in transformation strategies and difficulties in integration of the large DNA fragments. Here, we describe three different transformation strategies in genetically engineered silkworms, including transcription-activator-like effector nuclease (TALEN)-mediated fibroin light chain (FibL) fusion (BmFibL-F), TALEN-mediated FibH replacement (BmFibH-R), and transposon-mediated genetic transformation with the silk gland-specific fibroin heavy chain (FibH) promoter (BmFibH-T). As the result, the yields of exogenous silk proteins, a 160 kDa major ampullate spidroin 2 (MaSp2) from the orb-weaving spider Nephila clavipes and a 226 kDa fibroin heavy chain protein (EvFibH) from the bagworm Eumeta variegate, reach 51.02 and 64.13% in BmFibH-R transformed cocoon shells, respectively. Moreover, the presence of MaSp2 or EvFibH significantly enhances the toughness of genetically engineered silk fibers by ∼86% in BmFibH-T and ∼80% in BmFibH-R silkworms, respectively. Structural analysis reveals a substantial ∼40% increase in fiber crystallinity, primarily attributed to the presence of unique polyalanines in the repetitive sequences of MaSp2 or EvFibH. In addition, RNA-seq analysis reveals that BmFibH-R system only causes minor impact on the expression of endogenous genes. Our study thus provides insights into developing custom-designed silk production using the genetically engineered silkworm as the bioreactor.

18.
J Agric Food Chem ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38607252

ABSTRACT

Glycosidically bound linalool plays important roles in the formation of excellent tea flavor, while their enantiomeric distribution in teas and the actual transformations with free linalool are still unclear. In this study, a novel chiral ultrahigh performance liquid chromatography-mass spectrometry/mass spectrometry approach to directly analyze linalyl-ß-primeveroside and linalyl-ß-d-glucopyranoside enantiomers in teas was established and then applied in 30 tea samples. A close transformation relationship existed between the two states of linalool for their consistent dominant configurations (most S-form) and corresponding distribution trend in most teas (r up to 0.81). The acidolysis characterization indicated that free linalool might be slowly released from linalyl-ß-primeveroside with stable enantiomeric ratios during long-term withering of white tea in a weakly acidic environment, along with other isomerized products, e.g., geraniol, nerol, α-terpineol, etc. Furthermore, a novel online thermal desorption-gas chromatography-mass spectrometry approach was established to simulate the pyrolysis releasing of linalyl-ß-primeveroside during tea processing. Interestingly, free linalool was not the selected pyrolysis product of linalyl-ß-primeveroside but rather trans/cis-2,6-dimethyl-2,6-octadiene during the high-fire roasting or baking step of oolong and green teas. The identification of above high-fire chemical marks presented great potential to scientifically evaluate the proper thermal conditions in the practical production of tea.

19.
Heliyon ; 10(7): e28755, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38586372

ABSTRACT

Fish mint, Houttuynia cordata Thunb. (HCT) is an edible vegetable that has also been used in traditional folk medicines. As both a medicinal herb and a dietary source, HCT has been clinically proven to be a pivotal ingredient in formulas administered to alleviate COVID-19 symptoms. With the increasing market demand for imported materials, ensuring the quality consistency of HCT becomes a significant concern. In this study, the growing time for hydroponically-cultivated HCT with seaweed extract and amino acids added (HCTW) reduced by half compared to conventional soil-cultivated HCT (HCTS). Key quantified components in HCTW, flavonoid glycosides and caffeoylquinic acid derivatives, exhibited a 143% increase over HCTS. These crucial constituents were responsible for possessing antioxidant activity (IC50 < 25 µg/mL) and anti-nitrite oxide production (IC50 < 20 µg/mL). An economically-designed hydroponic system with appropriate additives is proposed to replace HCTS with improvements of growth time, overall production yields, and bioactive qualities.

20.
Sensors (Basel) ; 24(7)2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38610514

ABSTRACT

As multiprocessor systems continue to grow in processor scale, the incidence of faults also increases. As a result, fault diagnosis is becoming a key mechanism for maintaining the normal operation of multiprocessor systems. To explore more effective diagnostic methods, Somani et al. introduced a generalized pessimistic diagnostic strategy, named t/k-diagnosis, in which all faulty nodes are isolated in a set of nodes and at most k fault-free nodes are misdiagnosed, provided that the quantity of faults is limited by t. By imposing certain conditions or restrictions, the t/k-diagnosability of some regular networks under the Preparata, Metze, and Chien (PMC) model has been determined. However, the t/k-diagnosability of many networks under the comparison model remains unidentified. In this paper, we provide new insights into the study of t/k-diagnosability under the comparison model. After introducing some new notions, such as the 0-test unit, 0-test set and 0-test subgraph, under the comparison model, we study the relationship in a system G between the 0-test subgraphs and the components of G-F, where F is the set of faulty nodes, and we obtain some important correlation properties. Based on these results, we study t/k-diagnosability under the comparison model. As a result, the t/k-diagnosability of some regular interconnection networks can be efficiently determined.

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