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Stretchable organic phototransistor arrays have potential applications in artificial visual systems due to their capacity to perceive ultraweak light across a broad spectrum. Ensuring uniform mechanical and electrical performance of individual devices within these arrays requires semiconductor films with large-area scale, well-defined orientation, and stretchability. However, the progress of stretchable phototransistors is primarily impeded by their limited electrical properties and photodetection capabilities. Herein, wafer-scale and well-oriented semiconductor films were successfully prepared using a solution shearing process. The electrical properties and photodetection capabilities were optimized by improving the polymer chain alignment. Furthermore, a stretchable 10 × 10 transistor array with high device uniformity was fabricated, demonstrating excellent mechanical robustness and photosensitive imaging ability. These arrays based on highly stretchable and well-oriented wafer-scale semiconductor films have great application potential in the field of electronic eye and artificial visual systems.
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In this study, tannic acid (TA) was applied as a stabilizing agent for synthesizing bimetallic copper-gold (CuAu) nanoparticles. Cu(NO3)2 and NaAuCl4 were used as the sources of copper and gold ions, respectively, and NaBH4 was employed as a reducing agent. The prepared TA-CuAu nanoparticles were extensively characterized via ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction, and zeta potential analyses. To evaluate their catalytic activity, the TA-CuAu nanoparticles and NaBH4 were applied in the degradation of 4-nitrophenol (4-NP) and rhodamine B (RB) individually and in a mixture. The individual degradation of 4-NP and RB was completed within 10 min, and the apparent rate constants were calculated as 0.3046 and 0.2628 min-1, respectively, emphasizing the efficient catalytic activity of the TA-CuAu nanoparticles. Additionally, controlled experiments were performed for the degradation of 4-NP and RB in the absence of catalysts or NaBH4 to investigate the kinetic feasibility of the catalytic reactions. A mixture of 4-NP and RB was successfully degraded within 10 min using the TA-CuAu nanoparticles as catalysts. Furthermore, the reuse of the catalysts after five successive cycles demonstrates an outstanding performance with no significant loss in the catalytic activity. Finally, the successful treatment of the tap and lake water samples spiked with 4-NP and RB using the TA-CuAu nanoparticles further confirmed their application potential as catalysts in environmental water remediation.
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Neisseria meningitidis, commonly known as the meningococcus, leads to substantial illness and death among children and young adults globally, revealing as either epidemic or sporadic meningitis and/or septicemia. In this study, we have designed a novel peptide-based chimeric vaccine candidate against the N. meningitidis strain 331,401 serogroup X. Through rigorous analysis of subtractive genomics, two essential cytoplasmic proteins, namely UPI000012E8E0(UDP-3-O-acyl-GlcNAc deacetylase) and UPI0000ECF4A9(UDP-N-acetylglucosamine acyltransferase) emerged as potential drug targets. Additionally, using reverse vaccinology, the outer membrane protein UPI0001F4D537 (Membrane fusion protein MtrC) identified by subcellular localization and recognized for its known indispensable role in bacterial survival was identified as a novel chimeric vaccine target. Following a careful comparison of MHC-I, MHC-II, T-cell, and B-cell epitopes, three epitopes derived from UPI0001F4D537 were linked with three types of linkers-GGGS, EAAAK, and the essential PADRE-for vaccine construction. This resulted in eight distinct vaccine models (V1-V8). Among them V1 model was selected as the final vaccine construct. It exhibits exceptional immunogenicity, safety, and enhanced antigenicity, with 97.7 % of its residues in the Ramachandran plot's most favored region. Subsequently, the vaccine structure was docked with the TLR4/MD2 complex and six different HLA allele receptors using the HADDOCK server. The docking resulted in the lowest HADDOCK score of 39.3 ± 9.0 for TLR/MD2. Immune stimulation showed a strong immune response, including antibodies creation and the activation of B-cells, T Cytotoxic cells, T Helper cells, Natural Killer cells, and interleukins. Furthermore, the vaccine construct was successfully expressed in the Escherichia coli system by reverse transcription, optimization, and ligation in the pET-28a (+) vector for the expression study. The current study proposes V1 construct has the potential to elicit both cellular and humoral responses, crucial for the developing an epitope-based vaccine against N. meningitidis strain 331,401 serogroup X.
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Vacinas Meningocócicas , Neisseria meningitidis , Neisseria meningitidis/imunologia , Neisseria meningitidis/genética , Humanos , Vacinas Meningocócicas/imunologia , Vacinologia/métodos , Genômica , Simulação por Computador , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/genéticaRESUMO
Distant metastasis is a major cause of treatment failure in cancer patients and a key challenge to improving cancer care today. We hypothesized that enhancing anti-cancer immune response and inhibiting circulating tumor cells (CTCs) adhesion and transendothelial migration through synergistic multi-target approaches may effectively prevent cancer metastasis. "Fuyuan Decoction" (FYD) is a traditional Chinese medicine compound that is widely used to prevent postoperative metastasis in cancer patients, but its underlying mechanism remains unclear. In this work, we systematically elucidated the underlying molecular mechanism by which FYD prevents cancer metastasis through multi-compound and multi-target synergies in vitro and in vivo. FYD significantly prevented cancer metastasis at non-cytotoxic concentrations by suppressing the adhesion of CTCs to endothelial cells and their subsequent transendothelial migration, as well as enhancing anti-cancer immune response. Mechanistically, FYD interrupts adhesion of CTCs to vascular endothelium by inhibiting TNF-α-induced CAMs expression via regulation of the NF-κB signaling pathway in endothelial cells. FYD inhibits invasion and migration of CTCs by suppressing EMT, PI3K/AKT and FAK signaling pathways. Moreover, FYD enhances the anti-cancer immune response by significantly increasing the population of Tc and NK cells in the peripheral immune system. In addition, the chemical composition of FYD was determined by UPLC-HRMS, and the results indicated that multiple compounds in FYD prevents cancer metastasis through multi-target synergistic treatment. This study provides a modern medical basis for the application of FYD in the prevention of cancer metastasis, and suggesting that multi-drug and multi-target synergistic therapy may be one of the most effective ways to prevent cancer metastasis.
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Lung cancer is the most common cancer in the world due to its high incidence and recurrence. Genetic instability is one of the main factors leading to its occurrence, development and poor prognosis. Decreased xeroderma pigmentosum group C (XPC) expression notably enhances the stem cell properties of lung cancer cells and increases their proliferation and migration. Additionally, patients with lung cancer and low XPC expression had a poor prognosis. The purpose of the present study was to analyze the effect of XPC and IFN-γ on the clinical prognosis of patients with non-small cell lung cancer (NSCLC). Lung adenocarcinoma specimens were collected from a total of 140 patients with NSCLC. Additionally, from these 140 patients, 48 paracarcinoma tissue specimens were also collected, which were later used to construct tissue microarrays. The expression of XPC and IFN-γ in cancer tissues and in paraneoplastic tissues was detected using immunohistochemistry. The prognosis and overall survival of patients were determined through telephone follow-up. The results showed a positive correlation between expression of XPC and IFN-γ in NSCLC. Additionally, high expression of both markers was associated with a favorable prognosis in patients with NSCLC. The aforementioned findings suggest that the expression of XPC and IFN-γ has prognostic value in clinical practice and is expected to become a marker for clinical application.
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E2F transcription factor 5 (E2F5) gene is a transcription factor, plays an important role in the development of a variety of cells. E2F5 is expressed in human and mouse adipocytes, but its specific function in adipogenesis is unclear. Krüppel-like factor 7 (KLF7) facilitates proliferation and inhibits differentiation in chicken preadipocytes. Our previous KLF7 chromatin immunoprecipitation-sequencing analysis revealed a KLF7-binding peak in the 3' flanking region of the E2F5, indicating a regulatory role of KLF7 in this region. In the present study, we investigated E2F5 potential role, the overexpression and knockdown analyses revealed that E2F5 inhibited the differentiation and promoted the proliferation of chicken preadipocytes. Moreover, we identified enhancer activity in the 3' flanking region (nucleotides +22661/+22900) of E2F5 and found that KLF7 overexpression increased E2F5 expression and luciferase activity in this region. Deleting the putative KLF7-binding site eliminated the promoting effect of KLF7 overexpression on E2F5 expression. Further, E2F5 reversed the KLF7-induced decrease in preadipocyte differentiation and increase in preadipocyte proliferation. Taken together, our findings demonstrate that KLF7 inhibits differentiation and promotes proliferation in preadipocytes by enhancing E2F5 transcription.
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Adipócitos , Adipogenia , Diferenciação Celular , Proliferação de Células , Galinhas , Fatores de Transcrição Kruppel-Like , Animais , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Adipogenia/fisiologia , Galinhas/genética , Adipócitos/metabolismo , Adipócitos/fisiologia , Fator de Transcrição E2F5/metabolismo , Fator de Transcrição E2F5/genética , Fator de Transcrição E2F5/fisiologia , Proteínas Aviárias/metabolismo , Proteínas Aviárias/genéticaRESUMO
BACKGROUND: Owing to poor organ function reserve, older adults have a high risk of postoperative complications. However, there is no well-established system for assessing the risk of complications after hepatectomy in older adults. METHODS: This study aimed to design a risk assessment tool to predict the risk of complications after hepatectomy in adults older than 75 years. A total of 326 patients were identified. A logistic regression equation was used to create the Risk Assessment System of Hepatectomy in Adults (RASHA) for the prediction of complications (ClavienâDindo classification ≥ II). RESULTS: Multivariate correlation analysis revealed that comorbidity (≥ 5 kinds of disease or < 5 kinds of disease, odds ratio [OR] = 5.552, P < 0.001), fatigue (yes or no, OR = 4.630, P = 0.009), ChildâPugh (B or A, OR = 4.211, P = 0.004), number of liver segments to be removed (≥ 3 or ≤ 2, OR = 4.101, P = 0.001), and adjacent organ resection (yes or no, OR = 1.523, P = 0.010) were independent risk factors for postoperative complications after hepatectomy in older persons (aged ≥ 75 years). A binomial logistic regression model was established to evaluate the RASHA score (including the RASHA scale and RASHA formula). The area under the curve (AUC) for the RASHA scale was 0.916, and the cut-off value was 12.5. The AUC for the RASHA formula was 0.801, and the cut-off value was 0.2106. CONCLUSION: RASHA can be used to effectively predict the postoperative complications of hepatectomy through perioperative variables in adults older than 75 years. TRIAL REGISTRATION: The Research Registry: researchregistry8531. https://www.researchregistry.com/browse-the-registry#home/registrationdetails/63901824ae49230021a5a0cf/ .
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Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Artéria Hepática/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Infusões Intra-ArteriaisRESUMO
BACKGROUND: Ganoderma lucidum ( G . lucidum ) is a traditional Chinese herbal medicine that has shown potential as an alternative adjuvant therapy for cancer patients. However, the mechanisms and adjuvant therapeutic effects of G . lucidum in cancer treatment remain unclear. METHODS: In this work, G . lucidum spore oil (GanoOil), a newly developed oily G . lucidum spore extract was used to investigate the mechanisms and adjuvant therapeutic effects of GanoOil in conjunction with the chemotherapeutic drug cyclophosphamide (CTX) for preventing breast cancer metastasis. RESULTS: In the model of lung metastasis, orally administered GanoOil increased the population of CD8 + T cells and interleukin (IL)-6 cytokine levels in mouse blood, whereas also enhancing the activity of natural killer cells in the spleen. Furthermore, the combination of GanoOil and CTX effectively suppressed the lung metastasis of circulating breast cancer cells, alleviated CTX-induced weight loss, and reduced the ratio of lung and spleen weight to body weight in mice. Moreover, high concentrations of GanoOil exhibited no significant toxicity or side effects in both in vitro and in vivo experiments. CONCLUSION: In conclusion, GanoOil is a safe drug that can enhance immune activity in mice to achieve therapeutic effects on cancer, and can also synergistically inhibit tumor metastasis with CTX.
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Neoplasias da Mama , Neoplasias Pulmonares , Segunda Neoplasia Primária , Reishi , Humanos , Animais , Camundongos , Feminino , Neoplasias da Mama/patologia , Esporos Fúngicos , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Interleucina-6 , Neoplasias Pulmonares/prevenção & controleRESUMO
Currently, the association between prostate volume (PV) or prostate weight with pathological outcomes in patients with prostate cancer (PCa) is not well understood. This study aimed to explore whether PV can predict the adverse pathological outcomes of PCa patients after radical prostatectomy (RP). A total of 1063 men with confirmed localized PCa who underwent RP at the First Affiliated Hospital of Zhejiang University from January 2014 to April 2019 were retrospectively analyzed. Patients were assigned into small, medium and large groups based on the PV. The analysis of variance, χ2 test or Student t test was performed to compare differences among groups. Univariate and multivariate analyses were performed to identify significant predictors of pathological outcomes upgrading. Among the 1063 cases, approximately 35.0% had an upgrade of postoperative pathology. Compared with the small prostate group, more patients in the large prostate group achieved a Gleason score (GS) 6 and International Society of Urological Pathology (ISUP) grade 1 of postoperative pathological findings, clinical cT1c and cT2a stages and pathological pT2a and pT2b stages; the incidence of positive surgical margins and extraprostatic extension was relatively low (all Pâ <â .001). In multiple logistic regression, PV served as a significant predictor of any Gleason score upgrading (GSU) (odds ratio [OR] 0.988, 95% confidence interval [CI] 0.978-0.998), major GSU (OR 0.980, 95% CI 0.965-0.995) and any ISUP grade group upgrading (GGU) (OR 0.989, 95% CI 0.979-0.999). This study shows that PV can predict adverse pathological outcomes in PCa patients after radical prostatectomy. Pca patients with smaller prostate volume tend to have the high-grade disease at postoperative pathology as well as pathological outcome upgrading.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/cirurgia , Próstata/patologia , Estudos Retrospectivos , Prostatectomia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Gradação de TumoresRESUMO
BACKGROUND: The FRAIL scale for evaluating frailty consists of five items: fatigue, resistance, aerobic, illness, and loss of weight. However, it is difficult to obtain a specific weight loss value. Since the Timed Up and Go Test (TUGT) is simple, accurate, and easy to perform, we replaced weight loss with the TUGT in the FRAIL scale, with the remaining four items unchanged, and named it the FRAIT scale. The aim of this study was to determine the value of the FRAIT scale in predicting the peri-operative outcome of hepatectomy. METHODS: This model development study was conducted between January 2017 and December 2021. The reliability, validity and area under the curve (AUC) of the FRAIL/FRAIT scales were calculated. The frailty status of patients aged ≥ 75 years who underwent hepatectomy was measured using the FRAIL/FRAIT scales. Logistic regression was used to compare the relationship between FRAIL/FRAIT scores/grades and perioperative outcomes. RESULTS: The AUCs for predicting operation duration, intraoperative bleeding, complications, and death based on the FRAIL score were 0.692, 0.740, 0.709, and 0.733, respectively, and those based on the FRAIT score were 0.700, 0.745, 0.708, and 0.724, respectively. The AUCs for predicting operation duration, intraoperative bleeding, complications, and death based on the FRAIL grade were 0.693, 0.735, 0.695, and 0.755, respectively, and those based on the FRAIT grades were 0.700, 0.758, 0.699, and 0.750, respectively. The FRAIL score has three effective predictors (intraoperative bleeding, complications, and death), while the FRAIT score has four effective predictors (operation duration, intraoperative bleeding, complications, and death). The FRAIL grade has two effective predictors (intraoperative bleeding and death), while the FRAIT grade has three effective predictors (operation duration, intraoperative bleeding, and death). CONCLUSIONS: This study describes a new and more effective tool for the assessment of preoperative frailty in older adults undergoing hepatectomy. The items of the FRAIT scale are easier to obtain than those of the FRAIL scale, and the predictive effect of the FRAIT scale is stronger than that of the FRAIL scale.
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Idoso Fragilizado , Fragilidade , Idoso , Humanos , Fragilidade/diagnóstico , Hepatectomia , Equilíbrio Postural , Reprodutibilidade dos Testes , Avaliação Geriátrica , Estudos de Tempo e Movimento , Redução de PesoRESUMO
Mulching and nitrogen (N) fertilization are the main drivers for sustainable crop production. The sole use of nitrogen fertilizer threatened both the physiology and production of maize in rain-fed areas. Therefore, we proposed that wheat straw mulching with N fertilization would increase maize yield by improving soil fertility, physiology, and nitrogen use efficiency. A two-year field study evaluated the effects of CK (control), N (nitrogen application at 172 kg ha-1), HS (half wheat straw mulch, 2500 kg ha-1), HS+N (half wheat straw, 2500 kg ha-1 plus 172 kg N ha-1), FS (full wheat straw, 5000 kg ha-1), and FS+N (full wheat straw, 5000 kg ha-1 plus 172 kg N ha-1) on maize growth, physiology, and biochemistry. Compared with the control, the FS+N treatment resulted in the increase of 56% photosynthetic efficiency, 9.6% nitrogen use efficiency, 60% nitrogen uptake, 80% soluble sugar, 59% starches, 48% biomass, and 29% grain yield of maize. In addition, the FS+N regime increased 47%, 42%, and 106% of soil organic carbon and available P and N content in comparison with the control. Maize grain and biomass yields were positively correlated with N uptake, photosynthesis, soil organic carbon, and soil available N and P contents. Conclusively, the use of wheat straw at 5000 kg ha-1, along with 172 kg N ha-1, is a promising option for building a sustainable wheat-maize cropping system to achieve optimal crop yield and improved plant and soil health in a semi-arid region of China.
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In this study, we investigated the mechanism underlying the perturbation of hepatic lipid metabolism in response to micro/nanoplastic (MP/NP) exposure at environmentally relevant concentrations. Polystyrene (PS) MPs/NPs with different sizes (0.1, 0.5, and 5.0 µm) were studied for their effects on the homeostasis and function of Nile tilapia (Oreochromis niloticus) liver. Results showed that PS MPs/NPs were readily internalized and accumulated in various internal organs/tissues, especially in fish liver and muscle. Smaller-sized NPs caused more severe toxicity than larger MPs, including hepatic steatosis, inflammatory response, and disturbed liver function. Mechanistically, PS NPs with a particle size of 100 nm perturbed protein homeostasis in the endoplasmic reticulum (ER) by inhibiting the expression of chaperone proteins and genes involved in ER-associated degradation. This led to the activation of the PERK-eIF2α pathway, which caused dysfunction of hepatic lipid metabolism. Induction of oxidative stress and activation of the Nrf2/Keap1 pathway were also involved in the PS NP-induced hepatic lipid accumulation. These findings highlight the potential adverse effects of environmental MPs/NPs on aquatic organisms, raising concerns about their ecotoxicity and food safety.
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Metabolismo dos Lipídeos , Microplásticos , Animais , Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , Homeostase , Fígado , Estresse Oxidativo , Retículo EndoplasmáticoRESUMO
The practical application of aqueous Zn-ion batteries is still greatly hindered by the unstable Zn anode with severe Zn dendrites growth and side reactions. As it is accessible and economical, the exploitation of electrolyte additives is one of the most promising strategies to stabilize the Zn electrode/electrolyte interface. Herein, the penta-potassium triphosphate (KTPP) as a novel trifunctional electrolyte additive is introduced to tune the electrode/electrolyte interface. First, the KTPP additive can induce an ion-conducting and mechanically robust solid electrolyte interphase film to stabilize the Zn anode. Second, the KTPP can complex with Zn2+ ions to reconstitute the dissolution sheath structure of the Zn2+ ion. Finally, the K+ cations in KTPP adsorb on the tips of the Zn anode surface as a shielding film to regulate Zn2+ ion flux. As a result, Zn//Zn symmetric cells can achieve significantly prolonged cycling stability (e.g., from 1077 to 3800 h at 1 mA cm-2 /1 mAh cm-2 , from 256 to 2500 h at 2 mA cm-2 /2 mAh cm-2 ), and ultrahigh cumulative capacity of 6400/7200 mAh cm-2 at high current density (40/20 mA cm-2 ). A four-layer Zn-MnO2 pouch full cell with a high capacity of 9 mAh can be constructed, showing impressive practical application potential.
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Cytokinin oxidase/dehydrogenase (CKX) irreversibly degrades cytokinin, regulates growth and development, and helps plants to respond to environmental stress. Although the CKX gene has been well characterized in various plants, its role in soybean remains elusive. Therefore, in this study, the evolutionary relationship, chromosomal location, gene structure, motifs, cis-regulatory elements, collinearity, and gene expression patterns of GmCKXs were analyzed using RNA-seq, quantitative real-time PCR (qRT-PCR), and bioinformatics. We identified 18 GmCKX genes from the soybean genome and grouped them into five clades, each comprising members with similar gene structures and motifs. Cis-acting elements involved in hormones, resistance, and physiological metabolism were detected in the promoter regions of GmCKXs. Synteny analysis indicated that segmental duplication events contributed to the expansion of the soybean CKX family. The expression profiling of the GmCKXs genes using qRT-PCR showed tissue-specific expression patterns. The RNA-seq analysis also indicated that GmCKXs play an important role in response to salt and drought stresses at the seedling stage. The responses of the genes to salt, drought, synthetic cytokinin 6-benzyl aminopurine (6-BA), and the auxin indole-3-acetic acid (IAA) at the germination stage were further evaluated by qRT-PCR. Specifically, the GmCKX14 gene was downregulated in the roots and the radicles at the germination stage. The hormones 6-BA and IAA repressed the expression levels of GmCKX1, GmCKX6, and GmCKX9 genes but upregulated the expression levels of GmCKX10 and GmCKX18 genes. The three abiotic stresses also decreased the zeatin content in soybean radicle but enhanced the activity of the CKX enzymes. Conversely, the 6-BA and IAA treatments enhanced the CKX enzymes' activity but reduced the zeatin content in the radicles. This study, therefore, provides a reference for the functional analysis of GmCKXs in soybean in response to abiotic stresses.
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Regulation of tumor cell death is a fundamental mechanism for tumor treatment. However, most tumors are resistant to cell death. Triggering inflammatory cell death, pyroptosis, may provide a new view of enhancing tumor cell death. Here we report a new role of Ganoderma lucidum extract (GLE) in pyroptotic cell death. Treatment with GLE (50-200 µg/mL) significantly elevated reactive oxygen species (ROS) levels and caused pyroptotic cell death in breast cancer cells. Mechanistically, GLE activates caspase 3 and further cleaves the gasdermin E (GSDME) protein to form pores on the cell membrane, releasing massive amounts of inflammatory factors in breast cancer cells. We also showed that GLE enhanced antitumor immune responses by substantially increasing the subsets of natural killer (NK) and CD8+T cells in the peripheral immune system and tumor microenvironment. In addition, GLE destroys multiple steps of tumor metastasis, including adhesion, migration, invasion, colonization, and angiogenesis. Collectively, these results suggest that GLE provides a potential approach for breast cancer treatment, which may complement chemotherapy or immunotherapy for cancer metastasis.
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Neoplasias da Mama , Reishi , Humanos , Feminino , Piroptose , Microambiente TumoralRESUMO
Krüppel-like factor 7 (KLF7) is a negative regulator of preadipocyte differentiation. Our previous KLF7 ChIP-seq analysis showed that the binding motif of PU.1 was found among the KLF7 binding peaks, indicating that an interaction between KLF7 and PU.1 at preadipocyte gene promoters and other regulatory elements might be common. Here, Co-IP and FRET assays are used to confirm that PU.1 can directly bind to KLF7 and enhance the transcription activity of cyclin-dependent kinase inhibitor 3 ( CDKN3), which is a downstream target gene of KLF7. We show that the PU.1 expression level is decreased during preadipocyte differentiation. Furthermore, PU.1 overexpression and knockdown experiments reveal that PU.1 negatively regulates chicken preadipocyte differentiation, as evidenced by appropriate changes in lipid droplet accumulation and altered expressions of PPARγ, FAS, and PLIN. In addition, PU.1 overexpression promotes preadipocyte proliferation, while knockdown of PU. 1 inhibits preadipocyte proliferation. We further demonstrate that PU.1 inhibits differentiation and promotes proliferation in preadipocytes, in part by directly interacting with KLF7.
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Galinhas , Fatores de Transcrição Kruppel-Like , Animais , Diferenciação Celular , Proliferação de Células/fisiologia , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismoRESUMO
Krüppel-like factor 7 (KLF7) negatively regulates adipocyte differentiation; however, the mechanism underlying its activity in mammals and birds remains poorly understood. To identify genome-wide KLF7-binding motifs in preadipocytes, we conducted a chromatin immunoprecipitation-sequencing analysis of immortalized chicken preadipocytes (ICP2), which revealed 11,063 specific binding sites. Intergenic binding site analysis showed that KLF7 regulates several novel factors whose functions in chicken and mammal adipogenesis are underexplored. We identified a novel regulator, troponin I2 (TNNI2), which is positively regulated by KLF7. TNNI2 is downregulated during preadipocyte differentiation and acts as an adipogenic repressor at least in part by repressing FABP4 promoter activity. In conclusion, we demonstrated that KLF7 functions through cis-regulation of TNNI2, which inhibits adipogenesis. Our findings not only provide the first genome-wide picture of KLF7 associations in preadipocytes but also identify a novel function of TNNI2.
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Galinhas , Troponina I , Animais , Adipogenia/genética , Galinhas/genética , Galinhas/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Mamíferos/metabolismo , Regiões Promotoras Genéticas , Troponina I/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismoRESUMO
These days, the usage of machine-learning-enabled dynamic Internet of Medical Things (IoMT) systems with multiple technologies for digital healthcare applications has been growing progressively in practice. Machine learning plays a vital role in the IoMT system to balance the load between delay and energy. However, the traditional learning models fraud on the data in the distributed IoMT system for healthcare applications are still a critical research problem in practice. The study devises a federated learning-based blockchain-enabled task scheduling (FL-BETS) framework with different dynamic heuristics. The study considers the different healthcare applications that have both hard constraint (e.g., deadline) and resource energy consumption (e.g., soft constraint) during execution on the distributed fog and cloud nodes. The goal of FL-BETS is to identify and ensure the privacy preservation and fraud of data at various levels, such as local fog nodes and remote clouds, with minimum energy consumption and delay, and to satisfy the deadlines of healthcare workloads. The study introduces the mathematical model. In the performance evaluation, FL-BETS outperforms all existing machine learning and blockchain mechanisms in fraud analysis, data validation, energy and delay constraints for healthcare applications.