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1.
World J Hepatol ; 16(9): 1258-1268, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39351516

RESUMEN

Inherited metabolic liver diseases arise from genetic mutations that lead to disruptions in liver metabolic pathways and are predominantly observed in pediatric populations. The spectrum of genetic metabolic liver disorders is diverse, encompassing a range of conditions associated with aberrations in iron, copper, carbohydrate, lipid, protein, and amino acid metabolism. Historically, research in the domain of genetic metabolic liver diseases has predominantly concentrated on hepatic parenchymal cell alterations. Nevertheless, emerging studies suggest that inherited metabolic liver diseases exert significant influences on the immune microenvironment, both within the liver and systemically. This review endeavors to encapsulate the immunological features of genetic metabolic liver diseases, aiming to expand the horizons of researchers in this discipline, and to elucidate the underlying pathophysiological mechanisms pertinent to hereditary metabolic liver diseases and to propose innovative therapeutic approaches.

2.
Eur J Med Chem ; 280: 116943, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39369480

RESUMEN

P-glycoprotein (P-gp)-caused multidrug resistance (MDR) is a crucial factor in the cancer chemotherapy failure. Herein, a total of twenty two azo-containing WK-X-34 (WK34, a third generation P-gp inhibitor) derivatives were synthesized as novel P-gp inhibitors. Biological evaluation revealed that compound 7i effectively reversed P-gp-mediated MDR in K562/A02 cells, with a higher reversal fold (RF) value than WK34 (142.79 vs. 64.41). Further investigation indicated that 7i dose-dependently inhibited P-gp function, without affecting its expression. CETSA results illustrated that 7i could obviously improve P-gp stability, suggesting its high affinity with P-gp. Molecular docking analysis revealed that 7i fit well into P-gp's binding pocket, thus displaying potent reversal effect on P-gp-mediated tumor MDR Optical properties evaluation confirmed that azo-containing 7i can undergo reversible changes in the cis and trans configurations under the irradiation of 365 nm and 520 nm wavelength of light. Notably, the configuration change of azo might affect the MDR-reversal potency, and cis-7i has a lower RF value than trans-7i (122.70 vs. 142.79), suggesting that development of photoswitchable P-gp inhibitors might be a novel strategy to reduce the systemic toxicity caused by indiscriminate inhibition of P-gp by traditional inhibitors. Collectively, 7i, as a novel P-gp inhibitor, warranted further investigation.

3.
Gastroenterology ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39393543

RESUMEN

BACKGROUND AND AIMS: Therapy failure in patients with metastatic colorectal cancer (mCRC, ∼80% occur in the liver) remains an overarching challenge. Preclinical studies demonstrated that HER3 promotes CRC cell survival, but therapies blocking the neuregulin-induced canonical HER3 signaling have made little impact in the clinic. Recent studies suggest that the liver microenvironment promotes CRC growth by activating HER3 in a neuregulin-independent fashion, thus elucidation of these mechanisms may reveal new strategies for treating patients with mCRC. METHODS: Patient-derived primary liver endothelial cells (ECs) were used to interrogate EC-CRC crosstalk. We conducted proteomic analysis to identify EC-secreted factor(s) that triggers non-canonical HER3 activation in CRC, and determined the subsequent effects on mCRC using diverse murine mCRC models. In vitro studies with genetic and pharmacological interventions were used to map the non-canonical HER3 pathway. RESULTS: We demonstrated that EC-secreted leucine-rich alpha-2-glycoprotein 1 (LRG1) directly binds and activates HER3 and promotes CRC growth distinct from neuregulin, the canonical HER3 ligand. Blocking host-derived LRG1 by gene knockout or a neutralizing antibody impaired mCRC outgrowth in the liver and prolonged mouse survival. We identified protein synthesis activated by the PI3K-PDK1-RSK-eIF4B axis as the biologically relevant signaling cascade downstream of the LRG1-HER3 interaction, which was not blocked by conventional HER3-specific antibodies that failed in prior clinical trials. CONCLUSIONS: LRG1 is a novel HER3 ligand and mediates liver-mCRC crosstalk. The LRG1-HER3 signaling axis is distinct from canonical HER3 signaling and represents a new therapeutic opportunity to treat patients with mCRC, and potentially other types of liver metastases.

4.
Sci Rep ; 14(1): 23215, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39369047

RESUMEN

Mosaic ceramics are not limited to use solely as building materials, they also possess artistic value. Artists can create images by arranging and combining mosaic ceramics, resulting in a perfect fusion of large-scale public art for external walls and ceramic materials. However, the current approach for artists to create mosaic ceramic exterior wall art images involves manual laying and assembling of individual mosaic ceramics. This manual process suffers from issues such as low efficiency, eye fatigue, selection errors, and the risk of high-altitude operations. These challenges significantly impact the quality and efficiency of creating mosaic ceramic exterior wall art image images. To address these problems, this paper proposes an automatic mosaic ceramic art image stitching method based on subpixel edge fitting positioning and collaborative operation of multiple robotic arms. Additionally, a new U + I type conveying method is designed for efficient and space-saving transportation of mosaic ceramics. Experimental results demonstrate a high success rate of recognition, absorption, and placement of multi-color mosaic ceramics using this method reaching 95.45%, with a positioning error within 0.5 mm. The method can also adapt to varying levels of light intensity or noise interference. This approach effectively enhances the quality and efficiency of creating mosaic ceramic exterior wall art images and promotes the development of mosaic ceramic exterior wall public art creation.

5.
Ann Hematol ; 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39402313

RESUMEN

BACKGROUND: Anti-human T lymphocyte porcine immunoglobulin (p-ATG) is a potent immunosuppressive agent derived from porcine sources used in various immunotherapy applications. It is compared with similar products derived from other species, such as rabbit anti-thymocyte globulin (r-ATG) and ATG-Fresenius (ATG-F), which have distinct biological and therapeutic properties. This study aims to elucidate the mechanisms of action and comparative efficacy of p-ATG in relation to r-ATG and ATG-F through a comprehensive in vitro analysis. METHODS: A comparative analysis of p-ATG, r-ATG and ATG-F was performed, focusing on E rosette inhibitory potency, lymphocyte toxic potency, blocking activities of 24 CD molecules, and flow quantitative potency. Flow cytometric analysis was used to quantify these characteristics and assess the potency of the immunoglobulins. RESULTS: p-ATG exhibited lower E rosette inhibitory and lymphocyte toxic potencies compared to r-ATG but was significantly more potent than ATG-F at equivalent concentrations. At protein concentrations above 12.5 µg/mL, p-ATG showed slightly lower potency than r-ATG and much higher potency than ATG-F in flow cytometry assays. Both p-ATG and r-ATG exhibited similar killing effects on lymphocytes within the peripheral blood mononuclear cells (PBMCs), including CD3 + T cells, with a dose-dependent response. Notably, p-ATG displayed more pronounced blocking activities against CD8, CD99, and TCR α/ß compared to r-ATG. CONCLUSION: p-ATG offers certain advantages over r-ATG and ATG-F, particularly in its ability to inhibit specific CD molecules and its overall potency in immunosuppressive assays, providing valuable insights for assisting clinical decision-making regarding the selection of ATG types based on patient-specific needs and treatment objectives.

6.
Fish Shellfish Immunol ; : 109968, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39419131

RESUMEN

TBK1 is an important IFN antiviral signalling factor, and in previous work black carp TBK1 (bcTBK1) and black carp IRF5 (bcIRF5) together promoted cell death in GCRV-infected cells. In this research, bcTBK1 and bcIRF5 were investigated both in vivo and in vitro to delineate their individual and combined functions. This study demonstrated that both bcTBK1 and bcIRF5 expressions were modulated in response to GCRV infection across the intestine, gill, kidney and spleen. In bcgill cells, overexpression of bcTBK1 and bcIRF5 initially suppressed the expression of cell death-related genes, including RIPK1, caspase1, caspase3 and bax, but this suppression was negated upon GCRV infection. In vivo, mRNA expression levels of RIPK1 and related genes varied by tissue following bcTBK1 or bcIRF5 overexpression and GCRV infection. Notably, intracellular co-overexpression of bcTBK1 and bcIRF5 led to significant upregulation of caspase3, caspase1, bax, and IL1ß, along with enhanced caspase3 activity post-GCRV infection. This co-expression correlated with higher survival rates in black carp during GCRV infection and increased caspase3 mRNA in the spleen and gills. Hematoxylin-eosin (HE) staining indicated disorganized spleen tissue and edematous, hyperplastic gill changes in co-transfected groups after infection. TUNEL staining of tissue sections showed that DNA breakage was significantly stronger in the co-transfected group than in the other groups during GCRV infection. Further phosphorylation experiments showed that bcIRF5 promoted phosphorylation modification of bcTBK1. Thus, these data suggest that bcIRF5 activates bcTBK1 by enhancing its phosphorylation and promotes PANoptosis in GCRV-infected cells.

7.
Clin Dermatol ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39260457

RESUMEN

Mentorship is a critical aspect of personal and professional development throughout anyone's life. Unlike many other fields, a medical career is a long multistep process that can begin in high school and continue throughout a physician's career. When considering competitive specialties such as dermatology, mentors are increasingly crucial in helping students successfully match to programs of their choice, but the variability and extent of mentorship can raise ethical concerns. We discuss the evolution of mentorship in dermatology and the potential ethical issues involved. We propose possible solutions to the ethical conflict between mentor and mentee.

8.
Org Lett ; 26(36): 7701-7706, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39230191

RESUMEN

We report a simple and convenient N-terminal thiazolidine (Thz) deprotection strategy and its application in one-pot multisegment ligation. In this strategy, O-benzylhydroxylamine (O-BHA) is used to efficiently and rapidly convert Thz into N-terminal cysteine. O-BHA can be easily separated from the ligation buffer by organic solvent extraction, avoiding the degradation of the peptide thioester by O-BHA. The utility of the O-BHA-based one-pot ligation strategy has been demonstrated in the assembly of CC chemokine ligand-2.

9.
Discov Oncol ; 15(1): 465, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298013

RESUMEN

The main cause of gastric cancer (GC)-related death is due to malignant cell unregulated distant metastasis and proliferation. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) has been shown to play an important role in carcinogenesis and the development of metastasis in several tumors. However, its downstream regulatory mechanism in GC is not well defined. Our study aims to investigate the function and regulatory mechanism of hnRNPA1 in GC. We analyzed the differential expression of hnRNPA1 in gastric cancer and paired adjacent normal tissues in the TCGA database. Kaplan-Meier analysis was employed for survival assessment. The expressions of hnRNPA1 in GC cells were measured by qRT-PCR and Western blot. Transwell assay, CCK8 and colony formation assay were used to detect the effect of hnRNPA1 on the metastasis and proliferation ability of GC cells. Additionally, Western blotting was performed to examine the expression of proteins related to the Wnt/ß-catenin signaling pathway as well as epithelial-mesenchymal transition (EMT), while further investigations were carried out to explore potential regulatory mechanisms. The results showed that hnRNPA1 was highly expressed differentially in GC over normal gastric tissue. Knocking down hnRNPA1 inhibited the metastasis and proliferation of human gastric cancer cells. Overexpression of hnRNPA1 significantly enhanced the metastatic potential and proliferative capacity of human GC cells. Further mechanism exploration revealed that knocking down hnRNPA1 inhibited the Wnt/ß-catenin signaling pathway and WNT1 inducible signaling pathway protein-2 (WISP2), an activator of the Wnt/ß-catenin signaling pathway. Whereas overexpression of hnRNPA1 had the opposite effects. Our results demonstrated that hnRNPA1 promoted metastasis and proliferation of GC cells by activating Wnt/ß-catenin signaling pathway via WISP2. hnRNPA1 may serve as a potential biomarker and novel therapeutic targets for GC.

10.
Clin Exp Nephrol ; 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39305454

RESUMEN

BACKGROUND: Angiogenesis and inflammation are key events leading to peritoneal morphologic alteration and ultrafiltration failure in patients undergoing peritoneal dialysis (PD). The current study aims to explore the role of ADAM17 in the angiogenetic and inflammatory responses of endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured and treated with a high glucose-containing medium. In parallel experiments, the expression of ADAM17 in HUVECs was inhibited by SiRNA interference. The mRNA and protein expression of ADAM17, GRO-α and CXCR2 were assessed by qPCR and Western blotting, respectively. The concentrations of GRO-α, VEGF, IL-6 and TNF-α in the cellular supernatants were determined by ELISA. Tube formation and migration of HUVECs were evaluated by Matrigel and transwell migration apparatus. RESULTS: High glucose increased the expression of ADAM17, CXCR2 and GRO-α in cultured HUVECs. RNA silencing of ADAM17 abolished high glucose-mediated increase of GRO-α and CXCR2, which were accompanied by reduced secretion of VEGF, IL-6, TNF-α, as well as tube formation and cell migration in HUVECs. CONCLUSIONS: Inhibition of ADAM17 ameliorates high glucose-induced angiogenic and inflammatory responses in endothelial cells partly through down-regulation of GRO-α/CXCR2 expression.

11.
CNS Neurosci Ther ; 30(9): e70033, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39267282

RESUMEN

AIMS: Ischemic stroke is a major cause of disability and mortality worldwide. Transcranial direct current stimulation (tDCS) and isoflurane (ISO) preconditioning exhibit neuroprotective properties. However, it remains unclear whether tDCS enhances the protective effect of ISO preconditioning on ischemic stroke, and the underlying mechanisms are yet to be clarified. METHOD: A model of middle cerebral artery occlusion (MCAO), a rat ischemia-reperfusion (I/R) injury model, and an in vitro oxygen-glucose deprivation/re-oxygenation (O/R) model of ischemic injury were developed. ISO preconditioning and tDCS were administered daily for 7 days before MCAO modeling. Triphenyltetrazolium chloride staining, modified neurological severity score, and hanging-wire test were conducted to assess infarct volume and neurological outcomes. Untargeted metabolomic experiments, adeno-associated virus, lentiviral vectors, and small interfering RNA techniques were used to explore the underlying mechanisms. RESULTS: tDCS/DCS enhanced the protective effects of ISO pretreatment on I/R injury-induced brain damage. This was evidenced by reduced infarct volume and improved neurological outcomes in rats with MCAO, as well as decreased cortical neuronal death after O/R injury. Untargeted metabolomic experiments identified oxidative phosphorylation (OXPHOS) as a critical pathological process for ISO-mediated neuroprotection from I/R injury. The combination of tDCS/DCS with ISO preconditioning significantly inhibited I/R injury-induced OXPHOS. Mechanistically, Akirin2, a small nuclear protein that regulates cell proliferation and differentiation, was found to decrease in the cortex of rats with MCAO and in cortical primary neurons subjected to O/R injury. Akirin2 functions upstream of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). tDCS/DCS was able to further upregulate Akirin2 levels and activate the Akirin2/PTEN signaling pathway in vivo and in vitro, compared with ISO pretreatment alone, thereby contributing to the improvement of cerebral I/R injury. CONCLUSION: tDCS treatment enhances the neuroprotective effects of ISO preconditioning on ischemic stroke by inhibiting oxidative stress and activating Akirin2-PTEN signaling pathway, highlighting potential of combination therapy in ischemic stroke.


Asunto(s)
Infarto de la Arteria Cerebral Media , Isoflurano , Ratas Sprague-Dawley , Daño por Reperfusión , Estimulación Transcraneal de Corriente Directa , Animales , Isoflurano/farmacología , Masculino , Daño por Reperfusión/prevención & control , Ratas , Estimulación Transcraneal de Corriente Directa/métodos , Precondicionamiento Isquémico/métodos , Isquemia Encefálica/prevención & control , Fármacos Neuroprotectores/farmacología , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Anestésicos por Inhalación/farmacología
12.
Clin Dermatol ; 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39218323

RESUMEN

Patient demand for procedures has increased in the evolving landscape of cosmetic dermatology. This has been fueled, in part, by social media and the growing normalization of cosmetic enhancements, developments that have led some patients to have potentially unrealistic expectations and place undue pressure on dermatologists to meet these often unrealistic demands. This pressure is exacerbated further by patients who are seen as difficult, demanding, and time-consuming and who may require extensive counseling. Physicians may adopt dynamic or differential pricing strategies to offset the additional time and effort that these patients require. We discuss the ethical concerns surrounding these pricing strategies in the cosmetic sphere, highlight the importance of transparency in pricing, and offer suggestions to promote clarity and fairness in cosmetic dermatology practices.

14.
Nat Commun ; 15(1): 8223, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300113

RESUMEN

Detection and Dissection of Anomalous Tissue Domains (DDATD) from multi-sample spatial transcriptomics (ST) data provides unprecedented opportunities to characterize anomalous tissue domains (ATDs), revealing both population-level and individual-specific pathogenic factors for understanding pathogenic heterogeneities behind diseases. However, no current methods can perform de novo DDATD from ST data, especially in the multi-sample context. Here, we introduce STANDS, an innovative framework based on Generative Adversarial Networks which integrates three core tasks in multi-sample DDATD: detecting, aligning, and subtyping ATDs. STANDS incorporates multimodal-learning, transfer-learning, and style-transfer techniques to effectively address major challenges in multi-sample DDATD, including complications caused by unalignable ATDs, under-utilization of multimodal information, and scarcity of normal ST datasets necessary for comparative analysis. Extensive benchmarks from diverse datasets demonstrate STAND's superiority in identifying both common and individual-specific ATDs and further dissecting them into biologically distinct subdomains. STANDS also provides clues to developing ATDs visually indistinguishable from surrounding normal tissues.


Asunto(s)
Transcriptoma , Humanos , Transcriptoma/genética , Perfilación de la Expresión Génica/métodos , Algoritmos , Biología Computacional/métodos
15.
Cell Rep Med ; 5(10): 101744, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39317190

RESUMEN

This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, ß4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both T cell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success.


Asunto(s)
Animales Modificados Genéticamente , Galactosiltransferasas , Rechazo de Injerto , Trasplante de Riñón , Porcinos Enanos , Trasplante Heterólogo , Animales , Porcinos , Humanos , Trasplante Heterólogo/métodos , Rechazo de Injerto/inmunología , Rechazo de Injerto/genética , Trasplante de Riñón/métodos , Galactosiltransferasas/genética , Xenoinjertos , Riñón/patología , Riñón/inmunología , Células Asesinas Naturales/inmunología
16.
Biotechnol Genet Eng Rev ; 40(1): 202-216, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-39312182

RESUMEN

To prospective research the efficacy of dual-energy computed tomography (DECT) in predicting contrast medium extravasation and secondary cerebral hemorrhage after stent thrombectomy in acute ischemic cerebral infarction. Ninety-two patients with acute ischemic stroke who underwent intra-arterial thrombolysis in our hospital from December 2019 to January 2022 have opted as the study subjects. DECT was performed immediately after stent thrombectomy. Images were generated through the image workstation and routine diagnosis was performed 24 hours after the operation. To analyze the diagnostic value of To analyze the diagnostic value of DECT, and to explore the diagnostic status of lesions with hemorrhagic transformation or increased hemorrhage and their correlation with iodine concentration. (1) 68 situations were confirmed, 56 positive and 12 negative with detection rates of 10.71% for hemorrhage, 75.00% for contrast agent extravasation, and 14.29% for extravasation combined with hemorrhage; (2) DECT diagnosed 8 cases of postoperative bleeding and 44 cases of extravasation of contrast media and 4 cases of extravasation of contrast media with hemorrhage ; The accuracy of DECT in diagnosing postoperative hemorrhage was 96.43%. The accuracy of diagnosis of extravasation was 96.43%. (3) The mean iodine concentration of lesions with increased hemorrhage or hemorrhagic transformation was higher compared to those without; (4) There was a correlation between hemorrhagic transformation or increased hemorrhage and iodine concentration. Dual-energy CT (DECT) can accurately distinguish the extravasation of contrast agent and secondary cerebral hemorrhage, and can predict the increased bleeding and bleeding transformation, with good diagnostic value and good predictive efficacy.


Asunto(s)
Hemorragia Cerebral , Medios de Contraste , Stents , Trombectomía , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Medios de Contraste/efectos adversos , Persona de Mediana Edad , Anciano , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/etiología , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/etiología , Extravasación de Materiales Terapéuticos y Diagnósticos/diagnóstico por imagen , Estudios Prospectivos , Anciano de 80 o más Años , Adulto , Isquemia Encefálica/diagnóstico por imagen
17.
J Agric Food Chem ; 72(34): 18809-18815, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39145990

RESUMEN

Novel approaches for pest control are essential to ensure a sufficient food supply for the growing global population. The development of new insecticides must meet rigorous regulatory requirements for safety and address the resistance issues of existing insecticides. Proteolysis-targeting chimeras (PROTACs), originally developed for human diseases, show promise in agriculture. They offer innovative insecticides tailored to overcome resistance, opening avenues for agricultural applications. In this study, we developed small-molecule degraders by incorporating pomalidomide as an E3 ligand. These degraders were linked to a ligand (spirotetratmat enol) targeting the ACC protein through a flexible chain, aiming to achieve the efficient control of insects. Compounds 9a-9d were designed, synthesized, and evaluated for biological activities and mechanisms. Among them, 9b exhibited superior potency against Aphis craccivora (LC50 = 107.8 µg mL-1) compared to others and effectively degraded ACC proteins through the ubiquitin-proteasome system. These findings highlight the potential of utilizing PROTAC-based approaches in the development of insecticides for efficient pest control.


Asunto(s)
Acetil-CoA Carboxilasa , Insecticidas , Proteolisis , Insecticidas/química , Insecticidas/farmacología , Animales , Acetil-CoA Carboxilasa/metabolismo , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/antagonistas & inhibidores , Acetil-CoA Carboxilasa/química , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/química , Diseño de Fármacos , Talidomida/química , Talidomida/análogos & derivados , Talidomida/farmacología
18.
ACS Nano ; 18(37): 25601-25613, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39213604

RESUMEN

Enhancing proton storage in the zinc-ion battery cathode material of MnO2 holds promise in promoting its electrochemical performance by mitigating the intense Coulombic interaction between divalent zinc ions and the host structure. However, challenges persist in addressing the structural instability caused by Jahn-Teller effects and accurately modulating H+ intercalation in MnO2. Herein, the doping of high-electronegativity Sb with fully occupied d-orbital in MnO2 is reported. The Sb doping strategy engenders the formation of Mn-O-Sb path in the structure with a strong dipole polarization field, which facilitates the delocalization of eg orbital electron in Mn and thus mitigates the Jahn-Teller effects. Simultaneously, adjusting the level of Sb doping in MnO2 leads to modulation of the p-band center of O, optimizing its interaction with hydrogen and thereby enhancing proton storage. Consequently, MnO2 doped with 6% Sb exhibits commendable performance in both rate capability and cycling endurance, delivering 113 mAh g-1 at 2 A g-1 after 2000 cycles. This investigation underscores the crucial role of electronic structural engineering in elevating the electrochemical performance of cathode materials for zinc-ion batteries.

19.
Fish Shellfish Immunol ; 153: 109805, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39102972

RESUMEN

The production of type I interferon is tightly regulated to prevent excessive immune activation. However, the role of selective autophagy receptor SQSTM1 in this regulation in teleost remains unknown. In this study, we cloned the triploid fish SQSTM1 (3nSQSTM1), which comprises 1371 nucleotides, encoding 457 amino acids. qRT-PCR data revealed that the transcript levels of SQSTM1 in triploid fish were increased both in vivo and in vitro following spring viraemia of carp virus (SVCV) infection. Immunofluorescence analysis confirmed that 3nSQSTM1 was mainly distributed in the cytoplasm. Luciferase reporter assay results showed that 3nSQSTM1 significantly blocked the activation of interferon promoters induced by 3nMDA5, 3nMAVS, 3nTBK1, and 3nIRF7. Co-immunoprecipitation assays further confirmed that 3nSQSTM1 could interact with both 3nTBK1 and 3nIRF7. Moreover, upon co-transfection, 3nSQSTM1 significantly inhibited the antiviral activity mediated by TBK1 and IRF7. Mechanistically, 3nSQSTM1 decreased the TBK1 phosphorylation and its interaction with 3nIRF7, thereby suppressing the subsequent antiviral response. Notably, we discovered that 3nSQSTM1 also interacted with SVCV N and P proteins, and these viral proteins may exploit 3nSQSTM1 to further limit the host's antiviral innate immune responses. In conclusion, our study demonstrates that 3nSQSTM1 plays a pivotal role in negatively regulating the interferon signaling pathway by targeting 3nTBK1 and 3nIRF7.


Asunto(s)
Carpas , Enfermedades de los Peces , Proteínas de Peces , Inmunidad Innata , Factor 7 Regulador del Interferón , Infecciones por Rhabdoviridae , Rhabdoviridae , Animales , Inmunidad Innata/genética , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/virología , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Factor 7 Regulador del Interferón/genética , Factor 7 Regulador del Interferón/inmunología , Rhabdoviridae/fisiología , Infecciones por Rhabdoviridae/inmunología , Infecciones por Rhabdoviridae/veterinaria , Carpas/inmunología , Carpas/genética , Proteína Sequestosoma-1/genética , Proteína Sequestosoma-1/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/inmunología , Proteínas Serina-Treonina Quinasas/metabolismo , Regulación de la Expresión Génica/inmunología , Transducción de Señal/inmunología , Triploidía , Filogenia , Secuencia de Aminoácidos , Alineación de Secuencia/veterinaria , Perfilación de la Expresión Génica/veterinaria
20.
Plants (Basel) ; 13(15)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39124227

RESUMEN

This study examines the impact of climate change on winter wheat production in Henan Province. The analysis, under the utilization of GLASS LAI data, focuses on shifts in the planting areas of winter wheat. In addition, a comprehensive assessment of the spatiotemporal trends in meteorological factors during the winter wheat growth period has also been conducted. The findings reveal a fluctuating increase in accumulated temperature across Henan Province, ranging from 3145 °C to 3424 °C and exhibiting a gradual rise from north to south. In particular, precipitation patterns from 1980 to 2019 showed limited significant trends, while notable abrupt changes were observed in 1983, 2004, 2009, and 2016. Geographically, southwestern Henan Province experiences greater precipitation than the northeast. Moreover, a fluctuating downward trend in sunshine hours has been observed, gradually decreasing from north to south. The study further highlights an increase in winter wheat planting frequency in the northwestern region of Luoyang and the northeastern part of Zhumadian, contrasted by a decrease in Zhengzhou and Kaifeng. Accumulated temperature is positively correlated with the expansion of winter wheat planting areas (R2 = 0.685), while sunshine hours exert a suppressive effect (R2 = 0.637). Among meteorological factors, accumulated temperature emerges as the most crucial determinant, followed by precipitation, with sunshine hours having a relatively minor influence. Yield demonstrates a positive association with accumulated temperature (R2 = 0.765) and a negative correlation with sunshine hours (R2 = -0.614). This finding is consistent with the impact of meteorological factors on winter wheat production. The results of this study enhance the understanding of how the underlying mechanisms of climate change impact crop yields.

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