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1.
PLoS Genet ; 18(11): e1010520, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36441771

RESUMEN

Ubiquitin-mediated proteolysis plays crucial roles in plant responses to environmental stress. However, the mechanism by which E3 ubiquitin ligases modulate plant stress response still needs to be elucidated. In this study, we found that rice PLANT U-BOX PROTEIN 16 (OsPUB16), a U-box E3 ubiquitin ligase, negatively regulates rice drought response. Loss-of-function mutants of OsPUB16 generated through CRISPR/Cas9 system exhibited the markedly enhanced water-deficit tolerance, while OsPUB16 overexpression lines were hypersensitive to water deficit stress. Moreover, OsPUB16 negatively regulated ABA and JA response, and ospub16 mutants produced more endogenous ABA and JA than wild type when exposed to water deficit. Mechanistic investigations revealed that OsPUB16 mediated the ubiquitination and degradation of OsMADS23, which is the substrate of OSMOTIC STRESS/ABA-ACTIVATED PROTEIN KINASE 9 (SAPK9) and increases rice drought tolerance by promoting ABA biosynthesis. Further, the ChIP-qPCR analysis and transient transactivation activity assays demonstrated that OsMADS23 activated the expression of JA-biosynthetic gene OsAOC by binding to its promoter. Interestingly, SAPK9-mediated phosphorylation on OsMADS23 reduced its ubiquitination level by interfering with the OsPUB16-OsMADS23 interaction, which thus enhanced OsMADS23 stability and promoted OsAOC expression. Collectively, our findings establish that OsPUB16 reduces plant water-deficit tolerance by modulating the 'SAPK9-OsMADS23-OsAOC' pathway to repress ABA and JA biosynthesis.


Asunto(s)
Oryza , Oryza/genética , Agua , Ubiquitina
2.
Proc Natl Acad Sci U S A ; 119(27): e2201275119, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35759672

RESUMEN

Fine audiovocal control is a hallmark of human speech production and depends on precisely coordinated muscle activity guided by sensory feedback. Little is known about shared audiovocal mechanisms between humans and other mammals. We hypothesized that real-time audiovocal control in bat echolocation uses the same computational principles as human speech. To test the prediction of this hypothesis, we applied state feedback control (SFC) theory to the analysis of call frequency adjustments in the echolocating bat, Hipposideros armiger. This model organism exhibits well-developed audiovocal control to sense its surroundings via echolocation. Our experimental paradigm was analogous to one implemented in human subjects. We measured the bats' vocal responses to spectrally altered echolocation calls. Individual bats exhibited highly distinct patterns of vocal compensation to these altered calls. Our findings mirror typical observations of speech control in humans listening to spectrally altered speech. Using mathematical modeling, we determined that the same computational principles of SFC apply to bat echolocation and human speech, confirming the prediction of our hypothesis.


Asunto(s)
Quirópteros , Ecolocación , Retroalimentación Sensorial , Vocalización Animal , Animales , Percepción Auditiva/fisiología , Quirópteros/fisiología , Ecolocación/fisiología , Retroalimentación Sensorial/fisiología , Femenino , Humanos , Modelos Biológicos , Habla/fisiología , Vocalización Animal/fisiología
3.
Nano Lett ; 24(11): 3462-3469, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38451166

RESUMEN

Two-dimensional (2D) room-temperature multiferroic materials are highly desirable but still very limited. Herein, we propose a potential strategy to obtain such materials in 2D metal-organic frameworks (MOFs) by utilizing the d-p direct spin coupling in conjunction with center-symmetry-breaking six-membered heterocyclic rings. Based on this strategy, a screening of 128 2D MOFs results in the identification of three multiferroics, that is, Cr(1,2-oxazine)2, Cr(1,2,4-triazine)2, and Cr(1,2,3,4-trazine)2, simultaneously exhibiting room-temperature ferrimagnetism and ferroelectricity/antiferroelectricity. The room-temperature ferrimagnetic order (306-495 K) in these MOFs originates from the strong d-p direct magnetic exchange interaction between Cr cations and ligand anions. Specifically, Cr(1,2-oxazine)2 exhibits ferroelectric behavior with an out-of-plane polarization of 4.24 pC/m, whereas the other two manifest antiferroelectric characteristics. Notably, all three materials present suitable polarization switching barriers (0.18-0.31 eV). Furthermore, these MOFs are all bipolar magnetic semiconductors with moderate band gaps, in which the spin direction of carriers can be manipulated by electrical gating.

4.
Nano Lett ; 24(21): 6425-6432, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38747348

RESUMEN

Two-dimensional semiconductor materials with vertical dipoles are promising photocatalysts as vertical dipoles not only promote the electron-hole separation but also enhance the carrier redox ability. However, the influence of vertical dipoles on carrier recombination in such materials, especially the competing relationship between vertical dipoles and band gaps, is not yet clear. Herein, first-principles calculations and nonadiabatic molecular dynamics simulations were combined to clarify the influence of band gap and vertical dipole on the carrier lifetime in Janus MoSSe monolayer. By comparing with the results of MoS2 and MoSe2 as well as exploring the carrier lifetime of MoSSe under strain regulation, it has been demonstrated that the vertical dipole, rather than the band gap, is the dominant factor affecting the carrier lifetime. Strikingly, a linear relationship between the carrier lifetime and vertical dipole is revealed. These findings have important implications for the design of high-performance photocatalysts and optoelectronic devices.

5.
Plant J ; 114(4): 914-933, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36906910

RESUMEN

The antagonism between gibberellin (GA) and abscisic acid (ABA) signaling pathways is vital to balance plant growth and stress response. Nevertheless, the mechanism by which plants determine the balance remains to be elucidated. Here, we report that rice NUCLEAR FACTOR-Y A3 (OsNF-YA3) modulates GA- and ABA-mediated balance between plant growth and osmotic stress tolerance. OsNF-YA3 loss-of-function mutants exhibit stunted growth, compromised GA biosynthetic gene expression, and decreased GA levels, while its overexpression lines have promoted growth and enhanced GA content. Chromatin immunoprecipitation-quantitative polymerase chain reaction analysis and transient transcriptional regulation assays demonstrate that OsNF-YA3 activates GA biosynthetic gene OsGA20ox1 expression. Furthermore, the DELLA protein SLENDER RICE1 (SLR1) physically interacts with OsNF-YA3 and thus inhibits its transcriptional activity. On the other side, OsNF-YA3 negatively regulates plant osmotic stress tolerance by repressing ABA response. OsNF-YA3 reduces ABA levels by transcriptionally regulating ABA catabolic genes OsABA8ox1 and OsABA8ox3 by binding to their promoters. Furthermore, OSMOTIC STRESS/ABA-ACTIVATED PROTEIN KINASE 9 (SAPK9), the positive component in ABA signaling, interacts with OsNF-YA3 and mediates OsNF-YA3 phosphorylation, resulting in its degradation in plants. Collectively, our findings establish OsNF-YA3 as an important transcription factor that positively modulates GA-regulated plant growth and negatively controls ABA-mediated water-deficit and salt tolerance. These findings shed light on the molecular mechanism underlying the balance between the growth and stress response of the plant.


Asunto(s)
Oryza , Oryza/metabolismo , Presión Osmótica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Giberelinas/metabolismo , Desarrollo de la Planta , Regulación de la Expresión Génica de las Plantas , Ácido Abscísico/metabolismo
6.
Mol Med ; 30(1): 184, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39455916

RESUMEN

BACKGROUND: Sepsis-associated acute kidney injury (AKI) is a serious complication of systemic infection with high morbidity and mortality in patients. However, no effective drugs are available for AKI treatment. Dexmedetomidine (DEX) is an alpha 2 adrenal receptor agonist with antioxidant and anti-apoptotic effects. This study aimed to investigate the therapeutic effects of DEX on sepsis-associated AKI and to elucidate the role of mitochondrial dynamics during this process. METHODS: A lipopolysaccharide (LPS)-induced AKI rat model and an NRK-52E cell model were used in the study. This study investigated the effects of DEX on sepsis-associated AKI and the molecular mechanisms using histologic assessment, biochemical analyses, ultrastructural observation, western blotting, immunofluorescence, immunohistochemistry, qRT-PCR, flow cytometry, and si-mRNA transfection. RESULTS: In rats, the results showed that administration of DEX protected kidney structure and function from LPS-induced septic AKI. In addition, we found that DEX upregulated the α2-AR/SIRT1/PGC-1α pathway, protected mitochondrial structure and function, and decreased oxidative stress and apoptosis compared to the LPS group. In NRK-52E cells, DEX regulated the mitochondrial dynamic balance by preventing intracellular Ca2+ overloading and activating CaMKII. CONCLUSIONS: DEX ameliorated septic AKI by reducing oxidative stress and apoptosis in addition to modulating mitochondrial dynamics via upregulation of the α2-AR/SIRT1/PGC-1α pathway. This is a confirmatory study about DEX pre-treatment to ameliorate septic AKI. Our research reveals a novel mechanistic molecular pathway by which DEX provides nephroprotection.


Asunto(s)
Lesión Renal Aguda , Dexmedetomidina , Dinámicas Mitocondriales , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Transducción de Señal , Sirtuina 1 , Animales , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Sirtuina 1/metabolismo , Sirtuina 1/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Ratas , Masculino , Dinámicas Mitocondriales/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Receptores Adrenérgicos alfa 2/metabolismo , Receptores Adrenérgicos alfa 2/genética , Estrés Oxidativo/efectos de los fármacos , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Línea Celular , Ratas Sprague-Dawley , Lipopolisacáridos/efectos adversos , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos
7.
BMC Med ; 22(1): 253, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902735

RESUMEN

BACKGROUND: Cognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients. METHODS: In this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, sham rTMS + active tDCS, sham rTMS + sham tDCS). Finally, 203 patients completed the study and received 10 treatment sessions over a 2-week period. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess patients' cognitive function at baseline and week 2. Also, we applied the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess patients' depressive symptoms at baseline and week 2. RESULTS: After 10 sessions of treatment, the rTMS combined with the tDCS group showed more significant improvements in the RBANS total score, immediate memory, and visuospatial/constructional index score (all p < 0.05). Moreover, post hoc tests revealed a significant increase in the RBANS total score and Visuospatial/Constructional in the combined treatment group compared to the other three groups but in the immediate memory, the combined treatment group only showed a better improvement than the sham group. The results also showed the RBANS total score increased significantly higher in the active rTMS group compared with the sham group. However, rTMS or tDCS alone was not superior to the sham group in terms of other cognitive performance. In addition, the rTMS combined with the tDCS group showed a greater reduction in HDRS-24 total score and a better depression response rate than the other three groups. CONCLUSIONS: rTMS combined with tDCS treatment is more effective than any single intervention in treating cognitive dysfunction and depressive symptoms in MDD patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052122).


Asunto(s)
Cognición , Trastorno Depresivo Mayor , Estimulación Transcraneal de Corriente Directa , Estimulación Magnética Transcraneal , Humanos , Trastorno Depresivo Mayor/terapia , Masculino , Femenino , Estimulación Transcraneal de Corriente Directa/métodos , Método Doble Ciego , Adulto , Estimulación Magnética Transcraneal/métodos , Persona de Mediana Edad , Cognición/fisiología , Resultado del Tratamiento , Terapia Combinada , Adulto Joven
8.
Small ; : e2311766, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39109952

RESUMEN

The concept of creating room-temperature ferromagnets from organic radicals proposed nearly sixty years ago, has recently experienced a resurgence due to advances in organic radical chemistry and materials. However, the lack of definitive design paradigms for achieving stable long-range ferromagnetic coupling between organic radicals presents an uncertain future for this research. Here, an innovative strategy is presented to achieve room-temperature ferromagnets by assembling π-conjugated radicals into π-π stacking aggregates. These aggregates, with ultra-close π-π distances and optimal π-π overlap, provide a platform for strong ferromagnetic (FM) interaction. The planar aromatic naphthalene diimide (NDI) anion radicals form nanorod aggregates with a π-π distance of just 3.26 Å, shorter than typical van der Waals distances. The suppressed electron paramagnetic resonance (EPR) signal and emergent near-infrared (NIR) absorption of the aggregates confirm strong interactions between the radicals. Magnetic measurements of NDI anion radical aggregates demonstrate room-temperature ferromagnetism with a saturated magnetization of 1.1 emu g-1, the highest among pure organic ferromagnets. Theoretical calculations reveal that π-stacks of NDI anion radicals with specific interlayer translational slippage favor ferromagnetic coupling over antiferromagnetic coupling.

9.
J Med Virol ; 96(3): e29454, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38445768

RESUMEN

Various vaccines have been challenged by SARS-CoV-2 variants. Here, we reported a yeast-derived recombinant bivalent vaccine (Bivalent wild-type [Wt]+De) based on the wt and Delta receptor-binding domain (RBD). Yeast derived RBD proteins based on the wt and Delta mutant were used as the prime vaccine. It was found that, in the presence of aluminium hydroxide (Alum) and unmethylated CpG-oligodeoxynucleotides (CpG) adjuvants, more cross-protective immunity against SARS-CoV-2 prototype and variants were elicited by bivalent vaccine than monovalent wtRBD or Delta RBD. Furthermore, a heterologous boosting strategy consisting of two doses of bivalent vaccines followed by one dose adenovirus vectored vaccine exhibited cross-neutralization capacity and specific T cell responses against Delta and Omicron (BA.1 and BA.4/5) variants in mice, superior to a homologous vaccination strategy. This study suggested that heterologous prime-boost vaccination with yeast-derived bivalent protein vaccine could be a potential approach to address the challenge of emerging variants.


Asunto(s)
COVID-19 , Vacunas , Animales , Ratones , Vacunas Combinadas , Proteínas Fúngicas , Saccharomyces cerevisiae/genética , COVID-19/prevención & control , SARS-CoV-2 , Vacunación
10.
Plant Physiol ; 193(4): 2825-2847, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37706533

RESUMEN

Regulation of seed dormancy/germination is of great importance for seedling establishment and crop production. Nuclear factor-Y (NF-Y) transcription factors regulate plant growth and development, as well as stress responses; however, their roles in seed germination remain largely unknown. In this study, we reported that NF-Y gene OsNF-YC5 knockout increased, while its overexpression reduced, the seed germination in rice (Oryza sativa L.). ABA-induced seed germination inhibition assays showed that the osnf-yc5 mutant was less sensitive but OsNF-YC5-overexpressing lines were more sensitive to exogenous ABA than the wild type. Meanwhile, MeJA treatment substantially enhanced the ABA sensitivity of OsNF-YC5-overexpressing lines during seed germination. Mechanistic investigations revealed that the interaction of OSMOTIC STRESS/ABA-ACTIVATED PROTEIN KINASE 9 (SAPK9) with OsNF-YC5 enhanced the stability of OsNF-YC5 by protein phosphorylation, while the interaction between JASMONATE ZIM-domain protein 9 (OsJAZ9) and OsNF-YC5 repressed OsNF-YC5 transcriptional activity and promoted its degradation. Furthermore, OsNF-YC5 transcriptionally activated ABA catabolic gene OsABA8ox3, reducing ABA levels in germinating seeds. However, the transcriptional regulation of OsABA8ox3 by OsNF-YC5 was repressed by addition of OsJAZ9. Notably, OsNF-YC5 improved seed germination under salinity conditions. Further investigation showed that OsNF-YC5 activated the high-affinity K+ transporter gene (OsHAK21) expression, and addition of SAPK9 could increase the transcriptional regulation of OsHAK21 by OsNF-YC5, thus substantially reducing the ROS levels to enhance seed germination under salt stress. Our findings establish that OsNF-YC5 integrates ABA and JA signaling during rice seed germination, shedding light on the molecular networks of ABA-JA synergistic interaction.


Asunto(s)
Germinación , Oryza , Germinación/genética , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Oryza/metabolismo , Semillas , Hormonas/metabolismo , Regulación de la Expresión Génica de las Plantas
11.
PLoS Biol ; 19(8): e3001382, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34398872

RESUMEN

[This corrects the article DOI: 10.1371/journal.pbio.3000435.].

12.
Microb Cell Fact ; 23(1): 113, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38622698

RESUMEN

BACKGROUND: Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs. RESULTS: Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield-980.8 mg/L of isatropolone A-achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date. CONCLUSION: In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.


Asunto(s)
Streptomyces , Streptomyces/metabolismo , Vías Biosintéticas/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Regiones Promotoras Genéticas , Familia de Multigenes
13.
Nanotechnology ; 35(36)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38865983

RESUMEN

Two-dimensional (2D) transition metal carbides and nitrides (MXenes) are a class of 2D nanomaterials that can offer excellent properties for high-performance supercapacitors. Nevertheless, irreversible restacking of MXene sheets decreases the interlayer spacing, which inhibits the ion intercalation between the MXene nanosheets and finally deteriorates the electrochemical performance of supercapacitors. Herein, aramid nanofibers (ANFs) are mixed with Ti3C2TxMXene to prepare MXene/ANFs composite films. The restacking of MXene sheets is inhibited by the electrostatic repulsion between ANFs and MXene. The ANFs act as intercalation agents to increase the interlayer spacing of the composite films, which can improve the ion storage ability of supercapacitors. Furthermore, the ANFs enhance the mechanical strength of the composite films due to the strong hydrogen bonding interaction and nanomechanical interlocking between ANFs and MXene, endowing the composite films with self-standing property. The resultant composite films are used as electrodes for flexible solid-state supercapacitors to achieve high specific capacitance (996.5 mF cm-2at 5 mV s-1) and outstanding cycling stability. Thus, this work provides a potential strategy to regulate the properties of 2D nanomaterials, which may expand the application of them in energy storage, ionic separation, osmotic energy conversion and beyond.

14.
J Fluoresc ; 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38639858

RESUMEN

Two fluorescent probes, Y1-2 were synthesized from 2-acetonaphthone, 4-acetylbiphenyl, and phenyl hydrazine by Vilsmeier-Haack reaction and Knoevenagel condensation. Their recognition efficacies for N2H4 were tested by UV-visible absorption spectroscopy and fluorescence emission spectroscopy. The recognition mechanism were studies by density-functional theory calculations, and the effect of pH on N2H4 recognition was also studied. The results showed that the probe Y1-2 has high selectivity and a low detection limit for N2H4, and the recognition of N2H4 can be accomplished at physiological pH. The probes have had obvious aggregation-induced luminescence effect, large Stokes shift, high sensitivity, and can be successfully applied to live cell imaging.

15.
Nephrology (Carlton) ; 29(11): 738-747, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39168961

RESUMEN

BACKGROUND: Kidney function can be impaired in patients with inflammatory bowel diseases (IBD), including Crohn's diseases (CD) and ulcerative colitis (UC). However, the causal relationship between IBD and chronic kidney diseases (CKD) remains unclear. METHODS: We determined the causal association between IBD and CKD by performing two-sample bidirectional mendelian randomization (MR) analyses. Independent genetic variants were selected as instrumental variables (IVs) of the exposure from open-access genome-wide association studies (GWAS) among European ancestry. IVs-outcome estimates were extracted from three separate GWAS for IBD and two for CKD, respectively. Inverse-variance-weighted model was used as the primary MR method. The pleiotropic effect and heterogeneity were evaluated. For either direction, analyses were performed per outcome database and were subsequently meta-analysed. RESULTS: Genetically predicted IBD was associated with higher risk of CKD (OR: 1.045, 95% CI: 1.016-1.073, P = 0.002) by including 42 344 IBD cases and 229 164 controls. Further analyses showed genetic liability to CD increased the risk of CKD (OR: 1.057, 95% CI: 1.027-1.087, p < 0.001) whereas UC did not (OR: 0.999, 95% CI:0.969-1.031, p = 0.970). In contrast, genetically predicted CKD was not associated with IBD (OR: 1.010, 95% CI: 0.965-1.056, p = 0.676), UC (OR: 1.011, 95% CI: 0.948-1.078, p = 0.746) and CD (OR: 1.024; 95% CI: 0.963-1.089, p = 0.447). CONCLUSIONS: We concluded that CD, but not UC, can increase the risk of CKD causally. CD, but not UC, can increase the risk of chronic kidney disease causally. These findings enhance our understanding of the differential impact of IBD subtypes on CKD. It may be necessary to monitor kidney function regularly in patients with CD.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Predisposición Genética a la Enfermedad , Insuficiencia Renal Crónica , Población Blanca , Humanos , Colitis Ulcerosa/genética , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/genética , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/diagnóstico , Europa (Continente)/epidemiología , Estudio de Asociación del Genoma Completo , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Análisis de la Aleatorización Mendeliana , Fenotipo , Polimorfismo de Nucleótido Simple , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Medición de Riesgo , Factores de Riesgo , Población Blanca/genética
16.
BMC Pulm Med ; 24(1): 393, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143553

RESUMEN

BACKGROUND: Lung cancer, a leading cause of cancer mortality, poses significant treatment challenges. The use of immune checkpoint inhibitors (ICIs) has revolutionized therapy, but it is associated with immune-related pneumonitis (IRP). This study systematically reviews and analyzes the impact of Chronic Obstructive Pulmonary Disease (COPD) on the risk of IRP in lung cancer patients undergoing immunotherapy. METHODS: Adhering to PRISMA guidelines and using the PICO framework, a comprehensive search across PubMed, Embase, Web of Science, and the Cochrane Library was conducted. Inclusion criteria encompassed peer-reviewed studies involving lung cancer patients treated with ICIs, comparing those with and without COPD. The primary outcome was the incidence and risk of IRP. The Newcastle-Ottawa Scale evaluated study quality. The effect size was calculated using random or fixed-effects models based on the observed heterogeneity. We assessed the heterogeneity between studies and conducted a sensitivity analysis. RESULTS: The search identified 1026 articles, with six meeting the criteria for inclusion. Studies varied in design and geography, predominantly retrospective cohort studies. Patients with COPD had an increased risk of IRP (OR = 1.54, 95% CI [1.24, 1.92, P < 0.01). Subgroup analysis based on radiation therapy exposure (< 40% and ≥ 40%) also indicated a heightened IRP risk in COPD patients. Sensitivity analysis affirmed the robustness of the results, and publication bias was not significant. CONCLUSIONS: Lung cancer patients with COPD undergoing immunotherapy have a significantly increased risk of developing IRP. This highlights the necessity for vigilant monitoring and individualized treatment strategies to improve the safety and effectiveness of immunotherapy in this group.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/terapia , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neumonía/epidemiología , Factores de Riesgo
17.
PLoS Genet ; 17(8): e1009699, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34343171

RESUMEN

Some of MADS-box transcription factors (TFs) have been shown to play essential roles in the adaptation of plant to abiotic stress. Still, the mechanisms that MADS-box proteins regulate plant stress response are not fully understood. Here, a stress-responsive MADS-box TF OsMADS23 from rice conferring the osmotic stress tolerance in plants is reported. Overexpression of OsMADS23 remarkably enhanced, but knockout of the gene greatly reduced the drought and salt tolerance in rice plants. Further, OsMADS23 was shown to promote the biosynthesis of endogenous ABA and proline by activating the transcription of target genes OsNCED2, OsNCED3, OsNCED4 and OsP5CR that are key components for ABA and proline biosynthesis, respectively. Then, the convincing evidence showed that the OsNCED2-knockout mutants had lower ABA levels and exhibited higher sensitivity to drought and oxidative stress than wild type, which is similar to osmads23 mutant. Interestingly, the SnRK2-type protein kinase SAPK9 was found to physically interact with and phosphorylate OsMADS23, and thus increase its stability and transcriptional activity. Furthermore, the activation of OsMADS23 by SAPK9-mediated phosphorylation is dependent on ABA in plants. Collectively, these findings establish a mechanism that OsMADS23 functions as a positive regulator in response to osmotic stress by regulating ABA biosynthesis, and provide a new strategy for improving drought and salt tolerance in rice.


Asunto(s)
Ácido Abscísico/metabolismo , Proteínas de Dominio MADS/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Oryza/fisiología , Sequías , Regulación de la Expresión Génica de las Plantas , Oryza/metabolismo , Presión Osmótica , Fosforilación , Proteínas de Plantas/metabolismo , Transducción de Señal
18.
Nano Lett ; 23(19): 9126-9132, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37781926

RESUMEN

Developing an efficient method to reversibly control materials' spin order is urgently needed but challenging in spintronics. Though various physical field control methods have been advancing, the chemical control of spin is little exploited. Here, we propose a chemical means for such spin manipulation, i.e., utilizing the well-known lactim-lactam tautomerization to reversibly modulate the magnetic phase transition in two-dimensional (2D) organometallic lattices. The proposal is verified by theoretically designing several 2D organometallic frameworks with antiferromagnetic to ferrimagnetic spin order transformation modulated by lactim-lactam tautomerization on organic linkers. The transition originates from the change in spin states of organic linkers (from singlet to doublet) via tautomerization. Such a transition further switches materials' electronic structures from normal semiconductors with zero spin polarization to bipolar magnetic semiconductors with valence and conduction band edges 100% spin polarized in opposite spin channels. Moreover, the magnitude of magnetic anisotropy energy also enhances by 5- to 9-fold.

19.
Nano Lett ; 23(17): 7890-7896, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37602760

RESUMEN

Generating pure spin currents is very desirable in spintronics, as it provides a promising way to substantially reduce Joule heating and achieve ultrahigh integration density. However, to date, most spintronic devices exhibit spin currents that are accompanied by charge currents. The generation of pure spin currents on the nanoscale, particularly at the single-molecule level, remains challenging. Here, we propose that by exploiting our recently reported bipolar magnetic molecules (BMMs) as the core component of single-molecule devices, where the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) come from different spin channels, the generation of pure spin currents can be easily realized via the spin Seebeck effect (SSE) with applied temperature gradient. Moreover, the spin Seebeck coefficient can be modulated over a wide range by applying an external gate voltage. The proposal is verified through first-principles calculations on two BMM-based molecular junctions.

20.
BMC Oral Health ; 24(1): 1243, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39425104

RESUMEN

BACKGROUND: When discolored teeth are repaired with porcelain veneers, the thickness of the restorations should be increased appropriately using opaque porcelain and bonded by applying opaque luting resin cement to cover discolored substrates. However, its impact on the opalescent performance has not been reported yet. PURPOSE: To analyze the effects of opacity, body porcelain layer thickness, and luting resin cement on the opalescence properties of porcelain veneer restorations for discolored teeth. METHODS: Ninety IPS d. SIGN A3 porcelain veneer specimens were prepared via powder-paste coating and sintering. Specimens were divided into three groups according to ceramic type and cement used or not: body porcelain group as control, body/opaque porcelain group and body/opaque porcelain-resin cement composite group. Each group was subdivided into three subgroups based on the thickness, 0.50, 0.75, and 1.00 mm (n = 10). Variolink N Bleach XL luting resin cement with thickness of 0.1 mm was applied to the bottoms of body/opaque porcelain specimens to produce body/opaque porcelain-resin cement composites. The opalescence (OP) values were calculated and the micromorphological characteristics were analyzed by scanning electron microscope (SEM). Statistical analysis was performed by using ANOVA test (P < 0.05). RESULTS: The opalescence values determined for the body porcelain groups with thicknesses of 0.50, 0.75, and 1.00 mm and body/opaque porcelain specimens with thicknesses of 0.45/0.05, 0.70/0.05, and 0.95/0.05 mm were 3.35 ± 0.15, 3.83 ± 0.10, 6.73 ± 0.25, 7.95 ± 0.34, 15.16 ± 0.60, and 16.49 ± 0.89, respectively. The specimens in the body and body/opaque porcelain groups exhibited significant increases in their opalescence values with increasing thickness (P = 0.00). The opalescence values of the specimens increased significantly with the addition of a 0.05 mm opaque porcelain layer (P = 0.00). The opalescence values of the composites containing body/opaque porcelain layers with thicknesses of 0.45/0.05, 0.70/0.05, and 0.95/0.05 mm and luting resin cement were 9.46 ± 0.17, 16.47 ± 0.15, and 18.38 ± 0.47, respectively. The opalescence values of the composite specimens increased significantly with an increase in the thickness of the porcelain layer(P = 0.00). CONCLUSIONS: The opaque porcelain layer and opaque resin cement can significantly improve the opalescence properties of porcelain laminate veneers for discolored teeth, but the opalescence performance is still poor than natural teeth. The body porcelain only contributes to opalescence within a certain thickness range.


Asunto(s)
Porcelana Dental , Coronas con Frente Estético , Cementos de Resina , Porcelana Dental/química , Cementos de Resina/química , Ensayo de Materiales , Propiedades de Superficie , Humanos , Microscopía Electrónica de Rastreo
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