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1.
Mol Cell ; 82(20): 3810-3825.e8, 2022 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-36108631

RESUMEN

Human mixed-lineage leukemia (MLL) family methyltransferases methylate histone H3 lysine 4 to different methylation states (me1/me2/me3) with distinct functional outputs, but the mechanism underlying the different product specificities of MLL proteins remains unclear. Here, we develop methodologies to quantitatively measure the methylation rate difference between mono-, di-, and tri-methylation steps and demonstrate that MLL proteins possess distinct product specificities in the context of the minimum MLL-RBBP5-ASH2L complex. Comparative structural analyses of MLL complexes by X-ray crystal structures, fluorine-19 nuclear magnetic resonance, and molecular dynamics simulations reveal that the dynamics of two conserved tyrosine residues at the "F/Y (phenylalanine/tyrosine) switch" positions fine-tune the product specificity. The variation in the intramolecular interaction between SET-N and SET-C affects the F/Y switch dynamics, thus determining the product specificities of MLL proteins. These results indicate a modified F/Y switch rule applicable for most SET domain methyltransferases and implicate the functional divergence of MLL proteins.


Asunto(s)
N-Metiltransferasa de Histona-Lisina , Leucemia , Humanos , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Lisina/metabolismo , Flúor/metabolismo , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Tirosina , Fenilalanina
2.
EMBO J ; 42(13): e112333, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-37183585

RESUMEN

Enteric bacteria use up to 15% of their cellular energy for ammonium assimilation via glutamine synthetase (GS)/glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH) in response to varying ammonium availability. However, the sensory mechanisms for effective and appropriate coordination between carbon metabolism and ammonium assimilation have not been fully elucidated. Here, we report that in Salmonella enterica, carbon metabolism coordinates the activities of GS/GDH via functionally reversible protein lysine acetylation. Glucose promotes Pat acetyltransferase-mediated acetylation and activation of adenylylated GS. Simultaneously, glucose induces GDH acetylation to inactivate the enzyme by impeding its catalytic centre, which is reversed upon GDH deacetylation by deacetylase CobB. Molecular dynamics (MD) simulations indicate that adenylylation is required for acetylation-dependent activation of GS. We show that acetylation and deacetylation occur within minutes of "glucose shock" to promptly adapt to ammonium/carbon variation and finely balance glutamine/glutamate synthesis. Finally, in a mouse infection model, reduced S. enterica growth caused by the expression of adenylylation-mimetic GS is rescued by acetylation-mimicking mutations. Thus, glucose-driven acetylation integrates signals from ammonium assimilation and carbon metabolism to fine-tune bacterial growth control.


Asunto(s)
Compuestos de Amonio , Salmonella enterica , Animales , Ratones , Compuestos de Amonio/metabolismo , Acetilación , Carbono/metabolismo , Glucosa , Glutamato Deshidrogenasa/metabolismo , Nitrógeno/metabolismo
3.
Mol Cell ; 76(1): 148-162.e7, 2019 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-31447391

RESUMEN

The rapid proliferation of cancer cells and dysregulated vasculature within the tumor leads to limited nutrient accessibility. Cancer cells often rewire their metabolic pathways for adaption to nutrient stress, and the underlying mechanism remains largely unknown. Glutamate dehydrogenase 1 (GDH1) is a key enzyme in glutaminolysis that converts glutamate to α-ketoglutarate (α-KG). Here, we show that, under low glucose, GDH1 is phosphorylated at serine (S) 384 and interacts with RelA and IKKß. GDH1-produced α-KG directly binds to and activates IKKß and nuclear factor κB (NF-κB) signaling, which promotes glucose uptake and tumor cell survival by upregulating GLUT1, thereby accelerating gliomagenesis. In addition, GDH1 S384 phosphorylation correlates with the malignancy and prognosis of human glioblastoma. Our finding reveals a unique role of α-KG to directly regulate signal pathway, uncovers a distinct mechanism of metabolite-mediated NF-κB activation, and also establishes the critical role of α-KG-activated NF-κB in brain tumor development.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Proliferación Celular , Metabolismo Energético , Glioblastoma/metabolismo , Glucosa/metabolismo , Glutamato Deshidrogenasa/metabolismo , Ácidos Cetoglutáricos/metabolismo , FN-kappa B/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Supervivencia Celular , Niño , Femenino , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Glioblastoma/patología , Glucosa/deficiencia , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Glutamato Deshidrogenasa/genética , Células HEK293 , Humanos , Quinasa I-kappa B/genética , Quinasa I-kappa B/metabolismo , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , FN-kappa B/genética , Clasificación del Tumor , Fosforilación , Transducción de Señal , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo , Adulto Joven
4.
Genes Dev ; 33(9-10): 536-549, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30842217

RESUMEN

The exosome functions in the degradation of diverse RNA species, yet how it is negatively regulated remains largely unknown. Here, we show that NRDE2 forms a 1:1 complex with MTR4, a nuclear exosome cofactor critical for exosome recruitment, via a conserved MTR4-interacting domain (MID). Unexpectedly, NRDE2 mainly localizes in nuclear speckles, where it inhibits MTR4 recruitment and RNA degradation, and thereby ensures efficient mRNA nuclear export. Structural and biochemical data revealed that NRDE2 interacts with MTR4's key residues, locks MTR4 in a closed conformation, and inhibits MTR4 interaction with the exosome as well as proteins important for MTR4 recruitment, such as the cap-binding complex (CBC) and ZFC3H1. Functionally, MID deletion results in the loss of self-renewal of mouse embryonic stem cells. Together, our data pinpoint NRDE2 as a nuclear exosome negative regulator that ensures mRNA stability and nuclear export.


Asunto(s)
Exosomas/genética , Exosomas/metabolismo , Proteínas Nucleares/fisiología , ARN Helicasas/metabolismo , Animales , Núcleo Celular/metabolismo , Células Madre Embrionarias , Células HEK293 , Células HeLa , Humanos , Ratones , Proteínas Nucleares/genética , Unión Proteica , Dominios Proteicos , Transporte de Proteínas/genética , Estabilidad del ARN/genética
5.
EMBO J ; 41(11): e109272, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35438208

RESUMEN

Double-stranded DNA is recognized as a danger signal by cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), triggering innate immune responses. Palmitoylation is an important post-translational modification (PTM) catalyzed by DHHC-palmitoyl transferases, which participate in the regulation of diverse biological processes. However, whether palmitoylation regulates cGAS function has not yet been explored. Here, we found that palmitoylation of cGAS at C474 restricted its enzymatic activity in the presence of double-stranded DNA. cGAS palmitoylation was catalyzed mainly by the palmitoyltransferase ZDHHC18 and double-stranded DNA promoted this modification. Mechanistically, palmitoylation of cGAS reduced the interaction between cGAS and double-stranded DNA, further inhibiting cGAS dimerization. Consistently, ZDHHC18 negatively regulated cGAS activation in human and mouse cell lines. In a more biologically relevant model system, Zdhhc18-deficient mice were found to be resistant to infection by DNA viruses, in agreement with the observation that ZDHHC18 negatively regulated cGAS mediated innate immune responses in human and mouse primary cells. In summary, the negative role of ZDHHC18-mediated cGAS palmitoylation may be a novel regulatory mechanism in the fine-tuning of innate immunity.


Asunto(s)
Lipoilación , Transducción de Señal , Animales , Ratones , ADN/metabolismo , Inmunidad Innata , Nucleotidiltransferasas/metabolismo , Transducción de Señal/genética
6.
Mol Cell ; 71(2): 201-215.e7, 2018 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-30029001

RESUMEN

Macrophages are a dominant leukocyte population in the tumor microenvironment and actively promote cancer progression. However, the molecular mechanism underlying the role of macrophages remains poorly understood. Here we show that polarized M2 macrophages enhance 3-phosphoinositide-dependent protein kinase 1 (PDPK1)-mediated phosphoglycerate kinase 1 (PGK1) threonine (T) 243 phosphorylation in tumor cells by secreting interleukin-6 (IL-6). This phosphorylation facilitates a PGK1-catalyzed reaction toward glycolysis by altering substrate affinity. Inhibition of PGK1 T243 phosphorylation or PDPK1 in tumor cells or neutralization of macrophage-derived IL-6 abrogates macrophage-promoted glycolysis, proliferation, and tumorigenesis. In addition, PGK1 T243 phosphorylation correlates with PDPK1 activation, IL-6 expression, and macrophage infiltration in human glioblastoma multiforme (GBM). Moreover, PGK1 T243 phosphorylation also correlates with malignance and prognosis of human GBM. Our findings demonstrate a novel mechanism of macrophage-promoted tumor growth by regulating tumor cell metabolism, implicating the therapeutic potential to disrupt the connection between macrophages and tumor cells by inhibiting PGK1 phosphorylation.


Asunto(s)
Macrófagos/metabolismo , Fosfoglicerato Quinasa/genética , Fosfoglicerato Quinasa/metabolismo , Proteínas Quinasas Dependientes de 3-Fosfoinosítido/genética , Proteínas Quinasas Dependientes de 3-Fosfoinosítido/metabolismo , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Carcinogénesis/metabolismo , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Femenino , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patología , Glucólisis , Humanos , Macrófagos/patología , Ratones , Ratones Desnudos , Mieloma Múltiple/genética , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Fosforilación , Pronóstico , Microambiente Tumoral
7.
EMBO Rep ; 24(7): e56458, 2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37249035

RESUMEN

DNA topoisomerase IIα (TOP2A) plays a vital role in replication and cell division by catalytically altering DNA topology. It is a prominent target for anticancer drugs, but clinical efficacy is often compromised due to chemoresistance. In this study, we investigate the role of TOP2A O-GlcNAcylation in breast cancer cells and patient tumor tissues. Our results demonstrate that elevated TOP2A, especially its O-GlcNAcylation, promotes breast cancer malignant progression and resistance to adriamycin (Adm). O-GlcNAcylation at Ser1469 enhances TOP2A chromatin DNA binding and catalytic activity, leading to resistance to Adm in breast cancer cells and xenograft models. Mechanistically, O-GlcNAcylation-modulated interactions between TOP2A and cell cycle regulators influence downstream gene expression and contribute to breast cancer drug resistance. These results reveal a previously unrecognized mechanistic role for TOP2A O-GlcNAcylation in breast cancer chemotherapy resistance and provide support for targeting TOP2A O-GlcNAcylation in cancer therapy.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Femenino , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Doxorrubicina/farmacología , Resistencia a Antineoplásicos
8.
Nature ; 571(7763): 127-131, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31243371

RESUMEN

Cancer metastasis is the primary cause of morbidity and mortality, and accounts for up to 95% of cancer-related deaths1. Cancer cells often reprogram their metabolism to efficiently support cell proliferation and survival2,3. However, whether and how those metabolic alterations contribute to the migration of tumour cells remain largely unknown. UDP-glucose 6-dehydrogenase (UGDH) is a key enzyme in the uronic acid pathway, and converts UDP-glucose to UDP-glucuronic acid4. Here we show that, after activation of EGFR, UGDH is phosphorylated at tyrosine 473 in human lung cancer cells. Phosphorylated UGDH interacts with Hu antigen R (HuR) and converts UDP-glucose to UDP-glucuronic acid, which attenuates the UDP-glucose-mediated inhibition of the association of HuR with SNAI1 mRNA and therefore enhances the stability of SNAI1 mRNA. Increased production of SNAIL initiates the epithelial-mesenchymal transition, thus promoting the migration of tumour cells and lung cancer metastasis. In addition, phosphorylation of UGDH at tyrosine 473 correlates with metastatic recurrence and poor prognosis of patients with lung cancer. Our findings reveal a tumour-suppressive role of UDP-glucose in lung cancer metastasis and uncover a mechanism by which UGDH promotes tumour metastasis by increasing the stability of SNAI1 mRNA.


Asunto(s)
Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/prevención & control , Estabilidad del ARN , Factores de Transcripción de la Familia Snail/genética , Uridina Difosfato Glucosa/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular , Proteína 1 Similar a ELAV/deficiencia , Proteína 1 Similar a ELAV/genética , Proteína 1 Similar a ELAV/metabolismo , Transición Epitelial-Mesenquimal , Femenino , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Desnudos , Fosfotirosina/metabolismo , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Factores de Transcripción de la Familia Snail/biosíntesis , Uridina Difosfato Glucosa Deshidrogenasa/química , Uridina Difosfato Glucosa Deshidrogenasa/genética , Uridina Difosfato Glucosa Deshidrogenasa/metabolismo , Uridina Difosfato Ácido Glucurónico/metabolismo
9.
Genomics ; : 110812, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38395205

RESUMEN

After consultation with external experts, the authors acknowledged discrepancies in the classification of certain Berberis samples discussed in the article. Berberis is one of the most complex plant genera, and identifications are very hard, limited to only a handful of experts due to rampant hybridizations and other issues of reticulate evolution. This article has therefore been withdrawn at the request of the authors and with the consent of the editor until the species identification issue has been resolved. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

10.
J Am Chem Soc ; 146(11): 7628-7639, 2024 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-38456823

RESUMEN

High binding affinity and selectivity of metal ions are essential to the function of metalloproteins. Thus, understanding the factors that determine these binding characteristics is of major interest for both fundamental mechanistic investigations and guiding of the design of novel metalloproteins. In this work, we perform QM cluster model calculations and quantum mechanics/molecular mechanics (QM/MM) free energy simulations to understand the binding selectivity of Ca2+ and Mg2+ in the wild-type carp parvalbumin and its mutant. While a nonpolarizable MM model (CHARMM36) does not lead to the correct experimental trend, treatment of the metal binding site with the DFTB3 model in a QM/MM framework leads to relative binding free energies (ΔΔGbind) comparable with experimental data. For the wild-type (WT) protein, the calculated ΔΔGbind is ∼6.6 kcal/mol in comparison with the experimental value of 5.6 kcal/mol. The good agreement highlights the value of a QM description of the metal binding site and supports the role of electronic polarization and charge transfer to metal binding selectivity. For the D51A/E101D/F102W mutant, different binding site models lead to considerable variations in computed binding affinities. With a coordination number of seven for Ca2+, which is shown by QM/MM metadynamics simulations to be the dominant coordination number for the mutant, the calculated relative binding affinity is ∼4.8 kcal/mol, in fair agreement with the experimental value of 1.6 kcal/mol. The WT protein is observed to feature a flexible binding site that accommodates a range of coordination numbers for Ca2+, which is essential to the high binding selectivity for Ca2+ over Mg2+. In the mutant, the E101D mutation reduces the flexibility of the binding site and limits the dominant coordination number of Ca2+ to be seven, thereby leading to reduced binding selectivity against Mg2+. Our results highlight that the binding selectivity of metal ions depends on both the structural and dynamical properties of the protein binding site.


Asunto(s)
Proteínas de Unión al Calcio , Metaloproteínas , Sitios de Unión , Unión Proteica , Metaloproteínas/química , Iones
11.
J Am Chem Soc ; 146(15): 10257-10262, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38578111

RESUMEN

Sorption-based atmospheric water harvesting (AWH) is a promising solution for addressing water scarcity. Developing cost-effective and stable water adsorbents with high water uptake capacity and a low-temperature regeneration requirement is a crucially important procedure. In this Communication, we present a novel and stable aluminophosphate (AlPO) molecular sieve (MS) named DNL-11 with 16-ring channels synthesized by using an affordable and commercialized organic structure directing agent (OSDA), whose crystallographic structure is elucidated by three-dimensional electron diffraction (3D ED). DNL-11 exhibits a significant water uptake capacity (189 mg/g) at a very low vapor pressure (5% relative humidity at 30 °C). In addition, most of the adsorbed water can be effortlessly removed by purging N2 at 25 °C under ambient pressure conditions. This may expand the possibility of AWH under extreme drought conditions.

12.
Opt Express ; 32(4): 6258-6265, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439333

RESUMEN

Quasi-two-dimensional perovskites have attracted widespread interest in developing low-cost high-quality small lasers. The nano cavity based on topologically protected valley edge states can be robust against special defects. Here, we report a high-quality two-dimensional perovskite topological photonic crystal laser based on the quantum valley Hall effect. By adjusting the position of the air holes relative to the pillar, radiation leakage in topological edge states is reduced to a large extent, electric field distribution becomes more uniform and the quality factor can be as high as 3.6 × 104. Our findings could provide opportunities for the development of high-power, stable perovskite lasers with topological protection.

13.
Insect Mol Biol ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38801334

RESUMEN

Ribosomal protein L13 (RPL13) is highly conserved in evolution. At present, the properties and functions of RPL13 have not been characterised in insects. In this study, Bombyx mori RPL13 (BmRPL13) was first found to be specifically recruited to the sites of ultraviolet (UV)-induced DNA damage and contributed to UV damage repair. Escherichia coli expressing BmRPL13 showed better resistance to UV radiation. After knocking down the expression of BmRPL13 in BmN cells, the repair speed of UV-damaged DNA slowed down. The further results showed that BmRPL13 interacted with B. mori nucleopolyhedrovirus (BmNPV) ORF65 (Bm65) protein to locate at the UV-induced DNA damage sites of BmNPV and helped repair UV-damaged viral DNA.

14.
BMC Cancer ; 24(1): 10, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166723

RESUMEN

BACKGROUND: Nervous system toxicity (NST) is one of the most frequent and dangerous side effects of chimeric antigen receptor T-cell (CAR-T) therapy, which is an effective treatment for related tumors in most relapsed/refractory (r/r) hematologic malignancies. Current clinical trial data do not fully reflect the real-world situation. Therefore, this study evaluated the NST of CAR-T therapy using the FDA Adverse Event Reporting System (FAERS). METHODS: Data were retrieved from FAERS for the period from January 1, 2017 to March 31, 2023. Disproportionality analysis and Bayesian analysis were used for data mining. The reporting odds ratio (ROR) for NST with 95% confidence interval (CI) was calculated for each CAR-T product. The time to onset (TTO) and clinical outcomes due to CAR-T therapy-associated NST were assessed. RESULTS: Overall, 6946 cases of NST associated with CAR-T therapy were identified. The patients had a median age of 61 years (interquartile range [IQR]: 47-69 years). Significant signals were observed for all CAR-T products (ROR: 2.19, 95% CI: 2.13-2.44). Anti-CD19 CAR-T products showed a higher NST signal than anti-B cell maturation antigen (BCMA) CAR-T products (ROR025 2.13 vs. 1.98). Brexucabtagene autoleucel (ROR: 3.17, 95% CI: 2.90-3.47) and axicabtagene ciloleucel (ROR: 2.92, 95% CI: 2.81-3.03) had the two highest NST signals. For the preferred term "brain edema," the highest signals were obtained for CD28 CAR-T products. The median TTO of NST for all CAR-T products was 7 days (IQR: 3-17 days). The proportion of death, life-threatening and hospitalization adverse events associated with NST was 20.06%, 7.21%, and 32.70%, respectively. The proportion of death outcomes was higher in patients treated with tisagenlecleucel (30.36%) than in those treated with other CAR-T products, except ciltacabtagene autoleucel (P < 0.001). The proportion of hospitalizations was significantly higher for lisocabtagene maraleucel-associated NST (53.85%) than for other drugs, except for ciltacabtagene autoleucel (P < 0.001). CONCLUSIONS: NST is more closely associated with anti-CD19 CAR-Ts and CAR-Ts containing CD28. Serious NST (brain oedema) is likely to occur with CAR-Ts that contain CD28. CAR-T-related NST warrants greater attention owing to the high proportion of serious adverse events and delayed NST.


Asunto(s)
Neoplasias Hematológicas , Receptores Quiméricos de Antígenos , Humanos , Persona de Mediana Edad , Anciano , Teorema de Bayes , Antígenos CD28 , Recurrencia Local de Neoplasia , Proteínas Adaptadoras Transductoras de Señales , Anticuerpos , Antígenos CD19/efectos adversos , Inmunoterapia Adoptiva/efectos adversos , Tratamiento Basado en Trasplante de Células y Tejidos
15.
Physiol Plant ; 176(2): e14230, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38413388

RESUMEN

The grain yield is closely associated with spikelet fertility in rice (Oryza sativa L.) under high temperatures, and nitrogen (N) plays a crucial role in yield formation. To investigate the effect of panicle N application on yield formation under high temperatures at the panicle initiation stage, two rice varieties [Liangyoupeijiu (LYPJ, heat susceptible) and Shanyou63 (SY63, heat tolerant)] were grown and exposed to high daytime temperature (HT) and control temperature (Control) during the panicle initiation stage. Low (LPN) and high (HPN) panicle N applications were conducted. HT markedly decreased the yields by 87% at LPN and 48% at HPN in LYPJ and 31% at LPN and 36% at HPN in SY63. The decrease in grain yield under HT was primarily attributed to the decline in spikelet fertility, HPN increased spikelet fertility. HT resulted in the abnormal development of anthers, which included disordered, enlarged, and broken anther wall layers, degraded and irregularly shaped microspores, delayed tapetum degradation, less vacuolated microspores per locule, abnormal and aborted pollen grains; however, HPN improved the development of anthers under HT, particularly in LYPJ. A high rate of evapotranspiration resulted in an approximately 1°C decrease in panicle temperatures at HPN compared with that at LPN in both varieties under HT. Overall, these results demonstrate that the increased panicle N application favors normal anther development in LYPJ by decreasing the panicle temperature, which results in high pollen viability and spikelet fertility, and consequently less yield loss under HT.


Asunto(s)
Oryza , Temperatura , Nitrógeno/farmacología , Calor , Polen
16.
Phys Chem Chem Phys ; 26(22): 16234-16239, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38804520

RESUMEN

Weak light detection is crucial in various practical applications such as night vision systems, flame monitoring, and underwater operations. Decreasing the dark current of a photodetector can effectively mitigate noises, consequently enhancing the signal-to-noise ratio and overall weak light detection performance. Herein, we demonstrate a 4H-SiC UV photodetector capable of detecting extremely weak UV light. This device comprises a photosensitive layer of 4H-SiC, two TiN electrodes and an atomically thin Al2O3 interfacial layer between TiN and the C surface of 4H-SiC. Under 360 nm UV light illumination, the proposed Al2O3 device demonstrates an ultra-low dark current of 18 fA, possibly benefiting from the effective passivation of interfacial carriers, and a boosted photo-to-dark current ratio of 6.7 × 107. Consequently, it achieves a weak-light detection limit as low as 31.8 pW cm-2, significantly outperforming the control device lacking Al2O3. When compared to previously reported SiC photodetectors, our Al2O3 device boasts an exceptional large linear dynamic range of 172 dB. Leveraging this, we construct a photodetector array capable of clearly imaging an object under ultra-weak light illumination below the 100 pW cm-2 level. The proposed photodetector represents a significant advancement in the development of highly sensitive image sensors for weak light detection.

17.
BMC Cardiovasc Disord ; 24(1): 75, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38281972

RESUMEN

BACKGROUND: This study aimed to uncover the changing prevalence of obesity and its association with hypertension across socioeconomic gradients in rural southwest China. METHODS: Data were collected from two cross-sectional health interviews and surveys from 2011 to 2021 among individuals aged ≥ 35 years in rural China. Each participant's height, weight, waist circumference, and blood pressure were measured. The overall prevalence of obesity, central obesity, and hypertension was directly standardized by age based on the total population of the two surveys. Multivariate logistic regression was used to analyze the association between obesity and prevalence of hypertension and an individual socioeconomic position (SEP) index was constructed using principal component analysis. RESULTS: From 2011 to 2021, the prevalence of obesity, central obesity, and hypertension increased substantially, from 5.9%, 50.2%, and 26.1-12.1%, 58.0%, and 40.4% (P < 0.01), respectively. These increasing rates existed in all subcategories, including sex, age, ethnicity, education, annual household income, access to medical services, and SEP (P < 0.05). In both 2011 and 2021, lower education level and poor access to medical services correlated with higher prevalence of central obesity, while higher SEP correlated with higher prevalence of obesity and central obesity (P < 0.01). Prevalence of obesity was higher in the Han ethnicity participants and individuals with poor access to medical services than in their counterparts (P < 0.01). Whereas the prevalence of central obesity was lower in Han participants than in ethnic minority participants in 2011 (P < 0.01), this trend reversed in 2021 (P < 0.01). A positive relationship between annual household income and prevalence of obesity and central obesity was only found in 2021 (P < 0.01). Obese and centrally obese participants were more likely to be hypertensive in both survey years (P < 0.01). CONCLUSIONS: Future interventions to prevent and manage obesity in rural China should give increased attention to high income, less educated, poor access to medical services, and high SEP individuals. The implementation of these obesity interventions would also help reduce the prevalence of hypertension.


Asunto(s)
Hipertensión , Obesidad Abdominal , Humanos , Obesidad Abdominal/diagnóstico , Obesidad Abdominal/epidemiología , Etnicidad , Prevalencia , Estudios Transversales , Grupos Minoritarios , China/epidemiología , Hipertensión/diagnóstico , Hipertensión/epidemiología , Obesidad/diagnóstico , Obesidad/epidemiología , Escolaridad , Población Rural , Factores de Riesgo , Factores Socioeconómicos
18.
Ethn Health ; : 1-12, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38682471

RESUMEN

OBJECTIVES: This study aimed to examine ethnic disparities in the prevalence of diabetes and its association with sleep disorders among the older adults Han and ethnic minority (Bai, Ha Ni, and Dai) population in rural southwest China. METHODS: A cross-sectional survey of 5,642 was conducted among the rural southwest population aged ≥60 years, consisting of a structured interview and measurement of fasting blood glucose, height, weight, and waist circumference. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. RESULTS: The overall prevalence of diabetes and sleep disorder was 10.2% and 40.1%, respectively. Bai participants had the highest prevalence of diabetes (15.9%) and obesity (9.9%)(P < 0.01), while Ha Ni participants had the lowest prevalence of diabetes (5.1%) and obesity (3.4%)(P < 0.01). The highest prevalence of sleep disorder (48.4%) was recorded in Bai participants, while Dai participants had the lowest prevalence of sleep disorder (25.6%)(P < 0.01). In all four studied ethnicities, females had a higher prevalence of sleep disorder than males (P < 0.01), and the prevalence of sleep disorder increased with age (P < 0.01). The results of multivariate logistic regression analysis indicated older adults with sleep disorder had a risk of developing diabetes (P < 0.05). Moreover, the higher educational level, family history of diabetes, and obesity were the main risk factors for diabetes in participants (P < 0.01). CONCLUSION: There are stark ethnic disparities in the prevalence of diabetes and sleep disorders in southwest China. Future diabetes prevention and control strategies should be tailored to address ethnicity, and improving sleep quality may reduce the prevalence of diabetes.

19.
Adv Exp Med Biol ; 1445: 11-36, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38967747

RESUMEN

Although V(D)J recombination and immunoglobulin (Ig) production are traditionally recognised to occur only in B lymphocytes and plasma cells, the expression of Igs in non-lymphoid cells, which we call non B cell-derived Igs (non B Igs), has been documented by growing studies. It has been demonstrated that non B-Igs can be widely expressed in most cell types, including, but not limited to, epithelial cells, cardiomyocytes, hematopoietic stem/progenitor cells, myeloid cells, and cells from immune-privileged sites, such as neurons and spermatogenic cells. In particular, malignant tumour cells express high level of IgG. Moreover, different from B-Igs that mainly localised on the B cell membrane and in the serum and perform immune defence function mainly, non B-Igs have been found to distribute more widely and play critical roles in immune defence, maintaining cell proliferation and survival, and promoting progression. The findings of non B-Igs may provide a wealthier breakthrough point for more therapeutic strategies for a wide range of immune-related diseases.


Asunto(s)
Inmunoglobulinas , Humanos , Animales , Inmunoglobulinas/genética , Inmunoglobulinas/metabolismo , Inmunoglobulinas/inmunología , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/inmunología , Células Madre Hematopoyéticas/citología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/inmunología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/inmunología , Células Mieloides/inmunología , Células Mieloides/metabolismo
20.
Physiol Mol Biol Plants ; 30(4): 527-542, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38737319

RESUMEN

The TIFY family consists of plant-specific genes that regulates multiple plant functions, including developmental and defense responses. Here, we performed a comprehensive genomic analysis of TIFY genes in Dendrobium huoshanense. Our analysis encompassed their phylogenetic relationships, gene structures, chromosomal distributions, promoter regions, and patterns of collinearity. A total of 16 DhTIFY genes were identified, and classified into distinct clusters named JAZ, PPD, ZIM, and TIFY based on their phylogenetic relationship. These DhTIFYs exhibited an uneven distribution across 7 chromosomes. The expansion of the DhTIFY gene family appears to have been significantly influenced by whole-genome and segmental duplication events. The ratio of non-synonymous to synonymous substitutions (Ka/Ks) implies that the purifying selection has been predominant, maintaining a constrained functional diversification after duplication events. Gene structure analysis indicated that DhTIFYs exhibited significant structural variation, particularly in terms of gene organization and intron numbers. Moreover, numerous cis-acting elements related to hormone signaling, developmental processes, and stress responses were identified within the promoter regions. Subsequently, qRT-PCR experiments demonstrated that the expression of DhTIFYs is modulated in response to MeJA (Methyl jasmonate), cold, and drought treatment. Collectively, these results enhance our understanding of the functional dynamics of TIFY genes in D. huoshanense and may pinpoint potential candidates for detailed examination of the biological roles of TIFY genes. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01442-9.

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