RESUMEN
Seed vigor in crops is important in terms of improving grain quality and germplasm conservation; however, little is known about its regulatory mechanisms through the encoded proteome and gene network. Comparative analyses of transcriptome (RNA sequencing [RNA-seq]) and broadly targeted metabolic profiling of two subspecific rice cultivars with distinct seed vigor during accelerated aging revealed various biological pathways and metabolic processes as key influences explaining trait differences. RNA-seq coexpression regulatory network analyses identified several transcription factors, including bZIP23 and bZIP42, that act as nodes in the gene network. Importantly, transgenic seeds of overexpression of bZIP23 enhanced seed vigor, whereas its gene knockout reduced seed vigor, suggesting that the protein it encodes functions as a positive regulator. Similarly, overexpression and knockout of PER1A that encodes a key player in the detoxification pathway enhanced and decreased seed vigor, respectively. We further demonstrated a direct interaction of the PER1A promoter with bZIP23 in seeds, which activates the expression of PER1A, and the genetic evidence suggested that bZIP23 most likely functions in a common pathway with and acts upstream of PER1A to modulate seed vigor. In addition, the control of seed vigor by the bZIP23-PER1A module was connected with that of the abscisic acid signaling pathway. Collectively, we revealed the genetic architecture of variation in seed vigor and uncovered the bZIP23-PER1A-mediated detoxification pathway that enhances the trait in rice.
Asunto(s)
Genoma de Planta , Vigor Híbrido , Metaboloma , Oryza/embriología , Peroxirredoxinas/metabolismo , Proteínas de Plantas/metabolismo , Semillas/fisiología , Ácido Abscísico/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Oryza/genética , Oryza/metabolismo , Semillas/metabolismo , Transducción de SeñalRESUMEN
Highly flexible and superelastic aerogels at large deformation have become urgent mechanical demands in practical uses, but both properties are usually exclusive. Here a trans-scale porosity design is proposed in graphene nanofibrous aerogels (GNFAs) to break the trade-off between high flexibility and superelasticity. The resulting GNFAs can completely recover after 1000 fatigue cycles at 60% folding strain, and notably maintain excellent structural integrity after 10000 cycles at 90% compressive strain, outperforming most of the reported aerogels. The mechanical robustness is demonstrated to be derived from the trans-scale porous structure, which is composed of hyperbolic micropores and porous nanofibers to enable the large elastic deformation capability. It is further revealed that flexible and superelastic GNFAs exhibit high sensitivity and ultrastability as an electrical sensors to detect tension and flexion deformation. As proof, The GNFA sensor is implemented onto a human finger and achieves the intelligent recognition of sign language with high accuracy by multi-layer artificial neural network. This study proposes a highly flexible and elastic graphene aerogel for wearable human-machine interfaces in sensor technology.
RESUMEN
Ecological divergence due to habitat difference plays a prominent role in the formation of new species, but the genetic architecture during ecological speciation and the mechanism underlying phenotypic divergence remain less understood. Two wild ancestors of rice (Oryza rufipogon and Oryza nivara) are a progenitor-derivative species pair with ecological divergence and provide a unique system for studying ecological adaptation/speciation. Here, we constructed a high-resolution linkage map and conducted a quantitative trait locus (QTL) analysis of 19 phenotypic traits using an F2 population generated from a cross between the two Oryza species. We identified 113 QTLs associated with interspecific divergence of 16 quantitative traits, with effect sizes ranging from 1.61% to 34.1% in terms of the percentage of variation explained (PVE). The distribution of effect sizes of QTLs followed a negative exponential, suggesting that a few genes of large effect and many genes of small effect were responsible for the phenotypic divergence. We observed 18 clusters of QTLs (QTL hotspots) on 11 chromosomes, significantly more than that expected by chance, demonstrating the importance of coinheritance of loci/genes in ecological adaptation/speciation. Analysis of effect direction and v-test statistics revealed that interspecific differentiation of most traits was driven by divergent natural selection, supporting the argument that ecological adaptation/speciation would proceed rapidly under coordinated selection on multiple traits. Our findings provide new insights into the understanding of genetic architecture of ecological adaptation and speciation in plants and help effective manipulation of specific genes or gene cluster in rice breeding.
Asunto(s)
Oryza , Oryza/genética , Fitomejoramiento , Mapeo Cromosómico , Fenotipo , Sitios de Carácter Cuantitativo/genéticaRESUMEN
For grain crops such as rice (Oryza sativa), grain size substantially affects yield. The histone acetyltransferase GRAIN WEIGHT 6a (GW6a) determines grain size and yield in rice. However, the gene regulatory network underlying GW6a-mediated regulation of grain size has remained elusive. In this study, we show that GW6a interacts with HOMOLOG OF DA1 ON RICE CHROMOSOME 3 (HDR3), a ubiquitin-interacting motif-containing ubiquitin receptor. Transgenic rice plants overexpressing HDR3 produced larger grains, whereas HDR3 knockout lines produce smaller grains compared to the control. Cytological data suggest that HDR3 modulates grain size in a similar manner to GW6a, by altering cell proliferation in spikelet hulls. Mechanistically, HDR3 physically interacts with and stabilizes GW6a in an ubiquitin-dependent manner, delaying protein degradation by the 26S proteasome. The delay in GW6a degradation results in dramatic enhancement of the local acetylation of H3 and H4 histones. Furthermore, RNA sequencing analysis and chromatin immunoprecipitation assays reveal that HDR3 and GW6a bind to the promoters of and modulate a common set of downstream genes. In addition, genetic analysis demonstrates that HDR3 functions in the same genetic pathway as GW6a to regulate the grain size. Therefore, we identified the grain size regulatory module HDR3-GW6a as a potential target for crop yield improvement.
Asunto(s)
Grano Comestible/crecimiento & desarrollo , Oryza/genética , Proteínas de Plantas/genética , Grano Comestible/genética , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/metabolismo , Oryza/enzimología , Oryza/crecimiento & desarrollo , Proteínas de Plantas/metabolismoRESUMEN
A novel conversion of 1,5-diynols into sulfonylated benzo[b]fluorenes is reported by a TFA-promoted cascade cyclization with sodium sulfinates under mild conditions. This strategy provides an efficient and practical approach for accessing various sulfonated benzo[b]fluorenes in moderate to excellent yields under metal-free conditions. On the basis of the control experimental results and density functional theory calculations, a possible cascade transformation mechanism consisting of the dehydration of propargylic alcohols, sulfonylation, allenylation, and Schmittel-type cyclization is proposed. It is worth noting that TFA played an important role in this cascade cyclization, which promoted C-SO2R bond cleavage in a propargylic sulfone intermediate to form allenyl sulfones, followed by Schmittel-type cyclization to give the target product.
RESUMEN
Castration-resistant prostate cancer (CRPC), especially metastatic castration-resistant prostate cancer (mCRPC) is one of the most prevalent malignancies and main cause of cancer-related death among men in the world. In addition, it is very difficult for clinical treatment because of the natural or acquired drug resistance of CRPC. Mechanisms of drug resistance are extremely complicated and how to overcome it remains an urgent clinical problem to be solved. Thus, a comprehensive and thorough understanding for mechanisms of drug resistance in mCRPC is indispensable to develop novel and better therapeutic strategies. In this review, we aim to review new insight of the treatment of mCRPC and elucidate mechanisms governing resistance to new drugs: taxanes, androgen receptor signaling inhibitors (ARSIs) and poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Most importantly, in order to improve efficacy of these drugs, strategies of overcoming drug resistance are also discussed based on their mechanisms respectively.
Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Resistencia a Antineoplásicos , Taxoides , Transducción de SeñalRESUMEN
Choroidal Neovascularization (CNV) is capable of inciting recurrent hemorrhage in the macular region, severely impairing patients' visual acuity. During the onset of CNV, infiltrating M2 macrophages play a crucial role in promoting angiogenesis. To control this disease, our study utilizes the RNA interference (RNAi)-based gene therapy to reprogram M2 macrophages to the M1 phenotype in CNV lesions. We synthesize the mannose-modified siRNA-loaded liposome specifically targeting M2 macrophages to inhibit the inhibitory kappa B kinase ß (IKKß) gene involved in the polarization of macrophages, consequently modulating macrophage polarization state. In vitro and in vivo, the mannose-modified IKKß siRNA-loaded liposome (siIKKß-ML) has been proven to effectively target M2 macrophages to repolarize them to M1 phenotype, and inhibit the progression of CNV. Collectively, our findings elucidate that siIKKß-ML holds the potential to control CNV by reprogramming the macrophage phenotype, indicating a promising therapeutic avenue for CNV management.
Asunto(s)
Neovascularización Coroidal , Quinasa I-kappa B , Humanos , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacología , Quinasa I-kappa B/genética , Quinasa I-kappa B/farmacología , Liposomas/farmacología , Manosa , Neovascularización Coroidal/genética , Macrófagos , Terapia GenéticaRESUMEN
PURPOSE: To evaluate the changes in macular structures following subthreshold micropulse laser (SHML) treatment for chronic central serous chorioretinopathy (cCSC). METHODS: Data of 33 eyes from 31 cCSC patients treated with SHML and followed up for at least 6 months has been included in this retrospective study. Main outcome measurements include resolution of subretinal fluid (SRF) and pigment epithelial detachment (PED), the recovery of ellipsoid zone (EZ) continuity, and the foveal outer nuclear layer (ONL) thickness along with its ratio. RESULTS: Mean observation period is 7.355 months (ranging from 6 to 24 months) and mean number of treatments administered is 1.839 (ranging from 1 to 5). 6 months after SHML treatment, there is a significant decrease in the area of SRF and PED (P < 0.001, P = 0.010, respectively). Additionally, the frequency of continuous EZ and the foveal ONL thickness reveal a significant increase (P<0.001, P = 0.005, respectively). The ratio of foveal ONL thickness is significantly higher after laser treatment, particularly in patients with a disease duration of ≤12 months (p = 0.022, P=0.036, respectively). CONCLUSION: SHML treatment proves to be effective in cCSC eyes, leading to satisfactory recovery of macular structures, especially the photoreceptor layer.
Asunto(s)
Coriorretinopatía Serosa Central , Terapia por Láser , Humanos , Coriorretinopatía Serosa Central/radioterapia , Coriorretinopatía Serosa Central/cirugía , Estudios Retrospectivos , Angiografía con Fluoresceína , Agudeza Visual , Retina , Tomografía de Coherencia Óptica , Enfermedad CrónicaRESUMEN
Supramolecular host-guest ferroelectrics based on solution processing are highly desirable because they are generally created with intrinsic piezoelectricity/ferroelectricity and do not need further poling. Poly(vinylidene fluoride) (PVDF) in the electric-active beta phase after stretching/annealing still shows no piezoelectric response unless poled. Although many supramolecular host-guest ferroelectrics have been discovered, their piezoelectricity is relatively small. Based on H/F substitution, we reported a supramolecular host-guest compound [(CF3-C6H4-NH3)(18-crown-6)][TFSA] (CF3-C6H4-NH3 = 4-trifluoromethylanilinium, TFSA = bis(trifluoromethanesulfonyl)ammonium) with a remarkable piezoelectric response of 42 pC/N under no poling condition. The introduction of F atoms increases phase transition temperature, polar axes, second harmonic generation (SHG) intensity, and piezoelectric coefficient d33. To our knowledge, such a large piezoelectric performance of [(CF3-C6H4-NH3)(18-crown-6)][TFSA] makes its d33, piezoelectric voltage coefficient g33, and mechanical quality factor Qm the highest among the reported supramolecular host-guest ferroelectric compounds and even larger than the values of PVDF. This work provides inspiration for optimizing piezoelectricity on molecular materials.
RESUMEN
Fullerenes offer versatile functionalities and are promising materials for a widespread range of applications from biomedicine and energy to electronics. Great efforts have been made to manipulate the symmetries of fullerene and its derivatives for studying material properties and novel effects, such as ferroelectricity with polar symmetry; however, no documentary report has been obtained to realize their ferroelectricity. Here, for the first time, we demonstrated clear ferroelectricity in a fullerene adduct formed by C60 and S8. More is different: the combination of the most symmetric molecule C60 with the highest Ih symmetry and molecule S8 with high D4d symmetry resulted in the polar C60S8 adduct with a low crystallographic symmetry of the C2v (mm2) point group at room temperature. The presented C60S8 undergoes polar-to-polar ferroelectric phase transition with the mm2Fm notation, whose ferroelectricity was confirmed by a ferroelectric hysteresis loop and ferroelectric domain switching. This finding opens up a new functionality for fullerenes and sheds light on the exploration of more ferroelectric fullerenes.
RESUMEN
Piezoelectric materials that enable electromechanical conversion have great application value in actuators, transducers, sensors, and energy harvesters. Large piezoelectric (d33) and piezoelectric voltage (g33) coefficients are highly desired and critical to their practical applications. However, obtaining a material with simultaneously large d33 and g33 has long been a huge challenge. Here, we reported a hybrid perovskite ferroelectric [Me3NCH2Cl]CdBrCl2 to mitigate and roughly address this issue by heavy halogen substitution. The introduction of a large-size halide element softens the metal-halide bonds and reduces the polarization switching barrier, resulting in excellent piezoelectric response with a large d33 (â¼440 pC/N), which realizes a significant optimization compared with that of previously reported [Me3NCH2Cl]CdCl3 (You et al. Science2017, 357, 306-309). More strikingly, [Me3NCH2Cl]CdBrCl2 simultaneously shows a giant g33 of 6215 × 10-3 V m/N, far exceeding those of polymers and conventional piezoelectric ceramics. Combined with simple solution preparation, easy processing of thin films, and a high Curie temperature of 373 K, these attributes make [Me3NCH2Cl]CdBrCl2 promising for high-performance piezoelectric sensors in flexible, wearable, and biomechanical devices.
RESUMEN
Infection with schistosome results in immunological changes that might influence the skeletal system by inducing immunological states affecting bone metabolism. We investigated the relationships between chronic schistosome infection and bone metabolism by using a mouse model of chronic schistosomiasis, affecting millions of humans worldwide. Results showed that schistosome infection resulted in aberrant osteoclast-mediated bone loss, which was accompanied with an increased level of receptor activator of nuclear factor-κB (NF-κB) Ligand (RANKL) and decreased level of osteoprotegerin (OPG). The blockade of RANKL by the anti-RANKL antibody could prevent bone loss in the context of schistosome infection. Meanwhile, both B cells and CD4+ T cells, particularly follicular helper T (Tfh) cell subset, were the important cellular sources of RANKL during schistosome infection. These results highlight the risk of bone loss in schistosome-infected patients and the potential benefit of coupling bone therapy with anti-schistosome treatment.
Asunto(s)
Resorción Ósea/metabolismo , Resorción Ósea/patología , Ligando RANK/metabolismo , Esquistosomiasis Japónica/complicaciones , Animales , Linfocitos B/metabolismo , Ratones , Schistosoma japonicum , Células T Auxiliares Foliculares/metabolismoRESUMEN
BACKGROUND: The triglyceride-glucose (TyG) index was significantly associated with insulin resistance (IR). Several studies have validated the effect of TyG index on cerebrovascular disease. However, the value of TyG index in patients with severe stroke requiring ICU admission remains unclear. The aim of this study was to investigate the association between the TyG index and clinical prognosis of critically ill patients with ischemic stroke (IS). METHODS: This study identified patients with severe IS requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-IV) database, and divided them into quartiles based on TyG index level. The outcomes included in-hospital mortality and ICU mortality. The association between the TyG index and clinical outcomes in critically ill patients with IS was elucidated using Cox proportional hazards regression analysis and restricted cubic splines. RESULTS: A total of 733 patients (55.8% male) were enrolled. The hospital mortality and intensive care unit (ICU) mortality reached 19.0% and 14.9%, respectively. Multivariate Cox proportional hazards analysis showed that the elevated TyG index was significantly related to all-cause death. After confounders adjusting, patients with an elevated TyG index had a significant association with hospital mortality (adjusted hazard ratio, 1.371; 95% confidence interval, 1.053-1.784; P = 0.013) and ICU mortality (adjusted hazard ratio, 1.653; 95% confidence interval, 1.244-2.197; P = 0.001). Restricted cubic splines revealed that a progressively increasing risk of all-cause mortality was related to an elevated TyG index. CONCLUSION: The TyG index has a significant association with hospital and ICU all-cause death in critically ill patients with IS. This finding demonstrates that the TyG index might be useful in identifying patients with IS at high risk of all-cause death.
Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Enfermedad Crítica , Mortalidad Hospitalaria , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , GlucosaRESUMEN
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielomonocítica Crónica , Humanos , Pronóstico , Trasplante Homólogo/efectos adversos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
An efficient and practical cascade cyclization of 1,5-diynols with (RO)2P(O)SH as the acid promoter and nucleophile under mild conditions was developed. A variety of highly substituted benzo[b]fluorenyl-containing S-alkyl phosphorothioates were successfully constructed in moderate to excellent yields. Furthermore, this protocol exhibited good functional group tolerance, a broad substrate scope, and potential practical applications, with water as the only byproduct. The reaction proceeded with allenyl thiophosphate as a key intermediate, followed by a Schmittel-type cyclization process to produce the target product.
RESUMEN
We present a highly efficient and practical method for synthesizing gem-dibromo 1,3-oxazines through 6-endo-dig cyclization of propargylic amides, using N-bromosuccinimide (NBS) as an electrophilic source. The metal-free reaction can be conducted under mild conditions with good functional group compatibility, delivering excellent yields of the desired products. Mechanistic studies suggest that the reaction proceeds via a double electrophilic attack by NBS on the propargylic amide substrate.
RESUMEN
Selective oxygenation of C(sp3)-H bonds adjacent to nitrogen atoms is a highly attractive strategy for synthesizing various formamide derivatives while preserving the substrate skeletons. Herein, an environmentally benign electrochemically enabled decyanative C(sp3)-H oxygenation of N-cyanomethylamines using H2O as a carbonyl oxygen atom source is described, leading to the synthesis of a large class of formamides in good to excellent yields with a broad substrate scope under metal- and oxidant-free conditions. This electrochemical technology highlights the facile incorporation of N-formyl into some important bioactive molecules.
RESUMEN
This study aimed to assess the prevalence of depression and anxiety in CHD patients and to explore the association between established cardiovascular risk factors and depression as well as anxiety. 2,216 patients with CHD confirmed by angiography were included in this cross-sectional study. Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Scale (GAD-7) were used to assess depression and anxiety symptoms. The frequencies of individual depressive and anxiety symptoms grouped by age and gender were analyzed. Binary logistic regression analyses were used to identify cardiovascular risk factors associated with anxiety and depression. The overall prevalence rates of depression and anxiety in CHD patients were 8.2% and 5.4%, respectively. There were significant differences in the frequency of depression and anxiety symptoms between genders. However, age differences among individual depression and anxiety symptoms were insignificant. In multivariable analysis, female gender, smoking, and hyperlipidemia were associated with a more frequent depression occurrence, and female gender was associated with more frequent anxiety. Depression and anxiety were not associated with other cardiovascular risk factors. These findings suggest that a substantial proportion of CHD patients experienced anxiety and depression symptoms. Differences in depressive or anxiety symptoms among the distribution of individual symptoms need more attention. Depression was significantly associated with female gender, smoking, and hyperlipidemia. No anxiety symptom associations with cardiovascular risk factors were demonstrated to be significant except for the female. More research is needed to unravel the mechanisms of depression, anxiety, and cardiovascular disease.
Asunto(s)
Enfermedades Cardiovasculares , Humanos , Femenino , Masculino , Prevalencia , Depresión/epidemiología , Estudios Transversales , Factores de Riesgo , Factores de Riesgo de Enfermedad CardiacaRESUMEN
Thermally triggered spatial symmetry breaking in traditional ferroelectrics has been extensively studied for manipulation of the ferroelectricity. However, photoinduced molecular orbital breaking, which is promising for optical control of ferroelectric polarization, has been rarely explored. Herein, for the first time, we synthesized a homochiral fulgide organic ferroelectric crystal (E)-(R)-3-methyl-3-cyclohexylidene-4-(diphenylmethylene)dihydro-2,5-furandione (1), which exhibits both ferroelectricity and photoisomerization. Significantly, 1 shows a photoinduced reversible change in its molecular orbitals from the 3â π molecular orbitals in the open-ring isomer to 2â π and 1â σ molecular orbitals in the closed-ring isomer, which enables reversible ferroelectric domain switching by optical manipulation. To our knowledge, this is the first report revealing the manipulation of ferroelectric polarization in homochiral ferroelectric crystal by photoinduced breaking of molecular orbitals. This finding sheds light on the exploration of molecular orbital breaking in ferroelectrics for optical manipulation of ferroelectricity.
RESUMEN
Chirality exists everywhere from natural amino acids to particle physics. The introduction of point chirality has recently been shown to be an efficient strategy for the construction of molecular ferroelectrics. In contrast to point chirality, however, axial chirality is rarely used to design ferroelectrics so far. Here, based on optically active 1,1'-bi-2-naphthol (BINOL), which has been applied extensively as a versatile chiral reagent in asymmetric catalysis, chiral recognition, and optics, we successfully design a pair of axial-chiral BINOL multiferroics, (R)-BINOL-DIPASi and (S)-BINOL-DIPASi. They experience a 2F1-type full ferroelectric/ferroelastic phase transition at a high temperature of 362 and 363 K, respectively. Piezoelectric force microscopy and polarization-voltage hysteresis loops demonstrate their ferroelectric domains and domain switching, and polarized light microscopy visualizes the evolution of stripe-shaped ferroelastic domains. The axial-chiral BINOL building block promotes the generation of the polar structure and ferroelectricity, and the organosilicon component increases the rotational energy barrier and thus the phase transition temperature. This work presents the first axial-chiral high-temperature multiferroic crystals, offering an efficient path for designing molecular multiferroics through the introduction of axial chirality.