The cereal endosperm is a major factor determining seed size and shape. However, the molecular mechanisms of endosperm development are not fully understood. Long noncoding RNAs (lncRNAs) function in ...various biological processes. Here we show a lncRNA, MISSEN, that plays an essential role in early endosperm development in rice (Oryza sativa). MISSEN is a parent-of-origin lncRNA expressed in endosperm, and negatively regulates endosperm development, leading to a prominent dent and bulge in the seed. Mechanistically, MISSEN functions through hijacking a helicase family protein (HeFP) to regulate tubulin function during endosperm nucleus division and endosperm cellularization, resulting in abnormal cytoskeletal polymerization. Finally, we revealed that the expression of MISSEN is inhibited by histone H3 lysine 27 trimethylation (H3K27me3) modification after pollination. Therefore, MISSEN is the first lncRNA identified as a regulator in endosperm development, highlighting the potential applications in rice breeding.
Growing evidence indicates that circulating lactoferrin (Lf) is implicated in peripheral cholesterol metabolism disorders. It has emerged that the distribution of Lf changes in astrocytes of aging ...brains and those exhibiting neurodegeneration; however, its physiological and/or pathological role remains unknown. Here, we demonstrate that astrocyte‐specific knockout of Lf (designated cKO) led to decreased body weight and cognitive abnormalities during early life in mice. Accordingly, there was a reduction in neuronal outgrowth and synaptic structure in cKO mice. Importantly, Lf deficiency in the primary astrocytes led to decreased sterol regulatory element binding protein 2 (Srebp2) activation and cholesterol production, and cholesterol content in cKO mice and/or in astrocytes was restored by exogenous Lf or a Srebp2 agonist. Moreover, neuronal dendritic complexity and total dendritic length were decreased after culture with the culture medium of the primary astrocytes derived from cKO mice and that this decrease was reversed after cholesterol supplementation. Alternatively, these alterations were associated with an activation of AMP‐activated protein kinase (AMPK) and inhibition of SREBP2 nuclear translocation. These data suggest that astrocytic Lf might directly or indirectly control in situ cholesterol synthesis, which may be implicated in neurodevelopment and several neurological diseases.
Main Points
Astrocytic lactoferrin (Lf) loss causes growth retardation and intellectual disabilities in mice.
Astrocytic Lf loss leads to a reduction in neuronal outgrowth and synaptic structure.
• Astrocytic lactoferrin controls in situ cholesterol synthesis in mice.
Rechargeable zinc-ion batteries (ZIBs) are promising for large scale energy storage and portable electronic applications due to their low cost, material abundance, high safety, acceptable energy ...density and environmental friendliness. This tutorial review presents an introduction to the fundamentals, challenges, recent advances and prospects related to ZIBs. Firstly, the intrinsic chemical properties, challenges and strategies of metallic zinc anodes are underscored. Then, the multiple types of cathode materials are classified and comparatively discussed in terms of their structural and electrochemical properties, issues and remedies. Specific attention is paid to the mechanistic understanding and structural transformation of cathode materials based on Zn ion-(de)intercalation chemistry. After that, the widely investigated electrolytes are elaborated by discussing their effect on Zn plating/stripping behaviours, reaction kinetics, electrode/electrolyte interface chemistries, and cell performances. Finally, the remaining challenges and future perspectives are outlined for the development of ZIBs.
This tutorial review presents an introduction to the fundamentals, challenges, recent advances and prospects of rechargeable zinc-ion batteries.
Topological defects, such as vortices and skyrmions, provide a wealth of splendid possibilities for new nanoscale devices because of their marvelous electronic, magnetic, and mechanical behaviors. ...Recently, great advances have been made in the study of the ferroelectric vortex in conventional perovskite oxides, such as BaTiO3 and BiFeO3. Despite extensive interest, however, no intriguing ferroelectric vortex structures have yet been found in organic–inorganic hybrid perovskites (OIHPs), which are desirable for their mechanical flexibility, ease of fabrication, and low acoustical impedance. We observed the robust vortex–antivortex topological configurations in a two-dimensional (2D) layered OIHP ferroelectric (4,4-DFPD)2PbI4 (4,4-DFPD is 4,4-difluoropiperidinium). This provides future directions for the study of perovskites and makes it a promising alternative for nanoscale ferroelectric devices in medical, micromechanical, and biomechanical applications.
Various methods have been exploited to replicate nacre features into artificial structural materials with impressive structural and mechanical similarity. However, it is still very challenging to ...produce nacre-mimetics in three-dimensional bulk form, especially for further scale-up. Herein, we demonstrate that large-sized, three-dimensional bulk artificial nacre with comprehensive mimicry of the hierarchical structures and the toughening mechanisms of natural nacre can be facilely fabricated via a bottom-up assembly process based on laminating pre-fabricated two-dimensional nacre-mimetic films. By optimizing the hierarchical architecture from molecular level to macroscopic level, the mechanical performance of the artificial nacre is superior to that of natural nacre and many engineering materials. This bottom-up strategy has no size restriction or fundamental barrier for further scale-up, and can be easily extended to other material systems, opening an avenue for mass production of high-performance bulk nacre-mimetic structural materials in an efficient and cost-effective way for practical applications.Artificial materials that replicate the mechanical properties of nacre represent important structural materials, but are difficult to produce in bulk. Here, the authors exploit the bottom-up assembly of 2D nacre-mimetic films to fabricate 3D bulk artificial nacre with an optimized architecture and excellent mechanical properties.
The high mortality rate of ovarian cancer is connected with the development of acquired resistance to multiple cancer drugs, especially cisplatin. Activation of cytoprotective autophagy has been ...implicated as a contributing mechanism for acquired cisplatin resistance in ovarian cancer cells. Hexokinase 2 (HK2) phosphorylates glucose to generate glucose-6-phosphate, the rate-limiting step in glycolysis. Higher HK2 expression has been associated with chemoresistance in ovarian cancer. However, whether HK2 functionally contributes to cisplatin resistance in ovarian cancer is unclear. In this study, we investigated the role of HK2 in regulating ovarian cancer cisplatin resistance. Increased HK2 levels were detected in drug-resistant human ovarian cancer cells and tissues. Cisplatin downregulated HK2 in cisplatin-sensitive but not in resistant ovarian cancer cells. HK2 knockdown sensitized resistant ovarian cancer cells to cisplatin-induced cell death and apoptosis. Conversely, HK2 overexpression in cisplatin-sensitive cells induced cisplatin resistance. Mechanistically, cisplatin increased ERK1/2 phosphorylation as well as autophagic activity. Blocking autophagy with the autophagy inhibitor 3-MA sensitized resistant ovarian cancer cells to cisplatin. HK2 overexpression enhanced cisplatin-induced ERK1/2 phosphorylation and autophagy while HK2 knockdown showed the opposite effects. Blocking the MEK/ERK pathway using the MEK inhibitor U0126 prevented cisplatin-induced autophagy enhanced by HK2 overexpression. Furthermore, HK2 knockdown sensitized resistance ovarian tumor xenografts to cisplatin in vivo. In conclusion, our data supported that HK2 promotes cisplatin resistance in ovarian cancer by enhancing drug-induced, ERK-mediated autophagy. Therefore, targeting HK2 may be a new therapeutic strategy to combat chemoresistance in ovarian cancer.
The long noncoding RNA (lncRNA) OTUD6B antisense RNA 1 (OTUD6B-AS1) is oriented in an antisense direction to the protein-coding gene OTUD6B on the opposite DNA strand. TCGA database data show that ...the expression of the lncRNA OTUD6B-AS1 is downregulated and that OTUD6B-AS1 acts as an antioncogene in a variety of tumors. However, the expression and biological functions of the lncRNA OTUD6B-AS1 are still unknown in tumors, including clear cell renal cell carcinoma (ccRCC).
The expression level of OTUD6B-AS1 was measured in 75 paired human ccRCC tissue and corresponding adjacent normal renal tissue samples. The correlations between the OTUD6B-AS1 expression level and clinicopathological features were evaluated using the chi-square test. The effects of OTUD6B-AS1 on ccRCC cells were determined via MTT assay, clone formation assay, transwell assay, and flow cytometry. Furthermore, the impact of OTUD6B-AS1 overexpression on the activation of the Wnt/β-catenin signaling pathway was investigated. Finally, ACHN cells with OTUD6B-AS1 overexpression were subcutaneously injected into nude mice to evaluate the influence of OTUD6B-AS1 on tumor growth in vivo.
In this study, we found that the expression of the lncRNA OTUD6B-AS1 was downregulated in ccRCC tissue samples and that patients with low OTUD6B-AS1 expression had shorter overall survival than patients with high OTUD6B-AS1 expression, which showed that the different expression level of OTUD6B-AS1 indirectly correlated with survival of patients. Lentivirus-mediated OTUD6B-AS1 overexpression significantly decreased the proliferation of ccRCC cells and promoted the apoptosis of the cells. Furthermore, OTUD6B-AS1 overexpression partly inhibited cell migration and invasion. The overexpression of OTUD6B-AS1 decreased the activity of the Wnt/β-catenin pathway and suppressed the expression of epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Snail) in ccRCC cells. In addition, compared with the parental ACHN cells, OTUD6B-AS1-overexpressing ACHN cells injected into nude mice exhibited decreased tumor growth in vivo.
Taken together, our findings present a road map for targeting the newly identified lncRNA OTUD6B-AS1 to suppress ccRCC progression in cell lines, and these results elucidate a novel potential therapeutic target for ccRCC treatment.
Semiconducting ferroelectricity is realized in hybrid perovskite‐type compounds (cyclohexylammonium)2PbBr4−4xI4x (x = 0–1). By adjusting the composition x, the bandgap is successfully tuned from ...previously reported 3.65 eV to as low as 2.74 eV, and the excellent ferroelectricity was kept intact. This finding may contribute to improving the photoelectronic and/or photovoltaic performance of hybrid perovskite‐type compounds.
Abundant chemical diversity and structural tunability make organic-inorganic hybrid perovskites (OIHPs) a rich ore for ferroelectrics. However, compared with their inorganic counterparts such as ...BaTiO
, their ferroelectric key properties, including large spontaneous polarization (P
), low coercive field (E
), and strong second harmonic generation (SHG) response, have long been great challenges, which hinder their commercial applications. Here, a quasi-one-dimensional OIHP DMAGeI
(DMA = Dimethylamine) is reported, with notable ferroelectric attributes at room temperature: a large P
of 24.14 μC/cm
(on a par with BaTiO
), a low E
below 2.2 kV/cm, and the strongest SHG intensity in OIHP family (about 12 times of KH
PO
(KDP)). Revealed by the first-principles calculations, its large P
originates from the synergistic effects of the stereochemically active 4s
lone pair of Ge
and the ordering of organic cations, and its low kinetic energy barrier of small DMA cations results in a low E
. Our work brings the comprehensive ferroelectric performances of OIHPs to a comparable level with commercial inorganic ferroelectric perovskites.
Background
Assessing the glymphatic function using diffusion tensor image analysis along the perivascular space (DTI‐ALPS) may be helpful for mild traumatic brain injury (mTBI) management.
Purpose
To ...assess glymphatic function using DTI‐ALPS and its associations with global white matter damage and cognitive impairment in mTBI.
Study Type
Prospective.
Population
Thirty‐four controls (44.1% female, mean age 49.2 years) and 58 mTBI subjects (43.1% female, mean age 48.7 years), including uncomplicated mTBI (N = 32) and complicated mTBI (N = 26).
Field Strength/Sequence
3‐T, single‐shot echo‐planar imaging sequence.
Assessment
Magnetic resonance imaging (MRI) was done within 1 month since injury. DTI‐ALPS was performed to assess glymphatic function, and peak width of skeletonized mean diffusivity (PSMD) was used to assess global white matter damage. Cognitive tests included Auditory Verbal Learning Test and Digit Span Test (forward and backward).
Statistical Tests
Neuroimaging findings comparisons were done between mTBI and control groups. Partial correlation and multivariable linear regression assessed the associations between DTI‐ALPS, PSMD, and cognitive impairment. Mediation effects of PSMD on the relationship between DTI‐ALPS and cognitive impairment were explored. P‐value <0.05 was considered statistically significant, except for cognitive correlational analyses with a Bonferroni‐corrected P‐value set at 0.05/3 ≈ 0.017.
Results
mTBI showed lower DTI‐ALPS and higher PSMD, especially in complicated mTBI. DTI‐ALPS was significantly correlated with verbal memory (r = 0.566), attention abilities (r = 0.792), executive function (r = 0.618), and PSMD (r = −0.533). DTI‐ALPS was associated with verbal memory (β = 8.77, 95% confidence interval CI 5.00, 12.54), attention abilities (β = 5.67, 95% CI 4.56, 6.97), executive function (β = 2.34, 95% CI 1.49, 3.20), and PSMD (β = −0.79, 95% CI −1.15, −0.43). PSMD mediated 46.29%, 20.46%, and 24.36% of the effects for the relationship between DTI‐ALPS and verbal memory, attention abilities, and executive function.
Data Conclusion
Glymphatic function may be impaired in mTBI reflected by DTI‐ALPS. Glymphatic dysfunction may cause cognitive impairment related to global white matter damage after mTBI.
Level of Evidence
2
Technical Efficacy
Stage 2
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