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"Yu, Meng"
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Diplomacy of quasi-alliances in the Middle East
Quasi-alliance refers to the ideation, mechanism and behavior of policy-makers to carry out security cooperation through informal political and security arrangements. As a \"gray zone\" between alliance and neutrality, quasi-alliance is a hidden national security statecraft. Based on declassified archives and secondary sources, this book probes the theory and practice of quasi-alliances in the Middle East. Four cases are chosen to test the hypotheses of quasi-alliance, one of which is the Anglo-French-Israeli quasi-alliance during the Suez Canal War of 1956.
Book
The parent-of-origin lncRNA MISSEN regulates rice endosperm development
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.
The cereal endosperm is a major determinant of seed size and shape. Here the authors show that a lncRNA,
MISSEN
, is expressed from the maternally derived allele in rice seeds and regulates a helicase family protein to support efficient nuclear division, distribution and cellularization in the endosperm.
Journal Article
Metal-free three-dimensional perovskite ferroelectrics
The perovskite structure accommodates many different combinations of elements, making it attractive for use in a wide variety of applications. Building perovskites out of only organic compounds is appealing because these materials tend to be flexible, fracture-resistant, and potentially easier to synthesize than their inorganic counterparts. Ye et al. describe a previously unknown family of all-organic perovskites, of which they synthesized 23 different family members (see the Perspective by Li and Ji). The compounds are attractive as ferroelectrics, including one compound with properties close to the well-known inorganic ferroelectric BaTiO 3 . Science , this issue p. 151 ; see also p. 132 A family of all-organic perovskites has attractive ferroelectric properties. Inorganic perovskite ferroelectrics are widely used in nonvolatile memory elements, capacitors, and sensors because of their excellent ferroelectric and other properties. Organic ferroelectrics are desirable for their mechanical flexibility, low weight, environmentally friendly processing, and low processing temperatures. Although almost a century has passed since the first ferroelectric, Rochelle salt, was discovered, examples of highly desirable organic perovskite ferroelectrics are lacking. We found a family of metal-free organic perovskite ferroelectrics with the characteristic three-dimensional structure, among which MDABCO ( N -methyl- N' -diazabicyclo[2.2.2]octonium)–ammonium triiodide has a spontaneous polarization of 22 microcoulombs per square centimeter [close to that of barium titanate (BTO)], a high phase transition temperature of 448 kelvins (above that of BTO), and eight possible polarization directions. These attributes make it attractive for use in flexible devices, soft robotics, biomedical devices, and other applications.
Journal Article
Cannabinoid CB1 receptors in the amygdalar cholecystokinin glutamatergic afferents to nucleus accumbens modulate depressive-like behavior
Major depressive disorder is a devastating psychiatric disease that afflicts up to 17% of the world’s population. Postmortem brain analyses and imaging studies of patients with depression have implicated basal lateral amygdala (BLA) dysfunction in the pathophysiology of depression. However, the circuit and molecular mechanisms through which BLA neurons modulate depressive behavior are largely uncharacterized. Here, in mice, we identified that BLA cholecystokinin (CCK) glutamatergic neurons mediated negative reinforcement via D2 medium spiny neurons (MSNs) in the nucleus accumbens (NAc) and that chronic social defeat selectively potentiated excitatory transmission of the CCKBLA–D2NAc circuit in susceptible mice via reduction of presynaptic cannabinoid type-1 receptor (CB1R). Knockdown of CB1R in the CCKBLA–D2NAc circuit elevated synaptic activity and promoted stress susceptibility. Notably, selective inhibition of the CCKBLA–D2NAc circuit or administration of synthetic cannabinoids in the NAc was sufficient to produce antidepressant-like effects. Overall, our studies reveal the circuit and molecular mechanisms of depression.Activating cannabinoid receptors in a newly identified neural circuit ameliorates depressive-like behaviors in mice.
Journal Article
Current Mechanistic Concepts in Ischemia and Reperfusion Injury
Ischemia-reperfusion injury is associated with serious clinical manifestations, including myocardial hibernation, acute heart failure, cerebral dysfunction, gastrointestinal dysfunction, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Ischemia-reperfusion injury is a critical medical condition that poses an important therapeutic challenge for physicians. In this review article, we present recent advances focusing on the basic pathophysiology of ischemia-reperfusion injury, especially the involvement of reactive oxygen species and cell death pathways. The involvement of the NADPH oxidase system, nitric oxide synthase system, and xanthine oxidase system are also described. When the blood supply is re-established after prolonged ischemia, local inflammation and ROS production increase, leading to secondary injury. Cell damage induced by prolonged ischemia-reperfusion injury may lead to apoptosis, autophagy, necrosis, and necroptosis. We highlight the latest mechanistic insights into reperfusion-injury-induced cell death via these different processes. The interlinked signaling pathways of cell death could offer new targets for therapeutic approaches. Treatment approaches for ischemia-reperfusion injury are also reviewed. We believe that understanding the pathophysiology ischemia-reperfusion injury will enable the development of novel treatment interventions.
Journal Article
Mass production of bulk artificial nacre with excellent mechanical properties
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.
Journal Article
Detection of Novel Coronavirus by RT-PCR in Stool Specimen from Asymptomatic Child, China
We report an asymptomatic child who was positive for a coronavirus by reverse transcription PCR in a stool specimen 17 days after the last virus exposure. The child was virus positive in stool specimens for at least an additional 9 days. Respiratory tract specimens were negative by reverse transcription PCR.
Journal Article
Superior ferroelectricity and nonlinear optical response in a hybrid germanium iodide hexagonal perovskite
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
3
, their ferroelectric key properties, including large spontaneous polarization (
P
s
), low coercive field (
E
c
), and strong second harmonic generation (SHG) response, have long been great challenges, which hinder their commercial applications. Here, a quasi-one-dimensional OIHP DMAGeI
3
(DMA = Dimethylamine) is reported, with notable ferroelectric attributes at room temperature: a large
P
s
of 24.14 μC/cm
2
(on a par with BaTiO
3
), a low
E
c
below 2.2 kV/cm, and the strongest SHG intensity in OIHP family (about 12 times of KH
2
PO
4
(KDP)). Revealed by the first-principles calculations, its large
P
s
originates from the synergistic effects of the stereochemically active 4
s
2
lone pair of Ge
2+
and the ordering of organic cations, and its low kinetic energy barrier of small DMA cations results in a low
E
c
. Our work brings the comprehensive ferroelectric performances of OIHPs to a comparable level with commercial inorganic ferroelectric perovskites.
The authors report on a quasi-one-dimensional organic-inorganic hybrid perovskite, DMAGeI
3
(DMA = Dimethylamine), with notable ferroelectric attributes at room temperature including large spontaneous polarisation, low coercive field, and strong second harmonic generation response.
Journal Article
PD-L1 dimerisation induced by biphenyl derivatives mediates anti-breast cancer activity via the non-immune PD-L1-AKT-mTOR/Bcl2 pathway
Recent studies on biphenyl-containing compounds, a type of PD-1/PD-L1 blocker which binds to PD-L1 and induces dimerisation, have focussed on its immune function. Herein, 10 novel biphenyl derivatives were designed and synthesised. The results of the CCK-8 showed that compounds have different anti-tumour activities for tumour cells in the absence of T cells. Particularly, 12j-4 can significantly induce the apoptosis of MDA-MB-231 cells (IC
50
= 2.68 ± 0.27 μM). In further studies, 12j-4 has been shown to prevent the phosphorylation of AKT by binding to cytoplasmic PD-L1, which induces apoptosis in MDA-MB-231 cells through non-immune pathways. The inhibition of AKT phosphorylation restores the activity of GSK-3β, ultimately resulting in the degradation of PD-L1. Besides, in vivo study indicated that 12j-4 repressed tumour growth in nude mice. As these biphenyls exert their anti-tumour effects mainly through non-immune pathways, they are worthy of further study as PD-L1 inhibitors.
Journal Article
Noncoding RNAs in cancer therapy resistance and targeted drug development
Noncoding RNAs (ncRNAs) represent a large segment of the human transcriptome and have been shown to play important roles in cellular physiology and disease pathogenesis. Increasing evidence on the functional roles of ncRNAs in cancer progression emphasizes the potential of ncRNAs for cancer treatment. Here, we summarize the roles of ncRNAs in disease relapse and resistance to current standard chemotherapy and radiotherapy; the current research progress on ncRNAs for clinical and/or potential translational applications, including the identification of ncRNAs as therapeutic targets; therapeutic approaches for ncRNA targeting; and ncRNA delivery strategies in potential clinical translation. Several ongoing clinical trials of novel RNA-based therapeutics were also emphasized. Finally, we discussed the perspectives and obstacles to different target combinations, delivery strategies, and system designs for ncRNA application. The next approved nucleic acid drug to treat cancer patients may realistically be on the horizon.
Journal Article