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"Yu-Jun, Liu"
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Two-dimensional non-Hermitian skin effect in an ultracold Fermi gas
The concept of non-Hermiticity has expanded the understanding of band topology, leading to the emergence of counter-intuitive phenomena. An example is the non-Hermitian skin effect (NHSE)
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,
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,
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,
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–
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, which involves the concentration of eigenstates at the boundary. However, despite the potential insights that can be gained from high-dimensional non-Hermitian quantum systems in areas such as curved space
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,
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–
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, high-order topological phases
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,
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and black holes
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,
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, the realization of this effect in high dimensions remains unexplored. Here we create a two-dimensional (2D) non-Hermitian topological band for ultracold fermions in spin–orbit-coupled optical lattices with tunable dissipation, which exhibits the NHSE. We first experimentally demonstrate pronounced nonzero spectral winding numbers in the complex energy plane with nonzero dissipation, which establishes the existence of 2D skin effect. Furthermore, we observe the real-space dynamical signature of NHSE in real space by monitoring the centre of mass motion of atoms. Finally, we also demonstrate that a pair of exceptional points are created in the momentum space, connected by an open-ended bulk Fermi arc, in contrast to closed loops found in Hermitian systems. The associated exceptional points emerge and shift with increasing dissipation, leading to the formation of the Fermi arc. Our work sets the stage for further investigation into simulating non-Hermitian physics in high dimensions and paves the way for understanding the interplay of quantum statistics with NHSE.
A two-dimensional non-Hermitian topological band is created in an ultracold system of fermions, which exhibits the non-Hermitian skin effect.
Journal Article
PEITC triggers multiple forms of cell death by GSH-iron-ROS regulation in K7M2 murine osteosarcoma cells
Phenethyl isothiocyanate (PEITC) is an isothiocyanate that largely exists in cruciferous vegetables and exhibits chemopreventive and chemotherapeutic potential against various cancers. However, it is little known about the molecular mechanisms of its antitumor action against osteosarcoma, which is the second highest cause of cancer-related death in children and adolescents. In this study, we investigated the effects of PEITC on K7M2 murine osteosarcoma both in vitro and in vivo. We found that treatment with PEITC dose-dependently inhibited the viability of K7M2 murine osteosarcoma cells with an IC
50
value of 33.49 μM at 24 h. PEITC (1, 15, 30 μM) dose-dependently inhibited the cell proliferation, caused G
2
/M cell cycle arrest, depleted glutathione (GSH), generated reactive oxygen species (ROS), altered iron metabolism, and triggered multiple forms of cell death, namely ferroptosis, apoptosis, and autophagy in K7M2 cells. We further revealed that PEITC treatment activated MAPK signaling pathway, and ROS generation was a major cause of PEITC-induced cell death. In a syngeneic orthotopic osteosarcoma mouse model, administration of PEITC (30, 60 mg/kg every day, ig, for 24 days) significantly inhibited the tumor growth, but higher dose of PEITC (90 mg/kg every day) compromised its anti-osteosarcoma effect. Histological examination showed that multiple cell death processes were initiated, iron metabolism was altered and MAPK signaling pathway was activated in the tumor tissues. In conclusion, we demonstrate that PEITC induces ferroptosis, autophagy, and apoptosis in K7M2 osteosarcoma cells by activating the ROS-related MAPK signaling pathway. PEITC has promising anti-osteosarcoma activity. This study sheds light on the redox signaling-based chemotherapeutics for cancers.
Journal Article
Complementarity fusion of boron-oxygen and carbazole blocks enables narrowband blue OLEDs with high performance
The development of ultra-high-definition organic light-emitting diodes (OLEDs) displays requires efficient and narrowband blue emission. Nevertheless, binary host-guest doped narrowband blue OLEDs still face significant challenges in simultaneously realizing high efficiency and negligible roll-off. Herein, a molecular construction strategy through the synergistic interplay between π-conjugation extension and functional complementarity fusion is proposed by incorporating a rigid boron-oxygen (BO) framework with carbazole building blocks. The constructed compounds exhibit increased triplet exciton recycling capability, high excited-state energy levels, and improved charge transporting features, showcasing significant potential as host matrices for blue devices. The sensitizer-free OLEDs achieve the narrowband blue emission with a CIEy value lower than 0.15, a maximum external quantum efficiency of 41.2%, and the suppressed efficiency roll-off at high luminance due to efficient energy transfer to blue guest emitters and elevated horizontal dipole orientation. This work strategically demonstrates a balance between high efficiency and reduced efficiency roll-off in binary narrowband blue OLEDs, representing a substantial advancement in blue electroluminescent technology.
The realization of high efficiency and negligible roll-off simultaneously for blue organic light-emitting diodes remains challenging. Here, the authors incorporate carbazole building blocks into rigid boron oxygen framework and achieve a maximum efficiency of 41.2% for sensitizer-free devices.
Journal Article
Morphological transformation of elongated MnS inclusions in non-quenched and tempered steel during isothermal heating
Elongated MnS inclusions in rolled non-quenched and tempered steel tend to cause the mechanical anisotropy of steel, deteriorate the mechanical properties and degrade the quality and service life of the steel products. To reveal the mechanisms of morphological transformation of strip-shaped MnS inclusions during isothermal heating, the effects of heat treatment time and temperature on the morphology, number density and size distribution of elongated MnS inclusions were systematically studied and discussed. A diffusion couple experiment was also conducted to clarify the diffusion mode of MnS inclusions. The experimental results showed that with the increase in isothermal heating time (from 0 to 10 h at 1473 K) and temperature (from 1173 to 1573 K for 3.0 h), the number density and average aspect ratio of MnS inclusions generally showed an increase and decrease trend, respectively, while the area fraction remained stable and only slightly fluctuated around 0.4%. In the diffusion couple, after the isothermal heating at 1473 K for 3.0 h, the elements Mn and S in the steel near the steel–MnS interface were very stable without any concentration gradient. The morphology change sequence of the elongated MnS inclusions in the rolled non-quenched and tempered steel during the isothermal heating was strip → cylinderization → spindle → spheroidization. Relationship between the diameter of MnS inclusion and the spacing between two MnS inclusions after splitting, and the fitting goodness of different
n
values under different experimental time and temperature confirmed that the driving force for the transformation of MnS inclusions during the isothermal heating was surface diffusion, instead of volume diffusion.
Journal Article
Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing
Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.
Journal Article
Chronic Administration of 13-cis-retinoic Acid Induces Depression-Like Behavior by Altering the Activity of Dentate Granule Cells
Depression is a common but serious mental disorder and can be caused by the side effects of medications. Evidence from abundant clinical case reports and experimental animal models has revealed the association between the classic anti-acne drug 13-cis-retinoic acid (13-cis-RA) and depressive symptoms. However, direct experimental evidence of this mechanism and information on appropriate therapeutic rescue strategies are lacking. Herein, our data revealed that chronic administration of 13-cis-RA to adolescent mice induced depression-like behavior but not anxiety-like behavior. We next demonstrated that chronic 13-cis-RA application increased neural activity in the dentate gyrus (DG) using c-Fos immunostaining, which may be critically involved in some aspects of depression-like behavior. Therefore, we assessed electrophysiological functions by obtaining whole-cell patch-clamp recordings of dentate granule cells (DGCs), which revealed that chronic 13-cis-RA treatment shifted the excitatory-inhibitory balance toward excitation and increased intrinsic excitability. Furthermore, a pharmacogenetic approach was performed to repeatedly silence DGCs, and this manipulation could rescue depression-like behavior in chronically 13-cis-RA-treated mice, suggesting DGCs as a potential cellular target for the direct alleviation of 13-cis-RA-induced depression.
Journal Article
A Plastid-Localized Pentatricopeptide Repeat Protein is Required for Both Pollen Development and Plant Growth in Rice
Several mitochondrial-targeted pentatricopeptide repeat (PPR) proteins involved in pollen development have been reported to be fertility restorer (Rf) proteins. However, the roles of plastid-localized PPR proteins in plant male reproduction are poorly defined. Here, we described a plastid-localized PPR-SMR protein, OsPPR676, which is required for plant growth and pollen development in rice. In this study, OsPPR676 was confirmed to be an interacted protein with Osj10gBTF3, β-subunit of nascent polypeptide-associated complex (β-NAC), by bimolecular fluorescence complementation assays, indicating that both proteins are probably involved in the same regulatory pathway of pollen development. Compared with other chloroplast-rich tissues, OsPPR676 was only weakly expressed in anther, but in the Mei and YM stages of pollen development, its expression was relatively strong in the tapetum. Disruption of OsPPR676 resulted in growth retardation of plants and partial sterility of pollens. Phenotypic analysis of different
osppr676
mutant lines implied that the SMR domain was not essential for the function of OsPPR676. We further demonstrated that OsPPR676 is essential for production of plastid
atpB
subunit, and then plays crucial roles in biosynthesis of fatty acids, carbohydrates, and other organic matters via affecting activity of ATP synthase.
Journal Article
Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial
Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry ( Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon ( Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934 , identifier ChiCTR1800015840.
Journal Article
Functional analysis for domains of maize PPR protein EMP5 in RNA editing and plant development in Arabidopsis
EMP5 and OTP72 are PPR proteins involved in mitochondrial same site RNA editing of rpl16 in maize and Arabidopsis, respectively. Besides rpl16, EMP5 also affects the editing efficiency of some editing sites in other mitochondrial transcripts. Loss of function of EMP5 causes arrested embryogenesis and endosperm development in maize, but no discernable defective phenotype is observed in Arabidopsis otp72 mutant plants. We here report that EMP5 can completely complement Arabidopsis otp72 for Ararpl16-440 editing, and E domain can’t be disrupted for normal function of EMP5. An interesting finding was that overexpression of a set of truncated EMP5s in Col-0 resulted in delayed bolting phenotypes and smaller plants. It seems some truncated EMP5s, such as EMP5-C and EMP5-D, have yet unknown functions, are not responsible for Ararpl16-440 editing any more. The phylogenetic analysis indicated that the functions of most EMP5 orthologs may be conserved, but EMP5 ortholog proteins from Nicotiana and Solanum can’t be found, and the C to U editing of Zmrpl16-458 site was not needed any more in the two species. Therefore, these two primary orthologs maybe already evolve new functions and change to different new proteins during evolutionary history. Overall, our studies revealed that E domain is crucial for mitochondrial RNA editing function of EMP5, and a set of truncated EMP5s still have functions for Arabidopsis normal growth and development, providing new insights into investigating the functions of EMP5 protein.
Journal Article