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1.
Cell ; 185(13): 2309-2323.e24, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35662414

RESUMO

The mitochondrial genome encodes 13 components of the oxidative phosphorylation system, and altered mitochondrial transcription drives various human pathologies. A polyadenylated, non-coding RNA molecule known as 7S RNA is transcribed from a region immediately downstream of the light strand promoter in mammalian cells, and its levels change rapidly in response to physiological conditions. Here, we report that 7S RNA has a regulatory function, as it controls levels of mitochondrial transcription both in vitro and in cultured human cells. Using cryo-EM, we show that POLRMT dimerization is induced by interactions with 7S RNA. The resulting POLRMT dimer interface sequesters domains necessary for promoter recognition and unwinding, thereby preventing transcription initiation. We propose that the non-coding 7S RNA molecule is a component of a negative feedback loop that regulates mitochondrial transcription in mammalian cells.


Assuntos
DNA Mitocondrial , Proteínas Mitocondriais , Animais , DNA Mitocondrial/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Dimerização , Humanos , Mamíferos/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , RNA/metabolismo , RNA Mitocondrial , RNA Citoplasmático Pequeno , Partícula de Reconhecimento de Sinal , Transcrição Gênica
2.
Mol Cell ; 82(19): 3646-3660.e9, 2022 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-36044900

RESUMO

The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism and supply cells with adequate levels of adenosine triphosphate. Central to this process is the idea that replication primers and gene products both arise via transcription from a single light strand promoter (LSP) such that primer formation can influence gene expression, with no consensus as to how this is regulated. Here, we report the discovery of a second light strand promoter (LSP2) in humans, with features characteristic of a bona fide mitochondrial promoter. We propose that the position of LSP2 on the mitochondrial genome allows replication and gene expression to be orchestrated from two distinct sites, which expands our long-held understanding of mitochondrial gene expression in humans.


Assuntos
Genoma Mitocondrial , Trifosfato de Adenosina/metabolismo , DNA Mitocondrial/metabolismo , Humanos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Transcrição Gênica
3.
Phys Rev Lett ; 132(19): 197202, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38804947

RESUMO

The higher-order topological phases have attracted intense attention in the past years, which reveals various intriguing topological properties. Meanwhile, the enrichment of group symmetries with projective symmetry algebras redefines the fundamentals of topological matter and makes Stiefel-Whitney (SW) classes in classical wave systems possible. Here, we report the experimental realization of higher-order topological nodal loop semimetal in an acoustic system and obtain the inherent SW topological invariants. In stark contrast to higher-order topological semimetals relating to complex vector bundles, the hinge and surface states in the SW topological phase are protected by two distinctive SW topological charges relevant to real vector bundles. Our findings push forward the studies of SW class topology in classical wave systems, which also show possibilities in robust high-Q-resonance-based sensing and energy harvesting.

4.
Semin Cancer Biol ; 86(Pt 2): 967-975, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-33812983

RESUMO

Gut microbes (GMs), dominated by bacteria, play important roles in many physiological processes. The structures and functions of GMs are closely related to human health, the occurrence and development of diseases and the rapid recovery of the body. Gastrointestinal cancers are the major diseases affecting human health worldwide. With the development of metagenomic technology and the wide application of new generation sequencing technology, a large number of studies suggest that complex GMs are related to the occurrence and development of gastrointestinal cancers. Fecal microbiota transplantation (FMT) and probiotics can treat and prevent the occurrence of gastrointestinal cancers. This article reviews the latest research progress of microbes in gastrointestinal cancers from the perspectives of the correlation, the influence mechanism and the application, so as to provide new directions for the prevention, early diagnosis and treatment of gastrointestinal cancers.


Assuntos
Microbioma Gastrointestinal , Neoplasias Gastrointestinais , Probióticos , Humanos , Transplante de Microbiota Fecal , Probióticos/uso terapêutico , Metagenômica , Neoplasias Gastrointestinais/etiologia , Neoplasias Gastrointestinais/terapia
5.
J Am Chem Soc ; 145(50): 27639-27649, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38054305

RESUMO

While chiral molecular rotors have unique frames and cavities to possibly generate switchable chiroptical functions, it still remains a formidable challenge to precisely restrict their rotations to activate certain functions such as fluorescence as well as circularly polarized luminescence (CPL), which are strongly related to the local molecular rotations. Herein, we design a pair of enantiopure helical cage rotors, which emit light neither at the molecular state nor in the crystal or aggregation states, although they contain luminophore groups. However, upon mounting with fluoroaromatic borane (TFPB) as a molecular brake, the phenyl rotation of the helical cage can be effectively hindered and fluorescence and CPL activities of the molecular cage are switched on. Crystal structure analysis reveals that the rotation is restricted through synergistic B-O-H-N bonding and a fluoroaromatic-aromatic (ArF-Ar) dipole interaction. Moreover, the helical cages are switched on stepwise with color-variable fluorescence and CPL by the inner brake in the molecular state and the outer brake in the supramolecular assemblies, respectively. This work not only provides the design idea of chiroptical molecular rotors but also unveils how fluorescence and CPL could be generated in cage rotor systems.

6.
Chirality ; 35(10): 692-699, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37013339

RESUMO

Because of its dynamic reversible nature and simple regulation properties, rotaxane systems provided a good route for the construction of responsive supramolecular chiral materials. Here, we covalently encapsulate the photo-responsive guest molecule azobenzene (Azo) in a chiral macrocycle ß-cyclodextrin (ß-CD) to prepare self-locked chiral [1]rotaxane [Azo-CD]. On this basis, the self-adaptive conformation of [Azo-CD] was manipulated by solvent and photoirradiation; meanwhile, dual orthogonal regulation of the [1]rotaxane chiroptical switching could also be realized.

7.
PLoS Genet ; 16(5): e1008798, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32469861

RESUMO

Alterations in epigenetic silencing have been associated with ageing and tumour formation. Although substantial efforts have been made towards understanding the mechanisms of gene silencing, novel regulators in this process remain to be identified. To systematically search for components governing epigenetic silencing, we developed a genome-wide silencing screen for yeast (Saccharomyces cerevisiae) silent mating type locus HMR. Unexpectedly, the screen identified the mismatch repair (MMR) components Pms1, Mlh1, and Msh2 as being required for silencing at this locus. We further found that the identified genes were also required for proper silencing in telomeres. More intriguingly, the MMR mutants caused a redistribution of Sir2 deacetylase, from silent mating type loci and telomeres to rDNA regions. As a consequence, acetylation levels at histone positions H3K14, H3K56, and H4K16 were increased at silent mating type loci and telomeres but were decreased in rDNA regions. Moreover, knockdown of MMR components in human HEK293T cells increased subtelomeric DUX4 gene expression. Our work reveals that MMR components are required for stable inheritance of gene silencing patterns and establishes a link between the MMR machinery and the control of epigenetic silencing.


Assuntos
Proteína 1 Homóloga a MutL/genética , Proteínas MutL/genética , Proteína 2 Homóloga a MutS/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Acetilação , Reparo de Erro de Pareamento de DNA , Epigênese Genética , Inativação Gênica , Genes Fúngicos Tipo Acasalamento , Hereditariedade , Histonas/metabolismo , Saccharomyces cerevisiae/genética , Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae/metabolismo , Sirtuína 2/metabolismo , Telômero/genética
8.
BMC Surg ; 23(1): 146, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37248522

RESUMO

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most serious complication and the main reason for morbidity and mortality after pancreaticoduodenectomy (PD). Currently, there exists no flawless pancreaticojejunal anastomosis approach. We presents a new approach called Chen's penetrating-suture technique for pancreaticojejunostomy (PPJ), which involves end-to-side pancreaticojejunostomy by suture penetrating the full-thickness of the pancreas and jejunum, and evaluates its safety and efficacy. METHODS: To assess this new approach, between May 2006 and July 2018, 193 consecutive patients who accepted the new Chen's Penetrating-Suture technique after a PD were enrolled in this study. Postoperative morbidity and mortality were evaluated. RESULTS: All cases recovered well after PD. The median operative time was 256 (range 208-352) min, with a median time of 12 (range 8-25) min for performing pancreaticojejunostomy. Postoperative morbidity was 19.7% (38/193) and mortality was zero. The POPF rate was 4.7% (9/193) for Grade A, 1.0% (2/193) for Grade B, and no Grade C cases and one urinary tract infection. CONCLUSION: PPJ is a simple, safe, and reliable technique with ideal postoperative clinical results.


Assuntos
Pancreaticoduodenectomia , Pancreaticojejunostomia , Humanos , Pancreaticojejunostomia/métodos , Pancreaticoduodenectomia/métodos , Anastomose Cirúrgica/métodos , Pâncreas/cirurgia , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/etiologia , Técnicas de Sutura/efeitos adversos
9.
Phys Rev Lett ; 128(6): 065701, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35213198

RESUMO

We demonstrate the transient parity-time (PT) symmetry in electronics. It is revealed by equivalent circuit transformation according to the switching states of electronic systems. With the phasor method and Laplace transformation, we derive the hidden PT-symmetric Hamiltonian in the switching oscillation, which are characterized by free oscillation modes. Both spectral and dynamic properties of the PT electronic structure demonstrate the phase transition with eigenmode orthogonality. Importantly, the observed transient PT symmetry enables exceptional-point-induced optimal switching oscillation suppression, which shows the significance of PT symmetry in electronic systems with temporary responses. Our work paves the way for breakthroughs in the PT symmetry theory and has essential applications such as anti-interference in switch-mode electronics.

10.
J Acoust Soc Am ; 151(1): 96, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35105000

RESUMO

The past decades have witnessed great efforts in the on-demand ultrasonic field design in which the time reversal technology was widely used in the whole-space acoustic hologram. In practice, the acoustic field of interest is usually bounded in a finite region with flexible distribution. Here, the use of prolate spheroidal wave functions to generate an arbitrary ultrasonic field in a finite region is proposed. The prolate spheroidal functions, which form a complete set of band limited functions and are orthogonal in the infinite and finite regions, can be efficiently reconstructed by the sampling theorem. To display the validation of the proposed method, two types of functional ultrasonic fields are numerically simulated. One type is the ultrasound standing wave field for which six nodes and two nodes are separately realized for two different types of standing waves in the limited range of (-2λ, 2λ). In addition, a composite standing wave field is stimulated with more complicated nodal distributions. The other type is the ultrasound focusing field, where three focal spots with the mainlobe sizes of λ, 0.5λ, and 0.35λ are demonstrated. It is worth noting that the nontrivial side lobes for super-oscillation focusing are designed to be about 3λ away from the central focal spot (the mainlobe size 0.35λ). This work has much significance in the applications of acoustic tweezing, ultrasonic imaging, and treatment.

11.
Nano Lett ; 21(16): 6952-6959, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34355915

RESUMO

CO2 electrochemical reduction in solid oxide electrolysis cells is an effective way to combine CO2 conversion and renewable electricity storage. A Au layer is often used as a current collector, whereas Au nanoparticles are rarely used as a cathode because it is difficult to keep nanosized Au at high temperatures. Here we dispersed a Au layer into Au nanoparticles (down to 2 nm) at 800 °C by applying high voltages. A 75-fold decrease in the polarization resistance was observed, accompanied by a 38-fold improvement in the cell current density. Combining electronic microscopy, in situ near-ambient pressure X-ray photoelectron spectroscopy, and theoretical calculations, we found that the interface between the Au layer and the electrolyte (yttria-stabilized zirconia (YSZ)) was reconstructed into nano-Au/Zr-suboxide interfaces, which are active sites that show a much lower reaction activation energy than that of the Au/YSZ interface. The formation of Zr-suboxides promotes Au dispersion and Au nanoparticle stabilization due to the strong interaction between Au and Zr-suboxides.

12.
Angew Chem Int Ed Engl ; 61(28): e202113979, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34693602

RESUMO

Chiral covalent organic frameworks (COFs) with circularly polarized luminescence (CPL) are intriguing as advanced chiroptical materials but have not been reported to date. We constructed chiroptical COF materials with CPL activity through the convenient Knoevenagel condensation of formyl-functionalized axially chiral linkers and C3-symmetric 1,3,5-benzenetriacetonitrile. Remarkably, the as-prepared chiral COFs showed high absorption and luminescent dissymmetric factors up to 0.02 (gabs ) and 0.04 (glum ), respectively. In contrast, the branched chiral polymers from the same starting monomers were CPL silent. Structural and spectral characterization revealed that the reticular frame was indispensable for CPL generation via confined chirality transfer. Moreover, reticular stacking boosted the CPL performance significantly due to the interlayer restriction of frame. This work demonstrates the first example of a CPL-active COF and provides insight into CPL generation through covalent reticular chemistry, which will play a constructive role in the future design of high-performance CPL materials.

13.
Angew Chem Int Ed Engl ; 61(3): e202114759, 2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34816570

RESUMO

Here, we propose a mechanically interlocked strategy to achieve a 2D chiral polyrotaxane (2D CPR) monolayer with emergent and steerable CPL activity by utilizing ß-cyclodextrin as the chiral wheel and a luminescent dynamic covalent organic framework as 2D polymeric axle. Such methodology, integrating host-guest and dynamic covalent chemistry, enabled the direct construction of a delaminated 2D CPR monolayer with extraordinarily large size (up to tens of micrometers) and simultaneously endowed chirality to the extended 2D CPR network to generate CPL activity. Importantly, not only the structure but also the CPL performance of the 2D CPR network can be further regulated by the feeding amount of ß-cyclodextrin. This work demonstrated a monolayered 2D CPR with CPL activity for the first time. The insightful structure-property relationship of the induced CPL will be of benefit for a deeper understanding of the excited-state chirality of 2D chiral nanomaterials.

14.
Angew Chem Int Ed Engl ; 61(19): e202200727, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35195948

RESUMO

Biomimetic ATP-driven supramolecular assembly is important to understand various biological processes and dissipative systems. Here, we report an ATP-driven chiral assembly exhibiting circularly polarized luminescence (CPL) via the interaction of an achiral terpyridine-based ZnII complex with nucleotides. It was found that while the metal complexes could co-assemble with the nucleotides to form fluorescent assemblies, only a combination of furan-substituted terpyridine complex and ATP showed an intense CPL with a dissymmetry factor (glum ) as high as 0.20. This means that the complex could recognize ATP using CPL as a readout signal, thus providing an example of ATP encryption. Interestingly, when ATP was transferred into ADP or AMP under enzymatic hydrolysis, the CPL decreases or disappears. Addition of ATP generates CPL again, thus producing an ATP-induced CPL system. This work presents the first example of ATP-induced CPL and encryption.


Assuntos
Luminescência , Nucleotídeos , Trifosfato de Adenosina
15.
Angew Chem Int Ed Engl ; 61(36): e202208574, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-35841178

RESUMO

It remains a formidable challenge to realize thermo-rulable circularly polarized luminescence (CPL). Herein, we propose a new strategy by covalently "potting" the emitter into a flexible chiral macrocycle as an adaptive chiral [1]rotaxane to address this issue. Different from its included analogue, the potted emitter [DS] showed adaptive conformers with tunable CPL in varied solvents. Significantly, upon controlled self-assembly, [DS] formed a channel-type nanoarchitecture ([DS]A ), which exhibited an extraordinary thermo-rulable CPL between 25-100 °C. Impressively, the glum was large as 0.024 at 25 °C, which was amplified to 0.040 at 90 °C with a decrease of QY (from 92 % to 80 %). By comparison, the assemblies of cage-type [DS]B and the unpotted emitter showed irreversible or unanswered thermal behaviors. The work demonstrated the thermo-rulable and durable CPL for the first time and provided an insightful understanding of thermal effect on high-temperature and switchable CPL materials.

16.
Angew Chem Int Ed Engl ; 61(41): e202210604, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-35989521

RESUMO

While helix has elegant biomimetic structures and functionalities, it still remains a big question how the nanoscale helicity evolved from the molecular chiral building blocks across length scales. Herein, macrocyclic triangles composed of achiral edges and chiral vertices were rationally designed, in which the planar chirality emerged due to the restriction of edge rotation by intermolecular stackings and led to a unique chiral self-assembly. In contrast to the solution systems where the chiroptical property is exclusively dominated by the point chiral vertices, the emerged planar chirality was found to control the chiral self-assembly, resulting the nanotwist with the handedness determined by the planar chirality. Our work unveiled the self-assembly behaviors of macrocyclic conformers for the first time and provided a deep understanding on the macrocyclic chirality evolution including the excited-state chirality.

17.
Opt Express ; 29(6): 8462-8476, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33820293

RESUMO

We investigate the topological skin effect in a ring resonator array which can be mapped into the square root of a Su-Schrieffer-Heeger (SSH) model with non-Hermitian asymmetric coupling. The asymmetric coupling is realized by integrating the same amount of gain and loss into the two half perimeters of linking rings that effectively couple two adjacent site rings. Such a square-root topological insulator inherits the properties from its parent Hamiltonian, which has the same phase transition points and exhibits non-Bloch features as well. We show the band closing points for open chain are different from that of periodic chain as a result of the skin effect. Moreover, the square-root insulator supports multiple topological edge modes as the number of band gaps is doubled compared to the original Hamiltonian. The full-wave simulations agree well with the theoretical analyses based on a tight-binding model. The study provides a promising approach to investigate the skin effect by utilizing ring resonators and may find potential applications in light trapping, lasers, and filters.

18.
Langmuir ; 37(33): 10241-10247, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34379419

RESUMO

Two enantiomeric hydrohelicenes containing a hydroxyl group and a π-conjugated nonplanar structure are assembled at the air/water interface. These molecules are found to form spreading films with well-defined surface pressure-area isotherms. Upon transferring the spreading film onto the mica surface, porous nanostructures are observed. The spreading film can be transferred onto solid substrates by the Langmuir-Schaefer (LS) method and the transferred LS films display optical activity as revealed by the circular dichroism (CD) spectra. The P- and M-hydrohelicene enantiomers showed mirrored CD spectra, suggesting that the chirality of the LS films was controlled by molecular chirality. When these molecules are spread on the aqueous solution containing metal ions such as Ag+, Cu2+, and Zn2+, a clear twisted ring nanostructure, which is similar to the Möbius strip, is observed. It is suggested that the interaction between the hydroxyl groups of helicenes and metal ions induced such a ring nanostructure.

19.
J Interv Cardiol ; 2021: 2829070, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34992506

RESUMO

AIMS: This study sought to describe left atrial macroreentry tachycardia (LAMRT) originating from the spontaneous scarring of left atrial anterior wall (LAAW) and its clinical and electrophysiological characteristics, mechanisms, and the formation of substrates. METHODS AND RESULTS: 9 of 123 patients (89% female, age 79.78 ± 5.59 years) had LAMRT originating from the LAAW with no cardiac surgery or prior left atrial (LA) ablation. The mean tachycardia cycle length (TCL) was 241.67 ± 38.00 milliseconds. Spontaneous scars areas and low voltage areas (LVAs) in the LAAW were found in all patients. Successful ablation of the critical isthmus caused termination of the LAMRT and was not inducible in all patients. Arrhythmogenic substrates of LAMRT were the spontaneous scars of LAAW, which matched with the aorta or/and pulmonary artery contact area. The area under the curve (AUC) of age and combination of gender and age for predicting the LAMRT originating from the LAAW were 0.918 and 0.951, respectively, with a cutoff value of ≥73.5 years of age and gender (female) predicting LAMRT with 88.9% sensitivity and 89% specificity. CONCLUSION: Combination of gender and age provides a simple and useful criterion to distinguish LAMRT from cavotricuspid isthmus- (CTI-) dependent atrial tachycardia in macroreentry atrial tachycardia (MRAT) in patients without a history of surgery or ablation. Aorta or/and pulmonary artery contacting LA may be related to spontaneous scars. Ablation the isthmus eliminated LAMRT in all patients.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/cirurgia , Cicatriz , Feminino , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Humanos , Masculino , Taquicardia , Resultado do Tratamento
20.
J Pharm Pharm Sci ; 24: 488-498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644525

RESUMO

PURPOSE: Silicosis is a serious occupational disease that is characterized by pulmonary infiltrates and fibrosis and is often refractory to current treatments. New therapeutic strategies for silicosis are needed. Hepatocyte growth factor (HGF) is a latent anti-inflammatory and anti-fibrotic growth factor. METHODS: We prepared a polyethyleneimine-polyethylene glycol/pHGF/hyaluronic acid (PEG-PEI/pHGF/HA) nanomaterials loaded with plasmid DNA encoding HGF gene to increase its transfection efficiency. The characterization, including DNA entrapment efficiency, morphology, particle size, and zeta-potential of PEG-PEI/pHGF/HA was studied. And a PEG-PEI/pHGF/HA (N/P=30:1) nanoparticle with low toxicity and high transfection efficiency was used in treatment for silicosis in mice. RESULTS: The results showed that the human HGF expression in the lungs of the mice was increased, and the inflammatory cell infiltration and fibrous collagen deposition was significantly reduced. CONCLUSION: Therefore, PEG-PEI/pHGF/HA nanoparticle warrant further investigation and may be a potential therapeutic strategy for silicosis.


Assuntos
Terapia Genética/métodos , Fator de Crescimento de Hepatócito/administração & dosagem , Sistemas de Liberação de Fármacos por Nanopartículas , Silicose/tratamento farmacológico , Células A549 , Animais , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/uso terapêutico , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasmídeos/genética , Silicose/patologia , Transfecção/métodos
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