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1.
Nature ; 613(7943): 280-286, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36631649

RESUMO

Macroscopic electric motors continue to have a large impact on almost every aspect of modern society. Consequently, the effort towards developing molecular motors1-3 that can be driven by electricity could not be more timely. Here we describe an electric molecular motor based on a [3]catenane4,5, in which two cyclobis(paraquat-p-phenylene)6 (CBPQT4+) rings are powered by electricity in solution to circumrotate unidirectionally around a 50-membered loop. The constitution of the loop ensures that both rings undergo highly (85%) unidirectional movement under the guidance of a flashing energy ratchet7,8, whereas the interactions between the two rings give rise to a two-dimensional potential energy surface (PES) similar to that shown by FOF1 ATP synthase9. The unidirectionality is powered by an oscillating10 voltage11,12 or external modulation of the redox potential13. Initially, we focused our attention on the homologous [2]catenane, only to find that the kinetic asymmetry was insufficient to support unidirectional movement of the sole ring. Accordingly, we incorporated a second CBPQT4+ ring to provide further symmetry breaking by interactions between the two mobile rings. This demonstration of electrically driven continual circumrotatory motion of two rings around a loop in a [3]catenane is free from the production of waste products and represents an important step towards surface-bound14 electric molecular motors.

2.
Nature ; 603(7900): 265-270, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35264758

RESUMO

Molecular recognition1-4 and supramolecular assembly5-8 cover a broad spectrum9-11 of non-covalently orchestrated phenomena between molecules. Catalysis12 of such processes, however, unlike that for the formation of covalent bonds, is limited to approaches13-16 that rely on sophisticated catalyst design. Here we establish a simple and versatile strategy to facilitate molecular recognition by extending electron catalysis17, which is widely applied18-21 in synthetic covalent chemistry, into the realm of supramolecular non-covalent chemistry. As a proof of principle, we show that the formation of a trisradical complex22 between a macrocyclic host and a dumbbell-shaped guest-a molecular recognition process that is kinetically forbidden under ambient conditions-can be accelerated substantially on the addition of catalytic amounts of a chemical electron source. It is, therefore, electrochemically possible to control23 the molecular recognition temporally and produce a nearly arbitrary molar ratio between the substrates and complexes ranging between zero and the equilibrium value. Such kinetically stable supramolecular systems24 are difficult to obtain precisely by other means. The use of the electron as a catalyst in molecular recognition will inspire chemists and biologists to explore strategies that can be used to fine-tune non-covalent events, control assembly at different length scales25-27 and ultimately create new forms of complex matter28-30.

3.
FASEB J ; 38(11): e23697, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38842874

RESUMO

Diabetic retinopathy (DR) is characterized by chronic, low-grade inflammation. This state may be related to the heightened production of neutrophil extracellular traps (NETs) induced by high glucose (HG). Human cathelicidin antimicrobial peptide (LL37) is an endogenous ligand of G protein-coupled chemoattractant receptor formyl peptide receptor 2 (FPR2), expressed on neutrophils and facilitating the formation and stabilization of the structure of NETs. In this study, we detected neutrophils cultured under different conditions, the retinal tissue of diabetic mice, and fibrovascular epiretinal membranes (FVM) samples of patients with proliferative diabetic retinopathy (PDR) to explore the regulating effect of LL37/FPR2 on neutrophil in the development of NETs during the process of DR. Specifically, HG or NG with LL37 upregulates the expression of FPR2 in neutrophils, induces the opening of mitochondrial permeability transition pore (mPTP), promotes the increase of reactive oxygen species and mitochondrial ROS, and then leads to the rise of NET production, which is mainly manifested by the release of DNA reticular structure and the increased expression of NETs-related markers. The PI3K/AKT signaling pathway was activated in neutrophils, and the phosphorylation level was enhanced by FPR2 agonists in vitro. In vivo, increased expression of NETs markers was detected in the retina of diabetic mice and in FVM, vitreous fluid, and serum of PDR patients. Transgenic FPR2 deletion led to decreased NETs in the retina of diabetic mice. Furthermore, in vitro, inhibition of the LL37/FPR2/mPTP axis and PI3K/AKT signaling pathway decreased NET production induced by high glucose. These results suggested that FPR2 plays an essential role in regulating the production of NETs induced by HG, thus may be considered as one of the potential therapeutic targets.


Assuntos
Peptídeos Catiônicos Antimicrobianos , Catelicidinas , Retinopatia Diabética , Armadilhas Extracelulares , Camundongos Endogâmicos C57BL , Neutrófilos , Receptores de Formil Peptídeo , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Armadilhas Extracelulares/metabolismo , Animais , Receptores de Formil Peptídeo/metabolismo , Receptores de Formil Peptídeo/genética , Humanos , Neutrófilos/metabolismo , Camundongos , Peptídeos Catiônicos Antimicrobianos/metabolismo , Masculino , Receptores de Lipoxinas/metabolismo , Receptores de Lipoxinas/genética , Diabetes Mellitus Experimental/metabolismo , Transdução de Sinais , Espécies Reativas de Oxigênio/metabolismo , Feminino , Pessoa de Meia-Idade
4.
Proc Natl Acad Sci U S A ; 119(12): e2118573119, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35290119

RESUMO

Although catenanes comprising two ring-shaped components can be made in large quantities by templation, the preparation of three-dimensional (3D) catenanes with cage-shaped components is still in its infancy. Here, we report the design and syntheses of two 3D catenanes by a sequence of SN2 reactions in one pot. The resulting triply mechanically interlocked molecules were fully characterized in both the solution and solid states. Mechanistic studies have revealed that a suit[3]ane, which contains a threefold symmetric cage component as the suit and a tribromide component as the body, is formed at elevated temperatures. This suit[3]ane was identified as the key reactive intermediate for the selective formation of the two 3D catenanes which do not represent thermodynamic minima. We foresee a future in which this particular synthetic strategy guides the rational design and production of mechanically interlocked molecules under kinetic control.


Assuntos
Catenanos , Rotaxanos , Catenanos/química , Cinética , Rotaxanos/química
5.
Nano Lett ; 24(2): 733-740, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38166427

RESUMO

The Hall effect has played a vital role in unraveling the intricate properties of electron transport in solid materials. Here, we report on a crystal symmetry-dependent in-plane Hall effect (CIHE) observed in a CuPt/CoPt ferromagnetic heterostructure. Unlike the planar Hall effect (PHE), the CIHE in CuPt/CoPt strongly depends on the current flowing direction (ϕI) with respect to the crystal structure. It reaches its maximum when the current is applied along the low crystal-symmetry axes and vanishes when applied along the high crystal-symmetry axes, exhibiting an unconventional angular dependence of cos(3ϕI). Utilizing a symmetry analysis based on the Invariant Theory, we demonstrate that the CIHE can exist in magnetic crystals possessing C3v symmetry. Using a tight-binding model and realistic first-principles calculations on the metallic heterostructure, we find that the CIHE originates from the trigonal warping of the Fermi surface. Our observations highlight the critical role of crystal symmetry in generating new types of Hall effects.

6.
Acc Chem Res ; 56(20): 2838-2850, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37751270

RESUMO

ConspectusCompared to traditionally used irreversible chemical reactions, dynamic covalent chemistry (DCC) including imine formation represents a more advanced technique in the preparation of molecules with complex structures and topologies, whose syntheses require the formation of many bonds. By allowing the occurrence of error checking and self-correcting, it is likely that the target molecules with high enough thermodynamic stability could be self-assembled in high or even quantitative yield. Two questions are raised herein. First, it becomes a central problem in self-assembly that how to endow a target product with high enough thermodynamic stability so that it can be produced as the major or the only product within the self-assembly library. Second, the reversible nature of dynamic bonds jeopardizes the intrinsic stability of the products. More specifically, the imine bond which represents the mostly used dynamic covalent bond, is apt to undergo hydrolysis in the presence of water. Developing new approaches to make imine more robust and compatible with water is thus of importance. In this account, we summarized the progress made in our group in the field of self-assembly based on C═N bond formation. In organic solvent where an imine bond is relatively robust, we focus on studying how to enhance the thermodynamic stability of a target molecule by introducing intramolecular forces. These noncovalent interactions either release enthalpy to favor the formation of the target molecule or preorganize the building blocks into specific conformations that mimic the product, so that the entropy loss of the formation of the latter is thus suppressed. In water, which often leads to imine hydrolysis, we developed two strategies to enhance the water-compatibility. By taking advantage of multivalency, namely, multiple bonds are often more robust than a single bond, self-assembly via condensation of imine was performed successfully in water, a solvent that is considered as forbidden zone of imine. Another approach is to replace typical imine with its more robust and water compatible derivatives, namely, either hydrazone or oxime, whose C═N bonds are generally less electrophilic compared to typical imine. With the water-compatible dynamic bonds in hand, a variety topological nontrivial molecules such as catenanes and knots was self-assembled successfully in aqueous media, driven by hydrophobic effect. When the self-assembled molecules in the form of rings and cages were designed for supramolecular purposes, water-compatibility endows a merit that allows the hosts to take advantage of hydrophobic effect to drive host-guest recognition, enabling various tasks to be accomplished, such as separation of guest isomers with similar physical properties, recognition of highly hydrated anions, as well as stabilization of guest dimers.

7.
BMC Infect Dis ; 24(1): 405, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622501

RESUMO

BACKGROUND: Genital infection with Chlamydia trachomatis (C. trachomatis) is a major public health issue worldwide. It can lead to cervicitis, urethritis, and infertility. This study was conducted to determine the characteristics of genital C. trachomatis infection among women attending to the infertility and gynecology clinics. METHODS: Endocervical swabs were collected from 8,221 women for C. trachomatis nucleotide screening and genotyping, while serum samples were collected for C. trachomatis pgp3 antibody determination using luciferase immunosorbent assays. RESULTS: High C. trachomatis DNA prevalence (3.76%) and seroprevalence (47.46%) rates were found, with genotype E (27.5%) being the most prevalent. C. trachomatis omp1 sense mutation was associated with cervical intraepithelial neoplasia (CIN) (odds ratio [OR] = 6.033, 95% confidence interval [CI] = 1.219-39.185, p = 0.045). No significant differences in C. trachomatis seroprevalence rates were observed between women with detectable C. trachomatis DNA in the infertility and routine physical examination groups (86.67% vs. 95%, p > 0.05); however, among women with negative C. trachomatis DNA, the former group had a markedly higher seroprevalence than the latter group (56.74% vs. 20.17%, p < 0.001). C. trachomatis DNA, but not pgp3 antibody, was significantly associated with CIN (OR = 4.087, 95% CI = 2.284-7.315, p < 0.001). CONCLUSION: Our results revealed a high prevalence, particularly seroprevalence, of C. trachomatis among women with infertility. Furthermore, we found an association between C. trachomatis omp1 sense mutations and CIN. Therefore, C. trachomatis serves as a risk factor for CIN.


Assuntos
Infecções por Chlamydia , Infertilidade , Humanos , Feminino , Chlamydia trachomatis/genética , Estudos Soroepidemiológicos , Infertilidade/epidemiologia , Infertilidade/complicações , Infecções por Chlamydia/diagnóstico , DNA , Genitália
8.
Environ Res ; 252(Pt 3): 118941, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38649015

RESUMO

The Zn/Zr-MOFs were synthesized via microwave-assisted ball milling and subsequently characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The thermal stability of the Zn/Zr-MOFs was evaluated through thermogravimetry (TGA). The results demonstrated the exceptional adsorption properties of the Zn/Zr-MOFs towards Lomefloxacin hydrochloride and Levofloxacin hydrochloride. At a concentration of 30 ppm for Lomefloxacin hydrochloride, the addition of 30 mg of Zn/Zr-MOFs material resulted in an adsorption capacity of 179.2 mg•g-1. Similarly, at a concentration of 40 ppm for Levofloxacin hydrochloride, the addition of 30 mg Zn/Zr-MOFs material led to an adsorption capacity of 187.1 mg•g-1. Kinetic analysis revealed that the experimental data aligned well with a pseudo-second order kinetic model. Overall, these findings highlight the significant potential application of Zn/Zr-MOF materials in wastewater treatment.


Assuntos
Fluoroquinolonas , Levofloxacino , Micro-Ondas , Águas Residuárias , Poluentes Químicos da Água , Zinco , Levofloxacino/química , Adsorção , Fluoroquinolonas/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Zinco/química , Águas Residuárias/química , Zircônio/química , Antibacterianos/química , Cinética , Estruturas Metalorgânicas/química
9.
J Am Chem Soc ; 145(49): 26756-26764, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38039269

RESUMO

The classical Au(I)/Au(III) redox couple chemistry has been limited to constructing C-C and C-X bonds, and thus, the exploration of the elementary reaction of gold redox coupling is very significant to enrich its organometallic features. Herein, we report the first visible-light-mediated, external oxidant-free Au(I)/Au(III) redox couple using commercially available Mn2(CO)10 to generate Mn-Au(III)-Mn intermediates for bimetallic redox coupling. A wide range of structurally diverse heterodinuclear and polynuclear L-Au(I)-Mn-L' complexes (19 examples, up to >99% yields) are readily constructed, providing a robust strategy for the concise construction of Au-Mn complexes under mild reaction conditions. The mechanistic studies together with DFT calculations support the radical oxidative addition of •Mn(CO)5 to gold and bimetallic reductive elimination mechanisms from highly active Mn-Au(III)-Mn species, representing an important step toward an elementary reaction in gold chemistry research. Furthermore, the resulting Au-Mn complexes exhibit unique catalytic activity, with which divergent reductive coupling of nitroarenes can readily afford azoxybenzenes, azobenzenes, and hydrazobenzenes in moderate to good yields.

10.
J Am Chem Soc ; 145(34): 18800-18811, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37590178

RESUMO

Supramolecular electronics provide an opportunity to introduce molecular assemblies into electronic devices through a combination of noncovalent interactions such as [π···π] and hydrogen-bonding interactions. The fidelity and dynamics of noncovalent interactions hold considerable promise when it comes to building devices with controllable and reproducible switching functions. Here, we demonstrate a strategy for building electronically robust switches by harnessing two different noncovalent interactions between a couple of pyridine derivatives. The single-supermolecule switch is turned ON when compressing the junction enabling [π···π] interactions to dominate the transport, while the switch is turned OFF by stretching the junction to form hydrogen-bonded dimers, leading to a dramatic decrease in conductance. The robustness and reproducibility of these single-supermolecule switches were achieved by modulating the junction with Ångström precision at frequencies of up to 190 Hz while obtaining high ON/OFF ratios of ∼600. The research presented herein opens up an avenue for designing robust bistable mechanoresponsive devices which will find applications in the building of integrated circuits for microelectromechanical systems.

11.
J Am Chem Soc ; 145(18): 10061-10070, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37098077

RESUMO

Triplet-triplet annihilation-based molecular photon upconversion (TTA-UC) is a photophysical phenomenon that can yield high-energy emitting photons from low-energy incident light. TTA-UC is believed to fuse two triplet excitons into a singlet exciton through several consecutive energy-conversion processes. When organic aromatic dyes─i.e., sensitizers and annihilators─are used in TTA-UC, intermolecular distances, as well as relative orientations between the two chromophores, are important in an attempt to attain high upconversion efficiencies. Herein, we demonstrate a host-guest strategy─e.g., a cage-like molecular container incorporating two porphyrinic sensitizers and encapsulating two perylene emitters inside its cavity─to harness photon upconversion. Central to this design is tailoring the cavity size (9.6-10.4 Å) of the molecular container so that it can host two annihilators with a suitable [π···π] distance (3.2-3.5 Å). The formation of a complex with a host:guest ratio of 1:2 between a porphyrinic molecular container and perylene was confirmed by NMR spectroscopy, mass spectrometry, and isothermal titration calorimetry (ITC) as well as by DFT calculations. We have obtained TTA-UC yielding blue emission at 470 nm when the complex is excited with low-energy photons. This proof-of-concept demonstrates that TTA-UC can take place in one supermolecule by bringing together the sensitizers and annihilators. Our investigations open up some new opportunities for addressing several issues associated with supramolecular photon upconversion, such as sample concentrations, molecular aggregation, and penetration depths, which have relevance to biological imaging applications.

12.
J Biochem Mol Toxicol ; 37(8): e23373, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37253097

RESUMO

Understanding the molecular mechanisms underlying osteoclast differentiation provides insights into bone loss and even osteoporosis. The specific mechanistic actions of cullin 4A (CUL4A) in osteoclast differentiation and resultant osteoporosis is poorly explored. We developed a mouse model of osteoporosis using bilateral ovariectomy (OVX) and examined CUL4A expression. It was noted that CUL4A expression was increased in the bone marrow of OVX mice. Overexpression of CUL4A promoted osteoclast differentiation, and knockdown of CUL4A alleviated osteoporosis symptoms of OVX mice. Bioinformatic analyses were applied to identify the downstream target genes of microRNA-340-5p (miR-340-5p), followed by interaction analysis. The bone marrow macrophages (BMMs) were isolated from femur of OVX mice, which were transfected with different plasmids to alter the expression of CUL4A, Zinc finer E-box binding homeobox 1 (ZEB1), miR-340-5p, and Toll-like receptor 4 (TLR4). ChIP assay was performed to detect enrichment of ZEB1 promoter by H3K4me3 antibody in BMMs. ZEB1 was overexpressed in the bone marrow of OVX mice. Overexpression of CUL4A mediated H3K4me3 methylation to increase ZEB1 expression, thus promoting osteoclast differentiation. Meanwhile, ZEB1 could inhibit miR-340-5p expression and upregulate HMGB1 to induce osteoclast differentiation. Overexpressed ZEB1 activated the TLR4 pathway by regulating the miR-340-5p/HMGB1 axis to induce osteoclast differentiation, thus promoting the development of osteoporosis. Overall, E3 ubiquitin ligase CUL4A can upregulate ZEB1 to repress miR-340-5p expression, leading to HMGB1 upregulation and the TLR4 pathway activation, which promotes osteoclast differentiation and the development of osteoporosis.


Assuntos
Proteína HMGB1 , MicroRNAs , Osteoporose , Feminino , Camundongos , Animais , Receptor 4 Toll-Like/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Regulação para Cima , Osteoporose/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Diferenciação Celular , Osteogênese/genética
13.
Exp Cell Res ; 421(2): 113388, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36257352

RESUMO

Defective DNA damage repair is a key mechanism affecting tumor susceptibility, treatment response, and survival outcome of endometrial cancer (EC). Fanconi anemia complementation group D2 (FANCD2) is the core component of the Fanconi anemia repair pathway. To explore the function of FANCD2 in EC, we examined the expression of FANCD2 in human specimens and databases, and discussed the possible mechanism of carcinogenesis by in vitro assays. Immunohistochemistry results showed overexpression of FANCD2 was detected in EC tissues compared to normal and atypical hyperplasia endometrium. Higher FANCD2 expression was correlated with deeper myometrial invasion (MI) and proficient mismatch repair status. The Cancer Genome Atlas (TCGA) database analysis showed FANCD2 was upregulated in EC compared with normal tissue. The high expression of FANCD2 was associated with poor overall survival in EC. Knockdown of FANCD2 expression in EC cell lines inhibited malignant proliferation and migration ability. We demonstrated that decreased FANCD2 expression results in increased DNA damage and decreased S-phase cells, leading to a decrease in proliferative capacity in EC cells. Down-regulated FANCD2 confers sensitivity of EC cells to interstrand crosslinking agents. This study provides evidence for the malignant progression and prognostic value of FANCD2 in EC.


Assuntos
Neoplasias do Endométrio , Anemia de Fanconi , Feminino , Humanos , Anemia de Fanconi/genética , Anemia de Fanconi/patologia , Prognóstico , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Dano ao DNA/genética , Neoplasias do Endométrio/genética , Endométrio/metabolismo , Reparo do DNA/genética
14.
Environ Res ; 237(Pt 2): 116950, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37660876

RESUMO

Uranium pollution in groundwater environment has become an important issue of global concern. In this study, a strain of Desulfovibrio desulfuricans was isolated from the tailings of acid heap leaching, and was shown to be able to remove uranium from water via biosorption, bio-reduction, passive biomineralization under uranium stress, and active metabolically dependent bioaccumulation. This research explored the effects of nutrients, pH, initial uranium and sulfate concentration on the functional groups, uranium valence, and crystal size and morphology of uranium immobilization products. Results showed that tetravalent and hexavalent phosphorus-containing uranium minerals was both formed. In sulfate-containing water where Desulfovibrio desulfuricans A3-21ZLL can grow, the sequestration of uranium by bio-reduction was significantly enhanced compared to that with no sulfate loading or no growth. Ungrown Desulfovibrio desulfuricans A3-21ZLL or dead ones released inorganic phosphate group in response to the stress of uranium, which associated with soluble uranyl ion to form insoluble uranium-containing precipitates. This study revealed the influence of hydrochemical conditions on the mineralogy characteristics and spatial distribution of microbial uranium immobilization products. This study is conducive to the long-term and stable bioremediation of groundwater in decommissioned uranium mining area.

15.
Graefes Arch Clin Exp Ophthalmol ; 261(4): 1187-1194, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36374312

RESUMO

PURPOSE: To evaluate the incidence of an opaque bubble layer (OBL) in femtosecond laser-assisted in situ keratomileusis (FS-LASIK) flaps created with VisuMax Flap 2.0 as a result of a modification in the parameters of the flap programming. METHODS: This retrospective study was comprised of 1400 eyes of 715 patients who received FS-LASIK surgery. OBLs were measured and reported as a percentage of the flap area to identify the incidence and extent. Flap creation, which is a modification technique, was performed with 8.1-mm flap diameters plus 0.3-mm enlarged interlamellar photodisruption (group Flap 2.0). The same flap diameters without extra photodisruption as the previous standard setting were also implemented (group Flap 1.0). The preoperative measurements, including sphere, cylinder, keratometry, and intraoperative characteristics such as flap size and thickness, were documented. Possible risk factors for the occurrence of OBLs were investigated in this study. RESULTS: The incidence of an OBL was reduced when using the Flap 2.0 program (31.4%) compared to the Flap 1.0 program (63.7%). The area of hard and soft OBLs created by the Flap 2.0 program is smaller than those created by the Flap 1.0 program (P = 0.007 and P < 0.001). Multivariate logistic regression indicated that a thinner flap (P = 0.038) and a higher sphere (P = 0.001) affected the chance of hard OBLs occurring. CONCLUSION: The VisuMax Flap 2.0 program promotes gas venting by enlarging the interlamellar photodisruption size. The incidence and extent of OBLs appear to be reduced significantly when the Flap 2.0 program is applied.


Assuntos
Ceratomileuse Assistida por Excimer Laser In Situ , Miopia , Humanos , Acuidade Visual , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Incidência , Estudos Retrospectivos , Lasers de Excimer/uso terapêutico , Substância Própria/cirurgia , Miopia/epidemiologia , Miopia/cirurgia , Paquimetria Corneana
16.
Ophthalmic Res ; 66(1): 681-691, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36805961

RESUMO

INTRODUCTION: In proliferative diabetic retinopathy (PDR), retinal neovascularization is the essential pathogenic process that is linked to endothelial-to-mesenchymal transition (EndoMT) induced by high glucose (HG). This pathophysiological process may be regulated by a G-protein-coupled chemoattractant receptor FPR2 (mouse Fpr2), involved in inflammatory cell migration and proliferation. In the current study, we investigated the role of Fpr2 in regulating EndoMT and the underlying mechanisms during diabetic retinopathy progression. METHODS: FPR2 agonist or inhibitor was added to human microvascular endothelial cells (HMECs) exposed to normal glucose or HG. Morphologic, phenotypic, and functional changes of HMECs as well as the formation of microvasculature related to EndoMT were assessed. EndoMT biomarkers were detected in the retinal tissues of diabetic mice and fibrovascular epiretinal membranes (FVMs) from patients with PDR. RESULTS: HG upregulated FPR2 in HMECs, which triggered morphological changes, and the cells acquired mesenchymal phenotype, with enhanced cell migration, viability, and angiogenic process shown by tube formation and aortic ring sprouting. Inhibition of FPR2 attenuated HG-induced EndoMT and endothelial cell migration to form vessel-like tube structures. RNA sequence and protein analysis further revealed that inhibition of FPR2 decreased the expression of genes associated with EndoMT. ERK1/2 and P38 signaling pathway was activated in HMECs, promoting neovascularization in HG-induced EndoMT of HMECs. In vivo, increased expression of mesenchymal markers was detected in the retina of diabetic mice and FVMs from patients with PDR. FPR2 deficiency was associated with diminished EndoMT-related phenotypic changes in the retina of diabetic mice. CONCLUSIONS: FPR2 is actively involved in the progression of EndoMT that may contribute to the pathogenesis of PDR. Thus, FPR2 may be a potential therapeutic target for PDR.


Assuntos
Retinopatia Diabética , Transição Endotélio-Mesênquima , Receptores de Formil Peptídeo , Animais , Humanos , Camundongos , Diabetes Mellitus Experimental/complicações , Retinopatia Diabética/patologia , Células Endoteliais/metabolismo , Glucose , Proteínas de Ligação ao GTP/metabolismo , Receptores de Formil Peptídeo/genética , Receptores de Formil Peptídeo/metabolismo
17.
World J Surg Oncol ; 21(1): 39, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36750844

RESUMO

BACKGROUND: Carbon nanoparticles (CNPs) are a new tracer for lymph node mapping, which can quickly reach and develop lymph nodes through a lymphatic network. This research investigated the characteristics of systematic lymph node dissection and sentinel lymph node biopsy mapped with CNPs in endometrial carcinoma. METHODS: We first applied CNPs to systematic lymph node dissection in 18 endometrial carcinoma patients as the study group and another 18 endometrial carcinoma patients who were not injected with anything served as the control group. Then, we applied CNPs to sentinel lymph nodes biopsy in 54 endometrial carcinoma patients. All 54 patients received systematic lymph node dissection after sentinel lymph node biopsy. The detection rate, sensitivity, specificity, and accuracy of systematic lymph node dissection and sentinel lymph node biopsy by CNPs were respectively analyzed. A nomogram model for predicting the success of sentinel lymph node mapping was established. RESULTS: The average number of lymph nodes removed in the CNP-labeled study group was higher than that in the control group (p<0.001). CNPs improved the number of lymph nodes with a diameter ≤ 0.5cm. The detection rate, sensitivity, specificity, and accuracy of sentinel lymph nodes biopsy by CNPs for endometrial carcinoma were 70.4%, 100%, 100%, and 100%, respectively. The nomogram model included factors of long menopause time, cervical cyst, and hard cervical texture, and the area of ROC curve was 0.816. CONCLUSIONS: CNPs improve the detection rate of small lymph nodes. CNPs can trace sentinel lymph nodes in evaluating lymph node metastasis in endometrial carcinoma.


Assuntos
Neoplasias do Endométrio , Nanopartículas , Linfonodo Sentinela , Feminino , Humanos , Biópsia de Linfonodo Sentinela , Excisão de Linfonodo , Linfonodos/patologia , Linfonodo Sentinela/patologia , Neoplasias do Endométrio/patologia , Carbono
18.
BMC Musculoskelet Disord ; 24(1): 728, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700293

RESUMO

BACKGROUND: To investigate the risk factors for new vertebral compression fractures (NVCFs) after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs) and to create a nomogram to predict the occurrence of new postoperative fractures. METHODS: This was a retrospective analysis of the clinical data of 529 OVCF patients who received PKP treatment in our hospital from June 2017 to June 2020. Based on whether there were new fractures within 2 years after surgery, the patients were divided into a new fracture group and a nonnew fracture group. Univariate and multivariate analyses were used to determine the risk factors for the occurrence of NVCFs after surgery. The data were randomly divided into a training set (75%) and a testing set (25%). Nomograms predicting the risk of NVCF occurrence were created based on the results of the multivariate analysis, and performance was evaluated using receiver operating characteristic curves (ROCs), calibration curves, and decision curve analyses (DCAs). A web calculator was created to give clinicians a more convenient interactive experience. RESULTS: A total of 56 patients (10.6%) had NVCFs after surgery. The univariate analysis showed significant differences in sex and the incidences of cerebrovascular disease, a positive fracture history, and bone cement intervertebral leakage between the two groups (P < 0.05). The multivariate analysis showed that sex [OR = 2.621, 95% CI (1.030-6.673), P = 0.043], cerebrovascular disease [OR = 28.522, 95% CI (8.749-92.989), P = 0.000], fracture history [OR = 12.298, 95% CI (6.250-24.199), P = 0.000], and bone cement intervertebral leakage [OR = 2.501, 95% CI (1.029-6.082), P = 0.043] were independent risk factors that were positively associated with the occurrence of NVCFs. The AUCs of the model were 0.795 (95% CI: 0.716-0.874) and 0.861 (95% CI: 0.749-0.974) in the training and testing sets, respectively, and the calibration curves showed high agreement between the predicted and actual states. The areas under the decision curve were 0.021 and 0.036, respectively. CONCLUSION: Female sex, cerebrovascular disease, fracture history and bone cement intervertebral leakage are risk factors for NVCF after PKP. Based on this, a highly accurate nomogram was developed, and a webpage calculator ( https://new-fracture.shinyapps.io/DynNomapp/ ) was created.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas da Coluna Vertebral , Idoso , Humanos , Feminino , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/epidemiologia , Fraturas por Compressão/etiologia , Nomogramas , Cimentos Ósseos/efeitos adversos , Cifoplastia/efeitos adversos , Estudos Retrospectivos
19.
Int J Neurosci ; 133(3): 296-306, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33843429

RESUMO

OBJECTIVE: To determine the developmental characteristics of flash visual evoked potentials (FVEP) and pattern-reversal visual evoked potentials (PVEP) of healthy children. METHODS: The data were collected with a Keypoint Workstation 9033A07; 168 children (2 months-13 years) were tested with FVEP and 101 (4-13 years) were tested with PVEP. RESULTS: A triphasic waveform with clear components (N2, P2, and N3) was recorded steadily after 1 year, with occurrence rates over 97% at all frequencies. FVEP latency significantly decreased with age. The amplitude difference of FVEP was greater for binocular than monocular fields. FVEP amplitude increased and amplitude differences decreased with stimulation frequency. The occurrence rate of PVEP was 100% after 4 years, and PVEP latency was significantly prolonged with age. N75 and P100 amplitudes and the N75-P100 amplitude difference increased with field of vision. CONCLUSION: FVEP can be evoked in normal children at less than 2 Hz. Stimulation frequency can be adjusted to improve early detection and verification of subclinical lesions. The PVEP waveform is simple and stable, and its results are easier to analyze and interpret than FVEP, but it is limited by visual acuity and fixation force, whereas FVEP is affected less by visual acuity. but it is necessary to establish normal reference values of each age in each laboratory because of complicated analysis. According to the specific situation of the patient (vision, fixation) and clinical demand, we need to choose the right stimulation.


Assuntos
Potenciais Evocados Visuais , Humanos , Criança , Acuidade Visual , Exame Neurológico , Estimulação Luminosa
20.
Angew Chem Int Ed Engl ; 62(1): e202211387, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36131604

RESUMO

The tetracationic cyclophane, cyclobis(paraquat-p-phenylene), also known as the little blue box, constitutes a modular receptor that has facilitated the discovery of many host-guest complexes and mechanically interlocked molecules during the past 35 years. Its versatility in binding small π-donors in its tetracationic state, as well as forming trisradical tricationic complexes with viologen radical cations in its doubly reduced bisradical dicationic state, renders it valuable for the construction of various stimuli-responsive materials. Since the first reports in 1988, the little blue box has been featured in over 500 publications in the literature. All this research activity would not have been possible without the seminal contributions carried out by Siegfried Hünig, who not only pioneered the syntheses of viologen-containing cyclophanes, but also revealed their rich redox chemistry in addition to their ability to undergo intramolecular π-dimerization. This Review describes how his pioneering research led to the design and synthesis of the little blue box, and how this redox-active host evolved into the key component of molecular shuttles, switches, and machines.


Assuntos
Paraquat , Viologênios , Paraquat/química
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