RESUMO
Rechargeable lithium (Li) metal batteries face challenges in achieving stable cycling due to the instability of the solid electrolyte interphase (SEI). The Li-ion solvation structure and its desolvation process are crucial for the formation of a stable SEI on Li metal anodes and improving Li plating/stripping kinetics. This research introduces an interfacial desolvation coating technique to actively modulate the Li-ion solvation structure at the Li metal interface and regulate the participation of the electrolyte solvent in SEI formation. Through experimental investigations conducted using a carbonate electrolyte with limited compatibility to Li metal, the optimized desolvation coating layer, composed of 12-crown-4 ether-modified silica materials, selectively displaces strongly coordinating solvents while simultaneously enriching weakly coordinating fluorinated solvents at the Li metal/electrolyte interface. This selective desolvation and enrichment effect reduce solvent participation to SEI and thus facilitate the formation of a LiF-dominant SEI with greatly reduced organic species on the Li metal surface, as conclusively verified through various characterization techniques including XPS, quantitative NMR, operando NMR, cryo-TEM, EELS, and EDS. The interfacial desolvation coating technique enables excellent rate cycling stability (i.e., 1C) of the Li metal anode and prolonged cycling life of the Li||LiCoO2 pouch cell in the conventional carbonate electrolyte (E/C 2.6 g/Ah), with 80% capacity retention after 333 cycles.
RESUMO
Histone 2A monoubiquitination (uH2A) underscores a key epigenetic regulation of gene expression. In this report, we show that the deubiquitinase for uH2A, ubiquitin-specific peptidase 16 (USP16), is modified by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation involves the installation of the O-GlcNAc moiety to Ser/Thr residues. It crosstalks with Ser/Thr phosphorylation, affects protein-protein interaction, alters enzyme activity or protein folding, and changes protein subcellular localization. In our study, we first confirmed that USP16 is glycosylated on Thr203 and Ser214, as reported in a previous chemoenzymatic screen. We then discovered that mutation of the O-GlcNAcylation site Thr203, which is adjacent to deubiquitination-required Cys204, reduces the deubiquitination activity toward H2AK119ub in vitro and in cells, while mutation on Ser214 had the opposite effects. Using USP16 Ser552 phosphorylation-specific antibodies, we demonstrated that O-GlcNAcylation antagonizes cyclin-dependent kinase 1-mediated phosphorylation and promotes USP16 nuclear export. O-GlcNAcylation of USP16 is also required for deubiquitination of Polo-like kinase 1, a mitotic master kinase, and the subsequent chromosome segregation and cytokinesis. In summary, our study revealed that O-GlcNAcylation of USP16 at Thr203 and Ser214 coordinates deubiquitination of uH2A and Polo-like kinase 1, thus ensuring proper cell cycle progression.
Assuntos
Acetilglucosamina , Ubiquitina Tiolesterase , Ubiquitinação , Humanos , Acetilglucosamina/metabolismo , Transporte Ativo do Núcleo Celular , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Glicosilação , Células HEK293 , Células HeLa , Histonas/metabolismo , Fosforilação , Quinase 1 Polo-Like , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genéticaRESUMO
ConspectusThe directed synthesis and functionalization of porous crystalline materials pose significant challenges for chemists. The synergistic integration of different functionalities within an ordered molecular material holds great significance for expanding its applications as functional materials. The presence of coordination bonds connected by inorganic and organic components in molecular materials can not only increase the structural diversity of materials but also modulate the electronic structure and band gap, which further regulates the physical and chemical properties of molecular materials. In fact, porous crystalline materials with coordination bonds, which inherit the merits of both organic and inorganic materials, already showcase their superior advantages in optical, electrical, and magnetic applications. In addition to the inorganic components that provide structural rigidity, organic ligands of various types serve as crucial connectors in the construction of functional porous crystalline materials. In addition, redox activity can endow organic linkers with electrochemical activity, thereby making them a perfect platform for the study of charge transfer with atom-resolved single-crystal structures, and they can additionally serve as stimuli-responsive sites in sensor devices and smart materials.In this Account, we introduce the synthesis, structural characteristics, and applications of porous crystalline materials based on the famous redox-active units, tetrathiafulvalene (TTF) and its analogues, by primarily focusing on metal-organic frameworks (MOFs) and covalent organic frameworks (COFs). TTF, a sulfur-rich conjugated molecule with two reversible and easily accessible oxidation states (i.e., radical TTFâ¢+ cation and TTF2+ dication), and its analogues boast special electrical characteristics that enable them to display switchable redox activity and stimuli-responsive properties. These inherent properties contribute to the enhancement of the optical, electrical, and magnetic characteristics of the resultant porous crystalline materials. Moreover, delving into the charge transfer phenomena, which is key for the electrochemical process within these materials, uncovers a myriad of potential functional applications. The Account is organized into five main sections that correspond to the different properties and applications of these materials: optical, electrical, and magnetic functionalities; energy storage and conversion; and catalysis. Each section provides detailed discussions of synthetic methods, structural characteristics, the physical and chemical properties, and the functional performances of highlighted examples. The Account also discusses future directions by emphasizing the exploration of novel organic units, the transformation between radical cation TTFâ¢+ and dication TTF2+, and the integration of multifunctionalities within these frameworks to foster the development of smart materials for enhanced performance across diverse applications. Through this Account, we aim to highlight the massive potential of TTF and its analogues-based porous crystals in chemistry and material science.
RESUMO
The global pandemic and excessive use of antibiotics have raised concerns about environmental health, and efforts are being made to develop alternative bactericidal agents for disinfection. Metal-based nanomaterials and their derivatives have emerged as promising candidates for antibacterial agents due to their broad-spectrum antibacterial activity, environmental friendliness, and excellent biocompatibility. However, the reported antibacterial mechanisms of these materials are complex and lack a comprehensive understanding from a coherent perspective. To address this issue, a new perspective is proposed in this review to demonstrate the toxic mechanisms and antibacterial activities of metal-based nanomaterials in terms of energy conversion and electron transfer. First, the antimicrobial mechanisms of different metal-based nanomaterials are discussed, and advanced research progresses are summarized. Then, the biological intelligence applications of these materials, such as biomedical implants, stimuli-responsive electronic devices, and biological monitoring, are concluded based on trappable electrical signals from electron transfer. Finally, current improvement strategies, future challenges, and possible resolutions are outlined to provide new insights into understanding the antimicrobial behaviors of metal-based materials and offer valuable inspiration and instructional suggestions for building future intelligent environmental health.
Assuntos
Anti-Infecciosos , Nanoestruturas , Elétrons , Nanoestruturas/toxicidade , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , MetaisRESUMO
In this study, we investigated CD70 as a promising target for renal cell carcinoma (RCC) therapy and developed a potent chimeric antigen receptor T (CAR-T) cells for potential clinical testing. CD70, found to be highly expressed in RCC tumors, was associated with decreased survival. We generated CAR-T cells expressing VHH sequence of various novel nanobodies from immunized alpaca and a single-chain variable fragment (scFv) derived from human antibody (41D12). In our in vitro experiments, anti-CD70 CAR-T cells effectively eliminated CD70-positive tumor cells while sparing CD70-negative cells. The nanobody-based CAR-T cells demonstrated significantly higher production of cytokines such as IL-2, IFN-γ and TNF-É during co-culture, indicating their potential for enhanced functionality. In xenograft mouse model, these CAR-T cells exhibited remarkable anti-tumor activity, leading to the eradication of RCC tumor cells. Importantly, human T cell expansion after infusion was significantly higher in the VHH groups compared to the scFv CAR-T group. Upon re-challenging mice with RCC tumor cells, the VHH CAR-T treated group remained tumor-free, suggesting a robust and long-lasting anti-tumor response. These findings provide strong support for the potential of nanobody-based CD70 CAR-T cells as a promising therapeutic option for RCC. This warrants further development and consideration for future clinical trials and applications.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Carcinoma de Células Renais/terapia , Linfócitos T , Linhagem Celular Tumoral , Neoplasias Renais/terapia , Imunoterapia Adotiva , Ensaios Antitumorais Modelo de Xenoenxerto , Ligante CD27RESUMO
BACKGROUND: Pancreatic cancer is one of the most lethal malignancies and the lack of treatment options makes it more deadly. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has revolutionized cancer treatment and made great breakthroughs in treating hematological malignancies, however its success in treating solid cancers remains limited mainly due to the lack of tumor-specific antigens. On the other hand, the prolonged traditional manufacturing process poses challenges, taking 2 to 6 weeks and impacting patient outcomes. CD276 has recently emerged as a potential therapeutic target for anti-solid cancer therapy. Here, we investigated the efficacy of CD276 CAR-T and rapidly-manufactured CAR-T against pancreatic cancer. METHODS: In the present study, CD276 CAR-T was prepared by CAR structure carrying 376.96 scFv sequence, CD8 hinge and transmembrane domain, 4-1BB and CD3ζ intracellular domains. Additionally, CD276 rapidly-manufactured CAR-T (named CD276 Dash CAR-T) was innovatively developed by shortening the duration of ex vitro culture to reduce CAR-T manufacturing time. We evaluated the anti-tumor efficacy of CD276 CAR-T and further compared the functional assessment of Dash CAR-T and conventional CAR-T in vitro and in vivo by detecting the immunophenotypes, killing ability, expansion capacity and tumor-eradicating effect of CAR-T. RESULTS: We found that CD276 was strongly expressed in multiple solid cancer cell lines and that CD276 CAR-T could efficiently kill these solid cancer cells. Moreover, Dash CAR-T was successfully manufactured within 48-72 h and the functional validation was carried out subsequently. In vitro, CD276 Dash CAR-T possessed a less-differentiated phenotype and robust proliferative ability compared to conventional CAR-T. In vivo xenograft mouse model, CD276 Dash CAR-T showed enhanced anti-pancreatic cancer efficacy and T cell expansion. Besides, except for the high-dose group, the body weight of mice was maintained stable, and the state of mice was normal. CONCLUSIONS: In this study, we proved CD276 CAR-T exhibited powerful activity against pancreatic cancer cells in vitro and in vivo. More importantly, we demonstrated the manufacturing feasibility, acceptable safety and superior anti-tumor efficacy of CD276 Dash CAR-T generated with reduced time. The results of the above studies indicated that CD276 Dash CAR-T immunotherapy might be a novel and promising strategy for pancreatic cancer treatment.
Assuntos
Antígenos B7 , Imunoterapia Adotiva , Neoplasias Pancreáticas , Receptores de Antígenos Quiméricos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Humanos , Animais , Linhagem Celular Tumoral , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Imunoterapia Adotiva/métodos , Antígenos B7/metabolismo , Antígenos B7/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos , Proliferação de Células , Linfócitos T/imunologiaRESUMO
The introduction of superconductivity to the Dirac surface states of a topological insulator leads to a topological superconductor, which may support topological quantum computing through Majorana zero modes1,2. The development of a scalable material platform is key to the realization of topological quantum computing3,4. Here we report on the growth and properties of high-quality (Bi,Sb)2Te3/graphene/gallium heterostructures. Our synthetic approach enables atomically sharp layers at both hetero-interfaces, which in turn promotes proximity-induced superconductivity that originates in the gallium film. A lithography-free, van der Waals tunnel junction is developed to perform transport tunnelling spectroscopy. We find a robust, proximity-induced superconducting gap formed in the Dirac surface states in 5-10 quintuple-layer (Bi,Sb)2Te3/graphene/gallium heterostructures. The presence of a single Abrikosov vortex, where the Majorana zero modes are expected to reside, manifests in discrete conductance changes. The present material platform opens up opportunities for understanding and harnessing the application potential of topological superconductivity.
RESUMO
Continuous-state network spreading models provide critical numerical and analytic insights into transmission processes in epidemiology, rumor propagation, knowledge dissemination, and many other areas. Most of these models reflect only local features such as adjacency, degree, and transitivity, so can exhibit substantial error in the presence of global correlations typical of empirical networks. Here, we propose mitigating this limitation via a network property ideally suited to capturing spreading. This is the network correlation dimension, which characterizes how the number of nodes within range of a source typically scales with distance. Applying the approach to susceptible-infected-recovered processes leads to a spreading model which, for a wide range of networks and epidemic parameters, can provide more accurate predictions of the early stages of a spreading process than important established models of substantially higher complexity. In addition, the proposed model leads to a basic reproduction number that provides information about the final state not available from popular established models.
RESUMO
Subsampling is a practical strategy for analyzing vast survival data, which are progressively encountered across diverse research domains. While the optimal subsampling method has been applied to inferences for Cox models and parametric accelerated failure time (AFT) models, its application to semi-parametric AFT models with rank-based estimation have received limited attention. The challenges arise from the non-smooth estimating function for regression coefficients and the seemingly zero contribution from censored observations in estimating functions in the commonly seen form. To address these challenges, we develop optimal subsampling probabilities for both event and censored observations by expressing the estimating functions through a well-defined stochastic process. Meanwhile, we apply an induced smoothing procedure to the non-smooth estimating functions. As the optimal subsampling probabilities depend on the unknown regression coefficients, we employ a two-step procedure to obtain a feasible estimation method. An additional benefit of the method is its ability to resolve the issue of underestimation of the variance when the subsample size approaches the full sample size. We validate the performance of our estimators through a simulation study and apply the methods to analyze the survival time of lymphoma patients in the surveillance, epidemiology, and end results program.
RESUMO
Mass spectrometry, coupled with innovative crosslinking techniques to decode protein conformations and interactions through uninterrupted signal connections, has undergone remarkable progress in recent years. It is crucial to develop selective crosslinking reagents that minimally disrupt protein structure and dynamics, providing insights into protein network regulation and biological functions. Compared to traditional crosslinkers, new bifunctional chemical crosslinkers exhibit high selectivity and specificity in connecting proximal amino acid residues, resulting in stable molecular crosslinked products. The conjugation with specific amino acid residues like lysine, cysteine, arginine and tyrosine expands the XL-MS toolbox, enabling more precise modeling of target substrates and leading to improved data quality and reliability. Another emerging crosslinking method utilizes unnatural amino acids (UAAs) derived from proximity-enabled reactivity with specific amino acids or sulfur-fluoride exchange (SuFEx) reactions with nucleophilic residues. These UAAs are genetically encoded into proteins for the formation of specific covalent bonds. This technique combines the benefits of genetic encoding for live cell compatibility with chemical crosslinking, providing a valuable method for capturing transient and weak protein-protein interactions (PPIs) for mapping PPI coordinates and improving the pharmacological properties of proteins. With continued advancements in technology and applications, crosslinking mass spectrometry is poised to play an increasingly significant role in guiding our understanding of protein dynamics and function in the future.
RESUMO
Natural medicines are a valuable resource for the development of new drugs. However, factors such as low solubility and poor bioavailability of certain constituents have hindered their efficacy and potential as pharmaceuticals. Structural modification of natural products has emerged as an important research area for drug development. Phosphorylation groups, as crucial endogenous active groups, have been extensively utilized for structural modification and development of new drugs based on natural molecules. Incorporating phosphate groups into natural molecules not only enhances their stability, bioavailability, and pharmacological properties, but also improves their biological activity by altering their charge, hydrogen bonding, and spatial structure. This review summarizes the phosphorylation mechanism, modification approaches, and biological activity enhancement of natural medicines. Notably, compounds such as polysaccharides, flavonoids, terpenoids, anthraquinones, and coumarins exhibit increased antioxidation, anticancer, antiviral, immune regulatory, Antiaging, enzyme inhibition, bacteriostasis, liver protection, and lipid-lowering effects following phosphorylation modification.
Assuntos
Produtos Biológicos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Fosforilação , Humanos , Animais , Flavonoides/química , Flavonoides/metabolismo , Flavonoides/farmacologia , Polissacarídeos/química , Polissacarídeos/metabolismo , Antioxidantes/farmacologia , Antioxidantes/química , Antraquinonas/química , Antraquinonas/farmacologiaRESUMO
BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.
RESUMO
Coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global public health challenge. This disease causes damage not only to the respiratory system, affecting the normal physiological function of the lungs, but also to other vital organs, such as the heart and testicles. Existing studies have shown that co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 is the main mechanism by which SARS-CoV-2 invades host cells. Angiotensin-converting enzyme 2-expressing cells are widespread in the corpus cavernosum, reproductive tract and testis of men, which has raised concerns. Furthermore, abnormal sex hormone levels and decreased semen parameters were observed in coronavirus disease 2019 patients. This study comprehensively assessed the effects of SARS-CoV-2 infection on the testis, semen parameters, sex hormone levels and erectile function, and discussed possible transmission routes during sexual intercourse and the effect of vaccination on male fertility.
Assuntos
COVID-19 , Humanos , Masculino , COVID-19/prevenção & controle , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2 , Peptidil Dipeptidase A , Fertilidade , Hormônios Esteroides Gonadais , VacinaçãoRESUMO
The contact wire wear is an important parameter to ensure the safety operation of electric railways. The contact wire may break if the wear is serious, which leads to transportation interruptions. This study proposes an optical measurement method of contact wire wear, using stereovision technology. The matching method of stereovision based on line-scan cameras is proposed. A lookup-table method is developed to exactly determine the image resolution caused by the contact wire being in different spatial positions. The wear width of the contact wire is extracted from catenaries' images, and the residual thickness of the contact wire is calculated. The method was verified by field tests. The round-robin tests of the residual thickness at the same location present excellent measurement repetitiveness. The maximum difference value between dynamic test results and ground measurement results is 0.13 mm. This research represents a potential way to implement condition-based maintenance for contact wire wear in the future in order to improve the maintenance efficiency and ensure the safety of catenary infrastructure.
RESUMO
Electrocatalytic nitric oxide reduction (eNORR) to ammonia (NH3) provides an environmental route to alleviate NO pollution and yield great-value chemicals. The evolution of eNORR has been primarily hindered, however, by the poor reaction kinetics and low solubility of the NO in aqueous electrolytes. Herein, we have rationally designed a cobalt-based composite with a heterostructure as a highly efficient eNORR catalyst. In addition, by integrating boron to modulate the electronic structure, the catalyst CoB/Co@C delivered a significant NH3 yield of 315.4 µmol h-1 cm-2 for eNORR and an outstanding power density of 3.68 mW cm-2 in a Zn-NO battery. The excellent electrochemical performance of CoB/Co@C is attributed to the enrichment of NO by cobalt and boron dual-site adsorption and fast charge-transfer kinetics. It is demonstrated that the boron is pivotal in the enhancement of NO, the suppression of hydrogen evolution, and Co oxidation to boost eNORR performance.
RESUMO
2,6-pyridine dicarboxylic acid (DPA) is an exceptional biomarker of notorious anthrax spores. Therefore, the rapid, sensitive, and selective quantitative detection of DPA is extremely significant and urgent. This paper reports a Zn(II) metal-organic framework with the formula of {[Zn6(NDA)6(DPBT)3] 2H2O·3DMF}n (MOF-1), which consists of 2,6-naphthalenedicarboxylic acid (2,6-NDA), 4,7-di(4-pyridyl)-2,1,3-benzothiadiazole (DPBT), and Zn(II) ions. Structural analysis indicated that MOF-1 is a three-dimensional (3D) network which crystallized in the monoclinic system with the C2/c space group, revealing high pH, solvent, and thermal stability. Luminescence sensing studies demonstrated that MOF-1 had the potential to be a highly selective, sensitive, and recyclable fluorescence sensor for the identification of DPA. Furthermore, fluorescent test paper was made to detect DPA promptly with color changes. The enhancement mechanism was established by the hydrogen-bonding interaction and photoinduced electron transfer transition between MOF-1 and DPA molecules.
Assuntos
Biomarcadores , Estruturas Metalorgânicas , Tiadiazóis , Zinco , Estruturas Metalorgânicas/química , Zinco/química , Zinco/análise , Tiadiazóis/química , Antraz/diagnóstico , Ácidos Picolínicos/química , Ácidos Picolínicos/análise , Bacillus anthracis , Modelos MolecularesRESUMO
OBJECTIVE: Deep venous thrombosis (DVT) is a common complication in patients with spinal fractures caused by high-energy injuries. Early identification of patients at high risk of postoperative DVT is essential for the prevention of thrombosis. This study aimed to develop and validate a prediction model based on a nomogram to predict DVT in patients with spinal fractures caused by high-energy injuries. METHODS: Clinical data were collected from 936 patients admitted to our hospital between January 2016 and December 2021 with spinal fractures caused by high-energy injuries. Multivariate logistic regression analysis was used to identify the risk factors for postoperative DVT and to develop a nomogram. The predictive performance of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and calibration curve. RESULTS: The incidence of preoperative DVT was 15.38% (144/936). The postoperative incidence of DVT was 20.5% (192/936). The multivariate analysis revealed that age, operation time, blood transfusion, duration of bed rest, American Spinal Injury Association (ASIA) score and D-dimer were risk factors for postoperative DVT. The area under the ROC curve of the nomogram was 0.835 and the calibration curve showed good calibration. CONCLUSIONS: The nomogram showed a good ability to predict postoperative DVT in patients with spinal fractures caused by high-energy injuries, which may benefit pre- and postoperative DVT prophylaxis strategy development.
Assuntos
Fraturas da Coluna Vertebral , Trombose Venosa , Humanos , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/cirurgia , Nomogramas , Fatores de Risco , Medição de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Injectable poly-D, L-lactic acid (PDLLA), under the brand name of AestheFill (Chaeum Pharma GmbH, Berlin, Germany), is a biocompatible, biodegradable, and biostimulatory product used to correct soft tissue volume loss. Its efficacy and safety have not been fully studied in a large cohort. OBJECTIVES: To evaluate the efficacy and safety of a novel dermal filler injectable poly-D, L-lactic acid. METHODS: This is an evaluator-blinded, multi-centered, randomized controlled trial to compare the efficacy and safety of PDLLA versus hyaluronic acid in the correction of nasolabial fold. Two hundred and sixty patients with moderate to severe nasolabial fold were enrolled and randomized to treatment group (PDLLA) or control group (hyaluronic acid). Each patient received PDLLA or hyaluronic acid injection for nasolabial fold augmentation and followed up for 52 weeks. Wrinkle Severity Rating Scale (WSRS) and Global Aesthetic Improvement Scale (GAIS) were used to evaluate topical nasolabial fold augmentation and overall improvement, respectively. RESULTS: At 24 weeks, 67.6% of patients in the PDLLA group had at least 1-grade improvement in WSRS, compared to 60.9% of patients in the control group with at least 1-grade improvement in WSRS (p<0.05). At each visit, PDLLA group showed more improvement from the baseline in WSRS than the control group. PDLLA was safe and well-tolerated with no severe adverse events. CONCLUSIONS: PDLLA shows non-inferior efficacy in correcting nasolabial fold compared to hyaluronic acid.
RESUMO
Correlations between exchange rates are valuable for illuminating the dynamics of international trade and the financial dynamics of countries. This paper explores the changing interactions of the US foreign exchange market based on detrended cross-correlation analysis. First, we propose an objective way to choose a time scale parameter appropriate for comparing different samples by maximizing the summed magnitude of all DCCA coefficients. We then build weighted signed networks under this optimized time scale, which can clearly display the complex relationships between different exchange rates. Our study shows negative cross-correlations have become pyramidally rare in the past three decades. Both the number and strength of positive cross-correlations have grown, paralleling the increase in global interconnectivity. The balanced strong triads are identified subsequently after the network centrality analysis. Generally, while the strong development links revealed by foreign exchange have begun to spread to Asia since 2010, Europe is still the center of world finance, with the euro and Danish krone consistently maintaining the closest balanced development relationship. Finally, we propose a fluctuation propagation algorithm to investigate the propagation pattern of fluctuations in the inferred exchange rate networks. The results show that, over time, fluctuation propagation patterns have become simpler and more predictable.
RESUMO
OBJECTIVES: To determine the genomic features of IMP-4-producing Klebsiella pneumoniae isolates recovered from paediatric patients and the transmission dynamics of blaIMP-4. METHODS: IMP-producing K. pneumoniae isolates were collected from paediatric patients in Shanghai Children's Medical Center from 2013 to 2020. WGS was performed for all isolates, and the complete genomes of three IMP-4-producing isolates were generated. The distribution of blaIMP-4-harbouring plasmids was determined, and a conjugation assay was employed to investigate the horizontal transfer of blaIMP-4-harbouring plasmids. RESULTS: We collected 21 blaIMP-carrying K. pneumoniae isolates, with IMP-4 (16/21, 76.2%) as the predominant subtype, followed by IMP-8 (nâ=â3) and IMP-26 (nâ=â2). IMP-4-producing isolates displayed a diverse population structure and all blaIMP-4 genes were located on plasmids, including IncN (nâ=â9), IncHI5 (nâ=â5), IncFII(K) (nâ=â1) and IncFII(pKP91) (nâ=â1), although only IncN plasmids were conjugative. Clonal transmission of ST101 strains carrying IncHI5 blaIMP-4-harbouring plasmids was observed, and the acquisition of blaIMP-4 by the international high-risk ST101 clone constituted a novel combination of ST101 clone and carbapenemase genes. Plasmid analysis demonstrated that the conjugal transfer of the IncHI5 blaIMP-4-harbouring plasmid might be blocked by the ST101 bacterial host. CONCLUSIONS: The horizontal transfer of IncN plasmids and clonal spread of the international high-risk ST101 clone facilitated the nosocomial dissemination of blaIMP-4 among K. pneumoniae. The emerging IMP-4-producing ST101 clone displays diverse combinations of carbapenemase genes, and this clone could be a continually evolving threat and warrants prospective monitoring.