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1.
Sci Bull (Beijing) ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36681587

RESUMO

Inorganic CsPbI3 perovskite is an important photovoltaic material due to its suitable band gap and high chemical stability. However, it is a challenge to grow high-quality CsPbI3 perovskite because the stability of perovskite phase is low and is sensitive to solvent. So far, most of CsPbI3 perovskites in high-performance perovskite solar cells (PSCs) were prepared from N,N-dimethylformamide, a highly toxic solvent, and no successful case has been reported for dimethyl sulfoxide (DMSO), which is environmentally-friendly with considerably higher complexation capability. Herein, we reveal that forming DMSO-based adduct is the main cause for limiting the quality of CsPbI3 perovskite from DMSO-based solutions, which would inhibit the formation of DMAPbI3 (DMA = dimethylammonium, (CH3)2NH2+) intermediate. Then, by introducing a vacuum treatment, DMSO molecules could be efficiently extracted from the adduct to induce the formation of DMAPbI3 intermediate. After annealing, the intermediate is transitioned to the CsPbI3 perovskite with enhanced crystallinity, high orientation, low defect density, and high uniformity. By using the CsPbI3 perovskite as a light absorber, the PSCs based on carbon electrode (C-PSCs) achieve an efficiency of 16.7%, a new record for inorganic C-PSCs.

2.
Cells ; 12(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36672154

RESUMO

Salicylic acid (SA) is a phenolic compound produced by all plants that has an important role in diverse processes of plant growth and stress responses. SA is also the principal metabolite of aspirin and is responsible for many of the anti-inflammatory, cardioprotective and antitumor activities of aspirin. As a result, the number of identified SA targets in both plants and humans is large and continues to increase. These SA targets include catalases/peroxidases, metabolic enzymes, protein kinases and phosphatases, nucleosomal and ribosomal proteins and regulatory and signaling proteins, which mediate the diverse actions of SA in plants and humans. While some of these SA targets and actions are unique to plants or humans, many others are conserved or share striking similarities in the two types of organisms, which underlie a host of common biological processes that are regulated or impacted by SA. In this review, we compare shared and related SA targets and activities to highlight the common nature of actions by SA as a hormone in plants versus a therapeutic agent in humans. The cross examination of SA targets and activities can help identify new actions of SA and better explain their underlying mechanisms in plants and humans.


Assuntos
Plantas , Ácido Salicílico , Humanos , Ácido Salicílico/metabolismo , Plantas/metabolismo , Aspirina
3.
Org Lett ; 25(2): 421-425, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36622839

RESUMO

α-(3-Indolyl)ketones are essential building blocks for the generation of biologically active molecules. We described a new method for the direct assembly of α-(3-indolyl)ketones through the cascade reaction of 2-alkynyl aryl azides with enecarbamates, in which the in situ generated α-imino gold carbene intermediate was trapped by enecarbamate to achieve umpolung reactivity of indole at the 3-position.

4.
Int J Biol Sci ; 19(1): 311-330, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36594091

RESUMO

Non-alcoholic fatty liver disease (NAFLD), as one of the main causes of chronic liver disease worldwide, encompasses a spectrum of liver conditions that are not caused by other etiology, such as overt alcohol consumption, from simple steatosis to more aggressive non-alcoholic steatohepatitis (NASH) that involves liver inflammation and fibrosis, and to the lethal cirrhosis that may result in liver cancer and liver failure. The molecular mechanisms governing the transition from steatosis to NASH remain not fully understood, but the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis, which also correlate with disease progression. With the tremendous advancement in the field of lipidomics in last two decades, a better understanding of the specific role of sphingolipids in fatty liver disease has taken shape. Among the numerous lipid subtypes that accumulate, ceramides are particularly impactful. On the one hand, excessive ceramides deposition in the liver cause hepatic steatosis. On the other hand, ceramides as lipotoxic lipid have significant effects on hepatic inflammation, apoptosis and insulin resistance that contribute to NAFLD. In this review, we summarize and evaluate current understanding of the multiple roles of ceramides in the onset of fatty liver disease and the pathogenic mechanisms underlying their effects, and we also discuss recent advances and challenges in pharmacological interventions targeting ceramide metabolism for the treatment of NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ceramidas/metabolismo , Ceramidas/farmacologia , Ceramidas/uso terapêutico , Fosfatos/metabolismo , Fígado/metabolismo , Esfingolipídeos/metabolismo
5.
bioRxiv ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36712101

RESUMO

Force can modulate the properties and functions of macromolecules by inducing conformational changes, such as coiling/uncoiling, zipping/unzipping, and folding/unfolding. Here we compared force-modulated bending/unbending of two purified integrin ectodomains, α 5 ß 1 and α V ß 3 , using single-molecule approaches. Similar to previously characterized mechano-sensitive macromolecules, the conformation of α 5 ß 1 is determined by a threshold head-to-tail tension, suggesting a canonical energy landscape with a deep energy well that traps the integrin in the bent state until sufficient force tilts the energy landscape to accelerate transition to the extended state. By comparison, α V ß 3 exhibits bi-stability even without force and can spontaneously transition between the bent and extended conformations in a wide range of forces without energy supplies. Molecular dynamics simulations revealed consecutive formation and disruption of 7 hydrogen bonds during α V ß 3 bending and unbending, respectively. Accordingly, we constructed an energy landscape with hexa-stable intermediate states to break down the energy barrier separating the bent and extended states into smaller ones, making it possible for the thermal agitation energy to overcome them sequentially and to be accumulated and converted into mechanical work required for α V ß 3 to bend against force. Our study elucidates the different inner workings of α 5 ß 1 and α V ß 3 at the sub-molecular level, sheds lights on how their respectively functions are facilitated by their distinctive mechano-sensitivities, helps understand their signal initiation processes, and provides critical concepts and useful design principles for engineering of protein-based biomechanical nanomachines.

6.
FASEB J ; 37(1): e22699, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36520055

RESUMO

Cardiac fibrosis is an essential pathological process in pressure overload (PO)-induced heart failure. Recently, myocyte-fibroblast communication is proven to be critical in heart failure, in which, pathological growth of cardiomyocytes (CMs) may promote fibrosis via miRNAs-containing exosomes (Exos). Peli1 regulates the activation of NF-κB and AP-1, which has been demonstrated to engage in miRNA transcription in cardiomyocytes. Therefore, we hypothesized that Peli1 in CMs regulates the activation of cardiac fibroblasts (CFs) through an exosomal miRNA-mediated paracrine mechanism, thereby promoting cardiac fibrosis. We found that CM-conditional deletion of Peli1 improved PO-induced cardiac fibrosis. Moreover, Exos from mechanical stretch (MS)-induced WT CMs (WT MS-Exos) promote activation of CFs, Peli1-/- MS-Exos reversed it. Furthermore, miRNA microarray and qPCR analysis showed that miR-494-3p was increased in WT MS-Exos while being down regulated in Peli1-/- MS-Exos. Mechanistically, Peli1 promoted miR-494-3p expression via NF-κB/AP-1 in CMs, and then miR-494-3p induced CFs activation by inhibiting PTEN and amplifying the phosphorylation of AKT, SMAD2/3, and ERK. Collectively, our study suggests that CMs Peli1 contributes to myocardial fibrosis via CMs-derived miR-494-3p-enriched exosomes under PO, and provides a potential exosomal miRNA-based therapy for cardiac fibrosis.


Assuntos
Comunicação Celular , Exossomos , Insuficiência Cardíaca , Miócitos Cardíacos , Humanos , Exossomos/genética , Exossomos/metabolismo , Fibrose/etiologia , Fibrose/genética , Fibrose/metabolismo , Fibrose/patologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fator de Transcrição AP-1/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Cardiopatias/etiologia , Cardiopatias/genética , Cardiopatias/metabolismo , Cardiopatias/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Comunicação Celular/genética , Comunicação Celular/fisiologia
7.
Pancreatology ; 23(1): 98-104, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36577553

RESUMO

BACKGROUND/OBJECTIVES: As the most frequent functional pancreatic neuroendocrine tumor, insulinomas may cause a plethora of symptoms and severe impairment in the living of patients by endogenous hyperinsulinemia and subsequent hypoglycemia. Surgery has been regarded as the first choice although a high risk of complications. Ethanol ablation is a promising non-surgical option that could achieve tumor shrinking in a short-term period. But the impact of symptom control and the long-term efficacy lack sufficient and good-quality evidence. METHODS: A total number of 14 endoscopic ultrasonography-guided ethanol ablations were performed in 9 patients between September 2016 and September 2018 in Peking Union Medical College Hospital. The data were collected and prospectively analyzed. RESULTS: The follow-up duration ranged from 21 to 1567 days in 9 patients, with a median of 994 days. 4 patients were free from relapse during a median follow-up of 1108 days (range: 994-1567 days). In 5 patients who suffered relapses, the median duration with symptom relief after the first ablation was 128 days (range: 13-393 days). If only repeated ablation was taken into consideration, the median duration with symptom relief was 26 days (range: 1-516 days). No complications happened during the procedures. The severe complication rate after the first ablation was 0.0% (0/9), compared to 7.14% (1/14) if each procedure was counted separately. The only severe complication documented was acute pancreatitis which was completely relieved after symptomatic treatment. CONCLUSIONS: For patients who are not suitable for surgical resections, endoscopic ultrasonography-guided ethanol ablation of insulinomas could be an effective and safe alternative to relieve symptoms of hypoglycemia.


Assuntos
Hipoglicemia , Insulinoma , Neoplasias Pancreáticas , Pancreatite , Humanos , Insulinoma/diagnóstico por imagem , Insulinoma/cirurgia , Etanol/uso terapêutico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/complicações , Endossonografia , Doença Aguda , Resultado do Tratamento , Pancreatite/complicações , Recidiva Local de Neoplasia , Hipoglicemia/etiologia
8.
J Agric Food Chem ; 71(1): 223-233, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36547223

RESUMO

Understanding the gene regulatory basis of plant response to heavy metals (HMs) is fundamental for the management of food safety and security. However, a comprehensive and comparative view of the plant responses to different HMs is still lacking. Here, we compared root transcriptomes in common bean under 9 HM treatments at 50 µM for three time points each. Cd, Cr, Co, Ni, and Pb caused most severe morphological and/or biochemical retardations. A total of 448 genes were found to be responsive to all nine HMs, which were mostly involved in photosynthesis, oxidization-reduction, and ion binding. Cd and Cu triggered the greatest number of unique differentially expressed genes (DEG)s, which were predominantly related to cellular transport/localization in the former and RNA binding in the latter. Short-term and prolonged HM treatments shaped very different DEG patterns. Weighted gene co-expression network analysis identified six co-expression modules showing exceptionally high transcripts abundance in specific HM × time scenarios. We experimentally verified the promoter activity of the gene GIP1 and the novel function of XTH23 under Cu/Cd stress. Collectively, the transcriptomic atlas provides valuable resources for better understanding the common and unique mechanisms of plant response to different HMs and offers a mass of candidate target genes/promoters for genetic engineering.


Assuntos
Metais Pesados , Phaseolus , Poluentes do Solo , Transcriptoma , Cádmio/toxicidade , Cádmio/análise , Metais Pesados/toxicidade , Metais Pesados/análise , Engenharia Genética , Poluentes do Solo/toxicidade , Poluentes do Solo/análise
9.
Clin Epigenetics ; 14(1): 164, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36461092

RESUMO

BACKGROUND: The role of JAM3 in different tumors is controversial. The epigenetic regulation and the mechanism of JAM3 remain to be elucidated in human esophageal cancer (EC). METHODS: Eleven EC cell lines, 49 cases of esophageal intraepithelial neoplasia (EIN) and 760 cases of primary EC samples were employed. Methylation-specific polymerase chain reaction, immunohistochemistry, MTT, western blot and xenograft mouse models were applied in this study. RESULTS: The inverse association between RNA expression and promoter region methylation of JAM3 was found by analyzing 185 cases of EC samples extracted from the TCGA database (p < 0.05). JAM3 was highly expressed in KYSE450, KYSE520, TE1 and YES2 cells, low level expressed in KYSE70 cells and unexpressed in KYSE30, KYSE150, KYSE410, KYSE510, TE13 and BIC1 cells. JAM3 was unmethylated in KYSE450, KYSE520, TE1 and YES2 cells, partial methylated in KYSE70 cells and completely methylated in KYSE30, KYSE150, KYSE410, KYSE510, TE13 and BIC1 cells. The expression of JAM3 is correlated with methylation status. The levels of JAM3 were unchanged in KYSE450, KYSE520, TE1 and YES2 cells, increased in KYSE70 cells and restored expression in KYSE30, KYSE150, KYSE410, KYSE510, TE13 and BIC1 cells after 5-aza-2'-deoxycytidine treatment, suggesting that the expression of JAM3 is regulated by promoter region methylation. JAM3 was methylated in 26.5% (13/49) of EIN and 51.1% (388/760) of primary EC, and methylation of JAM3 was associated significantly with tumor differentiation and family history (all p < 0.05). Methylation of JAM3 is an independent prognostic factor of poor 5-year overall survival (p < 0.05). JAM3 suppresses cell proliferation, colony formation, migration and invasion and induces G1/S arrest and apoptosis in EC. Further study demonstrated that JAM3 suppressed EC cells and xenograft tumor growth by inhibiting Wnt/ß-catenin signaling. CONCLUSION: JAM3 is frequently methylated in human EC, and the expression of JAM3 is regulated by promoter region methylation. JAM3 methylation is an early detection and prognostic marker of EC. JAM3 suppresses EC growth both in vitro and in vivo by inhibiting Wnt signaling.


Assuntos
Epigênese Genética , Neoplasias Esofágicas , Humanos , Camundongos , Animais , Via de Sinalização Wnt , Metilação de DNA , Neoplasias Esofágicas/genética , Processamento de Proteína Pós-Traducional , Decitabina , Moléculas de Adesão Celular/genética , Imunoglobulinas
11.
Materials (Basel) ; 15(23)2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36499785

RESUMO

The dispersibility of flexible polymer chains present at the emulsion's interface between the dispersed and continuous phase has obvious effects on rheology and dielectric properties of the whole emulsion. Cellulose nanofiber (CNF)-based Pickering emulsions are good systems to research these properties with respect to their microscopic phase structure, dielectric, and rheological properties by using CNF as a water-dispersible Pickering emulsifier, liquid paraffin as an oil phase, and didodecyldimethylammonium bromide (DDAB) as a cationic auxiliary surfactant. The CNF and DDAB contents were systematically varied while the water-to-paraffin oil ratio was kept constant to discern the influence of the Pickering emulsifiers. Polarized optical microscopic images reveal that the droplets tend to shrink at higher CNF content but grow bigger when increasing the DDAB content, which is proved by fluorescence analysis of the CNF dispersibility with varying DDAB content. The dielectric damping exhibits a minimum, whose value decreases with increasing DDAB and CNF content. Increasing the DDAB content promotes the solubilization of CNF in the aqueous phase, which will increase the overall viscosity and yield points. Similarly, a higher CNF content leads to a higher viscosity and yield point, but at high DDAB contents, the viscosity function exhibits an S-shape at intermediate CNF contents. To evaluate the results further, they were compared with CNF dispersions (without oil phase), which showed a surfactant effect slightly on maximum stress but strongly on yield stress τy, indicating that DDAB can promote the formation of a CNF network rather than the viscosity of the whole system. This paper provides information on how a systematical variation of the composition influences morphology and physico-chemical interactions as detected by broadband dielectric spectroscopy and rheological behavior.

12.
Plant J ; 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36495441

RESUMO

COP1 is a critical repressor of plant photomorphogenesis in darkness. However, COP1 plays distinct roles in the photoreceptor UVR8 pathway in Arabidopsis thaliana. COP1 interacts with ultraviolet B (UV-B)-activated UVR8 monomers and promotes their retention and accumulation in the nucleus. Moreover, COP1 has a function in UV-B signaling, which involves the binding of its WD40 domain to UVR8 and HY5 via conserved Val-Pro (VP) motifs of these proteins. UV-B-activated UVR8 interacts with COP1 via both the core domain and the VP motif, leading to the displacement of HY5 from COP1 and HY5 stabilization. However, it remains unclear whether the function of COP1 in UV-B signaling is solely dependent on its VP motif binding capacity and whether UV-B regulates the subcellular localization of COP1. Based on published structures of the COP1 WD40 domain, we generated a COP1 variant with a single amino acid substitution, COP1C509S , which cannot bind to VP motifs but retains the ability to interact with the UVR8 core domain. UV-B only marginally increased nuclear YFP-COP1 levels and significantly promoted YFP-COP1 accumulation in the cytosol, but did not exert the same effects on YFP-COP1C509S . Thus, the full UVR8-COP1 interaction is important for COP1 accumulation in the cytosol. Notably, UV-B signaling including activation of HY5 transcription was obviously inhibited in the Arabidopsis lines expressing YFP-COP1C509S , which cannot bind VP motifs. We conclude that the full binding of UVR8 to COP1 leads to the predominant accumulation of COP1 in the cytosol and that COP1 has an additional function in UV-B signaling besides VP binding-mediated protein destabilization.

13.
Phys Rev Lett ; 129(23): 231101, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36563204

RESUMO

For the newly discovered W-boson mass anomaly, one of the simplest dark matter (DM) models that can account for the anomaly without violating other astrophysical and experimental constraints is the inert two Higgs doublet model, in which the DM mass (m_{S}) is found to be within ∼54-74 GeV. In this model, the annihilation of DM via SS→bb[over ¯] and SS→WW^{*} would produce antiprotons and gamma rays, and may account for the excesses identified previously in both particles. Motivated by this, we reanalyze the AMS-02 antiproton and Fermi-LAT Galactic center γ-ray data. For the antiproton analysis, the novel treatment is the inclusion of the charge-sign-dependent three-dimensional solar modulation model as constrained by the time-dependent proton data. We find that the excess of antiprotons is more distinct than previous results based on the force-field solar modulation model. The interpretation of this excess as the annihilation of SS→WW^{*} (SS→bb[over ¯]) requires a DM mass of ∼40-80 (40-60) GeV and a velocity-averaged cross section of O(10^{-26}) cm^{3} s^{-1}. As for the γ-ray data analysis, besides adopting the widely used spatial template fitting, we employ an orthogonal approach with a data-driven spectral template analysis. The fitting to the GeV γ-ray excess yields DM model parameters overlapped with those to fit the antiproton excess via the WW^{*} channel. The consistency of the DM particle properties required to account for the W-boson mass anomaly, the GeV antiproton excess, and the GeV γ-ray excess suggests a common origin of them.

14.
Ann Palliat Med ; 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36571170

RESUMO

BACKGROUND: To compare the research hotspots of infections with the Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 2019 (COVID-19) pandemic and to identify future research trends. METHODS: Studies about Delta and Omicron variant infections published over the last 3 years were retrieved from the Web of Science (WoS) database. A comparative bibliometric analysis was conducted through machine learning and visualization tools, including VOSviewer, Bibliographic Item Co-Occurrence Matrix Builder, and Graphical Clustering Toolkit. Research hotspots and trends in the field were analyzed, and the contributions and collaborations of countries, institutions, and authors were documented. A cross-sectional analysis of the relevant studies registered at ClinicalTrials.gov was also performed to clarify the direction of future research. RESULTS: A total of 1,787 articles distributed in 107 countries and 374 publications from 77 countries focused on the Delta and Omicron variants were included in our bibliometric analysis. The top five productive countries in both variants were the USA, China, the UK, India, and Germany. In 5,999 and 1,107 keywords identified from articles on the Delta and Omicron, the top two frequent keywords were the same: "COVID-19" (occurrence: 713, total link strength: 1,525 in Delta; occurrence: 137, total link strength: 354 in Omicron), followed by "SARS-CoV-2" (occurrence: 553, total link strength: 1,478 in Delta; occurrences 132, total link strength: 395 in Omicron). Five theme clusters from articles on Delta variant were identified: transmission, molecular structure, activation mode, epidemiology, and co-infection. While other three theme clusters were recognized for the Omicron variant: vaccine, human immune response, and infection control. Meanwhile, 21 interventional studies had been registered up to April 2022, most of which aimed to evaluate the immunogenicity and safety of different kinds of vaccines in various populations. CONCLUSIONS: Publications and clinical trials related to COVID-19 increased annually. As the first comparative bibliometric analysis for Delta and Omicron variants, we noticed that the relevant research trends have shifted from vaccine development to infection control and management of complications. The ongoing clinical studies will verify the safety and efficacy of promising drugs.

15.
Nat Commun ; 13(1): 7138, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36414665

RESUMO

The process of recycling poly(ethylene terephthalate) (PET) remains a major challenge due to the enzymatic degradation of high-crystallinity PET (hcPET). Recently, a bacterial PET-degrading enzyme, PETase, was found to have the ability to degrade the hcPET, but with low enzymatic activity. Here we present an engineered whole-cell biocatalyst to simulate both the adsorption and degradation steps in the enzymatic degradation process of PETase to achieve the efficient degradation of hcPET. Our data shows that the adhesive unit hydrophobin and degradation unit PETase are functionally displayed on the surface of yeast cells. The turnover rate of the whole-cell biocatalyst toward hcPET (crystallinity of 45%) dramatically increases approximately 328.8-fold compared with that of purified PETase at 30 °C. In addition, molecular dynamics simulations explain how the enhanced adhesion can promote the enzymatic degradation of PET. This study demonstrates engineering the whole-cell catalyst is an efficient strategy for biodegradation of PET.


Assuntos
Ácidos Ftálicos , Polietilenotereftalatos , Polietilenotereftalatos/metabolismo , Hidrolases/metabolismo , Ácidos Ftálicos/metabolismo , Etilenos
16.
BMC Anesthesiol ; 22(1): 334, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319962

RESUMO

BACKGROUND: Developing adequate regional anaesthesia for knee surgeries without affecting lower limb mobilization is crucial to perioperative analgesia. However, reports in this regard are limited. We proposed a technique for ultrasound-guided peripatellar plexus (PP) block. Compared with the femoral nerve (FN) block, we hypothesized that this technique would provide a noninferior block duration and a complete cutaneous sensory block in the peripatellar region without affecting lower limb mobilization. An investigation was conducted to verify our hypothesis in cadavers and volunteers. METHODS: The study was designed in two parts. First, eight cadaveric lower limbs were dissected to verify the feasibility of PP block after methylene blue injection under ultrasound. Second, using a noninferiority study design, 50 healthy volunteers were randomized to receive either a PP block (PP group) or an FN block (FN group). The primary outcome was the duration of peripatellar cutaneous sensory block, with the prespecified noninferiority margin of -3.08 h; the secondary outcome was the area of peripatellar cutaneous sensory block; in addition, the number of complete anaesthesias of the incision line for total knee arthroplasty and the Bromage score 30 min after block were recorded. RESULTS: The PP was successfully dyed, whereas the FN and saphenous nerve were unstained in all cadaveric limbs. The mean difference of the block duration between the two groups was - 1.24 (95% CI, -2.81 - 0.33) h, and the lower boundary of the two-sided 95% CI was higher than the prespecified noninferiority margin (Pnoninferiority = 0.023), confirming the noninferiority of our technique over FN block. The cutaneous sensory loss covered the entire peripatellar region in the PP group. PP block achieved complete anaesthesia of the incision line used for total knee arthroplasty and a Bromage score of 0 in 25 volunteers, which differed significantly from that of volunteers who underwent FN block. CONCLUSION: Ultrasound-guided PP block is a feasible technique. Compared with FN block, PP block provides noninferior block duration and complete blocking of the peripatellar region without affecting lower limb mobilization. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2000041547, registration date 28/12/2020).


Assuntos
Anestesia por Condução , Bloqueio Nervoso , Humanos , Nervo Femoral , Bloqueio Nervoso/métodos , Anestésicos Locais , Cadáver , Ultrassonografia de Intervenção/métodos , Dor Pós-Operatória
17.
Science ; 378(6621): 747-754, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36395230

RESUMO

The mixtures of cations and anions used in hybrid halide perovskites for high-performance solar cells often undergo element and phase segregation, which limits device lifetime. We adapted Schelling's model of segregation to study individual cation migration and found that the initial film inhomogeneity accelerates materials degradation. We fabricated perovskite films (FA1-xCsxPbI3; where FA is formamidinium) through the addition of selenophene, which led to homogeneous cation distribution that retarded cation aggregation during materials processing and device operation. The resultant devices achieved enhanced efficiency and retained >91% of their initial efficiency after 3190 hours at the maximum power point under 1 sun illumination. We also observe prolonged operational lifetime in devices with initially homogeneous FACsPb(Br0.13I0.87)3 absorbers.

18.
Nat Commun ; 13(1): 7055, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36396644

RESUMO

Antigen recognition by the T cell receptor (TCR) of CD4+ T cells can be greatly enhanced by the coreceptor CD4. Yet, understanding of the molecular mechanism is hindered by the ultra-low affinity of CD4 binding to class-II peptide-major histocompatibility complexes (pMHC). Here we show, using two-dimensional (2D) mechanical-based assays, that the affinity of CD4-pMHC interaction is 3-4 logs lower than that of cognate TCR-pMHC interactions, and it is more susceptible to increased dissociation by forces (slip bond). In contrast, CD4 binds TCR-pre-bound pMHC at 3-6 logs higher affinity, forming TCR-pMHC-CD4 tri-molecular bonds that are prolonged by force (catch bond), and modulated by protein mobility on the cell membrane, indicating profound TCR-CD4 cooperativity. Consistent with a tri-crystal structure, using DNA origami as a molecular ruler to titrate spacing between TCR and CD4 we show that 7-nm proximity optimizes TCR-pMHC-CD4 tri-molecular bond formation with pMHC. Our results thus provide deep mechanistic insight into CD4 enhancement of TCR antigen recognition.


Assuntos
Antígenos , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos de Linfócitos T/metabolismo , Complexo Principal de Histocompatibilidade , Antígenos de Histocompatibilidade , Peptídeos/química
19.
Genes (Basel) ; 13(11)2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36360265

RESUMO

Dendropanax oligodontus, which belongs to the family Araliaceae, is an endemic and endangered species of Hainan Island, China. It has potential economic and medicinal value owing to the presence of phenylpropanoids, flavonoids, triterpenoids, etc. The analysis of the structure and characteristics of the D. oligodontus chloroplast genome (cpDNA) is crucial for understanding the genetic and phylogenetic evolution of this species. In this study, the cpDNA of D. oligodontus was sequenced for the first time using next-generation sequencing methods, assembled, and annotated. We observed a circular quadripartite structure comprising a large single-copy region (86,440 bp), a small single-copy region (18,075 bp), and a pair of inverted repeat regions (25,944 bp). The total length of the cpDNA was 156,403 bp, and the GC% was 37.99%. We found that the D. oligodontus chloroplast genome comprised 131 genes, with 86 protein-coding genes, 8 rRNA genes, and 37 tRNAs. Furthermore, we identified 26,514 codons, 13 repetitive sequences, and 43 simple sequence repeat sites in the D. oligodontus cpDNA. The most common amino acid encoded was leucine, with a strong A/T preference at the third position of the codon. The prediction of RNA editing sites in the protein-coding genes indicated that RNA editing was observed in 19 genes with a total of 54 editing sites, all of which involved C-to-T transitions. Finally, the cpDNA of 11 species of the family Araliaceae were selected for comparative analysis. The sequences of the untranslated regions and coding regions among 11 species were highly conserved, and minor differences were observed in the length of the inverted repeat regions; therefore, the cpDNAs were relatively stable and consistent among these 11 species. The variable hotspots in the genome included clpP, ycf1, rnK-rps16, rps16-trnQ, atpH-atpI, trnE-trnT, psbM-trnD, ycf3-trnS, and rpl32-trnL, providing valuable molecular markers for species authentication and regions for inferring phylogenetic relationships among them, as well as for evolutionary studies. Evolutionary selection pressure analysis indicated that the atpF gene was strongly subjected to positive environmental selection. Phylogenetic analysis indicated that D. oligodontus and Dendropanax dentiger were the most closely related species within the genus, and D. oligodontus was closely related to the genera Kalopanax and Metapanax in the Araliaceae family. Overall, the cp genomes reported in this study will provide resources for studying the genetic diversity and conservation of the endangered plant D. oligodontus, as well as resolving phylogenetic relationships within the family.


Assuntos
Genoma de Cloroplastos , Filogenia , DNA de Cloroplastos , Códon/genética , Repetições de Microssatélites
20.
J Surg Res ; 283: 9-18, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36347171

RESUMO

INTRODUCTION: Nicotinamide mononucleotide (NMN) is a nucleotide that is commonly recognized for its role as an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis with multiple pharmacological effects. The purpose of this study was to evaluate the protective effect of nicotinamide mononucleotide (NMN) against lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: We investigated the effect of NMN on ALI-induced inflammatory response, oxidative stress, and cell apoptosis. The ALI mouse model was performed by injecting LPS intratracheally at a dose of 10 mg/kg in 50 µL saline. Flow cytometry was used to detect neutrophil infiltration in bronchoalveolar lavage fluid (BALF), and ELISA was used to detect the contents of inflammatory cytokines TNF-α, IL-1ß and IL-6 in BALF. Oxidative stress was evaluated by determining the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in lung tissue. ROS formation was analyzed by immunofluorescence. Western blotting was performed to detect apoptotic levels and p38MAPK/NF-κB phosphorylation levels in lung tissue. RESULTS: In the ALI mouse model, NMN showed a significant therapeutic effect compared to the LPS group. NMN attenuated the pathological damage and cell apoptosis in lung tissue, decreased the levels of TNF-α, IL-1ß, and IL-6 in BALF, and reduced the number of total cells and neutrophils in BALF. In addition, NMN attenuated the LPS-induced elevation of dry-to-wet ratio, MDA content, p38 MAPK and p65 NF-κB phosphorylation levels, and the SOD activity was increased by NMN treatment. CONCLUSIONS: In conclusion, the present study showed that NMN exerted a protective effect on LPS-induced ALI with anti-inflammatory, antioxidative, and antiapoptotic effects.

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