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1.
Sci Total Environ ; 926: 171400, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38461974

RESUMO

The maximum Rubisco carboxylation rate normalized to 25 °C (Vcmax25) is a key parameter in terrestrial biosphere models for simulating carbon cycling. Recently, global distributions of Vcmax25 have been derived through various methods and different data, including field measurements, ecological optimality theory (EOT), leaf chlorophyll content (LCC), and solar-induced chlorophyll fluorescence (SIF). However, direct validation poses challenges due to high uncertainty arising from limited ground-based observations. This study conducted an indirect evaluation of four Vcmax25 datasets by assessing the accuracy of gross primary productivity (GPP) simulated using the Biosphere-atmosphere Exchange Process Simulator (BEPS) at both site and global scales. Results indicate that, compared to utilizing Vcmax25 fixed by plant functional types (PFT) derived from field measurements, incorporating Vcmax25 derived from SIF and LCC (SIF + LCC), or solely LCC, into BEPS significantly reduces simulated errors in the annual total GPP, with a 23.2 %-25.1 % decrease in the average absolute bias across 196 FLUXNET2015 sites. Daily GPP for evergreen needleleaf forests, deciduous broadleaf forests, shrublands, grasslands, and croplands shows a 7.8 %-27.6 % decrease in absolute bias, primarily attributed to reduced simulation errors during off-peak seasons of vegetation growth. Conversely, the annual total GPP error simulated using EOT-derived Vcmax25 increases slightly (2.2 %) compared to that simulated using PFT-fixed Vcmax25. This is primarily due to a significant overestimation in evergreen broadleaf forests and underestimation in croplands, despite slight increased accuracy for other PFTs. The global annual GPP simulated using Vcmax25 with seasonal variations (i.e., LCC Vcmax25 and SIF + LCC Vcmax25) yields a 4.3 %-7.3 % decrease compared to that simulated using PFT-fixed Vcmax25. Compared to FLUXCOM and GOSIF GPP products, the GPP simulated based on SIF + LCC Vcmax25 and LCC Vcmax25 demonstrates better consistency (R2 = 0.91-0.93, RMSE = 314.2-376.6 g C m-2 yr-1). This study underscores the importance of accurately characterizing the spatiotemporal variations in Vcmax25 for the accurate simulation of global vegetation productivity.


Assuntos
Clorofila , Fotossíntese , Fluorescência , Florestas , Estações do Ano , Plantas , Folhas de Planta , Ecossistema
2.
World Neurosurg ; 185: e1160-e1168, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499243

RESUMO

BACKGROUND: Paravertebral abscess represents a prevalent manifestation of thoracic tuberculosis, often necessitating surgical intervention. In this study, we introduced a novel approach by employing bilateral endoscopic debridement (BED) to address large Paravertebral abscesses associated with thoracic tuberculosis, a method not previously proposed in the literature. The clinical efficacy was examined through a comprehensive 4-year follow-up. METHODS: We conducted a retrospective analysis on patients diagnosed with thoracic tuberculosis and paravertebral abscess who underwent BED combined with local antituberculosis drugs (BED + LAD) between February 2015 and February 2019. A total of 29 eligible patients (12 males and 17 females) with a median (interquartile ranges) of 59.0(16.5) years were included in the study. All patients received the BED + LAD treatment. After the surgery, the patients were treated with a 4-drug antituberculosis therapy (Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol). All relevant indicators were meticulously recorded and analyzed. RESULTS: The surgical procedures were successfully completed for all subjects, with an average intraoperative bleeding volume of (25.2 ± 8.9) ml, an average surgical time of (68.4 ± 14.0) minutes, an average fluoroscopy frequency of (21.7 ± 8.2) times, an average hospital stay of (14.2 ± 4.3) days, and an average medication period of (42.1 ± 9.6) weeks. All subjects completed at least a 4-year follow-up period. At the final follow-up, ESR and CRP levels returned to normal, and there was no significant increase in the Cobb angle (P>0.05). CONCLUSIONS: The application of BED + LAD in the treatment of thoracic tuberculosis and paravertebral abscess proved to be a safe, effective, and feasible approach.


Assuntos
Antituberculosos , Desbridamento , Tuberculose da Coluna Vertebral , Humanos , Masculino , Feminino , Desbridamento/métodos , Pessoa de Meia-Idade , Antituberculosos/uso terapêutico , Antituberculosos/administração & dosagem , Estudos Retrospectivos , Idoso , Seguimentos , Adulto , Tuberculose da Coluna Vertebral/cirurgia , Tuberculose da Coluna Vertebral/tratamento farmacológico , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Abscesso/cirurgia , Abscesso/tratamento farmacológico , Resultado do Tratamento , Terapia Combinada , Neuroendoscopia/métodos
3.
Chemistry ; 30(23): e202304130, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38350013

RESUMO

Magnesium-based catalysts are becoming popular for hydroelementation reactions specially using p-block reagents. Based on the seminal report from Schäfer's group (ChemCatChem 2022, 14, e202201007), our study demonstrates that the reaction mechanisms exhibit a far greater degree of complexity than originally presumed. Magnesium has a variety of coordination modes (and access to different hybridizations) which allows this electron-deficient centre to modulate its catalytic power depending on the σ-donor properties of the reagent. DFT calculations demonstrate several reaction channels closely operating in these versatile catalysts. In addition, variations in limiting energy barriers resulting from catalyst modifications were examined as a function of the Hammett constant, thereby predicting enhanced efficiency in reaction conversions.

4.
Innovation (Camb) ; 4(6): 100515, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37786507

RESUMO

Forests are chiefly responsible for the terrestrial carbon sink that greatly reduces the buildup of CO2 concentrations in the atmosphere and alleviates climate change. Current predictions of terrestrial carbon sinks in the future have so far ignored the variation of forest carbon uptake with forest age. Here, we predict the role of China's current forest age in future carbon sink capacity by generating a high-resolution (30 m) forest age map in 2019 over China's landmass using satellite and forest inventory data and deriving forest growth curves using measurements of forest biomass and age in 3,121 plots. As China's forests currently have large proportions of young and middle-age stands, we project that China's forests will maintain high growth rates for about 15 years. However, as the forests grow older, their net primary productivity will decline by 5.0% ± 1.4% in 2050, 8.4% ± 1.6% in 2060, and 16.6% ± 2.8% in 2100, indicating weakened carbon sinks in the near future. The weakening of forest carbon sinks can be potentially mitigated by optimizing forest age structure through selective logging and implementing new or improved afforestation. This finding is important not only for the global carbon cycle and climate projections but also for developing forest management strategies to enhance land sinks by alleviating the age effect.

5.
Chemistry ; 29(63): e202302303, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37553318

RESUMO

Synthetic strategies to access high-valent iridium complexes usually require use of π donating ligands bearing electronegative atoms (e. g. amide or oxide) or σ donating electropositive atoms (e. g. boryl or hydride). Besides the η5 -(methyl)cyclopentadienyl derivatives, high-valent η1 carbon-ligated iridium complexes are challenging to synthesize. To meet this challenge, this work reports the oxidation behavior of an all-carbon-ligated anionic bis(CCC-pincer) IrIII complex. Being both σ and π donating, the diaryl dipyrido-annulated N-heterocyclic carbene (dpa-NHC) IrIII complex allowed a stepwise 4e- oxidation sequence. The first 2e- oxidation led to an oxidative coupling of two adjacent aryl groups, resulting in formation of a cationic chiral IrIII complex bearing a CCCC-tetradentate ligand. A further 2e- oxidation allowed isolation of a high-valent tricationic complex with a triplet ground state. These results close a synthetic gap for carbon-ligated iridium complexes and demonstrate the electronic tuning potential of organic π ligands for unusual electronic properties.

6.
Chemistry ; 29(70): e202302550, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-37643995

RESUMO

The formation of Lewis pairs is an important chemical concept. Recently, the complexation of Lewis acidic tris(pentafluorophenyl)borane with Lewis basic moieties and subsequent reduction has emerged as a fascinating strategy for designing novel reactions and structures. The impact of the complexation and subsequent reduction of antiaromatic systems bearing Lewis base moieties has been investigated. We found how Lewis adduct formation stabilizes an antiaromatic system consisting of 9,10-dicyanoanthracene and tris(pentafluorophenyl)borane by using synthesis, X-ray crystallography, spectroscopic analysis, and quantum chemical calculations.

7.
Cell Rep ; 42(8): 112860, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37494181

RESUMO

Bidirectional communication between the developing conceptus and endometrium is essential for pregnancy recognition and establishment in ruminants. We dissect the transcriptomic dynamics of sheep conceptus and corresponding endometrium at pre- and peri-implantation stages using single-cell RNA sequencing. Spherical blastocysts contain five cell types, with 68.62% trophectoderm cells. Strikingly, elongated conceptuses differentiate into 17 cell types, indicating dramatic cell fate specifications. Cell-type-specific gene expression delineates the features of distinctive trophectoderm lineages and indicates that the transition from polar trophectoderm to trophoblast increases interferon-tau expression and likely drives elongation initiation. We identify 13 endometrium-derived cell types and elucidate their molecular responses to conceptus development. Integrated analyses uncover multiple paired transcripts mediating the dialogues between extraembryonic membrane and endometrium, including IGF2-IGF1R, FGF19-FGFR1, NPY-NPY1R, PROS1-AXL, and ADGRE5-CD55. These data provide insight into the molecular regulation of conceptus elongation and represent a valuable resource for functional investigations of pre- and peri-implantation ruminant development.

8.
World J Orthop ; 14(5): 319-327, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37304195

RESUMO

BACKGROUND: Chronic large to massive rotator cuff tears are difficult to treat and re-tears are common even after surgical repair. We propose using a synthetic polypropylene mesh to increase the tensile strength of rotator cuff repairs. We hypothesize that using a polypropylene mesh to bridge the repair of large rotator cuff tears will increase the ultimate failure load of the repair. AIM: To investigate the mechanical properties of rotator cuff tears repaired with a polypropylene interposition graft in an ovine ex-vivo model. METHODS: A 20 mm length of infraspinatus tendon was resected from fifteen fresh sheep shoulders to simulate a large tear. We used a polypropylene mesh as an interposition graft between the ends of the tendon for repair. In seven specimens, the mesh was secured to remnant tendon by continuous stitching while mattress stitches were used for eight specimens. Five specimens with an intact tendon were tested. The specimens underwent cyclic loading to determine the ultimate failure load and gap formation. RESULTS: The mean gap formation after 3000 cycles was 1.67 mm in the continuous group, and 4.16 mm in the mattress group (P = 0.001). The mean ultimate failure load was significantly higher at 549.2 N in the continuous group, 426.4 N in the mattress group and 370 N in the intact group (P = 0.003). CONCLUSION: The use of a polypropylene mesh is biomechanically suitable as an interposition graft for large irreparable rotator cuff tears.

9.
Front Immunol ; 14: 1181561, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37138875

RESUMO

Objective: The aim of this study is to explore the prevalence and clinicopathological associations between anti-C1qA08 antibodies and anti-monomeric CRP (mCRP) a.a.35-47 antibodies and to explore the interaction between C1q and mCRP. Methods: Ninety patients with biopsy-proven lupus nephritis were included from a Chinese cohort. Plasma samples collected on the day of renal biopsy were tested for anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies. The associations between these two autoantibodies and clinicopathologic features and long-term prognosis were analyzed. The interaction between C1q and mCRP was further investigated by ELISA, and the key linear epitopes of the combination of cholesterol binding sequence (CBS; a.a.35-47) and C1qA08 were tested by competitive inhibition assays. The surface plasmon resonance (SPR) was used to further verify the results. Results: The prevalence of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were 50/90 (61.1%) and 45/90 (50.0%), respectively. Levels of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were negatively correlated with serum C3 concentrations ((0.5(0.22-1.19) g/L vs. 0.39(0.15-1.38) g/L, P=0.002) and (0.48(0.44-0.88) g/L vs. 0.41(0.15-1.38) g/L, P=0.028), respectively. Levels of anti-C1qA08 antibodies were correlated with the score of fibrous crescents and tubular atrophy (r=-0.256, P=0.014 and r=-0.25, P=0.016, respectively). The patients with double positive antibodies showed worse renal prognosis than that of the double negative group (HR 0.899 (95% CI: 0.739-1.059), P=0.0336). The binding of mCRP to C1q was confirmed by ELISA. The key linear epitopes of the combination were a.a.35-47 and C1qA08, which were confirmed by competitive inhibition experiments and SPR. Conclusion: The combination of anti-C1qA08 and anti-mCRP a.a.35-47 autoantibodies could predict a poor renal outcome. The key linear epitopes of the combination of C1q and mCRP were C1qA08 and a.a.35-47. A08 was an important epitope for the classical pathway complement activation and a.a.35-47 could inhibit this process.


Assuntos
Nefropatias , Nefrite Lúpica , Humanos , Rim , Prognóstico , Autoanticorpos , Epitopos
10.
Mol Immunol ; 157: 158-166, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37028130

RESUMO

Bystander activation of T cells is defined as induction of effector responses by innate cytokines in the absence of cognate antigens and independent of T cell receptor (TCR) signaling. Here we show that C-reactive protein (CRP), a soluble pattern-recognition receptor assembled noncovalently by five identical subunits, can instead trigger bystander activation of CD4 + T cells by evoking allosteric activation and spontaneous signaling of TCR in the absence of cognate antigens. The actions of CRP depend on pattern ligand-binding induced conformational changes that result in the generation of monomeric CRP (mCRP). mCRP binds cholesterol in plasma membranes of CD4 + T cells, thereby shifting the conformational equilibrium of TCR to the cholesterol-unbound, primed state. The spontaneous signaling of primed TCR leads to productive effector responses manifested by upregulation of surface activation markers and release of IFN-γ. Our results thus identify a novel mode of bystander T cell activation triggered by allosteric TCR signaling, and reveal an interesting paradigm wherein innate immune recognition of CRP transforms it to a direct activator that evokes immediate adaptive immune responses.


Assuntos
Proteína C-Reativa , Linfócitos T CD4-Positivos , Transdução de Sinais , Comunicação Celular , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T
11.
Kardiologiia ; 63(3): 55-60, 2023 Mar 31.
Artigo em Russo | MEDLINE | ID: mdl-37061861

RESUMO

Aim    To study platelet adhesion mediated by von Willebrand factor (VWF) in patients with premature ischemic heart disease (IHD).Material and methods    This study enrolled 58 patients with stable IHD, including 45 men younger than 55 years with the first manifestation of IHD at the age of <50 years and 13 women younger than 65 years with the first manifestation of IHD at the age of <60 years. The control group consisted of 33 patients, 13 men younger than 55 years and 20 women younger than 65 years without IHD. Platelet adhesion to the collagen surface at the shear rate of 1300 s-1 was studied by evaluating the intensity of scattered laser light from the collagen-coated optical substrate in a flow chamber of a microfluidic device after 15-min circulation of whole blood in the chamber. Decreases in platelet adhesion after addition to the blood of monoclonal antibodies (mAb) to platelet receptors glycoproteins Ib (GPIb) to inhibit the receptor interaction with VWF were compared for patients of both groups. Results    In patients with premature IHD, the decrease in platelet adhesion following the platelet GPIb receptor inhibition was significantly less than in patients of the control group (74.8 % (55.6; 82.7) vs. 28.9 % (-9.8; 50,5), p <0.001). For the entire sample, the median decrease in platelet adhesion following the GPIb receptor inhibition was 62.8 % (52.2; 71.2). With an adjustment for traditional risk factors of IHD, a decrease in platelet adhesion of >62.8% after blocking GPIb receptors increased the likelihood of premature IHD (OR=9.84, 95 % CI: 2.80-34.59; p <0.001).Conclusion    Blocking the interaction of GPIb receptors with VWF in patients with premature IHD and increased shear rate induced a greater decrease in platelet adhesion than in patients without this disease. This suggested that an excessive interaction of VWF with platelets might contribute to the pathogenesis of premature IHD.


Assuntos
Doença da Artéria Coronariana , Fator de von Willebrand , Humanos , Feminino , Pessoa de Meia-Idade , Fator de von Willebrand/farmacologia , Fator de von Willebrand/fisiologia , Doença da Artéria Coronariana/diagnóstico , Adesividade Plaquetária/fisiologia , Plaquetas , Complexo Glicoproteico GPIb-IX de Plaquetas , Colágeno
12.
J Immunol ; 210(6): 699-707, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36881905

RESUMO

C-reactive protein (CRP) is a highly conserved pentraxin with pattern recognition receptor-like activities. However, despite being used widely as a clinical marker of inflammation, the in vivo functions of CRP and its roles in health and disease remain largely unestablished. This is, to certain extent, due to the drastically different expression patterns of CRP in mice and rats, raising concerns about whether the functions of CRP are essential and conserved across species and how these model animals should be manipulated to examine the in vivo actions of human CRP. In this review, we discuss recent advances highlighting the essential and conserved functions of CRP across species, and propose that appropriately designed animal models can be used to understand the origin-, conformation-, and localization-dependent actions of human CRP in vivo. The improved model design will contribute to establishing the pathophysiological roles of CRP and facilitate the development of novel CRP-targeting strategies.


Assuntos
Proteína C-Reativa , Inflamação , Humanos , Animais , Camundongos , Ratos , Modelos Animais
13.
Heliyon ; 9(3): e14265, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36938448

RESUMO

Kai-Xin-San (KXS) is a Chinese medicine formulation that is commonly used to treat depression caused by dual deficiencies in the heart and spleen. Recent studies indicated that miRNAs were involved in the pathophysiology of depression. However, there have been few studies on the mechanism underlying the miRNAs directly mediating antidepressant at clinical level, especially in nature drugs and TCM compound. In this study, we identified circulating miRNAs defferentially expressed among the depression patients (DPs), DPs who underwent 8weeks of KXS treatment and health controls (HCs). A total of 45 miRNAs (17 were up-regulated and 28 were down-regulated) were significantly differentially expressed among three groups. Subsequently, qRT-PCR was used to verify 10 differentially expressed candidate miRNAs in more serum samples, and the results showed that 6 miRNAs (miR-1281, miR-365a-3p, miR-2861, miR-16-5p, miR-1202 and miR-451a) were consistent with the results of microarray. Among them, miR-1281, was the novel dynamically altered and appeared to be specifically related to depression and antidepressant effects of KXS. MicroRNA-gene-pathway-net analysis showed that miR-1281-regulated genes are mostly key nodes in the classical signaling pathway related to depression. Additionally, our data suggest that ADCY1 and DVL1 were the targets of miR-1281. Thus, based on the discovery of miRNA expression profiles in vivo, our findings suggest a new role for miR-1281 related to depression and demonstrated in vitro that KXS may activate cAMP/PKA/ERK/CREB and Wnt/ß-catenin signal transduction pathways by down-regulating miR-1281 that targets ADCY1 and DVL1 to achieve its role in neuronal cell protection.

14.
Chemistry ; 29(11): e202203163, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36417203

RESUMO

In this study, we afford explicit characterizations of the electronic and geometrical structures of recently reported hypervalent penta-coordinate carbon compounds by using gas-phase characterization techniques: photodissociation spectroscopy (PDS) and ion mobility-mass spectrometry (IM-MS). In particular for a compound with moderately electron-donating ligands, bearing p-methylthiophenyl substituents, the coexistence of tetra- and penta-coordinate isomers is confirmed, consistent with solution characterizations. It is in sharp contrast to the exclusive tetra-coordinate form (with normal valence of the central carbon atom) in the single crystal. This suggests that a non-polar environment makes the penta-coordinate structure thermodynamically most stable. This delicate difference between the tetra- and penta-coordinate structures, which depends on the environment, is a close reflection of the lower activation barrier of the SN 2 reaction found in neutral solvent or gas-phase reactions.

15.
Chemistry ; 29(9): e202203162, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36372771

RESUMO

To stabilize SN 2 transition state-like penta-coordinate carbon species, triaryl-substituted cationic carbon compounds bearing a moderately flexible 7-6-7-ring skeleton with sulfur donors were synthesized and characterized. Electronic effects of para substituents (R=Cl, F, H, CH3 , SMe, OMe) of the two equatorial aryl groups bound to the cationic central carbon were investigated systematically along with a planar bidentate thioxanthene derivative. X-ray analysis on their solid-state structures showed that the parent (R=H), chloro-, fluoro- and methyl-derivatives were tetracoordinate carbon (sulfonium) structures, while the p-MeO and thioxanthenyl system were pentacoordinate carbocation structures. The Hammett substituent constants for the para substituents (σp + ) correlates well with the bonding in these compounds. The methylthio-derivative with intermediate Hammett substituent constants (p-MeS; σp + =-0.60) showed a tetracooridnate solid-state structure, though solution UV-Vis properties suggested the presence of a penta-coordinate structure. These findings amount to the first unambiguous solution evidence of the hypervalent apical 3c-4e interactions in pentacoordinate carbon compounds.

16.
Biomed Pharmacother ; 153: 113321, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35759868

RESUMO

Muscarinic acetylcholine receptors (mAChRs) are widely expressed in various effector cells and have been proved to play vital roles in smooth muscle contraction and digestive secretion. However, there are relatively few literatures revealing the roles of mAChRs in inflammatory processes, and its underlying regulatory mechanisms have not been elucidated. Taking the advantages of live imaging of zebrafish, we found that inhibition of mAChRs resulted in increased neutrophils recruitment and proinflammatory cytokines expression, whereas activation of mAChRs led to opposite outcome. Subsequently, we found that mAChRs regulated the expression of arginases (args), and pharmacological intervention of args level could reverse the effects of mAChRs on neutrophils migration and cytokines expression, suggesting that args are important downstream proteins of mAChRs that mediate the regulation of inflammatory response. In this study, we identified args as novel downstream proteins of mAChRs in inflammatory responses, providing additional evidence for system immune regulation of cholinergic receptors.


Assuntos
Arginase , Peixe-Zebra , Animais , Citocinas , Receptores Muscarínicos/genética , Receptores Muscarínicos/metabolismo , Peixe-Zebra/metabolismo
17.
J Biol Chem ; 298(8): 102160, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35724961

RESUMO

C-reactive protein (CRP) is a major acute phase protein and inflammatory marker, the expression of which is largely liver specific and highly inducible. Enhancers are regulatory elements critical for the precise activation of gene expression, yet the contributions of enhancers to the expression pattern of CRP have not been well defined. Here, we identify a constitutively active enhancer (E1) located 37.7 kb upstream of the promoter of human CRP in hepatocytes. By using chromatin immunoprecipitation, luciferase reporter assay, in situ genetic manipulation, CRISPRi, and CRISPRa, we show that E1 is enriched in binding sites for transcription factors STAT3 and C/EBP-ß and is essential for the full induction of human CRP during the acute phase. Moreover, we demonstrate that E1 orchestrates with the promoter of CRP to determine its varied expression across tissues and species through surveying activities of E1-promoter hybrids and the associated epigenetic modifications. These results thus suggest an intriguing mode of molecular evolution wherein expression-changing mutations in distal regulatory elements initiate subsequent functional selection involving coupling among distal/proximal regulatory mutations and activity-changing coding mutations.


Assuntos
Proteína C-Reativa , Elementos Facilitadores Genéticos , Sítios de Ligação , Proteína C-Reativa/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Regulação da Expressão Gênica , Hepatócitos , Humanos , Regiões Promotoras Genéticas , Fator de Transcrição STAT3/metabolismo , Transcrição Gênica
18.
Dalton Trans ; 51(20): 7899-7906, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35535973

RESUMO

Stabilization of low oxidation gold anions as aurate or auride by organic ligands has long been a synthetic challenge, owing to the proneness of low-valent gold centres to cluster. Despite being the most electronegative metal, isolable gold(I) aurate complexes have only been obtained from a few σ-withdrawing organo- and organo-main group ligands. Stabilization of highly-reduced gold complexes by π-modulating redox active ligands has only been achieved by cyclic (amino)(alkyl)carbene (CAAC), which is limited to 1e--reduction to form neutral gold(0) complexes. This work reports a simple modular synthesis of a boron, nitrogen-containing heterocyclic carbene (ClBNC) at a gold(I) center through metal-assisted coupling between azadiboriridine and isocyanides. The anionic electrophilic ClBNC ligand in the gold(I) complex [(ClBNC)AuPMe3] (3a and 3b) allows a 2e--reduction to form the first η1-carbene aurate complex [(BNC)AuPMe3]Li(DME) (5a, DME = dimethoxyethane). Single crystal crystallographic analysis and computational studies of these complexes revealed a highly π-withdrawing character of the neutral 4π B,N-heterocyclic carbene (BNC) moiety and a 6π weakly aromatic character with π-donating properties to the gold(I) fragment in its reduced form, showcasing the first cyclic carbene ligand that allows electronic tunability between π-withdrawing (Fischer-type)- and π-donating (Schrock-type) properties.

19.
Commun Biol ; 5(1): 268, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35338247

RESUMO

Biophysical models suggest a dominant role of structural over functional constraints in shaping protein evolution. Selection on structural constraints is linked closely to expression levels of proteins, which together with structure-associated activities determine in vivo functions of proteins. Here we show that despite the up to two orders of magnitude differences in levels of C-reactive protein (CRP) in distinct species, the in vivo functions of CRP are paradoxically conserved. Such a pronounced level-function mismatch cannot be explained by activities associated with the conserved native structure, but is coupled to hidden activities associated with the unfolded, activated conformation. This is not the result of selection on structural constraints like foldability and stability, but is achieved by folding determinants-mediated functional selection that keeps a confined carrier structure to pass the stringent eukaryotic quality control on secretion. Further analysis suggests a folding threshold model which may partly explain the mismatch between the vast sequence space and the limited structure space of proteins.


Assuntos
Proteína C-Reativa , Dobramento de Proteína , Controle de Qualidade
20.
Chin J Integr Med ; 28(3): 257-262, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34731434

RESUMO

OBJECTIVE: To explore if acupoint injection can improve analgesic effects or delivery outcomes in parturients who received combined spinal-epidural analgesia (CSEA) and patient-controlled epidural analgesia (PCEA) for labor analgesia. METHODS: A total of 307 participants were prospectively collected from July 2017 to December 2019. The participants were randomized into the combined acupoint injection with CSEA plus PCEA group (AICP group, n=168) and CSEA plus PCEA group (CP group, n=139) for labor analgesia using a random number table. Both groups received CSEA plus PCEA at cervical dilation 3 cm during labor process, and parturients of the AICP group were implemented acupoint injection for which bilateral acupoint of Zusanli (ST 36) and Sanyinjiao (SP 6) were selected in addition. The primary outcome was Visual Analogue Scale (VAS) score, and the secondary outcomes were obstetric outcomes and requirement of anesthetics doses. Safety evaluations were performed after intervention. RESULTS: The VAS scores were significantly lower in the AICP group than in the CP group at 10, 30, 60, and 120 min after labor analgesia (all P<0.05). The latent phase of the AICP group was shorter than that of the CP group (P<0.05). There were less additional anesthetics consumption, lower incidences of uterine atony, fever, pruritus and urinary retention in the AICP group than those in the CP group (all P<0.05). CONCLUSION: Acupoint injection combined CSEA plus PCEA for labor analgesia can decrease the anesthetic consumption, improve analgesic quality, and reduce adverse reactions in the parturients. (Registration No. ChiMCTR-2000003120).


Assuntos
Analgesia Obstétrica , Anestésicos , Trabalho de Parto , Pontos de Acupuntura , Analgesia Obstétrica/efeitos adversos , Analgesia Controlada pelo Paciente/efeitos adversos , Anestésicos/farmacologia , Feminino , Humanos , Gravidez
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