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1.
Mater Horiz ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683199

RESUMO

The large inherent flexibility and highly modular nature of metal-organic frameworks (MOFs) make them ideal candidates for the study of negative thermal expansion (NTE). Among diverse organic ligands, the biphenyl unit, which can unrestrictedly rotate along its C-C single bond, can largely enhance the structural flexibility. Herein, we explored the thermal expansion behaviors of four indium biphenyl tetracarboxylates (BPTCs). Owing to the different dihedral angles of BPTC ligands and coordination mode of In3+, they show distinct topologies: InOF-1 (nti), InOF-2 (unc), InOF-12 (pts) and InOF-13 (nou). Intriguingly, it is found that the thermal expansion is highly dependent on the specific topology. The MOFs featuring mononuclear nodes show normal positive thermal expansion (PTE), and the magnitudes of coefficients follow the trend of InOF-2 < InOF-12 < InOF-13, inversely related to averaged molecular volumes. In contrast, the InOF-1, composed of a 1D chain of corner-shared InO6 octahedrons, shows pronounced NTE. Detailed high-resolution synchrotron powder X-ray diffraction and lattice dynamic analyses shed light on the fact that NTE in the InOF-1 is a synergy effect of the spring-like distortion of the inorganic 1D helical chain and twisting of the BPTC ligands. The present work shows how the topological arrangement of building blocks governs the thermal expansion behaviors.

2.
Small ; : e2311421, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38282177

RESUMO

To improve ion transport kinetics and electronic conductivity between the different phases in sodium/lithium-ion battery (LIB/SIB) anodes, heterointerface engineering is considered as a promising strategy due to the strong built-in electric field. However, the lattice mismatch and defects in the interphase structure can lead to large grain boundary resistance, reducing the ion transport kinetics and electronic conductivity. Herein, monometallic selenide Fe3 Se4 -Fe7 Se8 semi-coherent heterointerface embedded in 3D connected Nitrogen-doped carbon yolk-shell matrix (Fe3 Se4 -Fe7 Se8 @NC) is obtained via an in situ phase transition process. Such semi-coherent heterointerface between Fe3 Se4 and Fe7 Se8 shows the matched interfacial lattice and strong built-in electric field, resulting in the low interface impedance and fast reaction kinetics. Moreover, the yolk-shell structure is designed to confine all monometallic selenide Fe3 Se4 -Fe7 Se8 semi-coherent heterointerface nanoparticles, improving the structural stability and inhibiting the volume expansion effect. In particular, the 3D carbon bridge between multi-yolks shell structure improves the electronic conductivity and shortens the ion transport path. Therefore, the efficient reversible pseudocapacitance and electrochemical conversion reaction are enabled by the Fe3 Se4 -Fe7 Se8 @NC, leading to the high specific capacity of 439 mAh g-1 for SIB and 1010 mAh g-1 for LIB. This work provides a new strategy for constructing heterointerface of the anode for secondary batteries.

3.
Eye Contact Lens ; 50(3): 145-151, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37791837

RESUMO

OBJECTIVES: To investigate the sleep quality in patients with ocular graft-versus-host disease (oGVHD) compared with patients without oGVHD after allogeneic hematopoietic stem cell transplantation (alloHCT) and healthy controls. METHODS: This cross-sectional study analyzed 142 patients after alloHCT including 94 patients with oGVHD and 48 without. Fifty healthy controls were also enrolled. oGVHD was diagnosed according to International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. Sleep quality was assessed by the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI). Poor sleep quality was defined as CPQSI score greater than 6. RESULTS: Patients after alloHCT demonstrated a significantly higher CPQSI score than those of controls {7.0 [interquartile range (IQR) 5.0-10.0] vs. 5.5 [IQR 4.8-7.0], P =0.002}, especially in the oGVHD subgroup (7.5 [IQR 5.0-11.0] vs. 6.0 [IQR 5.0-8.0], P =0.04) with nearly double prevalence of poor sleep quality (58 [62%] vs. 18 [37%], P =0.006). Poor sleep quality was strikingly correlated with oGVHD diagnosis (adjusted odds ratio [OR]=2.55, 95% confidence interval [CI]: 1.02-6.34, P =0.04) and systemic immunosuppressants (adjusted OR=2.61, 95% CI: 1.32-5.71, P =0.02). Among the ocular parameters, poor sleep quality was significantly associated with higher ICOGCG score (adjusted OR=1.20, 95% CI: 1.03-1.39, P =0.02) and lower tear film break-up time (adjusted OR=0.85, 95% CI: 0.74-0.99, P =0.05). CONCLUSIONS: Poor sleep quality was associated with an increased severity of oGVHD and tear film instability in the long-term alloHCT survivorship.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Transversais , Qualidade do Sono , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/complicações , Olho
4.
Ocul Immunol Inflamm ; : 1-10, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37862586

RESUMO

PURPOSE: To evaluate the efficacy and safety of intense pulsed light combined with meibomian gland expression (IPL-MGX) for treating meibomian gland dysfunction (MGD) associated with chronic ocular graft-versus-host disease (oGVHD). METHODS: This retrospective study included 18 patients (18 eyes) with Fitzpatrick skin type ≤ IV, who underwent 3 to 8 sessions of IPL-MGX. Dry eye symptomology, ocular surface parameters, and adverse events were evaluated. RESULTS: Of 18 eyes, 83.3% and 66.7% showed severe oGVHD and severe MGD, respectively. At 4 weeks after the final session, significant improvements in the OSDI (P < 0.001), SPEED (P = 0.001), meibum expressibility (P < 0.001), and meibum quality (P = 0.016) were observed. At 12 weeks after, the OSDI (P = 0.009), SPEED (P = 0.002), and meibum expressibility (P = 0.008) significantly improved. No adverse events owing to IPL were reported. CONCLUSION: IPL-MGX may improve the ocular symptoms, ameliorate meibomian gland secretion, and is considered as a safe treatment for MGD in oGVHD patients.

5.
J Biol Chem ; 299(8): 104968, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37380075

RESUMO

Ykt6 is one of the most conserved SNARE (N-ethylmaleimide-sensitive factor attachment protein receptor) proteins involved in multiple intracellular membrane trafficking processes. The membrane-anchoring function of Ykt6 has been elucidated to result from its conformational transition from a closed state to an open state. Two ways of regulating the conformational transition were proposed: the C-terminal lipidation and the phosphorylation at the SNARE core. Despite many aspects of common properties, Ykt6 displays differential cellular localizations and functional behaviors in different species, such as yeast, mammals, and worms. The structure-function relationship underlying these differences remains elusive. Here, we combined biochemical characterization, single-molecule FRET measurement, and molecular dynamics simulation to compare the conformational dynamics of yeast and rat Ykt6. Compared to rat Ykt6 (rYkt6), yeast Ykt6 (yYkt6) has more open conformations and could not bind dodecylphosphocholine that inhibits rYkt6 in the closed state. A point mutation T46L/Q57A was shown to be able to convert yYkt6 to a more closed and dodecylphosphocholine-bound state, where Leu46 contributes key hydrophobic interactions for the closed state. We also demonstrated that the phospho-mutation S174D could shift the conformation of rYkt6 to a more open state, but the corresponding mutation S176D in yYkt6 leads to a slightly more closed conformation. These observations shed light on the regulatory mechanism underlying the variations of Ykt6 functions across species.


Assuntos
Proteínas SNARE , Saccharomyces cerevisiae , Animais , Ratos , Mamíferos/metabolismo , Proteínas R-SNARE/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas SNARE/genética , Proteínas SNARE/metabolismo
6.
Front Microbiol ; 14: 1137643, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37065116

RESUMO

Temperature is one of the main factors affecting aflatoxin (AF) biosynthesis in Aspergillus flavus. Previous studies showed that AF biosynthesis is elevated in A. flavus at temperatures between 28°C-30°C, while it is inhibited at temperatures above 30°C. However, little is known about the metabolic mechanism underlying temperature-regulated AF biosynthesis. In this study, we integrated metabolomic and lipidomic analyses to investigate the endogenous metabolism of A. flavus across 6 days of mycelia growth at 28°C (optimal AF production) and 37°C (no AF production). Results showed that both metabolite and lipid profiles were significantly altered at different temperatures. In particular, metabolites involved in carbohydrate and amino acid metabolism were up-regulated at 37°C on the second day but down-regulated from days three to six. Moreover, lipidomics and targeted fatty acids analyses of mycelia samples revealed a distinct pattern of lipid species and free fatty acids desaturation. High degrees of polyunsaturation of most lipid species at 28°C were positively correlated with AF production. These results provide new insights into the underlying metabolic changes in A. flavus under temperature stress.

7.
Graefes Arch Clin Exp Ophthalmol ; 261(2): 453-465, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36029303

RESUMO

PURPOSE: To compare the vision-specific and cancer-specific quality of life (QOL) between patients with and without ocular graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (alloHCT). METHODS: This cross-sectional observational study analyzed 142 patients after alloHCT including 94 patients with oGVHD and 48 without. oGVHD was diagnosed according to International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. QOL was assessed by using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). RESULTS: Compared with non-oGVHD patients, patients with oGVHD had worse vision-specific (NEI VFQ-25: 64.3 ± 20.3 vs. 77.6 ± 19.3, P < 0.001) and cancer-specific (EORTC QLQ-C30: 59.9 ± 20.3 vs. 67.4 ± 17.5, P = 0.03) QOL, as well as impaired cognitive function (72.7 ± 22.1 vs. 82.3 ± 19.0, P = 0.01). The vision-specific QOL was significantly correlated with ICOGCG score (ß = - 1.88, 95%CI: - 3.35 to - 0.41, P = 0.01) and post-alloHCT medical expense (ß = - 5.70, 95%CI: - 10.35 to - 1.05, P = 0.02), while cancer-specific QOL was strikingly correlated with post-alloHCT medical expense (ß = - 9.91, 95%CI: - 14.43 to - 5.39, P < 0.001), frequency of ophthalmic medication (ß = - 0.93, 95%CI: - 1.64 to - 0.21, P = 0.01), education (ß = - 6.97, 95%CI: - 13.31 to - 0.62, P = 0.03), and peripheral blood stem cell use (ß = - 6.42, 95%CI: - 12.59 to - 0.25, P = 0.04). CONCLUSIONS: Patients with oGVHD experienced significant impairment in both vision-specific and cancer-specific QOL including cognitive function when compared with those without after alloHCT. Multidimensional QOL assessment should be included in the long-term alloHCT survivorship care.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Humanos , Qualidade de Vida/psicologia , Estudos Transversais , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia
8.
Eye (Lond) ; 37(9): 1816-1821, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36115883

RESUMO

PURPOSE: To study the posterior segment complications (PSC) and the risk factors in patients after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This cross-sectional, case-control study enroled 143 patients who received allogeneic HSCT. Comprehensive ocular examinations were performed to evaluate PSC and ocular Graft-versus-Host Disease (oGVHD). PSC was diagnosed based on the characteristic fundus findings and auxiliary examinations. Visual-evoked potential was examined in patients with unexplained visual loss and suspected visual pathway pathology (VPP). Ocular surface disease index, corneal fluorescein staining, conjunctival injection and Schirmer's test were scored to diagnose oGVHD. RESULTS: PSC was detected in 36 (25.2%) patients, while 107 (74.8%) patients were not. Among them, 102 (71.3%) patients were diagnosed with oGVHD. The most common PSC included cytomegalovirus retinitis (13/143, 9.1%) and VPP (7/143, 4.9%). Central nervous system relapse of leukaemia was detected in four out of seven cases of VPP. Patients with PSC had worse visual acuity, lower prevalence and milder severity of oGVHD, and more donors from unrelated and human leucocyte antigen (HLA)-mismatch (all P < 0.05). PSC was associated with transplant from unrelated (OR = 6.494, 95% CI: 1.635-25.794, P = 0.008) and HLA-mismatched (OR = 7.193, 95% CI: 2.829-18.291, P < 0.001) donor but not with the occurrence of systemic GVHD or oGVHD. CONCLUSIONS: PSC in post-HSCT patients was more common than previously noted, deserving the concern of ophthalmologists, especially in patients with unrelated or HLA-mismatched donors.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Transversais , Estudos de Casos e Controles , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Fatores de Risco , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos
10.
J Agric Food Chem ; 70(50): 15928-15944, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36508213

RESUMO

Oxylipins play important signaling roles in aflatoxin (AF) biosynthesis in Aspergillus flavus. We previously showed that exogenous supply of autoxidated linolenic acid (AL) inhibited AF biosynthesis in A. flavus via oxylipins, but the molecular mechanism is still unknown. Here, we performed multiomics analyses of A. flavus grown in media with or without AL. Targeted metabolite analyses and quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) showed that the imizoquin (IMQ) biosynthetic pathway was distinctly upregulated in the presence of AL. 13C-glucose labeling confirmed in parallel that the tricarboxylic acid cycle was also enhanced by AL, consistent with observed increases in mycelial growth. Moreover, we integrated thermal proteome profiling and molecular dynamics simulations to identify a potential receptor of AL; AL was found to interact with a transporter (ImqJ) located in the IMQ gene cluster, primarily through hydrophobic interactions. Further analyses of strains with an IMQ pathway transcription factor overexpressed or knocked out confirmed that this pathway was critical for AL-mediated inhibition of AF biosynthesis. Comparison of 22 assembled A. flavus and Aspergillus oryzae genomes showed that genes involved in the IMQ pathway were positively selected in A. oryzae. Taken together, the results of our study provide novel insights into oxylipin-mediated regulation of AF biosynthesis and suggest potential methods for preventing AF contamination of crops.


Assuntos
Aflatoxinas , Aspergillus flavus , Aspergillus flavus/metabolismo , Oxilipinas/metabolismo , Ácido alfa-Linolênico , Fatores de Transcrição/metabolismo
12.
Food Funct ; 13(22): 11811-11824, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36306140

RESUMO

Gastrointestinal dysfunction is associated with a disturbance of immune homeostasis, changes in the intestinal microbiome, alteration of the composition of the bile acid pool, and dynamic imbalance of group 3 innate lymphoid cells (ILC3s). Curcumin (CUR), a polyphenolic compound isolated from turmeric, has been known to attenuate intestinal inflammation in potential therapies for gastrointestinal diseases. It was hypothesized that CUR could target the gut microbiome to modulate bile acid (BA) metabolism and the function of ILC3s in ameliorating lipopolysaccharide (LPS)-induced imbalance of intestinal homeostasis in chickens. Seven hundred and twenty 1-day-old crossbred chickens were randomly divided into four treatments, namely CON_saline (basal diet + saline control), CUR_saline (basal diet + 300 mg kg-1 curcumin + saline), CON_LPS (basal diet + LPS), and CUR_LPS (basal diet + 300 mg kg-1 curcumin + LPS), each consisting of 6 replicates of 30 birds. On days 14, 17, and 21, the chickens in the CON_LPS and CUR_LPS treatments were intraperitoneally injected with LPS at 0.5 mg per kg BW. Dietary CUR supplementation significantly decreased LPS-induced suppression of growth performance and injury to the intestinal tight junctions and decreased the vulnerability to LPS-induced acute inflammatory response by inhibiting pro-inflammatory (interleukin-1ß and tumor necrosis factor-α) cytokines. CUR reshaped the cecal microbial community and BA metabolism, contributing to regulation of the intestinal mucosal immunity by promoting the anti-inflammatory (interleukin 10, IL-10) cytokines and enhancing the concentrations of primary and secondary BA metabolites (chenodexycholic acid, lithocholic acid). LPS decreased farnesoid X receptor (FXR) and G protein-coupled receptor class C group 5 member A synthesis, which was reversed by CUR administration, along with an increase in interleukin 22 (IL-22) production from ILC3s. Dietary supplementation of CUR increased the prevalence of Butyricicoccus and Enterococcus and enhanced the tricarboxylic acid cycle of intestinal epithelial cells. In addition, curcumin supplementation significantly increased sirtuin 1 and sirtuin 5 transcription and protein expression, which contributes to regulating mitochondrial metabolic and oxidative stress responses to alleviate LPS-induced enteritis. Our findings demonstrated that curcumin played a pivotal role in regulating the structure of the intestinal microbiome for health promotion and the treatment of intestinal dysbiosis. The beneficial effects of CUR may be attributed to the modulation of the BA-FXR pathway and inhibition of inflammation that induces IL-22 secretion by ILC3s in the intestinal lamina propria.


Assuntos
Curcumina , Microbioma Gastrointestinal , Animais , Ácidos e Sais Biliares/farmacologia , Galinhas/fisiologia , Curcumina/farmacologia , Citocinas/genética , Citocinas/farmacologia , Homeostase , Imunidade Inata , Inflamação/induzido quimicamente , Lipopolissacarídeos/efeitos adversos , Linfócitos
13.
Methods Mol Biol ; 2478: 609-650, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36063336

RESUMO

Optical trapping has been instrumental for deciphering translocation mechanisms of the force-generating cytoskeletal proteins. However, studies of the dynamic interactions between microtubules (MTs) and MT-associated proteins (MAPs) with no motor activity are lagging. Investigating the motility of MAPs that can diffuse along MT walls is a particular challenge for optical-trapping assays because thermally driven motions rely on weak and highly transient interactions. Three-bead, ultrafast force-clamp (UFFC) spectroscopy has the potential to resolve static and diffusive translocations of different MAPs with sub-millisecond temporal resolution and sub-nanometer spatial precision. In this report, we present detailed procedures for implementing UFFC, including setup of the optical instrument and feedback control, immobilization and functionalization of pedestal beads, and preparation of MT dumbbells. Example results for strong static interactions were generated using the Kinesin-7 motor CENP-E in the presence of AMP-PNP. Time resolution for MAP-MT interactions in the UFFC assay is limited by the MT dumbbell relaxation time, which is significantly longer than reported for analogous experiments using actin filaments. UFFC, however, provides a unique opportunity for quantitative studies on MAPs that glide along MTs under a dragging force, as illustrated using the kinetochore-associated Ska complex.


Assuntos
Proteínas de Transporte , Proteínas dos Microtúbulos , Proteínas de Transporte/metabolismo , Cinetocoros/metabolismo , Proteínas dos Microtúbulos/análise , Proteínas dos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Análise Espectral
14.
Ann Transl Med ; 10(16): 855, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36111058

RESUMO

Background: After allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients are followed up by transplant clinicians. Finding an effective primary screening method that transplant clinicians or patients can master is essential in the early referral of suspected chronic ocular graft-versus-host disease (coGVHD) to an ophthalmologist. This study investigated if the ocular surface disease index (OSDI) questionnaire could be used for coGVHD primary screening. Methods: This case-controlled, cross-sectional study enrolled 161 allo-HSCT patients. All participants completed an OSDI questionnaire and underwent a silt-lamp examination. Bulbar conjunctival injection (BCI) was assessed using torchlight, while tear volume was measured via the Schirmer test (ST). The receiver operating characteristic curve was used to evaluate the sensitivity, specificity, and cutoff values of OSDI, ST, and BCI grading. Performance comparisons of the 3 tests applied in isolation, parallel, and series were made. Results: There were 84 patients with and 77 patients without coGVHD. Compared to those without coGVHD, patients with coGVHD had significantly higher median values of OSDI, corneal fluorescein staining, conjunctival injection, conjunctival fibrosis, and meibum quality, but lower ST scores (All P values <0.001). The cutoff values for OSDI, ST, and BCI grade in the diagnosis of coGVHD were 19.4 points, 7 mm, and grade 0, respectively. The sensitivity and specificity of the tests based on the cutoff values were, respectively, 89.3% and 89.6% for OSDI, 91.7% and 59.7% for ST, and 78.6% and 70.1% for BCI. The area under the curve (AUC) value of OSDI was significantly higher than that of ST (0.931 vs. 0.826; P=0.010) and BCI grade (0.931 vs. 0.781; P<0.001). The AUC values of the combinations were lower than that of OSDI alone. Conclusions: The OSDI questionnaire can be used as a simple screening test for coGVHD as demonstrated by its high sensitivity and specificity in the transplant clinic and patients' self-monitoring. An OSDI greater than 19.4 could be considered an ophthalmology referral criterion.

15.
Rice (N Y) ; 15(1): 34, 2022 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-35779169

RESUMO

Although type 2C protein phosphatases (PP2Cs) have been demonstrated to play important roles in regulating plant development and various stress responses, their specific roles in rice abiotic stress tolerance are still largely unknown. In this study, the functions of OsPP65 in rice osmotic and salt stress tolerance were investigated. Here, we report that OsPP65 is responsive to multiple stresses and is remarkably induced by osmotic and salt stress treatments. OsPP65 was highly expressed in rice seedlings and leaves and localized in the nucleus and cytoplasm. OsPP65 knockout rice plants showed enhanced tolerance to osmotic and salt stresses. Significantly higher induction of genes involved in jasmonic acid (JA) and abscisic acid (ABA) biosynthesis or signaling, as well as higher contents of endogenous JA and ABA, were observed in the OsPP65 knockout plants compared with the wild-type plants after osmotic stress treatment. Further analysis indicated that JA and ABA function independently in osmotic stress tolerance conferred by loss of OsPP65. Moreover, metabolomics analysis revealed higher endogenous levels of galactose and galactinol but a lower content of raffinose in the OsPP65 knockout plants than in the wild-type plants after osmotic stress treatment. These results together suggest that OsPP65 negatively regulates osmotic and salt stress tolerance through regulation of the JA and ABA signaling pathways and modulation of the raffinose family oligosaccharide metabolism pathway in rice. OsPP65 is a promising target for improvement of rice stress tolerance using gene editing.

16.
Chem Sci ; 13(8): 2363-2377, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35310482

RESUMO

The intrinsically disordered C-terminal domain (CTD) of protein 4.1G is able to specifically bind a 26-residue intrinsically disordered region of NuMA, forming a dynamic fuzzy complex. As one of a few cases of extremely fuzzy interactions between two intrinsically disordered proteins/regions (IDPs/IDRs) without induced folding, the principle of the binding is unknown. Here, we combined experimental and computational methods to explore the detailed mechanism of the interaction between 4.1G-CTD and NuMA. MD simulations suggest that the kinetic hub states in the structure ensemble of 4.1G-CTD are favorable in the fuzzy complex. The feature of these hub states is that the binding 'hot spot' motifs ßA and ßB exhibit ß strand propensities and are well packed to each other. The binding between 4.1G-CTD and NuMA is disrupted at low pH, which changes the intramolecular packing of 4.1G-CTD and weakens the packing between ßA and ßB motifs. Low pH conditions also lead to increased hydrodynamic radius and acceleration of backbone dynamics of 4.1G-CTD. All these results underscore the importance of tertiary structural arrangements and overall compactness of 4.1G-CTD in its binding to NuMA, i.e. the compact disordered state of 4.1G-CTD is crucial for binding. Different from the short linear motifs (SLiMs) that are often found to mediate IDP interactions, 4.1G-CTD functions as an intrinsically disordered domain (IDD), which is a functional and structural unit similar to conventional protein domains. This work sheds light on the molecular recognition mechanism of IDPs/IDRs and expands the conventional structure-function paradigm in protein biochemistry.

17.
Biochemistry ; 61(6): 433-445, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35226469

RESUMO

Protein-ligand interactions are crucial to many biological processes. Ligand binding and dissociation are the basic steps that allow proteins to function. Protein conformational dynamics have been shown to play important roles in ligand binding and dissociation. However, it is challenging to determine the ligand binding kinetics of dynamic proteins. Here, we undertook comprehensive single-molecule FRET (smFRET) measurements and kinetic model analysis to characterize the conformational dynamics coupled ligand binding of glutamine-binding protein (GlnBP). We showed that hinge and T118A mutations of GlnBP affect its conformational dynamics as well as the ligand binding affinity. Based on smFRET measurements, the kinetic model of ligand-GlnBP interactions was constructed. Using experimentally measured parameters, we solved the rate equations of the model and obtained the undetectable parameters of the model which allowed us to understand the ligand binding kinetics fully. Our results demonstrate that modulation of the conformational dynamics of GlnBP affects the ligand binding and dissociation rates. This study provides insights into the binding kinetics of ligands, which are related to the protein function itself.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Glutamina , Glutamina/metabolismo , Cinética , Ligantes , Ligação Proteica , Conformação Proteica
18.
Stress Biol ; 2(1): 48, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37676340

RESUMO

This paper reported a wine-derived lactic acid bacterium, Lactiplantibacillus plantarum XJ25, which exhibited higher cell viability under acid stress upon methionine supplementation. Cellular morphology and the composition of the cytomembrane phospholipids revealed a more solid membrane architecture presented in the acid-stressed cells treated with methionine supplementation. Transcriptional analysis showed L. plantarum XJ25 reduced methionine transport and homocysteine biosynthesis under acid stress. Subsequent overexpression assays proved that methionine supplementation could alleviate the cell toxicity from homocysteine accumulation under acid stress. Finally, L. plantarum XJ25 employed energy allocation strategy to response environmental changes by balancing the uptake methionine and adjusting saturated fatty acids (SFAs) in membrane. These data support a novel mechanism of acid resistance involving methionine utilization and cellular energy distribution in LAB and provide crucial theoretical clues for the mechanisms of acid resistance in other bacteria.

19.
Food Chem ; 372: 131342, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34818746

RESUMO

Black wolfberry is a commonly cultivated woody plant in China, and is rich in nutrients that are beneficial for human. To characterize the endogenous metabolite differences among black wolfberry fruits grown in different geographical regions, mass spectrometry-based metabolomic and lipidomic analyses were performed in black wolfberry grown in nine locations throughout five provinces in China, from which 204 primary and specialized metabolites, and 267 lipids were identified in their fruits. Three samples from Alxa Left Banner, Jinta, and Minqin showed dramatically altered metabolite profiles, displaying higher levels of phenolic acids, soluble sugars and flavonoids, but lower levels of tricarboxylic acid cycle intermediates and aromatic amino acids. Moreover, the lipid profile of the Alxa Left Banner sample was strikingly distinct from all other samples, with high levels of monogalactosyl diacylglycerol and sulfoquinovosyl diacylglycerol, which are positively correlated with their anti-inflammatory capacities. These findings thus prompt for further studies on black wolfberry fruit for their health benefits.


Assuntos
Lycium , Flavonoides , Frutas , Humanos , Lipídeos , Metabolômica
20.
Int J Gen Med ; 14: 9681-9687, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34934345

RESUMO

BACKGROUND: Pregnancy termination is the only effective treatment for preeclampsia. However, there are controversies on the selection of modes of delivery. The objective was to evaluate whether mode of delivery in labor differentially affected the rate of adverse maternal outcomes related to severe preeclampsia. OBJECTIVE: This study aimed to evaluate whether the modes and timings of delivery affects adverse maternal outcomes in pre-eclampsia. METHODS: Clinical data from 2516 singleton pregnant women with severe preeclampsia were collected in a multicenter, large-sample, cross-sectional study in mainland China. The patients were divided into cesarean-delivery (CD) and vaginal-delivery (VD) categories and then into Group 1 (≤27+ 6 weeks), Group 2 (28-33+ 6 weeks), Group 3 (34-36+ 6 weeks), and Group 4 (≥37 weeks) according to the mode of delivery and gestational weeks. All data were exported into the SPSS software and analyzed by the Student's t-tests or Mann-Whitney U-tests and the chi-squared test. RESULTS: A total of 2516 singleton pregnant women with severe preeclampsia were collected and the overall cesarean section rate was 84.9%. The vaginal delivery rates among the four groups were significantly different with 70%, 19.7%, 6.6%, 15.1% in groups 1, 2, 3, 4, respectively (P<0.05), while perinatal mortality was lower in the CD groups than VD groups (3.3% vs 50.4%, P<0.05). The neonatal asphyxia rate was significantly higher with CD than with VD in Group 2 (36.4% vs 12.9%, P<0.05). The perinatal mortality with CD, 3, and 4 was significantly lower than with VD (10.0% vs 68.5% in Groups 2, 2.3% vs 28.3% in Groups 3, 0.8% vs 5.6% in Groups 4, all P<0.05). CONCLUSION: Most pregnant women with severe preeclampsia opted for a cesarean section in China. The lower perinatal mortality was associated with cesarean section, but the rate of maternal PPH or mortality was not related with the mode of delivery. So cesarean section is the safer delivery mode for the pregnant women complicated with severe preeclampsia.

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