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1.
Nano Lett ; 24(5): 1544-1552, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38270095

RESUMEN

Lithium-metal (Li0) anodes potentially enable all-solid-state batteries with high energy density. However, it shows incompatibility with sulfide solid-state electrolytes (SEs). One strategy is introducing an interlayer, generally made of a mixed ionic-electronic conductor (MIEC). Yet, how Li behaves within MIEC remains unknown. Herein, we investigated the Li dynamics in a graphite interlayer, a typical MIEC, by using operando neutron imaging and Raman spectroscopy. This study revealed that intercalation-extrusion-dominated mechanochemical reactions during cell assembly transform the graphite into a Li-graphite interlayer consisting of SE, Li0, and graphite-intercalation compounds. During charging, Li+ preferentially deposited at the Li-graphite|SE interface. Upon further plating, Li0-dendrites formed, inducing short circuits and the reverse migration of Li0. Modeling indicates the interface has the lowest nucleation barrier, governing lithium transport paths. Our study elucidates intricate mechano-chemo-electrochemical processes in mixed conducting interlayers. The behavior of Li+ and Li0 in the interlayer is governed by multiple competing factors.

2.
Small ; 20(20): e2307019, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38111366

RESUMEN

The increasing demand for wearable electronics calls for advanced energy storage solutions that integrate high  electrochemical performances and mechanical robustness. Ionogel is a promising candidate due to its stretchability combined with high ionic conductivity. However, simultaneously optimizing both the electrochemical and mechanical performance of ionogels remains a challenge. This paper reports a tough and highly ion-conductive ionogel through ion impregnation and solvent exchange. The fabricated ionogel consists of double interpenetrating networks of long polymer chains that provide high stretchability. The polymer chains are crosslinked by hydrogen bonds that induce large energy dissipation for enhanced toughness. The resultant ionogel possesses mechanical stretchability of 26, tensile strength of 1.34 MPa, and fracture toughness of 4175 J m-2. Meanwhile, due to the high ion concentrations and ion mobility in the gel, a high ionic conductivity of 3.18 S m-1 at room temperature is achieved. A supercapacitor of this ionogel sandwiched with porous fiber electrodes provides remarkable areal capacitance (615 mF cm-2 at 1 mA cm-2), energy density (341.7 µWh cm-2 at 1 mA cm-2), and power density (20 mW cm-2 at 10 mA cm-2), offering significant advantages in applications where high efficiency, compact size, and rapid energy delivery are crucial, such as flexible and wearable electronics.

3.
Nano Lett ; 23(20): 9392-9398, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37819081

RESUMEN

Anode-free all-solid-state lithium metal batteries (ASLMBs) promise high energy density and safety but suffer from a low initial Coulombic efficiency and rapid capacity decay, especially at high cathode loadings. Using operando techniques, we concluded these issues were related to interfacial contact loss during lithium stripping. To address this, we introduce a conductive carbon felt elastic layer that self-adjusts the pressure at the anode side, ensuring consistent lithium-solid electrolyte contact. This layer simultaneously provides electronic conduction and releases the plating pressure. Consequently, the first Coulombic efficiency dramatically increases from 58.4% to 83.7% along with a >10-fold improvement in cycling stability. Overall, this study reveals an approach for enhancing anode-free ASLMB performance and longevity by mitigating lithium stripping inefficiency through self-adjusting interfacial pressure enabled by a conductive elastic interlayer.

4.
Small ; 19(14): e2206807, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36592423

RESUMEN

Conventional ion-selective membranes, that is ion-exchange and porous membranes, are unable to perform high conductivity and selectivity simultaneously due to the contradictions between their ion selecting and conducting mechanisms. In this work, a bifunctional ion-selective layer is developed via the combination of nanoporous boron nitride (PBN) and ion exchange groups from Nafion to achieve high ion conductivity through dual ion conducting mechanisms as well as high ion selectivity. A template-free method is adopted to synthesize flake-like PBN, which is further enmeshed with Nafion resin to form the bifunctional layer coated onto a porous polyetherimide membrane. The double-layer membrane exhibits excellent ion selectivity (1.49 × 108 mS cm-3  min), which is 22 times greater than that of the pristine porous polyetherimide membrane, with outstanding ion conductivity (64 mS cm-1 ). In a vanadium flow battery, the double-layer membrane achieves a high Coulombic efficiency of 97% and outstanding energy efficiency of 91% at 40 mA cm-2 with a stable cycling performance for over 700 cycles at 100 mA cm-2 . PBN with ion exchange groups may therefore offer a potential solution to the limitation between ion selectivity and conductivity in ion-selective membranes.

5.
Chembiochem ; 24(12): e202300165, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37170827

RESUMEN

We developed a synthetic route for producing 3-amino-2-hydroxy acetophenone (3AHAP) from m-nitroacetophenone (3NAP) using an in vitro approach. Various reaction systems were evaluated, and a direct reaction method with crude enzyme and supersaturated substrates for optimal catalytic efficiency was chosen. The reaction system included three enzymes and was enhanced by adjusting enzyme molar ratios and optimizing ribosomal binding sites. We performed substrate docking and alanine scanning to identify key sites in the enzymes nitrobenzene nitroreductase (nbzA) and hydroxylaminobenzene mutase (habA). The optimal mutant was obtained through site-directed mutagenesis, and incorporated into the reaction system, resulting in increased product yield. After optimization, the yield of 3AHAP increased from 75 mg/L to 580 mg/L within 5 hours, the highest reported yield using biosynthesis. This work provides a promising strategy for the efficient and sustainable production of 3AHAP, which has critical applications in the chemical and pharmaceutical industries.


Asunto(s)
Acetofenonas , Biosíntesis de Proteínas , Catálisis , Acetofenonas/metabolismo
6.
Cell Tissue Res ; 392(2): 565-579, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36575252

RESUMEN

Sertoli cells (SCs) preferentially use glucose to convert to lactate. As an energy source, lactate is essential for survival of developed germ cells (GCs) due to its anti-apoptotic effect. Failure to maintain lactate metabolism homeostasis leads to infertility or germ cell apoptosis. Several Sertoli cell-expressed genes, such as Foxq1 and Gata4, have been identified as critical regulators for lactate synthesis, but the pathways that potentially modulate their expression remain ill defined. Although recent work from our collaborators pointed to an involvement of STIP1 homology and U-box-containing protein 1 (STUB1) in the modulation of Sertoli cell response to GCs-derived IL-1α, a true physiological function of STUB1 signaling in SCs has not been demonstrated. We therefore conditionally ablated Stub1 in SCs using Amh-Cre. Stub1 knockout males exhibited impaired fertility due to oligozoospermia and asthenospermia, possibly caused by lactate deficiency. Furthermore, by means of chromatin immunoprecipitation, in vivo ubiquitination, and luciferase reporter assays, we showed that STUB1 directed forkhead box Q1 (FOXQ1)-mediated transactivation of the lactate dehydrogenase A (Ldha) gene via K63-linked non-proteolytic polyubiquitination, thus facilitating lactate production in follicle-stimulating hormone (FSH)-stimulated SCs. In agreement, overexpression of LDHA by lentivirus infection effectively rescued the lactate production in TM4Stub1-/- cells. Our results collectively identify STUB1-mediated transactivation of FOXQ1 signaling as a post-translationally modified transcriptional regulatory network underlying nursery function in SCs, which may nutritionally contribute to Sertoli cell dysfunction of male infertility.


Asunto(s)
Ácido Láctico , Células de Sertoli , Animales , Masculino , Ratones , Ácido Láctico/metabolismo , Activación Transcripcional/genética , Ubiquitinación , L-Lactato Deshidrogenasa
7.
Biotechnol Bioeng ; 120(12): 3557-3569, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37650151

RESUMEN

D-Amino acid oxidase (DAAO) selectively catalyzes the oxidative deamination of  D-amino acids, making it one of the most promising routes for synthesizing optically pure  L-amino acids, including  L-phosphinothricin ( L-PPT), a chiral herbicide with significant market potential. However, the native DAAOs that have been reported have low activity against unnatural acid substrate  D-PPT. Herein, we designed and screened a DAAO from Rhodotorula taiwanensis (RtwDAAO), and improved its catalytic potential toward  D-PPT through protein engineering. A semirational design approach was employed to create a mutation library based on the tunnel-pocket engineering. After three rounds of iterative saturation mutagenesis, the optimal variant M3rd -SHVG was obtained, exhibiting a >2000-fold increase in relative activity. The kinetic parameters showed that M3rd -SHVG improved the substrate binding affinity and turnover number. This is the optimal parameter reported so far. Further, molecular dynamics simulation revealed that the M3rd -SHVG reshapes the tunnel-pocket and corrects the direction of enzyme-substrate binding, allowing efficiently catalyze unnatural substrates. Our strategy demonstrates that the redesign of tunnel-pockets is effective in improving the activity and kinetic efficiency of DAAO, which provides a valuable reference for enzymatic catalysis. With the M3rd -SHVG as biocatalyst, 500 mM D, L-PPT was completely converted and the yield reached 98%. The results laid the foundation for further industrial production.


Asunto(s)
Aminoácidos , Ingeniería de Proteínas , Especificidad por Sustrato , Aminoácidos/metabolismo , Unión Proteica , Oxidorreductasas/metabolismo , D-Aminoácido Oxidasa/genética , D-Aminoácido Oxidasa/química , D-Aminoácido Oxidasa/metabolismo , Cinética
8.
Mar Drugs ; 21(11)2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37999397

RESUMEN

Several sialoglycopeptides were isolated from several fish eggs and exerted anti-osteoporosis effects. However, few papers have explored sialoglycopeptide from tuna eggs (T-ES). Here, a novel T-ES was prepared through extraction with KCl solution and subsequent enzymolysis. Pure T-ES was obtained through DEAE-Sepharose ion exchange chromatography and sephacryl S-300 gel filtration chromatography. The T-ES was composed of 14.07% protein, 73.54% hexose, and 8.28% Neu5Ac, with a molecular weight of 9481 Da. The backbone carbohydrate in the T-ES was →4)-ß-D-GlcN-(1→3)-α-D-GalN-(1→3)-ß-D-Glc-(1→2)-α-D-Gal-(1→2)-α-D-Gal-(1→3)-α-D-Man-(1→, with two branches of ß-D-GlcN-(1→ and α-D-GalN-(1→ linking at o-4 in →2,4)-α-D-Gal-(1→. Neu5Ac in the T-ES was linked to the branch of α-D-GlcN-(1→. A peptide chain, Ala-Asp-Asn-Lys-Ser*-Met-Ile that was connected to the carbohydrate chain through O-glycosylation at the -OH of serine. Furthermore, in vitro data revealed that T-ES could remarkably enhance bone density, bone biomechanical properties, and bone microstructure in SAMP mice. The T-ES elevated serum osteogenesis-related markers and reduced bone resorption-related markers in serum and urine. The present study's results demonstrated that T-ES, a novel sialoglycopeptide, showed significant anti-osteoporosis effects, which will accelerate the utilization of T-ES as an alternative marine drug or functional food for anti-osteoporosis.


Asunto(s)
Sialoglicoproteínas , Atún , Humanos , Ratones , Animales , Secuencia de Carbohidratos , Carbohidratos , Hexosas
9.
Mar Drugs ; 21(4)2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-37103360

RESUMEN

Several studies have isolated chondroitin sulphate (CHS) from sharks' jaws or cartilage. However, there has been little research on CHS from shark skin. In the present study, we extracted a novel CHS from Halaelurus burgeri skin, which has a novel chemical structure and bioactivity on improvement in insulin resistance. Results using Fourier transform-infrared spectroscopy (FT-IR), 1H-nuclear magnetic resonance spectroscopy (1H-NMR), and methylation analysis showed that the structure of the CHS was [4)-ß-D-GlcpA-(1→3)-ß-D-GlcpNAc-(1→]n with 17.40% of sulfate group concentration. Its molecular weight was 238.35 kDa, and the yield was 17.81%. Experiments on animals showed that this CHS could dramatically decrease body weight, reduce blood glucose and insulin levels, lower lipid concentrations both in the serum and the liver, improve glucose tolerance and insulin sensitivity, and regulate serum-inflammatory factors. These results demonstrated that the CHS from H. burgeri skin has a positive effect in reducing insulin resistance because of its novel structure, which provides a significant implication for the polysaccharide as a functional food.


Asunto(s)
Resistencia a la Insulina , Tiburones , Animales , Sulfatos de Condroitina/química , Espectroscopía Infrarroja por Transformada de Fourier , Glucemia
10.
Zhonghua Nan Ke Xue ; 29(10): 916-921, 2023 Oct.
Artículo en Zh | MEDLINE | ID: mdl-38639662

RESUMEN

OBJECTIVE: To explore the effect of chromosomal polymorphic variations on the outcome of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) treatment for infertile couples. Methods: In this retrospective study, 418 infertile couples, who received their first IVF/ICSI-ET treatment cycles in Reproductive Medicine Center of Xi'an People's Hospital (Xi'an Fourth Hospital) from Jan. 2021to Jan. 2023, were included and divided into two groups: group A (the infertile couples with normal chromosome) and group B(with chromosomal polymorphic variations); The group B divided into 2 groups, group C(male carrier, n= 44), group D (female carrier, n= 37). The No. of oocyte, 2PN fertilization rate, fertilization rate,multi-PN fertilization rate, quality embryo rate, cleavage rate, normal cleavage rate, blastocyst formation rate,clinical pregnancy rate after IVF/ICSI-ET treatment were compared and analyzed. Logistic regression analysis was performed to study the relationship between clinical pregnancy rate and chromosome variation. Results: A total of 418 infertile couples received IVF/ICSI-ET treatment were enrolled, with 81 in the chromosomal polymorphic group (group A), and 337 in the normal chromosomal group (group B). The quality embryo rate were signifcantly higher in the group A(59.21% vs 52.42%,P<0.05),the other outcomes have no significant differences between the two groups ( P>0.05). The No. of oocyte, 2PN fertilization rate, fertilization rate,multi-PN fertilization rate, quality embryo rate, cleavage rate, normal cleavage rate, blastocyst formation rate showed no signifcantdiferences among group A, group C and group D (P>0.05). The clinical pregnancy rate in group A is higer than group C and group D (56.7% vs 52.3% vs 40.5%), But there were no signifcantly diferent among the three groups (P>0.05). Logistic regression analysis indicated that the Chromosomal polymorphisms were not associated with clinical pregnancy rate (P>0.05).Conclusion: Chromosomal polymorphisms appear to have no significant effect on the outcome of IVF/ICSI-ET treatment for infertile couples.


Asunto(s)
Infertilidad , Semen , Embarazo , Masculino , Humanos , Femenino , Estudios Retrospectivos , Transferencia de Embrión , Fertilización In Vitro , Índice de Embarazo , Cromosomas
11.
Angew Chem Int Ed Engl ; 62(20): e202302363, 2023 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-36917787

RESUMEN

Due to its outstanding safety and high energy density, all-solid-state lithium-sulfur batteries (ASLSBs) are considered as a potential future energy storage technology. The electrochemical reaction pathway in ASLSBs with inorganic solid-state electrolytes is different from Li-S batteries with liquid electrolytes, but the mechanism remains unclear. By combining operando Raman spectroscopy and ex situ X-ray absorption spectroscopy, we investigated the reaction mechanism of sulfur (S8 ) in ASLSBs. Our results revealed that no Li2 S8, Li2 S6, and Li2 S4 were formed, yet Li2 S2 was detected. Furthermore, first-principles structural calculations were employed to disclose the formation energy of solid state Li2 Sn (1≤n≤8), in which Li2 S2 was a metastable phase, consistent with experimental observations. Meanwhile, partial S8 and Li2 S2 remained at the full lithiation stage, suggesting incomplete reaction due to sluggish reaction kinetics in ASLSBs.

12.
Small ; 18(6): e2105678, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34851029

RESUMEN

Porous carbon plays a significant role in all-solid-state lithium-sulfur batteries (ASSLSBs) to enhance the electronic conductivity of sulfur. However, the conventional porous carbon used in cell with liquid electrolyte exhibits low efficiency in ASSLSBs because the immobile solid electrolyte (SE) cannot reach sulfur confined in the deep pores. The structure and distribution of pores in carbon highly impact the electrochemical performance of ASSLSBs. Herein, a N-doped carbon fiber with micropores located only at the surface with an ultrahigh surface area of 1519 m2  g-1 is designed. As the porous layer is only on the surface, the sulfur hosted in the pores can effectively contact SE; meanwhile the dense core provides excellent electrical conductivity. Therefore, this structurally designed carbon fiber enhances both electron and ion accessibilities, promotes charge transfer, and thus dramatically improves the reaction kinetic in the ASSLSBs and boosts sulfur utilization. Compared to the vapor grown carbon fibers, the ASSLSBs using PAN-derived porous carbon fibers exhibit three times enhancement in the initial capacity of 1166 mAh g-1 at C/20. An exceedingly cycling stability of 710 mAh g-1 is maintained after 220 cycles at C/10, and satisfactory rate capability of 889 mAh g-1 at C/2 is achieved.

13.
Small ; 18(2): e2104320, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34747120

RESUMEN

Large-scale salinity gradient power energy harvesting has generated broad attention in recent years, in which affordable ion-selective membranes (ISMs) are essential for its practical implementation. In this study, for the first time, ISMs derived from natural loofah sponge are reported, which have features of high hydrophilicity, superior ion conductivity, and 3D interconnected long fibers. The permselectivity and ion conductivity of loofah-based anion-selective membranes (ASMs) and cation-selective membranes (CSMs) are designed by chemical modification of the surface functional groups of loofah fibers and followed with compression and the resin filling. The charged nanochannels inside the ISMs are served as ion conductive and selective channels based on the nanofluidic effects and Donnan exclusion. Meanwhile, the unique isotropic structure endows excellent dimensional stability under the NaCl solution for months. When ISMs are used for salinity gradient power generation from the gradient of artificial seawater and river water, the maximum power density is 18.3 mW m-2 . When ten units of loofah-based ISMs are stacked in series, a voltage as high as 1.55 V is achieved. The results highlight the great potential of natural fibers for fabricating affordable, durable, and high performance ISMs, paving a sustainable pathway for developing high-performance, durable, and low-cost salinity gradient power generators.


Asunto(s)
Luffa , Salinidad , Agua Dulce/química , Membranas Artificiales , Agua de Mar/química
14.
Mar Drugs ; 20(7)2022 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-35877704

RESUMEN

There are resourceful phospholipids in the eggs of the crab, Portunus trituberculatus (Pt-PL). However, their components and bioactivities regarding obesity were unclear. Here, we investigated the composition of Pt-PL and their fatty acids. Moreover, its effects on obesity and gut microbiota were also evaluated in high fat diet (HFD)-fed mice. The results showed that Pt-PL contained 12 kinds of phospholipids, mainly including phosphatidylcholine (PC, 32.28%), phosphatidylserine (PS, 26.51%), phosphatidic acid (PA, 19.61%), phosphatidylethanolamine (PE, 8.81%), and phosphatidylinositol (PI, 7.96%). Polyunsaturated fatty acids (PUFAs) predominated in the fatty acids components of Pt-PL, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Animal experiments demonstrated that Pt-PL significantly alleviated body weight gain, adipose gain, hepatic gain, fasting blood glucose, serum insulin, lipid levels in serum and the liver, and systematic inflammation in HFD-fed mice. Furthermore, Pt-PL regulated gut microbiota, especially in a dramatic reduction in the ratio of Firmicutes to Bacteroidetes at phylum level, as well as significant amelioration in their subordinate categories. Pt-PL reduced fecal lipopolysaccharide and total bile acids, and elevated fecal short chain fatty acid (SCFA) concentrations, particularly acetate and butyrate. These findings suggest that Pt-PL possesses anti-obesity effects and can alter gut microbiota owing to the abundance of PUFAs. Therefore, Pt-PL may be developed as an effective food supplement for anti-obesity and regulation of human gut health.


Asunto(s)
Braquiuros , Microbioma Gastrointestinal , Animales , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos/farmacología , Humanos , Ratones , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/etiología , Fosfolípidos/farmacología
15.
Plant Dis ; 106(2): 510-517, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34340560

RESUMEN

Pythium soft rot is a major soilborne disease of crops such as ginger (Zingiber officinale). Our objective was to identify which Pythium species were associated with Pythium soft rot of ginger in China, where approximately 20% of global ginger production is located. Oomycetes infecting ginger rhizomes from seven provinces were investigated using two molecular markers, the internal transcribed spacer, and cytochrome c oxidase subunit II (CoxII). In total, 81 isolates were recovered; approximately 95% of the isolates were identified as Pythium myriotylum, and the other isolates were identified as either P. aphanidermatum or P. graminicola. Notably, the P. myriotylum isolates from China did not contain the single nucleotide polymorphism in the CoxII sequence found previously in the P. myriotylum isolates infecting ginger in Australia. A subset of 36 isolates was analyzed repeatedly by temperature-dependent growth, severity of disease on ginger plants, and aggressiveness of colonization on ginger rhizome sticks. In the pathogenicity assays, 32 of 36 isolates were able to significantly infect and cause severe disease symptoms on the ginger plants. A range of temperature-dependent growth, disease severity, and aggressiveness in colonization was found, with a significant moderate positive correlation between growth and aggressiveness of colonization of the ginger sticks. This study identified P. myriotylum as the major oomycete pathogen in China from infected ginger rhizomes and suggested that P. myriotylum should be a key target to control soft rot of ginger disease.


Asunto(s)
Pythium , Zingiber officinale , China , Productos Agrícolas , Extractos Vegetales
16.
J Biol Chem ; 295(10): 3115-3133, 2020 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-32005658

RESUMEN

The fortuitously discovered antiaging membrane protein αKlotho (Klotho) is highly expressed in the kidney, and deletion of the Klotho gene in mice causes a phenotype strikingly similar to that of chronic kidney disease (CKD). Klotho functions as a co-receptor for fibroblast growth factor 23 (FGF23) signaling, whereas its shed extracellular domain, soluble Klotho (sKlotho), carrying glycosidase activity, is a humoral factor that regulates renal health. Low sKlotho in CKD is associated with disease progression, and sKlotho supplementation has emerged as a potential therapeutic strategy for managing CKD. Here, we explored the structure-function relationship and post-translational modifications of sKlotho variants to guide the future design of sKlotho-based therapeutics. Chinese hamster ovary (CHO)- and human embryonic kidney (HEK)-derived WT sKlotho proteins had varied activities in FGF23 co-receptor and ß-glucuronidase assays in vitro and distinct properties in vivo Sialidase treatment of heavily sialylated CHO-sKlotho increased its co-receptor activity 3-fold, yet it remained less active than hyposialylated HEK-sKlotho. MS and glycopeptide-mapping analyses revealed that HEK-sKlotho is uniquely modified with an unusual N-glycan structure consisting of N,N'-di-N-acetyllactose diamine at multiple N-linked sites, one of which at Asn-126 was adjacent to a putative GalNAc transfer motif. Site-directed mutagenesis and structural modeling analyses directly implicated N-glycans in Klotho's protein folding and function. Moreover, the introduction of two catalytic glutamate residues conserved across glycosidases into sKlotho enhanced its glucuronidase activity but decreased its FGF23 co-receptor activity, suggesting that these two functions might be structurally divergent. These findings open up opportunities for rational engineering of pharmacologically enhanced sKlotho therapeutics for managing kidney disease.


Asunto(s)
Glucuronidasa/metabolismo , Insuficiencia Renal Crónica/patología , Animales , Células CHO , Dominio Catalítico , Cromatografía Líquida de Alta Presión , Cricetinae , Cricetulus , Factor-23 de Crecimiento de Fibroblastos , Tasa de Filtración Glomerular/efectos de los fármacos , Glucuronidasa/química , Glucuronidasa/genética , Glicopéptidos/análisis , Células HEK293 , Semivida , Humanos , Proteínas Klotho , Espectrometría de Masas , Mutagénesis Sitio-Dirigida , Procesamiento Proteico-Postraduccional , Ratas , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Insuficiencia Renal Crónica/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Daño por Reperfusión/veterinaria , Relación Estructura-Actividad
17.
Artif Organs ; 45(10): 1229-1239, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34101875

RESUMEN

Oxidative damage caused by the ferryl hemoglobin is one of the major clinical adverse reactions of hemoglobin-based oxygen carriers (HBOCs), while the production of reactive oxygen species in a pathological state can oxidize hemoglobin (HbFe2+ ) to ferryl Hb, which can then enter the pseudoperoxidase cycle, making hemoglobin highly toxic. In this study, we found that ferrous hemoglobin and polymerized porcine hemoglobin (one of the HBOCs) have the peroxidase activity different from the pseudoperoxidase activity of ferric hemoglobin. Ferrous hemoglobin can catalyze the reaction of tyrosine (Tyr) with hydrogen peroxide. In addition, the results also indicated that ferrous hemoglobin and pPolyHb have a strong inhibitory effect on the pseudoperoxidase activity of ferric hemoglobin. Therefore, hydrogen peroxide was consumed in a large amount, which greatly prevented hemoglobin from becoming oxidized and entering the pseudoperoxidase cycle, thus inhibiting ferryl Hb toxicity. We further cultured human umbilical vein endothelial cells and monitored cell morphology, viability, cell cycle, apoptosis, lactate dehydrogenase (LDH) release, and malondialdehydes (MDAs) formation when incubated with H2 O2 , Tyr, and HbFe2+ . HbFe2+ and pPolyHb reduced cell cycle arrest, apoptosis, LDH release, and MDA formation. These results showed that reducing oxidative damage induced by H2 O2 and converted hemoglobin from a molecule that is toxic to one that inhibits oxidative damage, suggesting a new strategy for development of a safer HBOCs.


Asunto(s)
Sustitutos Sanguíneos/química , Sustitutos Sanguíneos/farmacología , Hemoglobinas/farmacología , Peróxido de Hidrógeno/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Hemoglobinas/química , Células Endoteliales de la Vena Umbilical Humana , Humanos , Peróxido de Hidrógeno/metabolismo , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Peroxidasas/química , Porcinos
18.
Mar Drugs ; 20(1)2021 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-35049893

RESUMEN

Fucoidans from sea cucumber (SC-FUC) have been proven to alleviate insulin resistance in several species. However, there are few studies that clarify the relationship between their structure and bioactivity. The present study evaluated the influence of molecular weight (Mw), sulfation concentrations (Cs), and sulfation position on improving insulin resistance using SC-FUC. Results showed that fucoidans with lower Mw exerted stronger effects. Having a similar Mw, Acaudina molpadioides fucoidans (Am-FUC) with lower Cs and Holothuria tubulosa fucoidans with higher Cs showed similar activities. However, Isostichopus badionotus fucoidans (higher Cs) activity was superior to that of low-Mw Thelenota ananas fucoidans (Ta-LFUC, lower Cs). Eliminating the effects of Mw and Cs, the bioactivity of Am-FUC with sulfation at meta-fucose exceeded that of Ta-FUC with sulfation at ortho-position. Moreover, the effects of Pearsonothuria graeffei fucoidans with 4-O-sulfation were superior to those of Am-LFUC with 2-O-sulfation. These data indicate that low Mw, 4-O-sulfation, and sulfation at meta-fucose contributed considerably to insulin resistance alleviation by SC-FUC, which could accelerate the development of SC-FUC as a potential food supplement to alleviate insulin resistance.


Asunto(s)
Hipoglucemiantes/farmacología , Polisacáridos/farmacología , Pepinos de Mar , Animales , Organismos Acuáticos , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Fucosa , Hipoglucemiantes/química , Resistencia a la Insulina , Masculino , Ratones , Ratones Endogámicos C57BL , Peso Molecular , Polisacáridos/química , Relación Estructura-Actividad , Sulfatos
19.
BMC Musculoskelet Disord ; 22(1): 649, 2021 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-34330243

RESUMEN

BACKGROUND: At present, the most effective and mature treatment after ACL injury and tear is ACL reconstruction, but the rehabilitation process after ACL reconstruction that is very long, so it is very important to find early MRI positive findings of knee instability. METHODS: We retrospectively collected the clinical and imaging data of 70 patients who underwent ACL reconstruction from January 2016 to December 2019; Based on clinical criteria, the patients were divided into a stable group (n = 57) and an unstable group (n = 13); We measured the MRI imaging evaluation indexes, including the position of the bone tunnel, graft status, and the anatomical factors; Statistical methods were used to compare the differences of imaging evaluation indexes between the two groups; The prediction equation was constructed and ROC curve was used to compare the prediction efficiency of independent prediction factors and prediction equation. RESULTS: There were significant differences in the abnormal position of tibial tunnel entrance, percentage of the position of tibial tunnel entrance, position of tibial tunnel exit, lateral tibial posterior slope (LTPS), width of intercondylar notch between stable knee joint group and unstable knee joint group after ACL reconstruction (P < 0.05); The position of tibial tunnel exits and the lateral tibial posterior slope (LTPS) and the sagittal obliquity of the graft were independent predictors among surgical factors and self-anatomical factors (P < 0.05); The prediction equation of postoperative knee stability was established: Logit(P) = -1.067-0.231*position of tibial tunnel exit + 0.509*lateral tibial posterior slope (LTPS)-2.105*sagittal obliquity of the graft; The prediction equation predicted that the AUC of knee instability was 0.915, the sensitivity was 84.6%, and the specificity was 91.2%. CONCLUSIONS: We found that abnormalities of the position of the exit of the bone tunnel, lateral tibial posterior slope (LTPS) and sagittal obliquity of the graft were the early MRI positive findings of knee instability after ACL reconstruction. It is helpful for clinicians to predict the stability of knee joint after ACL reconstruction.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior/efectos adversos , Estudios de Factibilidad , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Imagen por Resonancia Magnética , Estudios Retrospectivos , Tibia/cirugía
20.
Genomics ; 112(5): 3597-3608, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32320818

RESUMEN

OBJECTIVE: The objective was to find the role of long-non-coding RNA zinc finger antisense 1 (lncRNA ZFAS1)/microRNA (miR)-129/high-mobility group box protein 1 (HMGB1) axis in polycystic ovary syndrome (PCOS). METHODS: Ovarian granulosa cells from non-PCOS patients and PCOS patients were collected, and HMGB1, miR-129 and lncRNA ZFAS1 expression were detected. Ovarian granulosa cells were transfected with si-ZFAS1 or miR-129 mimics to verify their roles in P4 and E2 secretion, and the biological functions of ovarian granulosa cells. RESULTS: LncRNA ZFAS1 and HMGB1 were elevated, while miR-129 was down-regulated in ovarian granulosa cells of PCOS patients. Down-regulated lncRNA ZFAS1 or overexpressed miR-129 could decrease HMGB1 expression, increase P4 and E2 secretion, promote proliferation activity while inhibit apoptosis of ovarian granulosa cells in PCOS. CONCLUSION: LncRNA ZFAS1 could bind to miR-129 to promote HMGB1 expression, thereby affecting the endocrine disturbance, proliferation and apoptosis of ovarian granulosa cells in PCOS.


Asunto(s)
Apoptosis/genética , Proliferación Celular/genética , Regulación hacia Abajo , Células de la Granulosa/patología , Proteína HMGB1/genética , MicroARNs/genética , Síndrome del Ovario Poliquístico/patología , ARN Largo no Codificante/genética , Regulación hacia Arriba , Progresión de la Enfermedad , Femenino , Humanos , Síndrome del Ovario Poliquístico/genética
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