RESUMEN
The present study aimed to explore the pathogenic spectrum and risk factors of peritoneal dialysis-associated peritonitis (Peritoneal dialysis associated peritonitis, PDAP) in Yongzhou, Hunan, China. The clinical and epidemiological data on regular peritoneal dialysis (Peritoneal dialysis, PD) between January 2016 and December 2020 in Yongzhou were collected for retrospective analysis. The related factors of peritonitis were evaluated by single-factor analysis, while risk factors of refractory PDAP were evaluated by multivariate logistic regression analysis.172/331 172 (51.9%) patients developed peritonitis. The risk factors of PDAP in PD patients included high C-reactive protein (C-reactive protein, CRP), low albumin(Albumin, ALB), low hemoglobin (Hemoglobin, Hb), low educational level (junior high school or lower), preference of spicy food, irregular diet, low annual household income, unfavorable fluid exchange conditions, unstable employment (including working as a farmer), and unfavorable humidity conditions (P < 0.05). 63/172 (36.6%) PDAP patients were intractable cases with a pathogenic bacteria positive rate of 74.60% in the peritoneal dialysate cultures, and 109/172 patients were non-intractable cases with a pathogenic bacteria positive rate of 53.21%. Gram-positive bacteria (G+) were detected in most of the dialysate cultures, with Staphylococcus epidermidis (S. epidermidis) as the most common type, while Escherichia coli (E. coli) was the most common Gram-negative bacteria (G-). Gram-positive bacteria were sensitive to vancomycin and linezolid, while G- bacteria were sensitive to imipenem and amikacin. Lifestyle, educational level, and environmental factors are the major contributors to PDAP in PD patients. Fungal and multi-bacterial infections are the major causes of death; PD is stopped for such patients.
Asunto(s)
Antibacterianos , Diálisis Peritoneal , Peritonitis , Humanos , Estudios Retrospectivos , Masculino , Peritonitis/microbiología , Peritonitis/epidemiología , Peritonitis/etiología , Persona de Mediana Edad , Femenino , Factores de Riesgo , Diálisis Peritoneal/efectos adversos , China/epidemiología , Adulto , Anciano , Antibacterianos/uso terapéutico , Bacterias/aislamiento & purificación , Bacterias/clasificaciónRESUMEN
C19 steroids and C22 steroids are vital intermediates for the synthesis of steroid drugs. Compared with C19 steroids, C22 steroids are more suitable for synthesizing progesterone and adrenocortical hormones, albeit less developed. 9,22-dihydroxy-23,24-bisnorchol-4-ene-3-one(9-OHBA), due to its substituents at positions C-9 and C-22, is a beneficial and innovative steroid derivative for synthesizing corticosteroids. We focused on the C22 pathway in Mycobacterium fortuitum ATCC 35855, aiming to develop a productive strain that produces 9-OHBA. We used a mutant strain, MFΔkstD, that knocked out kstds from Mycobacterium fortuitum ATCC 35855 named MFKD in this study as the original strain. Hsd4A and FadA5 are key enzymes in controlling the C19 metabolic pathway of steroids in Mycobacterium fortuitum ATCC 35855. After knocking out hsd4A, MFKDΔhsd4A accumulated 81.47% 9-OHBA compared with 4.13% 9-OHBA in the strain MFKD. The double mutant MFKDΔhsd4AΔfadA5 further improved the selectivity of 9-OHBA to 95.13%, and 9α-hydroxy-4-androstenedione (9-OHAD) decreased to 0.90% from 4.19%. In the end, we obtained 6.81 g/L 9-OHBA from 10 g/L phytosterols with a molar yield of 80.33%, which showed the best performance compared with formerly reported strains.
Asunto(s)
Mycobacterium fortuitum , Fitosteroles , Mycobacterium fortuitum/genética , Androstenodiona , Diente Molar , ProgesteronaRESUMEN
The difficulty of short-process bonded Nd-Fe-B magnet waste recycling lies in the effective removal of the cured polymer matrix while protecting the magnetic powder. In this study, the polymer matrix in bonded Nd-Fe-B magnet waste was destroyed using sodium hydroxide ethanol solution, and the effect of the recycling process on the magnetic powders was studied. The nonmagnetic polymer matrix was removed, while the magnetic phase was not destroyed. The carbon and oxygen contents of the recycled magnetic powders decreased by 92.96 and 89.30%, respectively, while the MS (saturation magnetization), Mr (remanence), and Hcj (coercivity) values of the recycled magnetic powders were 99.8, 98.5, and 95.9% of the original magnetic powders, respectively. The curing and decomposition processes of the polymer matrix were also analyzed. During the curing process, dicyandiamide and bisphenol A epoxy resin acted as bridges and skeletons, respectively, finally forming a thermosetting three-dimensional network structure. In the alkaline alcohol solution, the bridges and skeletons were destroyed by the free hydroxyl groups and free hydrogen radicals in ethanol, and small molecular products were dissolved in the solution.
RESUMEN
BACKGROUND: 9α-hydroxyandrost-4-ene-3,17-dione (9-OHAD) is a significant intermediate for the synthesis of glucocorticoid drugs. However, in the process of phytosterol biotransformation to manufacture 9-OHAD, product degradation, and by-products restrict 9-OHAD output. In this study, to construct a stable and high-yield 9-OHAD producer, we investigated a combined strategy of blocking Δ1dehydrogenation and regulating metabolic flux. RESULTS: Five 3-Ketosteroid-Δ1-dehydrogenases (KstD) were identified in Mycobacterium fortuitum ATCC 35855. KstD2 showed the highest catalytic activity on 3-ketosteroids, followed by KstD3, KstD1, KstD4, and KstD5, respectively. In particular, KstD2 had a much higher catalytic activity for C9 hydroxylated steroids than for C9 non-hydroxylated steroids, whereas KstD3 showed the opposite characteristics. The deletion of kstDs indicated that KstD2 and KstD3 were the main causes of 9-OHAD degradation. Compared with the wild type M. fortuitum ATCC 35855, MFΔkstD, the five kstDs deficient strain, realized stable accumulation of 9-OHAD, and its yield increased by 42.57%. The knockout of opccr or the overexpression of hsd4A alone could not reduce the metabolic flux of the C22 pathway, while the overexpression of hsd4A based on the knockout of opccr in MFΔkstD could remarkably reduce the contents of 9,21 dihydroxy20methylpregna4en3one (9-OHHP) by-products. The inactivation of FadE28-29 leads to a large accumulation of incomplete side-chain degradation products. Therefore, hsd4A and fadE28-29 were co-expressed in MFΔkstDΔopccr successfully eliminating the two by-products. Compared with MFΔkstD, the purity of 9-OHAD improved from 80.24 to 90.14%. Ultimately, 9OHAD production reached 12.21 g/L (83.74% molar yield) and the productivity of 9-OHAD was 0.0927 g/L/h from 20 g/L phytosterol. CONCLUSIONS: KstD2 and KstD3 are the main dehydrogenases that lead to 9-OHAD degradation. Hsd4A and Opccr are key enzymes regulating the metabolic flux of the C19- and C22-pathways. Overexpression of fadE28-29 can reduce the accumulation of incomplete degradation products of the side chains. According to the above findings, the MF-FA5020 transformant was successfully constructed to rapidly and stably accumulate 9-OHAD from phytosterols. These results contribute to the understanding of the diversity and complexity of steroid catabolism regulation in actinobacteria and provide a theoretical basis for further optimizing industrial microbial catalysts.
Asunto(s)
Mycobacterium fortuitum , Fitosteroles , Fitosteroles/metabolismo , Mycobacterium fortuitum/metabolismo , Androstenodiona , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Esteroides/metabolismoRESUMEN
C22 steroid drug intermediates are suitable for corticosteroids synthesis, and the production of C22 steroids is unsatisfactory due to the intricate steroid metabolism. Among the C22 steroids, 21-hydroxy-20-methyl-pregna-1,4-dien-3-one (1,4-HP) could be used for Δ1-steroid drug synthesis, such as prednisolone. Nevertheless, the production of 1,4-HP remains unsatisfactory. In this study, an ideal 1,4-HP producing strain was constructed. By the knockout of 3-ketosteroid-9-hydroxylase (KshA) genes and 17ß-hydroxysteroid dehydrogenase (Hsd4A) gene, the steroid nucleus degradation and the accumulation of C19 steroids in Mycolicibacterium neoaurum were blocked. The mutant strain could transform phytosterols into 1,4-HP as the main product and 21-hydroxy-20-methyl-pregna-4-ene-3-one as a by-product. Subsequently, the purity of 1,4-HP improved to 95.2% by the enhancement of 3-ketosteroid-Δ1-dehydrogenase (KSTD) activity, and the production of 1,4-HP was improved by overexpressing NADH oxidase (NOX) and catalase (KATE) genes. Consequently, the yield of 1,4-HP achieved 10.5 g/L. The molar yield and the purity of 1,4-HP were optimal so far, and the production of 1,4-HP provides a new intermediate for the pharmaceutical steroid industry. KEY POINTS: ⢠A third 3-ketosteroid-9-hydroxylase was identified in Mycolicibacterium neoaurum. ⢠An 1,4-HP producer was constructed by KshA and Hsd4A deficiency. ⢠The production of 1,4-HP was improved by KSTD, NOX, and KATE overexpression.
Asunto(s)
Mycobacterium , Fitosteroles , Mycobacterium/genética , Oxigenasas de Función Mixta/metabolismo , Esteroides/metabolismo , Cetosteroides/metabolismoRESUMEN
Acyl-CoA dehydrogenase (ChsE) is involved in the steroid side-chain degradation process. However, their function in vivo remains unclear. In this study, three ChsE, ChsE1-ChsE2, ChsE3, and ChsE4-ChsE5, were identified in Mycolicibacterium neoaurum, and their functions in vivo are studied and compared with those from Mycobacterium tuberculosis in vitro. By gene knockout, complementation, and the bioconversion of phytosterols, the function of ChsE was elucidated that ChsE4-ChsE5 could utilize C27, C24, and C22 steroids in vivo. ChsE3 could utilize C27 and C24 steroids in vivo. ChsE1-ChsE2 could utilize C27, C24, and C22 steroids in vivo. What is more, the production strain of a C22 steroid, 3-oxo-4,17-pregadiene-20-carboxylic acid methyl ester (PDCE), is constructed with ChsE overexpression. This study improved the understanding of the steroid bioconversion pathway and proposed a method of the production of a new C22 steroid. KEY POINTS: ⢠Three ChsE paralogs from M. neoaurum are identified and studied. ⢠The function of ChsE is overlapped in vivo. ⢠A C22 steroid (PDCE) producer was constructed with ChsE overexpression.
Asunto(s)
Mycobacterium tuberculosis , Fitosteroles , Esteroides/metabolismo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Acil-CoA DeshidrogenasaRESUMEN
Androst-4-ene-3,17-dione (AD) and 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) are important drug intermediates that can be biosynthesized from phytosterols. However, the C9 hydroxylation of steroids via 3-ketosteroid 9α-hydroxylase (KSH) limits AD and 4-HBC accumulation. Five active KshAs, the oxidation component of KSH, were identified in Mycobacterium fortuitum ATCC 35855 for the first time. The deletion of kshAs indicated that the five KshA genes were jointly responsible for C9 hydroxylation during phytosterol biotransformation. MFKDΔkshA, the five KshAs deficient strain, blocked C9 hydroxylation and produced 5.37 g/L AD and 0.55 g/L 4-HBC. The dual function reductase Opccr knockout and 17ß-hydroxysteroid dehydrogenase Hsd4A enhancement reduced 4-HBC content from 8.75 to 1.72% and increased AD content from 84.13 to 91.34%, with 8.24 g/L AD being accumulated from 15 g/L phytosterol. In contrast, hsd4A and thioesterase fadA5 knockout resulted in the accumulation of 5.36 g/L 4-HBC from 10 g/L phytosterol. We constructed efficient AD (MFKDΔkshAΔopccr_hsd4A) and 4-HBC (MFKDΔkshAΔhsd4AΔfadA5) producers and provided insights for further metabolic engineering of the M. fortuitum ATCC 35855 strain for steroid productions. KEY POINTS: ⢠Five active KshAs were first identified in M. fortuitum ATCC 35855. ⢠Deactivation of all five KshAs blocks the steroid C9 hydroxylation reaction. ⢠AD or 4-HBC production was improved by Hsd4A, FadA5, and Opccr modification.
Asunto(s)
Mycobacterium fortuitum , Mycobacterium , Fitosteroles , Mycobacterium fortuitum/metabolismo , Mycobacterium/genética , Oxigenasas de Función Mixta/metabolismo , Esteroides/metabolismo , BiotransformaciónRESUMEN
Mycobacterium neoaurum DSM 1381 originated from Mycobacterium neoaurum ATCC 25790 by mutagenesis screening is a strain of degrading phytosterols and accumulating important C22 steroid intermediates, including 22-hydroxy-23, 24-bisnorchola-4-en-3-one (4-HP) and 22-hydroxy-23, 24-bisnorchola-1,4-dien-3-one (HPD). However, the metabolic mechanism of these C22 products in M. neoaurum DSM 1381 remains unknown. Therefore, the whole-genome sequencing and comparative genomics analysis of M. neoaurum DSM 1381 and its parent strain M. neoaurum ATCC 25790 were performed to figure out the mechanism. As a result, 28 nonsynonymous single nucleotide variants (SNVs), 17 coding region Indels, and eight non-coding region Indels were found between the genomes of the two strains. When the wild-type 3-ketosteroid-9α-hydroxylase subunit A1 (KshA1) and ß-hydroxyacyl-CoA dehydrogenase (Hsd4A) were overexpressed in M. neoaurum DSM 1381, the steroids were transformed into the 4-androstene-3, 17- dione (AD) and 1,4-androstadiene-3,17-dione (ADD) instead of C22 intermediates. This result indicated that 173N of KshA1 and 171K of Hsd4A are indispensable to maintaining their activity, respectively. Amino acid sequence alignment analysis show that both N173D in KshA1 and K171E in Hsd4A are conservative sites. The 3D models of these two enzymes were predicted by SWISS-MODEL and AlphaFold2 to understand the inactivation of the two key enzymes. These results indicate that K171E in Hsd4A may destroy the inaction between the NAD+ with the NH3+ and N173D in KshA1 and may disrupt the binding of the catalytic domain to the substrate. A C22 steroid intermediates-accumulating mechanism in M. neoaurum DSM 1381 is proposed, in which the K171E in Hsd4A leads to the enzyme's inactivation, which intercepts the C19 sub-pathways and accelerates the C22 sub-pathways, and the N173D in KshA1 leads to the enzyme's inactivation, which blocks the degradation of C22 intermediates. In conclusion, this study explained the reasons for the accumulation of C22 intermediates in M. neoaurum DSM 1381 by exploring the inactivation mechanism of the two key enzymes.
Asunto(s)
Mycobacteriaceae , Mycobacterium , Fitosteroles , Mycobacterium/genética , Mycobacterium/metabolismo , Esteroides/metabolismo , Mycobacteriaceae/genética , Mycobacteriaceae/metabolismo , Oxigenasas de Función Mixta/metabolismo , Fitosteroles/metabolismoRESUMEN
Steroid drug precursors, including C19 and C22 steroids, are crucial to steroid drug synthesis and development. However, C22 steroids are less developed due to the intricacy of the steroid metabolic pathway. In this study, a C22 steroid drug precursor, 9-hydroxy-3-oxo-4,17-pregadiene-20-carboxylic acid methyl ester (9-OH-PDCE), was successfully obtained from Mycolicibacterium neoaurum by 3-ketosteroid-Δ1-dehydrogenase and enoyl-CoA hydratase ChsH deficiency. The production of 9-OH-PDCE was improved by the overexpression of 17ß-hydroxysteroid dehydrogenase Hsd4A and acyl-CoA dehydrogenase ChsE1-ChsE2 to reduce the accumulation of by-products. The purity of 9-OH-PDCE in fermentation broth was improved from 71.7% to 89.7%. Hence, the molar yield of 9-OH-PDCE was improved from 66.7% to 86.7%, with a yield of 0.78 g/L. Furthermore, enoyl-CoA hydratase ChsH1-ChsH2 was identified to form an indispensable complex in Mycolicibacterium neoaurum DSM 44704. IMPORTANCE C22 steroids are valuable precursors for steroid drug synthesis, but the development of C22 steroids remains unsatisfactory. This study presented a strategy for the one-step bioconversion of phytosterols to a C22 steroid drug precursor, 9-hydroxy-3-oxo-4,17-pregadiene-20-carboxylic acid methyl ester (9-OH-PDCE), by 3-ketosteroid-Δ1-dehydrogenase and enoyl-CoA hydratase deficiency with overexpression of 17ß-hydroxysteroid dehydrogenase acyl-CoA dehydrogenase in Mycolicibacterium. The function of the enoyl-CoA hydratase ChsH in vivo was revealed. Construction of the novel C22 steroid drug precursor producer provided more potential for steroid drug synthesis, and the characterization of the function of ChsH and the transformation of steroids further revealed the steroid metabolic pathway.
Asunto(s)
Acil-CoA Deshidrogenasas , Fitosteroles , Profármacos , Fitosteroles/metabolismo , Oxidorreductasas/metabolismo , Enoil-CoA Hidratasa/genética , Enoil-CoA Hidratasa/metabolismo , Esteroides/metabolismo , Acilcoenzima A , Ácidos Carboxílicos , Cetosteroides , ÉsteresRESUMEN
BACKGROUND: Steroid drugs are essential for disease prevention and clinical treatment. However, due to intricated steroid structure, traditional chemical methods are rarely implemented into the whole synthetic process for generating steroid intermediates. Novel steroid drug precursors and their ideal bacterial strains for industrial production have yet to be developed. Among these, 9,21-dihydroxy-20-methyl-pregna-4-en-3-one (9-OH-4-HP) is a novel steroid drug precursor, suitable for the synthesis of corticosteroids. In this study, a combined strategy of blocking Δ1-dehydrogenation and the C19 pathway as well as improving the intracellular environment was investigated to construct an effective 9-OH-4-HP-producing strain. RESULTS: The Δ1-dehydrogenation-deficient strain of wild-type Mycobacterium neoaurum DSM 44074 produces 9-OH-4-HP with a molar yield of 4.8%. Hsd4A, encoding a ß-hydroxyacyl-CoA dehydrogenase, and fadA5, encoding an acyl-CoA thiolase, were separately knocked out to block the C19 pathway in the Δ1-dehydrogenation-deficient strain. The two engineered strains were able to accumulate 0.59 g L-1 and 0.47 g L-1 9-OH-4-HP from 1 g L-1 phytosterols, respectively. Furthermore, hsd4A and fadA5 were knocked out simultaneously in the Δ1-dehydrogenation-deficient strain. The 9-OH-4-HP production from the Hsd4A and FadA5 deficient strain was 11.9% higher than that of the Hsd4A deficient strain and 40.4% higher than that of the strain with FadA5 deficiency strain, respectively. The purity of 9-OH-4-HP obtained from the Hsd4A and FadA5 deficient strain has reached 94.9%. Subsequently, the catalase katE from Mycobacterium neoaurum and an NADH oxidase, nox, from Bacillus subtilis were overexpressed to improve the intracellular environment, leading to a higher 9-OH-4-HP production. Ultimately, 9-OH-4-HP production reached 3.58 g L-1 from 5 g L-1 phytosterols, and the purity of 9-OH-4-HP improved to 97%. The final 9-OH-4-HP production strain showed the best molar yield of 85.5%, compared with the previous reported strain with 30% molar yield of 9-OH-4-HP. CONCLUSION: KstD, Hsd4A, and FadA5 are key enzymes for phytosterol side-chain degradation in the C19 pathway. Double deletion of hsd4A and fadA5 contributes to the blockage of the C19 pathway. Improving the intracellular environment of Mycobacterium neoaurum during phytosterol bioconversion could accelerate the conversion process and enhance the productivity of target sterol derivatives.
Asunto(s)
Redes y Vías Metabólicas , Mycobacteriaceae/genética , Mycobacteriaceae/metabolismo , Fitosteroles/metabolismo , Profármacos/metabolismo , Esteroides/metabolismo , Proteínas Bacterianas/genética , Coenzima A Transferasas/genética , Edición Génica , Técnicas de Inactivación de Genes , Genoma Bacteriano , Hidroliasas/genética , Oxidorreductasas/genéticaRESUMEN
The anisotropy of crystalline materials results in different physical and chemical properties on different facets, which warrants an in-depth investigation. Macroscopically facet-tuned, high-purity gallium nitride (GaN) single crystals were synthesised and machined, and the electrocatalytic hydrogen evolution reaction (HER) was used as the model reaction to show the differences among the facets. DFT calculations revealed that the Ga and N sites of GaN (100) had a considerably smaller ΔGH* value than those of the metal Ga site of GaN (001) or N site of GaN (00-1), thereby indicating that GaN (100) should be more catalytically active for the HER on account of its nonpolar facet. Subsequent experiments testified that the electrocatalytic performance of GaN (100) was considerably more efficient than that of other facets for both acidic and alkaline HERs. Moreover, the GaN crystal with a preferentially (100) active facet had an excellently durable alkaline electrocatalytic HER for more than 10â days. This work provides fundamental insights into the exploration of the intrinsic properties of materials and designing advanced materials for physicochemical applications.
RESUMEN
Δ1-Dehydrogenation is one of the most important reactions for steroid drug modification. Numerous 3-ketosteroid-Δ1-dehydrogenases (KstDs) catalyzing this reaction were observed in various organisms. However, only a few have been characterized and used for substrate conversion. In this study, a promising enzyme (KstD2) from Mycobacterium neoaurum DSM 1381 was purified and characterized. Interestingly, KstD2 displayed a high activity on a range of substrates, including 17α-hydroxypregn-4-ene-3,20-dione (17α-OH-P); androsta-4,9(11)-diene-3,17-dione (NSC 44826); and 4-androstene-3,17-dione (AD). These reactions were performed under optimal conditions at 40 °C and pH 8.0. Noteworthy, both the activity and stability of the enzyme were sensitive to various metal ions. After optimizing the expression and biocatalyst conditions, up to 1586 U mg-1 intracellular KstD activity on AD could be produced. Furthermore, the associated conversion rate was 99% with 30 g L-1 AD after 8 h. On the other hand, we obtained 99%, 90%, and over 80% of conversion with 20 g L-1 NSC 44826; 10 g L-1 16,17α-epoxyprogesterone; and 20 g L-1 17α-OH-P or canrenone, respectively, after 24 h. Sequence homology and structural analyses indicated that the residue R178 located in a unique short loop among cluster 2 is crucial for substrate recognition which was confirmed by mutagenesis. In summary, this study reports on the first purification and characterization of a KstD from cluster 2. Its remarkable properties deserve more attention to potentially lead to further industrial applications.
Asunto(s)
Mycobacterium/enzimología , Oxidorreductasas/aislamiento & purificación , Oxidorreductasas/metabolismo , Sitios de Unión , Estabilidad de Enzimas , Concentración de Iones de Hidrógeno , Oxidorreductasas/química , Oxidorreductasas/genética , Conformación Proteica , Homología de Secuencia de Aminoácido , Especificidad por Sustrato , TemperaturaRESUMEN
Obesity is correlated with increased colorectal cancer (CRC) risk, but few studies have investigated lifetime body mass index (BMI) metrics and CRC risk. In a cohort of 139 229 subjects in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we analysed the effects of life-course BMI trajectories on CRC risk. At 13 years of follow-up, 2031 subjects developed CRC. Compared with subjects who were never overweight/obese, subjects who first exceeded the threshold of 25 kg m-2 at age 20 had a higher CRC risk (HR = 1.28, 95% confidence interval (CI) = 1.11-1.48). A body weight gain of ≥15 kg between 20 and 50 years of age (HR = 1.34, 95% CI = 1.18-1.52) and baseline (HR = 1.24, 95% CI = 1.08-1.43) was significantly associated with increased CRC risk. BMI trajectory analyses revealed that the CRC risk increased gradually over the three BMI trajectories (HR = 1.11-1.27, Ptrend = 0.005) compared with subjects who maintained a normal BMI. Being overweight/obese at the onset of adulthood and BMI trajectories over the lifespan that result in obesity lead to an increased CRC risk.
Asunto(s)
Neoplasias Colorrectales/epidemiología , Obesidad/epidemiología , Sobrepeso/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/patología , Detección Precoz del Cáncer , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/patología , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/patología , Sobrepeso/complicaciones , Sobrepeso/patología , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , Factores de Riesgo , Aumento de Peso/fisiologíaRESUMEN
BACKGROUND: 3-Ketosteroid-Δ1-dehydrogenase (KstD) is a key enzyme in the metabolic pathway for chemical modifications of steroid hormones. Only a few KstDs have thus far been characterized biochemically and applied for the production of steroidal pharmaceutical intermediates. Three KstDs, KstD1, KstD2, and KstD3, were identified in Mycobacterium neoaurum DSM 1381, and they shared up to 99, 85 and 97% amino acid identity with previously reported KstDs, respectively. In this paper, KstDs from M. neoaurum DSM 1381 were investigated and exemplified their potential application for industrial steroid transformation. RESULTS: The recombinant KstD2 from Bacillus subtilis exhibited higher enzymatic activity when 4-androstene-3,17-dione (AD) and 22-hydroxy-23, 24-bisnorchol-4-ene-3-one (4HP) were used as the substrates, and resulted in specific activities of 22.40 and 19.19 U mg-1, respectively. However, the specific activities of recombinant KstD2 from Escherichia coli, recombinant KstD1 from B. subtilis and E. coli, and recombinant KstD3, also fed with AD and 4HP, had significantly lower specific activities. We achieved up to 99% bioconversion rate of 1,4-androstadiene-3,17-dione (ADD) from 8 g L-1 AD after 15 h of fermentation using E. coli transformant BL21-kstD2. And in vivo transcriptional analysis revealed that the expression of kstD1 in M. neoaurum DSM 1381 increased by 60.5-fold with phytosterols as the substrate, while the mRNA levels of kstD2 and kstD3 were bearly affected by the phytosterols. Therefore, we attempted to create a 4HP producing strain without kstD1, which could covert 20 g L-1 phytosterols to 14.18 g L-1 4HP. CONCLUSIONS: In vitro assay employing the recombinant enzymes revealed that KstD2 was the most promising candidate for biocatalysis in biotransformation of AD. However, in vivo analysis showed that the cellular regulation of kstD1 was much more active than those of the other kstDs in response to the presence of phytosterols. Based on the findings above, we successfully constructed E. coli transformant BL21-kstD2 for ADD production from AD and M. neoaurum DSM 1381 ΔkstD1 strain for 4HP production using phytosterols as the substrate.
Asunto(s)
Proteínas Bacterianas/metabolismo , Isoenzimas/metabolismo , Mycobacterium/metabolismo , Oxidorreductasas/metabolismo , Esteroides/metabolismo , Mycobacterium/genéticaRESUMEN
The high-intensity low-frequency acoustic sources have essential applications in acoustic biological effects research, airport bird repelling, and boiler ash removal. However, generating high-intensity low-frequency acoustic waves in open space is difficult. In this paper, a low-frequency acoustic generator with a resonant cavity used to enhance the acoustic intensity in open space was developed, which is an aerodynamic acoustic generator to radiates a high-intensity acoustic wave of 52Hz. Some experiments were carried out to measure this generator's internal flow field and radiated acoustic field characteristics, including the propagation characteristics at 100m. The experimental results show that the resonant enhancement effect is presented near the predetermined resonance frequency, and the enhanced value is about 4dB. The acoustic intensity for 52Hz at 1m position is 124dB. By combining the Helmholtz resonator with the airflow modulator, the airflow resonance in the resonator enhances the air pressure pulsation inside the chamber and increases the disturbance of acoustic radiation to the air. So as to improve the sound intensity and radiation efficiency in the low-frequency range.
Asunto(s)
Acústica , Sonido , Vibración , Fenómenos Fisiológicos RespiratoriosRESUMEN
Silicon-based material is regarded as one of the most promising anodes for next-generation high-performance lithium-ion batteries (LIBs) due to its high theoretical capacity and low cost. Harnessing silicon carbide's robustness, we designed a novel porous silicon with a sandwich structure of carbon/silicon carbide/Ag-modified porous silicon (Ag-PSi@SiC@C). Different from the conventional SiC interface characterized by a frail connection, a robust dual covalent bond configuration, dependent on SiC and SiOC, has been successfully established. Moreover, the innovative sandwich structure effectively reduces detrimental side reactions on the surface, eases volume expansion, and bolsters the structural integrity of the silicon anode. The incorporation of silver nanoparticles contributes to an improvement in overall electron transport capacity and enhances the kinetics of the overall reaction. Consequently, the Ag-PSi@SiC@C electrode, benefiting from the aforementioned advantages, demonstrates a notably elevated lithium-ion mobility (2.4 * 10-9 cm2·s-1), surpassing that of silicon (5.1 * 10-12 cm2·s-1). The half-cell featuring Ag-PSi@SiC@C as the anode demonstrated robust rate cycling stability at 2.0 A/g, maintaining a capacity of 1321.7 mAh/g, and after 200 cycles, it retained 962.6 mAh/g. Additionally, the full-cell, featuring an Ag-PSi@SiC@C anode and a LiFePO4 (LFP) cathode, exhibits outstanding longevity. Hence, the proposed approach has the potential to unearth novel avenues for the extended exploration of high-performance silicon-carbon anodes for LIBs.
RESUMEN
Transition-metal species embedded in carbon have sparked intense interest in the fields of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). However, improvement of the electrocatalytic kinetics remains a challenge caused by the synergistic assembly. Here, we propose a biochemical strategy to fabricate the Co nanoparticles (NPs) and Co/Ni-N4-C co-embedded N-doped porous carbon (CoNPs&Co/Ni-N4-C@NC) catalysts via constructing the zeolitic imidazolate framework (ZIF)@yeast precursor. The rich amino groups provide the possibility for the anchorage of Co2+/Ni2+ ions as well as the construction of Co/Ni-ZIF@yeast through the yeast cell biomineralization effect. The functional design induces the formation of CoNPs and Co/Ni-N4-C sites in N-doped carbon as well as regulates the porosity for exposing such sites. Synergy of CoNPs, Co/Ni-N4-C, and porous N-doped carbon delivered excellent electrocatalytic kinetics (the ORR Tafel slope of 76.3 mV dec-1 and the OER Tafel slope of 80.4 mV dec-1) and a high voltage of 1.15 V at 10 mA cm-2 for the discharge process in zinc air batteries. It provides an effective strategy to fabricate high-performance catalysts.
RESUMEN
Semiconductor heterojunctions can significantly enhance photocatalytic degradation efficiency by facilitating rapid interfacial charge transfer. This article is based on the galvanic-cell driven principle; porous silicon (P-Si) was prepared by the carbon-catalytic etching method, and ZnO was loaded on its surface via electroless chemical deposition technology to form a P-Si/ZnO heterojunction, which was applied to the degradation of Rhodamine B (RhB). At a deposition temperature of 90 °C, a flawless 1D hexagonal prism structure of ZnO was formed, allowing the P-Si/ZnO heterojunction to completely degrade RhB within 2 hours with a degradation rate of 100%. Compared with a single P-Si material, the degradation performance is improved by 1.7 times. The formation of the built-in electric field and the rapid charge transfer at the heterojunction interface realized the complete degradation of RhB organic pollutants. After 20 cycles of use, the photocatalytic degradation rate remains above 70%, demonstrating excellent stability and recyclability.
RESUMEN
The development of low-cost RE-Fe-B sintered magnets with large La/Ce content is of great significance for the balanced utilization of rare earth (RE) resources, but it is limited by reduced magnetic properties. In this work, the coercivity (Hcj ), remanence (Br ), maximum energy product [(BH)max ], and temperature stability are simultaneously enhanced for magnets with LaCe accounting for 40 wt% of the total RE. The synergistic regulation of the REFe2 phase, Ce-valence, and grain boundaries (GBs) in RE-Fe-B sintered magnets is realized for the first time by introducing appropriate La elements. The La elements inhibit the generation of the REFe2 phase and tend to stay in the triple junctions, promoting the segregation of the RE/Cu/Ga elements and contributing to the formation of Ce/Nd/Cu/Ga-rich continuous thicker lamellar GBs, and as a result, weakening the detrimental effect on HA caused by La element substitution and enhancing Hcj . In addition, partial La atoms entering the RE2 Fe14 B phase are beneficial for improving the Br and temperature stability of the magnets and promoting the Ce3+ ion ratio, which also provides additional benefit for Br . The findings provide an effective and feasible way to co-enhance the remanence and coercivity of RE-Fe-B sintered magnets with high Ce content.
RESUMEN
BACKGROUND: Primary intracranial leiomyosarcoma (LMS) is a rare tumor of the central nervous system and therefore has only been reported sporadically. METHODS: The MEDLINE database was searched for relevant case reports and series published in English from 1969 to March 2012. These papers were reviewed to identify clinical and histopathological features, treatment modalities, and prognoses of patients with primary intracranial LMS. RESULTS: We reviewed 37 patients, including our patient, with primary intracranial LMS. Of these cases, 16 (43.2%) involved immunosuppression, 4 (10.8%) involved radiation-induced LMS, 3 (8.1%) cases involved a potential leiomyosarcomatous transformation of a brain lesion, and 7 (18.9%) cases, including the presented case, had no specific medical history. The treatment for these cases included resection (33/37, 89.2%), postoperative radiotherapy (20/37, 54.1%), and chemotherapy (7/37, 18.9%). CONCLUSIONS: The best method for the treatment of LMS could not be determined due to the limited number of cases that have been reported. However, optimized surgical resection, postoperative radiotherapy, and sarcoma-based chemotherapy may improve treatment outcomes.