RESUMEN
Four experiments were performed to investigate the role of the mitogen-activated protein kinase (MAPK) signaling pathway in intestinal absorption of phosphorus (P) and calcium (Ca) in broiler chickens. Experiment 1 assessed how dietary levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) influence the gene expression of intestinal P and Ca transporters in broilers. Experiment 2 evaluated the effects of 1,25(OH)2D3 administered via intraperitoneal injection on the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways. Experiments 3 and 4 investigated the effect of ERK and p38MAPK inhibitors on the expression of intestinal P and Ca transporters. The findings demonstrated that broilers (1-21 days old) fed a 1,25(OH)2D3-deficient diet (0.625 µg/kg) exhibited reduced body weight, tibia P and Ca levels, and mRNA levels of P transporters (NaPi-IIb, PiT-1, and PiT-2), Ca transporters (NCX1, PMCA1b, and CaBP-D28k), vitamin D receptors (VDR), ERK, and p38MAPK in the duodenum (Experiment 1) (P < 0.05). By comparison, the growth, bone quality, and mRNA levels of genes (except for duodenal NaPi-IIb) in broilers were similar to those in broilers fed the control diet when dietary 1,25(OH)2D3 was adequate (5 µg/kg) (Experiment 1) (P > 0.05). After intraperitoneal injection of 1,25(OH)2D3, the mRNA level of jejunal NaPi-IIb and the protein level of p-p38MAPK/t-p38MAPK in broilers (9-14 days old) decreased (P < 0.05), whereas the mRNA level of CaBP-D28k and the protein level of p-ERK/t-ERK increased (Experiment 2) (P < 0.05). The mRNA and protein expression of jejunal NaPi-IIb and the protein expression of CaBP-D28k in broilers (9-17 days old) treated with the ERK inhibitor PD98059 were greater than those in the control group (Experiment 3) (P < 0.05). Similarly, compared with control broilers, broilers (9-17 days old) treated with the p38MAPK inhibitor SB203580 showed elevated mRNA expression of jejunal NaPi-IIb and CaBP-D28k (Experiment 4) (P < 0.05). These results suggest that adequate supplementation with 1,25(OH)2D3 (5 µg/kg) can restore broiler growth and bone quality by upregulating the transcription of genes involved in intestinal P and Ca absorption. Additionally, the ERK and p38MAPK signaling pathways are implicated in the modulatory effect of 1,25(OH)2D3 on the absorption of P and Ca in broilers.
Asunto(s)
Aorta , Subunidad alfa del Factor 1 Inducible por Hipoxia , Músculo Liso Vascular , Miocitos del Músculo Liso , Fenotipo , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citología , Aorta/metabolismo , Aorta/citología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Miocitos del Músculo Liso/metabolismoRESUMEN
PURPOSE: To determine the correlation between HPV (human papillomavirus) 52 viral load, multiple infections and ThinPrep cytology test (TCT), to inform clinical management of HPV52-positive women after cervical cancer screening. METHODS: A total of 1,882 female patients who had positive quantitative HPV tests at Yuebei People's Hospital from January 2020 to December 2022, of whom 533 tested positive for HPV52. We excluded patients who combined HPV16 and/or HPV 18 positivity and whom HPV52 viral load could not be calculated. The final enrollment was 488 patients, including 400 NILM, 48 ASC-US, 28 LSIL and 12 HSIL. The HPV test is a quantitative multiplexed fluorescent PCR assay that provides both HPV genotyping and viral load. RESULTS: In our study, there were differences in the median distribution of viral loads among various cytological class categories. The risk of TCT results (LSIL or worse) was increased with the increase of HPV52 viral load, for every LOG unit increase in HPV52 viral load, the risk increased by 26.6%. More importantly, we found a nonlinear relationship between HPV52 viral load and TCT results (LSIL or worse) in both single and multiple infections. When the viral load reaches a threshold, the risk of abnormal cytological results increases significantly. CONCLUSION: HPV52 viral load is an independent risk factor for TCT results (LSIL or worse). The relationship between HPV52 viral load and TCT results (LSIL or worse) is not linear. Viral load may be used as a triage indicator for HPV52-positive patients, thus improving the post-screening clinical management of HPV52-positive women.
Asunto(s)
Virus del Papiloma Humano , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Carga Viral , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Coinfección/virología , ADN Viral/genética , Detección Precoz del Cáncer/métodos , Genotipo , Virus del Papiloma Humano/clasificación , Virus del Papiloma Humano/aislamiento & purificación , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/diagnóstico , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Frotis VaginalRESUMEN
Radiative cooling technology is well known for its subambient temperature cooling performance under sunlight radiation. However, the intrinsic maximum cooling power of radiative cooling limits the performance when the objects meet the thermal shock. Here, a dual-function strategy composed of radiative cooling and latent heat storage simultaneously enabling the efficient subambient cooling and high-efficiency thermal-shock resistance performance is proposed. The electrospinning and absorption-pressing methods are used to assemble the dual-function cooler. The high sunlight reflectivity and high mid-infrared emissivity of radiative film allow excellent subambient temperature of 5.1 °C. When subjected the thermal shock, the dual-function cooler demonstrates a pinning effect of huge temperature drop of 39 °C and stable low-temperature level by isothermal heat absorption compared with the traditional radiative cooler. The molten phase change materials provide the heat-time transfer effect by converting thermal-shock heat to the delayed preservation. This strategy paves a powerful way to protect the objects from thermal accumulation and high-temperature damage, expanding the applications of radiative cooling and latent heat storage technologies.
RESUMEN
Anammox is one of the most innovative nitrogen removal technologies, while its functional bacteria-anaerobic ammonia-oxidizing bacteria (AAOB) is sensitive to the impurities in the wastewater. In this study, the long-term effects of sulfide at different concentrations (0, 5, 10, 20, 30, 50, 25â mg L-1) on low substrate Anammox process were studied. The results showed that when the sulfide was 25-30â mg L-1, AAOB was well coupled with sulfide-denitrifying bacteria and the total nitrogen removal efficiency (TNRE) reached a maximum of 91.0%. The hydroxylamine oxidoreductase activity and Heme-c reached 1.678 EU g-1 SS and 0.0023â mmol g-1 SS, respectively, with the hzo and nosZ gene concentrations as 2.52 × 108 and 4.45 × 107 copies mL-1. 50â mg L-1 sulfide inhibited the nitrogen removal by AAOB, resulting in the TNRE decreasing to 81.7%. The experimental results provide a reference for the practical application of Anammox in treating sulfur-containing wastewater.
Asunto(s)
Microbiota , Aguas Residuales , Desnitrificación , Nitrógeno/análisis , Oxidación Anaeróbica del Amoníaco , Reactores Biológicos/microbiología , Oxidación-Reducción , Bacterias/genética , Sulfuros , Aguas del AlcantarilladoRESUMEN
Protein post-translational modifications (PTMs) with various acyl groups play central roles in Streptomyces. But whether these acyl groups can be further modified, and the influences of these potential modifications on bacterial physiology have not been addressed. Here in Streptomyces roseosporus with rich crotonylation, a luciferase monooxygenase LimB is identified to elaborately regulate the crotonylation level, morphological development and antibiotic production by oxidation on the crotonyl groups of an acetyl-CoA synthetase Acs. This chemical modification on crotonylation leads to Acs degradation via the protease ClpP1/2 pathway and lowered intracellular crotonyl-CoA pool. Thus, we show that acyl groups after PTMs can be further modified, herein named post-PTM modification (PPM), and LimB is a PTM modifier to control the substrate protein turnover for cell development of Streptomyces. These findings expand our understanding of the complexity of chemical modifications on proteins for physiological regulation, and also suggest that PPM would be widespread.
Asunto(s)
Ligasas , Streptomyces , Acetilcoenzima A , Oxigenasas de Función Mixta , ProteínasRESUMEN
Objective: Ultra-fast channel anesthesia (UFTA) can reduce the dosage of opioid narcotic drugs, allow for a rapid postoperative extubation and reduce the harmful stress response during perioperative period. However, there has been limited information about the application of UFTA during thoracoscopic closure of ventricular septal defect (VSD). The aim of this study was to assess the feasibility and safety of UFTA technique in patients undergoing totally thoracoscopic closure of VSD. Methods: Seventy-eight patients were randomly divided into study (UFTA) and control (standard general anesthesia) group. Totally thoracoscopic closure of VSD was performed in all patients. Extubation in the study and control group was attempted in the operating room and the intensive care unit, respectively. Results: All patients in the study group were extubated in the operating room immediately after surgery, but 2 (6.1%) required reintubation. All the control group patients were extubated after a period of mechanical ventilation (3.0 ± 3.7 h vs 0 h in the study group, p = 0.001) in the intensive care unit. The intensive care and hospital stays in the study group were shorter than in the control group (4.3 ± 2.5 vs 13.4 ± 4.4 h, p = 0.003, and 5.8 ± 0.8 vs 6.5 ± 1.2 d, p = 0.047). The total costs for the treatment in the study group was lower than in the control group (5264 ± 514 vs 4662 ± 461 US dollars, p = 0.02). Conclusions: UFTA and operating room extubation was feasible and safe in the majority of patients following totally thoracoscopic closure of VSD. This technique was associated with a shorter intensive care stay and lower overall costs for the surgical treatment.
RESUMEN
Cytochrome P450 enzymes are promising biocatalysts for industrial use because they catalyze site-selective C-H oxidation and have diverse catalytic reactions and a broad substrate range. In this study, the 2α-hydroxylation activity of CYP154C2 from Streptomyces avermitilis MA-4680T toward androstenedione (ASD) was identified by an in vitro conversion assay. The testosterone (TES)-bound structure of CYP154C2 was solved at 1.42 Å, and this structure was used to design eight mutants, including single, double, and triple mutants, to improve the conversion efficiency. Mutants L88F/M191F and M191F/V285L were found to enhance the conversion rates significantly (i.e., 8.9-fold and 7.4-fold for TES, 46.5-fold and 19.5-fold for ASD, respectively) compared with the wild-type (WT) enzyme while retaining high 2α-position selectivity. The substrate binding affinity of the L88F/M191F mutant toward TES and ASD was enhanced compared with that of WT CYP154C2, supporting the measured increase in the conversion efficiencies. Moreover, the total turnover number and kcat/Km of the L88F/M191F and M191F/V285L mutants increased significantly. Interestingly, all mutants containing L88F generated 16α-hydroxylation products, suggesting that L88 in CYP154C2 plays a vital role in substrate selectivity and that the amino acid corresponding to L88 in the 154C subfamily affects the orientation of steroid binding and substrate selectivity. IMPORTANCE Hydroxylated derivatives of steroids play essential roles in medicine. Cytochrome P450 enzymes selectively hydroxylate methyne groups on steroids, which can dramatically change their polarity, biological activity and toxicity. There is a paucity of reports on the 2α-hydroxylation of steroids, and documented 2α-hydroxylate P450s show extremely low conversion efficiency and/or low regio- and stereoselectivity. This study conducted crystal structure analysis and structure-guided rational engineering of CYP154C2 and efficiently enhanced the conversion efficiency of TES and ASD with high regio- and stereoselectivity. Our results provide an effective strategy and theoretical basis for the 2α-hydroxylation of steroids, and the structure-guided rational design of P450s should facilitate P450 applications in the biosynthesis of steroid drugs.
Asunto(s)
Sistema Enzimático del Citocromo P-450 , Esteroides , Hidroxilación , Esteroides/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Oxidación-Reducción , Testosterona/metabolismo , Especificidad por SustratoRESUMEN
Production of estradiol (E2) by the placenta during human pregnancy ensures successful maintenance of placental development and fetal growth by stimulating trophoblast proliferation and the differentiation of cytotrophoblasts into syncytiotrophoblasts. Decreased levels of E2 are closely associated with obstetrical diseases such as preeclampsia (PE) in the clinic. However, the mechanisms underlying the inhibition of placental E2 biosynthesis remain poorly understood. Here, we report that regulator of G-protein signaling 2 (RGS2) affects E2 levels by regulating aromatase, a rate-limiting enzyme for E2 biosynthesis, by using human trophoblast-derived JEG-3 cells and human placental villus tissues. RGS2 enhanced the protein degradation of the transcription factor heart and neural crest derivatives expressed 1 (HAND1) by suppressing ubiquitin-specific protease 14 (USP14)-mediated deubiquitination of HAND1, resulting in the restoration of HAND1-induced trans-inactivation of the aromatase gene and subsequent increases in E2 levels. However, aromatase bound to RGS2 and repressed RGS2 GTPase activating protein (GAP) activity. Moreover, we observed a positive correlation between RGS2 and aromatase expression in clinical normal and preeclamptic placental tissues. Our results uncover a hitherto uncharacterized role of the RGS2-aromatase axis in the regulation of E2 production by human placental trophoblasts, which may pinpoint the molecular pathogenesis and highlight potential biomarkers for related obstetrical diseases.
Asunto(s)
Preeclampsia , Proteínas RGS , Humanos , Embarazo , Femenino , Trofoblastos/metabolismo , Placenta , Estradiol , Aromatasa/genética , Aromatasa/metabolismo , Línea Celular Tumoral , Preeclampsia/genética , Proteínas RGS/genética , Proteínas RGS/metabolismo , Ubiquitina Tiolesterasa/metabolismoRESUMEN
In this study, the regulation effect of the external quorum sensing signals, N-dodecanoyl homoserine lactone (C12-HSL) on CANON process were investigated in a membrane bioreactor. C12-HSL significantly enhanced the aerobic ammonia-oxidizing bacteria and improved the ammonia monooxygenase activity to 0.134 from 0.076 µg NO2--N mg-1 protein min-1, while suppressed anaerobic ammonia-oxidizing bacteria and limited the TN removal to 0.07 from 0.22 kg m-3 d-1. Key enzymes synthesis were enhanced during the operation without C12-HSL addition, enabling the resistance of CANON system to high C12-HSL. As a result, the hydroxylamine oxidoreductase and nitrite reductase activity reached 35.9 EU g-1 SS and 1.28 µg NO2--N mg-1 protein min-1, respectively; Nitrosomonas and Candidatus Kuenenia, with the abundance as 12.5 % and 22.9 %, cooperatively contributed to the TN removal, which maintained at 0.19 kg m-3 d-1. C12-HSL was profitable for aerobic ammonia oxidation, which could be adopted for regulating the nitrite production rate.
Asunto(s)
Amoníaco , Percepción de Quorum , Dióxido de Nitrógeno , 4-Butirolactona , Bacterias/metabolismo , Reactores Biológicos/microbiologíaRESUMEN
In2YSbO7 and In2YSbO7/BiSnSbO6 heterojunction photocatalyst were prepared by a solvothermal method for the first time. The structural characteristics of In2YSbO7 had been represented. The outcomes showed that In2YSbO7 crystallized well and possessed pyrochlore constitution, a stable cubic crystal system and space group Fd3m. The lattice parameter of In2YSbO7 was discovered to be a = 11.102698 Å and the band gap energy of In2YSbO7 was discovered to be 2.68 eV, separately. After visible-light irradiation of 120 minutes (VLGI-120M), the removal rate (ROR) of indigo carmine (IC) reached 99.42% with In2YSbO7/BiSnSbO6 heterojunction (IBH) as a photocatalyst. The ROR of total organic carbon (TOC) reached 93.10% with IBH as a photocatalyst after VLGI-120M. Additionally, the dynamics constant k which was taken from the dynamic curve toward (DCT) IC density and VLGI time with IBH as a catalyst reached 0.02950 min-1. The dynamics constant k which came from the DCT TOC density and VLGI time with IBH as a photocatalyst reached 0.01783 min-1. The photocatalytic degradation of IC in dye wastewater (DW) with IBH as a photocatalyst under VLGI was in accordance with the first-order kinetic curves. IBH was used to degrade IC in DW for three cycles of experiments under VLGI, and the ROR of IC reached 98.74%, 96.89% and 94.88%, respectively, after VLGI-120M, indicating that IBH had high stability. Compared with superoxide anions or holes, hydroxyl radicals possessed the largest oxidative ability for removing IC in DW, as demonstrated by experiments with the addition of trapping agents. Lastly, the probable degradation mechanism and degradation pathway of IC were revealed in detail. The results showed that a visible-light-responsive heterojunction photocatalyst which possessed high catalytic activity and a photocatalytic reaction system which could effectively remove IC in DW were obtained. This work provided a fresh scientific research idea for improving the performance of a single catalyst.
RESUMEN
Liver is a central metabolic organ, which is sensitive to heat stress. Liver damage affects animals' health and endangers the livestock and poultry industry. This study aimed to investigate the mechanism of chronic heat stress-induced liver damage in broiler chickens. Broilers were divided into 3 treatments: normal control group (NOR, 22°C), heat stress group (HS, 32°C) and pair-feeding group (PF, 22°C) for a 7-d and 14-d trial. The results showed that 7 d heat exposure caused microvesicular steatosis and reduced glutamine synthetase activity in broiler liver (P < 0.05). After 14 d of heat exposure, heat stress caused vacuolar degeneration and apoptosis in the liver; elevated liver relative weight and liver glutaminase activity as well as plasma ammonia level (P < 0.05). Additionally, heat stress enhanced GRP78 protein expression and the mRNA expressions of endoplasmic reticulum (ER) stress responses genes and apoptosis-related genes in broiler liver after 14 d of heat exposure (P < 0.05). In conclusion, chronic heat stress triggered ER stress-induced apoptosis and caused liver damage, which may compromise ammonia detoxification in broiler liver.
Asunto(s)
Pollos , Trastornos de Estrés por Calor , Amoníaco/metabolismo , Animales , Apoptosis , Pollos/fisiología , Estrés del Retículo Endoplásmico , Glutamato-Amoníaco Ligasa/metabolismo , Glutaminasa/metabolismo , Trastornos de Estrés por Calor/genética , Trastornos de Estrés por Calor/veterinaria , Respuesta al Choque Térmico , Hígado/metabolismo , ARN Mensajero/metabolismoRESUMEN
A new photocatalyst, Er2FeSbO7, was prepared by solid phase sintering using the high-temperature synthesis method for the first time in this paper. Er2FeSbO7/BiTiSbO6 heterojunction (EBH) catalyst was prepared by the solvent thermal method for the first time. Er2FeSbO7 compound crystallized in the pyrochlore-type architecture and cubelike crystal system; the interspace group of Er2FeSbO7 was Fd3m and the crystal cellular parameter a of Er2FeSbO7 was 10.179902 Å. The band gap (BDG) width of Er2FeSbO7 was 1.88 eV. After visible light irradiation of 150 minutes (VLGI-150min) with EBH as a photocatalyst, the removal rate (RR) of enrofloxacin (ENR) concentration was 99.16%, and the total organic carbon (TOC) concentration RR was 94.96%. The power mechanics invariable k toward ENR consistency and visible light irradiation (VLGI) time with EBH as a photocatalyzer attained 0.02296 min−1. The power mechanics invariable k which was involved with TOC attained 0.01535 min−1. The experimental results showed that the photocatalytic degradation (PCD) of ENR within pharmaceutical waste water with EBH as a photocatalyzer under VLGI was in keeping with the single-order reactivity power mechanics. The RR of ENR with EBH as a photocatalyzer was 1.151 times, 1.269 times or 2.524 times that with Er2FeSbO7 as a photocatalyst, BiTiSbO6 as a photocatalyst, or N-doping TiO2 (N-TO) as a photocatalyst after VLGI-150min. The photocatalytic activity, which ranged from high to low among above four photocatalysts, was as follows: EBHP > Er2FeSbO7 > BiTiSbO6 > N-TO. After VLGI-150min toward three periods of the project with EBH as a photocatalyst, the RR of ENR attained 98.00%, 96.76% and 95.60%. The results showed that the stability of EBH was very high. With appending trapping agent, it could be proved that the oxidative capability for degrading ENR, which ranged from strong to weak among three oxidic radicals, was as follows: superoxide anion > hydroxyl radicals (HRS) > holes. This work provides a scientific basis for the research and oriented leader development of efficient heterojunction catalysts.
RESUMEN
Increasing evidence suggests that numerous edible oils may function as adjuvant dietary therapies to treat cancer. We previously reported that the odd-chain saturated fatty acid (OCSFA), heptadecanoic acid (C17:0), profoundly inhibits non-small-cell lung cancer (NSCLC) cell proliferation. However, the antitumor potential of edible lipids rich in C17:0 remains unclear. Here, we determined that sheep tail fat (STF) is a dietary lipid rich in C17:0 and exhibited the greatest inhibitory effect against three NSCLC cell lines (A549, PC-9, and PC-9/GR) among common dietary lipids. Cell migration experiments demonstrated that STF could significantly inhibit the wound healing capacity of three NSCLC cell lines by promoting the generation of reactive oxygen species (ROS) and subsequent cell death. Mechanistic studies showed that STF suppressed NSCLC cell growth by downregulating the Akt/S6K signaling pathway. Furthermore, administration of STF reduced tumor growth, weight, and expression of the proliferative marker Ki-67 in nude mice bearing A549 xenografts. Collectively, our data show that STF has antitumor activity against NSCLC, implying that dietary intake of C17:0-rich STF may be a potential adjuvant therapy for NSCLC.
RESUMEN
Originally, the new catalyst Bi2SmSbO7 was synthesized by the hydrothermal synthesis method or by the solid-phase sintering method at a lofty temperature. A solvothermal method was utilized to prepare a Bi2SmSbO7/ZnBiYO4 heterojunction photocatalyst (BZHP). The crystal structure of Bi2SmSbO7 belonged to the pyrochlore structure and face-centered cubic crystal system by the space group of Fd3m. The cell parameter a was equivalent to 10.835(1) Å (Bi2SmSbO7). With Bi2SmSbO7/ZnBiYO4 heterojunction (BZH) as the photocatalyst, the removal rate (RR) of direct orange (DO) and the total organic carbon were 99.10% and 96.21% after visible light irradiation of 160 min (VLI-160M). The kinetic constant k toward DO concentration and visible light irradiation time (VLI) with BZH as photocatalyst reached 2.167 min−1. The kinetic constant k, which was concerned with total organic carbon, reached 0.047 min−1. The kinetic curve that came from DO degradation with BZH as a catalyst under VLI conformed to the second-order reaction kinetics. After VLI-160M, the photocatalytic degradation (PD) removal percentage of DO with BZH as the photocatalyst was 1.200 times, 1.268 times or 3.019 times that with Bi2SmSbO7 as the photocatalyst, ZnBiYO4 as the photocatalyst or with nitrogen-doped titanium dioxide as the photocatalyst. The photocatalytic activity (PA) was as following: BZH > Bi2SmSbO7 > ZnBiYO4 > nitrogen-doped titanium dioxide. After VLI-160M for three cycles of experiments with BZH as the photocatalyst, the RR of DO reached 98.03%, 96.73% and 95.43%, respectively, which meant that BZHP possessed high stability. By using the experiment of adding a trapping agent, the oxidative purifying capability for degradation of direct orange, which was in gradual depressed order, was as following: hydroxyl radical > superoxide anion > holes. Finally, the possible degradation pathway and degradation mechanism of DO were discussed systematically. A new high active heterojunction catalyst BZHP, which could efficiently remove toxic organic pollutants such as DO from dye wastewater after VLI, was obtained. Our research was meant to improve the photocatalytic property of the single photocatalyst.
RESUMEN
Cytochrome P450 enzymes (CYPs or P450s) are ubiquitous heme-dependent enzymes that catalyze the monooxygenation of non-activated C-H bonds to modify the structure of the substrate. In this study, we heterologously expressed CYP107X1 from Streptomyces avermitilis and conducted inâ vitro substrate screening using the alternative redox partners putidaredoxin and putidaredoxin reductase. CYP107X1 catalyzed the 16α-hydroxylation of progesterone with regio- and stereoselectivity. The spectroscopic analyses showed that CYP107X1 bound progesterone with a relatively high Kd value of 65.3±38.9â µM. The Km and kcat values for progesterone were estimated to be 47.7±12.0â µM and 0.30â min-1 , respectively. Furthermore, a crystal structure was obtained of CYP107X1 bound with glycerol from the buffer solution. Interestingly, a conserved threonine was replaced with asparagine in CYP107X1, indicating that it may adopt an unnatural proton transfer process and play a crucial role in its catalytic activity.
Asunto(s)
Progesterona , Streptomyces , Sistema Enzimático del Citocromo P-450/metabolismo , Hidroxilación , Progesterona/metabolismo , Streptomyces/metabolismoRESUMEN
Anammox was a promising technology for nitrogen removal, and has been applied for treating many kinds of nitrogenous wastewaters. Considering the risk in high salinity of the municipal sewage in coastal city, the feasibility of Anammox process for treating low ammonia wastewater (around 50 mg L-1) with increasing salinity was investigated in this study. The results showed that the salinity in low concentrations (1-5 g L-1) had slight impact on the nitrogen removal and activity of Anammox bacteria but significantly improved its growth. The moderate salinity (10-40 g L-1) decreased the specific Anammox activity (SAA) to 8.11 from the initial 13.15 mg N g-1 SS h-1, but increased the abundance to 52.3% from 30.1% (Candidatus Kuenenia). High salinity (50-60 g L-1) performed severe inhibition on activity and abundance both, with the SAA decreased to 0 and abundance to 11.9%. The self-recovery performance was unsatisfactory when salinity was unavailable. A quadratic curve between the SAA and salinity concentration was fitted, and the IC50 was calculated as 42.1 g L-1 (NaCl). Anammox process could be directly adopted for treating low ammonia sewage with low salinity, whereas activity enhancement or adaption improvement should be pre-presented for treating sewage with moderate or high salinity.
Asunto(s)
Salinidad , Aguas Residuales , Oxidación Anaeróbica del Amoníaco , Reactores Biológicos , Oxidación-ReducciónRESUMEN
Introduction: Colorectal cancer (CRC) is a serious threat to human health. Screening new biomarkers can provide basis for improving the prognosis and individualized treatment of CRC. Although some members of the defensin family were found increased in pancreatic cancer and CRC, their exact function and clinical significance remain unclear. Methods: In this study, the expression, correlation, mutation, and functional enrichment of several defensin family members in pancreatic cancer and CRC were analyzed using tumor public databases and verified in several patients. Results: Results showed no significant correlation between the expression levels of DEFA1-4 and CRC. The expression levels of DEFA5 and DEFA6 significantly increased in CRC tissues compared with those in normal tissues. DEFA5 may be associated with better prognosis of CRC, while DEFA6 may be associated with poor prognosis. Immunohistochemistry (IHC) experiments showed that the expression of DEFA6 was significantly higher in adenoma than in normal mucosa and slightly higher in carcinoma than in normal mucosa. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that DEFAs were closely related to hsa05202: transcriptional misregulation in cancer and Hsa04015: Rap1 signaling pathway. DEFA5 may be a stable and good prognostic marker, and DEFA6 may be a poor prognostic marker in CRC of metastasis. Conclusion: Overall, DEFA5 and DEFA6 have a certain degree of sensitivity and specificity in predicting CRC.
RESUMEN
Cytochrome P450 enzymes (P450s) are versatile biocatalysts, which insert a molecular oxygen into inactivated C-H bonds under mild conditions. CYP105D7 from Streptomyces avermitilis has been reported as a bacterial substrate-promiscuous P450 which catalyzes the hydroxylation of 1-deoxypentalenic acid, diclofenac, naringenin, compactin and steroids. In this study, CYP105D7 catalyzes hydroxylation, epoxidation and dehydrogenation of capsaicin, a pharmaceutical agent, revealing its functional diversity. The kinetic parameters of the CYP105D7 oxidation of capsaicin were determined as Km =311.60±87.30â µM and kcat =2.01±0.33â min-1 . In addition, we conducted molecular docking, mutagenesis and substrate binding analysis, indicating that Arg81 plays crucial role in the capsaicin binding and catalysis. To our best knowledge, this study presents the first report to illustrate that capsaicin can be catalyzed by prokaryotic P450s.
Asunto(s)
Capsaicina/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Streptomyces/enzimología , Biocatálisis , Capsaicina/química , Hidrogenación , Hidroxilación , Simulación del Acoplamiento Molecular , Estructura MolecularRESUMEN
BACKGROUND: Minimally invasive cardiac surgery is an attractive approach for both surgeons and patients. This study aims to describe the experience of mitral valve replacement (MVR) with Ma's tri-port totally thoracoscopic cardiac surgery technique (MTCST) and to prove the feasibility and safety of this technique. METHODS: A total of 490 consecutive patients undergoing MVR were divided into MTCST group (MT group, n=267) and conventional median sternotomy group (MS group, n=223). The perioperative characteristics and the follow-up information were recorded and analyzed between the two groups. RESULTS: The in-hospital mortality and re-operation rate were not significant between the two groups. Compared with the MS group, cardiopulmonary bypass time and aortic cross-clamp time were both longer in the MT group while total operative time was similar to the MS group. Patients in the MT group had less pain and required a decreased analgesic administration than that in the MS group. Intraoperative blood loss, perioperative blood transfusion and the postoperative drainage were all significantly reduced in the MT group as compared to the MS group. Mechanical ventilation time, ICU duration, hospitalization time and hospitalization cost were decreased in the MT group. Patients undergoing MVR with MTCST had a higher Medical Treatment Satisfactory Score than those with conventional sternotomy. CONCLUSIONS: MTCST for mitral valve disease was technically safe and feasible. The results showed that MTCST was a suitable minimally invasive alternative to the conventional sternotomy approach and was a desirable approach for patients with mitral valve disease.