NR6A1 regulates lipid metabolism through mammalian target of rapamycin complex 1 in HepG2 cells.

BACKGROUND: Lipogenesis is required for the optimal growth of many types of cancer cells, it is shown to control the biosynthesis of the lipid bilayer membrane during rapid proliferation and metastasis, provides cancer cells with signaling lipid molecules to support cancer development and make cancer cells more resistant to oxidative stress-induced cell death. Though multiple lipogenic enzymes have been identified to mediate this metabolic change, how the expression of these lipogenic enzymes are transcriptionally regulated remains unclear. METHODS: Gain- and loss-of-function experiments were conducted to assess the role of transcriptional repressor, nuclear receptor sub-family 6, group A, member 1 (NR6A1) in HepG2 cells. RT-qPCR method was performed to investigate target gene of NR6A1. Western blot was employed to determine the mechanisms by which NR6A1 regulates lipid accumulation in HepG2 cells. RESULTS: We provide evidence that NR6A1 is a novel regulator of lipid metabolism in HepG2 cells. NR6A1 knockdown can increase lipid accumulation as well as insulin-induced proliferation and migration of HepG2 cells. The lipogenic effect correlated well with the expression of lipogenic genes, including fatty acid synthase (FAS), diglyceride acyltransferase-2 (DGAT2), malic enzyme 1 (ME1), microsomal triglyceride transfer protein (MTTP) and phosphoenolpyruvate carboxykinase (PEPCK). NR6A1 knockdown also increased the expression of carnitine palmitoyltransferase 1A (CPT1a), the rate-limiting enzyme in fatty acid oxidation. Furthermore, NR6A1 knockdown induced lipid accumulation through mammalian target of rapamycin complex 1 (mTORC1), but not mTORC2. Moreover, siRNA-mediated knockdown of NR6A1 increased expression of insulin receptor (INSR) and potentitated insulin-induced phosphorylation of mTOR and AKT partly via miR-205-5p in HepG2 cells. CONCLUSIONS: These findings provide important new insights into the role of NR6A1 in the lipogenesis in HepG2 cells. .

[Comparison of clinical efficacy of heated humidified high flow nasal cannula versus nasal continuous positive airway pressure in treatment of respiratory distress syndrome in very low birth weight infants].

OBJECTIVE: To compare the differences of clinical efficacy between heated humidified high-flow nasal cannula (HHHFNC) ventilation and nasal continuous positive airway pressure (NCPAP) in the treatment of respiratory distress syndrome (RDS) in very low birth weight (VLBW) infants. METHODS: A total of 66 VLBW infants who were admitted to the neonatal intensive care unit were diagnosed with RDS, and they were randomly assigned to HHHFNC group and NCPAP group after receiving treatment with porcine pulmonary surfactant and conventional treatment. The changes in clinical symptoms and the incidence of complications were observed in the two groups. RESULTS: The HHHFN group had significantly earlier first milk feeding and full enteral feeding, significantly shorter oxygen exposure time and invasive ventilation time, and significantly lower incidences of second intubation within 7 days, nasal injury, air leak, and abdominal distention, as compared with the NCPAP group. CONCLUSIONS: Compared with NCPAP, HHHFNC causes slighter injury and has better tolerability, and it can be considered as the first choice of noninvasive ventilation in the treatment of RDS in VLBW infants.

Polyphenols from Prunus mume: extraction, purification, and anticancer activity.

Prunus mume is an ancient medicinal herb and food that are commonly used in Asian countries with high nutritional ingredients and biological activities. Polyphenols are important functional components in Prunus mume. To obtain a more efficient extraction process of Prunus mume polyphenols, a single-factor test and response surface method were used. After extraction and purification, the final polyphenol content of Prunus mume (L1) was up to 90%. Biological experiments showed that L1 had high anticancer activity against HeLa (125.28 µg mL-1), HepG2 (117.24 µg mL-1), MCF-7 (170.19 µg mL-1), and A549 (121.78 µg mL-1) in vitro by MTT assay. The combination of DDP and DOX significantly enhanced the anticancer activity of the four cell lines, especially L1-DOX had the smallest IC50 value of 0.04 µg mL-1 against HepG2 cells, indicating the combination of drugs had synergistic effects. It is further demonstrated that L1 could inhibit cell proliferation by inducing apoptosis with ROS detection and confocal fluorescence images. The relative tumor proliferation rate (T/C) was 40.6%, and the tumor inhibition rate was 57.9%, indicating L1 to have no significant toxicity but high anti-HepG2 activity in vivo. Although the study is very limited, it is anticipated to provide a reference for further exploration of the functionality of the plant.

Five blueberry anthocyanins and their antioxidant, hypoglycemic, and hypolipidemic effects in vitro.

The dual epidemic of obesity and diabetes mellitus is becoming an important worldwide public health issue. "Diabesity" is the term used to describe the combined detrimental health effects of both diabetes mellitus and obesity/overweight. Currently, food-derived bioactive compounds are suggested to alleviate diabesity. Blueberries are rich in bioactive anthocyanins, which are associated with contributing to preventing obesity and diabetes mellitus. However, the accurate active compounds and the underlying mechanism are still unclear. The objective of this study was to investigate the beneficial effects of blueberry anthocyanin on diabesity. In total, five anthocyanins (delphinidin-3-O-galactoside, delphinidin-3-O-glucoside, petunidin-3-O-galactoside, petunidin-3-O-glucoside, and malvidin-3-O-galactoside) were isolated from rabbiteye blueberry (Vaccinium virgatum) cultivar "Garden blue." All these anthocyanins exhibited oxygen radical absorbance capacity (ORAC), scavenging power of ABTS+, and DPPH-free radical and inhibitory activity of α-glucosidase in vitro. Moreover, some compounds improved glucose uptake and attenuated lipid accumulation in high glucose and oleic acid-treated HepG2 cells. All these results suggest that blueberry anthocyanins have potential antioxidant, hypoglycemic, and hypolipidemic effects, which may benefit the treatment of diabesity.

Blueberry and Blackberry Anthocyanins Ameliorate Metabolic Syndrome by Modulating Gut Microbiota and Short-Chain Fatty Acids Metabolism in High-Fat Diet-Fed C57BL/6J Mice.

In this study, blueberry (Vaccinium ssp.) anthocyanins (VA) and blackberry (Rubus L.) anthocyanins (RA) were used to investigate the effects on metabolic syndrome (MetS) and the potential mechanisms. Importantly, all of the data presented in this study were obtained from experiments conducted on mice. As a result, VA and RA reduced body weight gain and fat accumulation while improving liver damage, inflammation, glucose, and lipid metabolism induced by a high-fat diet. Moreover, VA and RA regulated the gut microbiota composition, decreasing the pro-obesity and proinflammation bacteria taxa, such as the phylum Actinobacterium and the genera Allobaculum and Bifidobacterium, and increasing those negatively associated with obesity and inflammation, such as the phylum Bacteroidetes and the genera Prevotella and Oscillospira. Additionally, the supplementation with VA and RA reversed the elevated levels of valeric, caproic, and isovaleric acids observed in the high-fat diet (HFD) group, bringing them closer to the levels observed in the Chow group. This reversal indicated that alterations in the composition and abundance of gut microbiota may contribute to the restoration of short-chain fatty acids (SCFAs) levels. Additionally, PICRUSt2 exhibited that cyanamino acid metabolism and betalain biosynthesis might be the major metabolic pathways in the HVA group compared with the HFD group, while in the HRA group, it was the phosphotransferase system. These findings suggest that VA and RA can ameliorate MetS by modulating the gut microbiota and production of SCFAs.

Impact of Changes in Early Respiratory Support Management on Respiratory Outcomes of Preterm Infants.

BACKGROUND: In the period immediately after birth, preterm infants are highly susceptible to lung injury. Ventilator-induced lung injury has been recognized as a major contributing factor for bronchopulmonary dysplasia (BPD) in preterm infants. Noninvasive respiratory support (NIRS) could decrease lung injury, and early respiratory support management might affect pulmonary outcomes. We conducted a study to evaluate the changes in early respiratory support management and their impact on respiratory outcome and complications of preterm infants in 3 different time periods over the last 13 years. METHODS: This study was a retrospective, single-center cohort study. We retrospectively reviewed the medical records of preterm infants < 32 weeks of gestational age born in our hospital from 2007-2020. The study period was divided into three 3-y discrete periods: 2007-2009 (period A), 2013-2015 (period B), and 2018-2020 (period C). Changes in early respiratory support management were assessed in the 3 periods. The outcomes measured included mortality, BPD, other major neonatal complications, initial respiratory support, and duration of mechanical ventilation. RESULTS: In all, 1,880 clinical records were assessed in our study, with 358 in period A, 825 in period B, and 697 in period C. The use of antenatal corticosteroids increased over time (56.1% in period A, 56.7% in period B, and 74.0% in period C (P < .001). The need for surfactant decreased from 65.6% in period A to 40.7% in period B and 45.9% in period C. Increased utilization of NIRS was associated with decreased invasive mechanical ventilation within 24 h after birth. NIRS only during the hospital stay increased from 22.9% in period A to 36.8% and 45.1% in the latter 2 periods (P < .001). Oxygen therapy duration decreased from 24.3 d in period A to 14.4 d in period B and 17.2 d in period C (P < .001). The overall incidence of BPD was 32.4% in the first period, 23.9% in the second period, and 25.4% in the third period (P < .001). The moderate-to-severe forms of BPD decreased from 12.8% in period A to 7.9% in period B and 7.6% in period C (P = .009). Other neonatal complications, such as pneumothorax, pulmonary hemorrhage, persistent pulmonary hypertension of the newborn, surgical necrotizing enterocolitis, intraventricular hemorrhage grade III/IV, and periventricular leukomalacia, were unchanged among the 3 periods. CONCLUSIONS: From 2007-2020, respiratory management was characterized by a marked reduction in invasive mechanical ventilation and an increase in the use of NIRS. Changes in early respiratory support management resulted in improved respiratory outcomes with a decrease in the overall incidence of BPD. It is likely that our aim to reduce lung injury by improving our respiratory management has contributed to a favorable outcome.

Divergent responses of soil fungal communities to soil erosion and deposition as evidenced in topsoil and subsoil.

Despite the pivotal functional roles dominating the pace of nutrient cycles in terrestrial ecosystems, soil fungal communities at erosional and depositional sites have not been comparatively investigated when assessing the ecosystem stability of eroding landscapes. In this study, soil fungal communities in topsoil (0-5 cm) and subsoil (5-10 cm) on simulated eroding slopes of three slope gradients, i.e., 5°, 10°, and 20°, and in the corresponding depositional zones were examined from 2015 to 2017 in the region of the Chinese Loess Plateau. The results showed that, compared with that in the 5° reference slopes, soil fungal richness in the topsoil and subsoil of the 10° and 20° eroding slopes was 11.8-24.9% lower. However, the richness increased by 2.3-22.7% in the subsoil of the depositional zones, yet not in the topsoil. Soil fungal community compositions in both topsoil and subsoil differed between depositional zones and reference slopes but not between eroding slopes and reference slopes. The differentiation of fungal richness and community compositions between eroding slopes and depositional zones increased with slope gradients, regardless of the topsoil and the subsoil. Saprotrophic fungi levels were 22.5-48.0% lower and pathogenic fungi were 45.2-193.3% higher in the subsoil of the depositional zones with 10° and 20° slopes than in the subsoil of the 5° reference slopes. Soil fungal network on the eroding slope was more complex than that in the depositional zone, suggesting more extensive interactions of fungal taxa and higher community stability potential on eroding slopes. The decreasing soil moisture, organic matter, and other properties on the eroding slopes, in contrast with these properties increasing in the depositional zones, were responsible for the variations in fungal richness and community composition. The divergent responses of soil fungal communities to soil erosion and deposition emphasized the complexity and variability of fungal communities during the soil erosion-deposition processes.

The Comparison of HHHFNC and NCPAP in Extremely Low-Birth-Weight Preterm Infants After Extubation: A Single-Center Randomized Controlled Trial.

Objectives: To compare the clinical efficacy of heated, humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (NCPAP) in extremely low-birth-weight preterm infants (ELBWI) after extubation. Methods: This trial included 94 extremely low-birth-weight infants (ELBWI), within 7 days after birth, and prepared for tracheal extubation and a change to non-invasive ventilation in the neonatal intensive care unit (NICU) admitted to our hospital from January 2015 to December 2018, with 48 infants in the HHHFNC group and 46 infants in the NCPAP group. Reintubation rate within 72 h after initial extubation, total ventilation time, non-invasive ventilation time, total oxygen inhalation time, and the time to reach full enteral feeding were the primary outcome measures. Total intestinal feeding time, average weight gain rate, days of hospitalization, costs of hospitalization, and complication rates, including nasal injury, IVH, BPD, NEC, ROP, and PDA, were used as secondary outcomes. Data were analyzed using Student's t-test or the Mann-Whitney U-test with a Chi-square test or Fisher's exact test, as appropriate, in SPSS (25.0). Results: HHHFNC not only shortened the oxygen exposure time but also effectively reduced the incidence of nasal injury (6.25 vs. 36.96%) and NEC (10.42 vs. 28.26%) (P < 0.05). Additionally, HHHFNC achieved a significant advance in the time to reach full enteral feeding (31.24 ± 11.35 vs. 34.21 ± 14.09 days); increased the average weight gain rate (16.07 ± 3.10 vs. 13.74 ± 4.21) and reduced the days of hospitalization (73.45 ± 18.84 vs. 79.24 ± 19.75), with a lower cost of hospitalization (16.04 ± 3.64 vs.18.79 ± 4.13) thousand dollars (all P < 0.05). Conclusions: Compared with NCPAP, HHHFNC was effective in preventing extubation failure in mechanically ventilated preterm ELBWI. HHHFNC shortens oxygen consumption time and significantly reduces the incidence of nasal injury and necrotizing enterocolitis; moreover, it can also reduce the length of stay and the hospitalization costs.

Impact of topsoil removal on soil CO2 emission and temperature sensitivity in Chinese Loess Plateau.

Soil redistribution by terrace construction, as one of the most evident anthropogenic imprints on hill-slopes, may influence soil organic carbon (SOC) dynamics through re-shaping topography and altering water and oxygen availability. However, the fundamental role and mechanisms by which terrace construction affects in situ soil CO2 emissions and its temperature sensitivity (Q10) remain poorly understood. In this study, topsoil removal-addition approach was used to simulate topsoil redistribution during terrace construction. Compared with the nearby undisturbed soil, the average annual soil CO2 emission over two years was reduced by 24% in the topsoil removed field but enhanced by 33% in the topsoil added field. The decreased soil CO2 emission at the topsoil removed field was largely associated with the depletion of SOC stocks and microbial biomass carbon, while the increments of SOC available for decomposition at the topsoil added field contributed to its increased soil CO2 emissions. However, the average Q10 value in the topsoil removed field was 23% greater at seasonal scale and 28% greater at diurnal scale than that in the undisturbed soil. The increased Q10 in the topsoil removed field is mainly due to higher aromaticity of water-extractable organic carbon (WEOC) and the domination of Actinobacteria in keystone taxa. Overall, our results show that changes in both aromaticity of WEOC and soil microbial community composition induced by soil redistribution during terrace construction may alter the response of soil CO2 emission to elevated temperature. Our study indicates that the impact of man-made soil redistribution should not be neglected when studying regional carbon cycling.

Temperature sensitivity of soil respiration: Synthetic effects of nitrogen and phosphorus fertilization on Chinese Loess Plateau.

Nitrogen (N) and phosphorus (P) fertilization has the potential to alter soil respiration temperature sensitivity (Q10) by changing soil biochemical and crop physiological process. A four-year field experiment was conducted to determine how Q10 responded to these biochemical and physiological changes in rain-fed agro-ecosystems on the semi-arid Loess Plateau. Soil respiration, as well as biotic and abiotic factors were measured in winter wheat (Triticum aestivum L.), with three fertilization treatments: (no fertilization (CK), 160kgNhm-1 (N), and 160kgNha-1 with 39kgPha-1 (N+P). Mean annual soil respiration rate (calculated by averaging the four years) in the N treatment and N+P treatment was 18% and 48% higher than that in the CK treatment, respectively; and it was increased by 26% (14%-48%) in the N+P treatment as compared with that in the N treatment. The decrease of Q10 in the N and N+P treatments against the CK treatment was not stable for each year, ranging from 0.01 to 0.28. The maximum decrease of Q10 in the N and N+P treatments was 10% and 15% in 2014-2015, while in other years the decrease of Q10 was numerical but not significant. Soil microbial biomass carbon (SMBC) was increased by 10% and 50%, dissolved organic carbon (DOC) was increased by 6% and 21%, and photosynthesis rate was increased ranging from 6% to 33% with N and N+P fertilization. The relative abundance of Acidobacteria, Actinobacteria and Chloroflexi were significantly higher by 32.9%-54.1% in N addition soils (N and N+P) compared to CK treatment, whereas additional P application into soils increased the relative abundance of the family Micrococcaceae, Nocardioidaceae and Chitinophagaceae. Soil respiration was positively related to SMBC, DOC and photosynthesis rate (p<0.05). However, variation in Q10 may be related to the increase of soil mineral N content and variation of the relative abundance of soil microbial community in our study. Nitrogen and additional phosphorus fertilization regimes affect soil respiration and temperature sensitivity differently.

[Response of Soil Respiration to Extreme Precipitation in Semi-arid Regions].

Evaluating the response of soil microbial respiration to extreme precipitation event is significant for a better understanding about the influence of the change of precipitation regime on soil carbon cycling under global warming. A simulated experiment of extreme precipitations was conducted during the rainy season (July-September 2015) in the Changwu State Key Agro-Ecological Station, Shaanxi, China. The treatments consisted of three total precipitations in rainy season (600 mm, 300 mm, and 150 mm) and two precipitation regimes (10 mm, 150 mm; P10, P150). Soil microbial respiration varied differently in the same single rainfall event among three precipitations. The variation coefficient of soil microbial respiration under 600 mm total precipitation was 36% (P150) and 33% (P10), and 28% and 22% under 300 mm total precipitation, 43% and 29% under 150 mm total precipitation. Under 600 mm total precipitation, the cumulative soil microbial respiration under P150 was 20% less than that under P10; however, the cumulative soil respiration of P150 under 150 mm total precipitation was 22% more than that under P10; and there was no significant difference between P10 and P150 under 300 mm total precipitation. Therefore, the duration in soil water stress must be considered to estimate soil microbial respirations under extreme precipitations.

[Variation of Soil CO2 Flux and Environmental Factors Across Erosion-Deposition Sites Under Simulation Experiment].

The CO2 flux from soil is an important component of global carbon cycle, and a small variation of soil CO2 flux can prominently influence atmospheric CO2 concentration and soil organic carbon stock. Soil erosion significantly influences soil CO2 emission. However, the process of soil CO2 flux during soil erosion and soil deposition remains uncertain. At the present study, a simulated experiment on soil erosion and deposition was conducted at Changwu State Key Agro-Ecological Station, Shaanxi, China. From July to September in 2014 and 2015, soil CO2 flux was periodically measured using an automated CO2 flux system LI-8100 (LI-COR, Lincoln, NE, USA) and soil temperature and moisture were collected by series data collection system of soil temperature and soil moisture (EM50, DECAGON, USA). The measurement frequency of soil CO2 flux was once a week during 09:00 and 11:00. Soil temperature and soil moisture of 10 cm topsoil were measured continuously (at an interval of 30 minutes) during the experiment. At the same time, runoff and sediment were collected as well in each rain event, and then SOC content in sediment was measured. The results showed that soil CO2 flux between erosion and deposition sites had a significant difference (P<0.05), and soil CO2 flux at deposition site [mean value 1.38 µmol·(m2·s)-1] was 31% higher than that of soil CO2 flux at deposition site [1.05 µmol·(m2·s)-1], while temperature sensitivity at deposition site (Q10:8.14) was 3 times as high as that at erosion site (2.34). Soil moisture at deposition site was 19% higher than that at erosion site (P<0.05). Soil temperature was slightly higher at erosion site. The average SOC content (7.26 g·kg-1) increased by 6% in the sediment compared with the initial SOC content (6.83 g·kg-1). Soil moisture and SOC redistribution across erosion and deposition sites were influencing factors for soil CO2 flux under erosional environment. In conclusion, soil CO2 flux showed a significant variation at erosion site and deposition site. Changes in soil moisture and SOC contributed much to the difference in soil CO2 flux across erosion and deposition sites.

Phosphorus Accumulation and Sorption in Calcareous Soil under Long-Term Fertilization.

Application of phosphorus (P) fertilizers to P-deficient soils can also result in P accumulation. In this study, soil P status and P uptake by apple trees were investigated in 5-, 10-, and 15-year-old orchards in the semi-arid Loess Plateau, China, and subset soils with different soil P statuses (14-90 Olsen-P mg kg(-1)) were selected to evaluate the characteristic P adsorption. Due to the low P-use efficiency (4-6%), total soil P increased from 540 mg kg(-1) to 904 mg kg(-1), Olsen-P ranged from 3.4 mg kg(-1) to 30.7 mg kg(-1), and CaCl2-P increased from less than 0.1 mg kg(-1) to 0.66 mg kg(-1) under continuous P fertilization. The P sorption isotherms for each apple orchard were found to fit the Langmuir isotherm model (R2 = 0.91-0.98). K (binding energy) and Qm (P sorption maximum) decreased, whereas DPS (degree of phosphorus sorption) increased with increasing P concentration. CaCl2-P increased significantly with the increase of Olsen-P, especially above the change point of 46.1 mg kg(-1). Application of surplus P could result in P enrichment in P-deficient soil which has high P fixation capacity, thus posing a significant environmental risk.