Xanthine oxidase (XO) is a crucial enzyme in the development of hyperuricemia and gout. This study focuses on LWM and ALPM, two food-derived inhibitors of XO. We used molecular docking to obtain ...three systems and then conducted 200 ns molecular dynamics simulations for the Apo, LWM, and ALPM systems. The results reveal a stronger binding affinity of the LWM peptide to XO, potentially due to increased hydrogen bond formation. Notable changes were observed in the XO tunnel upon inhibitor binding, particularly with LWM, which showed a thinner, longer, and more twisted configuration compared to ALPM. The study highlights the importance of residue F914 in the allosteric pathway. Methodologically, we utilized the perturbed response scan (PRS) based on Python, enhancing tools for MD analysis. These findings deepen our understanding of food-derived anti-XO inhibitors and could inform the development of food-based therapeutics for reducing uric acid levels with minimal side effects.
Improving winter wheat grain yield and water use efficiency (WUE) with minimum irrigation is very important for ensuring agricultural and ecological sustainability in the Northern China Plain (NCP). ...A three-year field experiment was conducted to determine how single irrigation can improve grain yield and WUE by manipulating the "sink-source" relationships. To achieve this, no-irrigation after sowing (W0) as a control, and five single irrigation treatments after sowing (75 mm of each irrigation) were established. They included irrigation at upstanding (WU), irrigation at jointing (WJ), irrigation at booting (WB), irrigation at anthesis (WA) and irrigation at medium milk (WM). Results showed that compared with no-irrigation after sowing (W0), WU, WJ, WB, WA and WM significantly improved mean grain yield by 14.1%, 19.9%, 17.9%, 11.6%, and 7.5%, respectively. WJ achieved the highest grain yield (8653.1 kg ha-1) and WUE (20.3 kg ha-1 mm-1), and WB observed the same level of grain yield and WUE as WJ. In comparison to WU, WJ and WB coordinated pre- and post-anthesis water use while reducing pre-anthesis and total evapotranspiration (ET). They also retained higher soil water content above 180 cm soil layers at anthesis, increased post-anthesis water use, and ultimately increased WUE. WJ and WB optimized population quantity and individual leaf size, delayed leaf senescence, extended grain-filling duration, improved post-anthesis biomass and biomass remobilization (source supply capacity) as well as post-anthesis biomass per unit anthesis leaf area (PostBA-leaf ratio). WJ also optimized the allocation of assimilation, increased the spike partitioning index (SPI, spike biomass/biomass at anthesis) and grain production efficiency (GPE, the ratio of grain number to biomass at anthesis), thus improved mean sink capacity by 28.1%, 5.7%, 21.9%, and 26.7% in comparison to W0, WU, WA and WM, respectively. Compared with WA and WM, WJ and WB also increased sink capacity, post-anthesis biomass and biomass remobilization. These results demonstrated that single irrigation at jointing or booting could improve grain yield and WUE via coordinating the "source-sink" relationships with the high sink capacity and source supply capacity. Therefore, we propose that under adequate soil moisture conditions before sowing, single irrigation scheme from jointing to booting with 75 mm irrigation amount is the optimal minimum irrigation practice for wheat production in this region.
Wheat seedlings are becoming popular for its high nutritional value. Effects of White (W), White + Red (WR), and White + Blue (WB) light-emitting diodes (LEDs) treatments on growth, nutritional ...characteristics and antioxidant properties of wheat seedlings were studied in a plant factory. The results showed that height, leaf area, shoot fresh, and shoot dry weight per wheat seedling were the highest under WR at 13 and 22 days after planting. Soluble sugar content in leaves and stems were 22.3 and 65% respectively higher under WB than those under W. Soluble protein content in leaves and stems were 36.8 and 15.2% respectively lower under WR than those under W. Contents of total flavonoids, glutathione (GSH) and ascorbic acid (ASA) in leaves were the highest under WB, whereas malondialdehyde (MDA) content in leaves was the lowest under WB. The activities of antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX) in leaves and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability were also the highest under WB. In conclusion, WR promoted the growth of wheat seedlings, and WB promoted antioxidant level and nutritional accumulation. This study provides guidance for wheat seedlings to carry out preferential production (biomass or quality).
One of the problems of optical remote sensing of crop above-ground biomass (AGB) is that vegetation indices (VIs) often saturate from the middle to late growth stages. This study focuses on combining ...VIs acquired by a consumer-grade multiple-spectral UAV and machine learning regression techniques to (i) determine the optimal time window for AGB estimation of winter wheat and to (ii) determine the optimal combination of multi-spectral VIs and regression algorithms. UAV-based multi-spectral data and manually measured AGB of winter wheat, under five nitrogen rates, were obtained from the jointing stage until 25 days after flowering in the growing season 2020/2021. Forty-four multi-spectral VIs were used in the linear regression (LR), partial least squares regression (PLSR), and random forest (RF) models in this study. Results of LR models showed that the heading stage was the most suitable stage for AGB prediction, with R2 values varying from 0.48 to 0.93. Three PLSR models based on different datasets performed differently in estimating AGB in the training dataset (R2 = 0.74~0.92, RMSE = 0.95~2.87 t/ha, MAE = 0.75~2.18 t/ha, and RPD = 2.00~3.67) and validation dataset (R2 = 0.50~0.75, RMSE = 1.56~2.57 t/ha, MAE = 1.44~2.05 t/ha, RPD = 1.45~1.89). Compared with PLSR models, the performance of the RF models was more stable in the prediction of AGB in the training dataset (R2 = 0.95~0.97, RMSE = 0.58~1.08 t/ha, MAE = 0.46~0.89 t/ha, and RPD = 3.95~6.35) and validation dataset (R2 = 0.83~0.93, RMSE = 0.93~2.34 t/ha, MAE = 0.72~2.01 t/ha, RPD = 1.36~3.79). Monitoring AGB prior to flowering was found to be more effective than post-flowering. Moreover, this study demonstrates that it is feasible to estimate AGB for multiple growth stages of winter wheat by combining the optimal VIs and PLSR and RF models, which overcomes the saturation problem of using individual VI-based linear regression models.
Introduction
Locoregional interventional therapy including transcatheter arterial chemoembolization (TACE) and ablation are the current standard of treatment for early-to-mid-stage hepatocellular ...carcinoma (HCC). However, questions remain unanswered regarding the management of recurrence after locoregional treatment. PD-1 inhibitors can block inhibitory signals of T-cell activation and proliferation to reduce the recurrence. We conducted a single-arm phase 2 trial to evaluate the efficacy and safety of PD-1 inhibitors following locoregional interventional therapy in HCC patients with high recurrence risk guided by our novel scoring system.
Methods
Patients enrolled initially treated by TACE combined with ablation, then willingly joined the experimental group. One month later, they received the anti-PD-1 adjuvant therapy (intravenous injection of 200 mg), which was repeated every 3 weeks for a total of 4 or 8 cycles. Within this same period, other patients were screened into the control group to match the experimental group by 1:1 based on the propensity score matching method (PSM). The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS) recurrence modality, safety, and quality of life.
Result
At the time of data cutoff, the median RFS of the control group was 7.0 months while the experimental group had not reached it. Moreover, the 1-year RFS rate was 73.3% in the experimental group and 46.7% in the control group, showing a significant difference (P =0.02). The rate of local tumor progression in the experimental group was clearly lower than that in the control group (P = 0.027). Benefits associated with anti-PD-1 adjuvant therapy were observed in patients with multiple tumors and tumor size ≤2cm. Univariate and multivariate analyses demonstrated that anti-PD-1 adjuvant therapy was an independent favorable prognostic factor for RFS in HCC patients. The most frequent AE observed in this study was RCCEP, and other AEs included diarrhea, hepatotoxicity, rash, pruritus, and fatigue. The incidence of GRADE ≥3 AE and withdrawal in this study was low with no deaths recorded.
Conclusions
Interim analysis from the study suggest the addition of anti-PD-1 adjuvant therapy after TACE combined with ablation could significantly prolong RFS with controllable safety for early-to-mid-stage HCC patients with high recurrence risk.
Improving winter wheat yield and resource utilization efficiency (i.e., sustainable intensification) under water-restricted condition is crucial for ensuring food security in arid regions such as the ...North China Plain. Developing more effective cultivation measures is one of the directions to achieve sustainable intensification. This study was a two-year cultivation experiment in the North China Plain, aimed to explore the effects of the combination of water-fertilizer coupling and various planting densities at early (October 10, D10), optimum (October 17, D17), and delayed (October 24, D24) sowing dates. As a consequence, we proposed a limited-irrigation and high-yield cultivation pattern that included 15 m3 ha-1 chicken manure, 192kgha-1 nitrogen (N), 138kgha-1 P2O5, 112.5kgha-1 K2O, and irrigated twice, while the limited-irrigation and low-yield cultivation pattern (similar to regional farmers' average yield) irrigated once. Compared to the limited-irrigation and low-yield treatment, the limited-irrigation and high-yield treatment increased yield, water use efficiency, and partial factor productivity from applied N by about 22.4%, 11.4%, and 23.0%, respectively. The limited-irrigation and high-yield treatment increased the nitrogen distribution in top second to fourth leaves, while decreasing it in glume, top first stem, and top second stem at filling stage, which contributed to higher yield and resource use efficiency. As such, pursuing higher nitrogen distribution in top second to fourth leaves at filling stage is an effective direction for sustainable intensification under water-restricted condition. These results will provide cultivation measures for winter wheat sustainable intensification in arid regions, and found a theoretical basis for elaboration of water-fertilizer coupling effect on the accumulation and distribution of dry matter and nitrogen in wheat plants.
Display omitted
•Water-fertilizer coupling with various planting densities promoted wheat sustainable intensification.•Limited-irrigation treatments resulted in high yield and efficiency at different sowing dates.•Nitrogen spatial distribution in plant under limited-irrigation treatments was mapped.•Nitrogen distribution in top second to fourth leaves was the key for yield and efficiency formation.
CO2 enhanced oil recovery (CO2-EOR) has become significantly crucial to the petroleum industry, in particular, CO2 miscible flooding can greatly improve the efficiency of EOR. Minimum miscibility ...pressure (MMP) is a vital factor affecting CO2 flooding, which determines the yield and economic benefit of oil recovery. Therefore, it is important to predict this property for a successful field development plan. In this study, a novel model based on molecular dynamics to determine MMP was developed. The model characterized a miscible state by calculating the ratio of CO2 and crude oil atoms that pass through the initial interface. The whole process was not affected by other external objective factors. We compared our model with several famous empirical correlations, and obtained satisfactory results—the relative errors were 8.53% and 13.71% for the two equations derived from our model. Furthermore, we found the MMPs predicted by different reference materials (i.e., CO2/crude oil) were approximately linear (R2 = 0.955). We also confirmed the linear relationship between MMP and reservoir temperature (TR). The correlation coefficient was about 0.15 MPa/K in the present study.
Dry rivers could be effectively recovered by reclaimed water in North China, while river water quality would be an important issue. Therefore, it is important to understand the spatiotemporal ...variation and controlling factors of river water. Water samples were collected during March, May, July, September, and November in the year 2010, then 20 parameters were analyzed. The water environment was oxidizing and alkaline, which was beneficial for nitrification. Nitrate was the main nitrogen form. Depleted and enriched isotopes were found in reclaimed water and river water, respectively. Total nitrogen (TN) and total phosphorus (TP) of reclaimed water exceed the threshold of reclaimed water reuse standard and Class V in the surface water quality criteria. Most river water was at the severe eutrophication level. The sodium adsorption ratio indicated a medium harmful level for irrigation purpose. Significant spatial and temporal variation was explored by cluster analysis. Five months and nine stations were both classified into two distinct clusters. It was found that 6 parameters (chloride: Cl−, sulphate: SO42−, potassium: K+, sodium: Na+, magnesium: Mg2+, and total dissolved solids: TDS) had significant upward temporal variation, and 12 parameters (dissolved oxygen: DO, electric conductivity: EC, bicarbonate: HCO3−, K+, Na+, Ca2+, TDS, nitrite-nitrogen: NO2-N, nitrate nitrogen: NO3-N, TN, TP, and chlorophyll a: Chl.a) and 4 parameters (Mg2+, ammonia nitrogen: NH3-N, and the oxygen-18 and hydron-2 stable isotope: δ18O and δ2H) had a significant downward and upward spatial trend, respectively. The Gibbs plot showed that river water chemistry was mainly controlled by a water–rock interaction. The ionic relationship and principal component analysis showed that river water had undergone the dissolution of carbonate, calcite, and silicate minerals, cation exchange, a process of nitrification, photosynthesis of phytoplankton, and stable isotope enrichment. In addition, gypsum and salt rock have a potential dissolution process.
Sustainable intensification is an agricultural development direction internationally. However, little is known about the yield sustainability of winter wheat (Triticum aestivum L.) under limited ...irrigation schemes on the North China Plain (NCP). A 28-year field experiment from 1991 to 2018 at Wuqiao Experimental Station was used to characterize long-term yield, evapotranspiration (ET), and water use efficiency (WUE) trends under three irrigation treatments (W1, irrigation just before sowing; W2, irrigation before sowing and at jointing stage; W3, irrigation before sowing, at jointing stage, and at anthesis). Yield gaps and the effects of genetic improvement, climate change, and climate variables on wheat yield and key phenological stages were estimated using the Agricultural Production Systems Simulator (APSIM) model. Grain yield and WUE of winter wheat increased during the 28 years under the three irrigation treatments, and the upward trend of WUE followed a saturation curve pattern. ET increased slightly. Simulation results showed that genetic improvement dramatically prolonged the phenological stages of vegetative growth period and contributed to yield increase by 0.03%–15.6%. The rapid increase in yield with lower water use was associated mainly with an increase in biomass with genetic improvement and partly with an increase in harvest index. A curvilinear relationship between WUE and yield emphasized the importance of obtaining high yields for high WUE. The yield gaps between potential yield and yield under W1 treatment increased from 1991 to 2018 but were relatively constant for the W2 and W3 treatments. Elevated atmospheric CO2 concentration offset the negative effects of temperature increase on yield, leading to minor (−2.3% to 0.3%) changes in yield under climate change. Thus, genetic improvement played a dominant role in yield increase, and limited-irrigation schemes (W2 and W3) can increase wheat yield and promote sustainability of crop production on the NCP.
Spinal cord injury (SCI) is one of the most debilitating injuries. Inflammatory response plays a central role in regulating the pathogenesis of acute and chronic SCI. Our study explores the role of ...miR-127 in inflammatory injury induced by LPS. PC-12 cells were treated with LPS to induce inflammatory injury. The expression of miR-127 and PDCD4 was altered by transient transfection. Cell viability was measured using CCK-8 assay and apoptosis using flow cytometry. The expression of miR-127 was measured by qRT-PCR. The concentrations of TNF-α and IL-6 were detected by ELISA. The levels of TLR4, PDCD4, BCL6, core factors of JNK and NF-κB pathway were assessed by RT-PCR/western blot. Dual luciferase reporter assay was conducted to verify the relationship between miR-127 and BCL6. LPS induced inflammatory injury in PC-12 cells. LPS also increased the expression of miR-127 and PDCD4. miR-127 overexpression promoted the LPS-induced inflammatory injury while miR-127 suppression inhibited the injury. BCL6 was a target of miR-127 in PC-12 cells. In addition, miR-127 positively regulated PDCD4 expression, and PDCD4 showed a similar effect on LPS-induced injury in PC-12 cells. We also found that miR-127 and PDCD4 enhanced the activation of JNK and NF-κB pathway. Further, the expressions of miR-127 and PDCD4 were both upregulated in ASCI rats. Our present study demonstrated that miR-127 inhibition might exert a protective role in LPS-injured PC-12 cells through regulation of PDCD4 expression and the further downstream signaling pathway.
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