Rational Design of PARP1/c-Met Dual Inhibitors for Overcoming PARP1 Inhibitor Resistance Induced by c-Met Overexpression.

The emergence of resistance to PARP1 inhibitors poses a current therapeutic challenge, necessitating the development of novel strategies to overcome this obstacle. The present study describes the design and synthesis of a series of small molecules that target both PARP1 and c-Met. Among them, compound 16 is identified as a highly potent dual inhibitor, exhibiting excellent inhibitory activities against PARP1 (IC50 = 3.3 nM) and c-Met (IC50 = 32.2 nM), as well as demonstrating good antiproliferative effects on HR-proficient cancer cell lines and those resistant to PARP1 inhibitors. Importantly, compound 16 demonstrates superior antitumor potency compared to the PARP1 inhibitor Olaparib and the c-Met inhibitor Crizotinib, either alone or in combination, in MDA-MB-231 and HCT116OR xenograft models. These findings highlight the potential of PARP1/c-Met dual inhibitors for expanding the indications of PARP1 inhibitors and overcoming tumor cells' resistance to them.

Optimization of the spatial layout of animal husbandry based on comprehensive competitive advantage evaluation and nutrient balance: a case study of Heilongjiang province.

The optimization of the spatial layout of animal husbandry has great significance for the sustainable development of animal husbandry. However, limited research has focused on the optimization of the spatial layout of animal husbandry based on comprehensive competitive advantage evaluation and nutrient balance between planting and breeding. This study established a comprehensive competitive advantage evaluation model of animal husbandry. Based on this model, we performed comprehensive competitive advantage evaluation of animal husbandry. We further calculated the land-carrying capacity index of animal manure and potential land-carrying capacity of animal according to the principle of nutrient balance. Finally, the spatial layout of animal husbandry was optimized using Geographic Information System spatial analysis. Results showed that Harbin had obvious comprehensive competitive advantage in pig, cattle, sheep, and poultry breeding. Daqing had obvious comprehensive competitive advantage in cattle and sheep breeding. The land-carrying capacity index of animal manure of Daxing'anling constantly exceeded 1. The potential land-carrying capacity of animal in Heilongjiang province was uneven, and most regions in Heilongjiang province had development potential of animal husbandry. The optimized target regions of the spatial layout of pig, cattle, sheep, and poultry breeding were all Harbin. A total of 77 956.03 pig equivalent in Daxing'anling was recommended to be transferred to Harbin. Our results are useful for the spatial layout of animal husbandry, environmental pollution prevention from animal husbandry, and optimization of animal products structure.

Potential reduction of greenhouse gas emissions from pig production in China on the basis of households' pork consumption.

In the past decades, the greenhouse gas (GHG) emissions from pig production in China have been increasing rapidly, which has become a huge challenge in fulfilling China's "carbon neutral" commitment. However, few studies have focused on reducing the GHG emissions from pig production in view of households' pork consumption. This study analyzed the temporal and spatial pattern of the GHG emissions from pig production in China in 2001-2020 through geographical information system, optimized the pig production in China, and estimated thepotentialGHG emissions reduction from pig production in China in 2020 through spatial analysis based on pork surplus or deficit. Results show that the temporal and spatial pattern of the GHG emissions from pig production and its proportion in the total GHG emissions from livestock production in China in 2001-2020 varied differently at the province level and conformed to the "Hu Huanyong Line" mode. The largest and smallest GHG emissions from pig production were 108.93 million tons (MT) in 2014 and 78.10 MT in 2020, respectively. The largest and smallest proportions of GHG emissions from pig production in the total GHG emissions from livestock production were 77.52% in Zhejiang in 2013 and 0.13% in Tibet in 2009, respectively. Moreover, a potential optimization scheme of pig production in China in 2020 was provided and a method of GHG emissions reduction from pig production is proposed. The results indicate that the total potentialGHG emissions reduction from pig production on the basis of households' pork consumption could reach 35.21 MT, accounting for 45.09% of the total GHG emissions from pig production and 10.27% of the total GHG emissions from livestock production in China in 2020. These findings areusefulin the spatial layout planning of pig production, agricultural GHG reduction, and global warming mitigation.

Biogas potential from agricultural waste and its CO2 emission reduction: a case study of Hubei Province, China.

Biogas produced from agricultural waste can have potential benefits, such as offer clean renewable energy, protect the ecological environment, and reduce CO2 emission. However, few studies have been conducted on the biogas potential from agricultural waste and its CO2 emission reduction at the county level. Herein, the biogas potential from agricultural waste was calculated, and its spatial distribution in Hubei Province in 2017 was determined using a geographic information system. Then, an evaluation model for the competitive advantage of the biogas potential from agricultural waste was established using entropy weight and linear weighting methods. Moreover, the space partition of the biogas potential from agricultural waste was obtained through hot spot analysis. Lastly, the standard coal equivalent of biogas, the equivalent of coal consumption of biogas, and the CO2 emission reduction based on the space partition result were estimated. Results showed that the total and average biogas potentials from agricultural waste in Hubei Province were 18,498,317,558.54 and 222,871,295.89 m3, respectively. Qianjiang City, Jianli County, Xiantao City, and Zaoyang City had a high competitive advantage in the biogas potential from agricultural waste. The CO2 emission reduction of the biogas potential from agricultural waste was mainly in classes I and II.

Dissipative soliton generation and real-time dynamics in microresonator-filtered fiber lasers.

Optical frequency combs in microresonators (microcombs) have a wide range of applications in science and technology, due to its compact size and access to considerably larger comb spacing. Despite recent successes, the problems of self-starting, high mode efficiency as well as high output power have not been fully addressed for conventional soliton microcombs. Recent demonstration of laser cavity soliton microcombs by nesting a microresonator into a fiber cavity, shows great potential to solve the problems. Here we study the dissipative soliton generation and interaction dynamics in a microresonator-filtered fiber laser in both theory and experiment. We bring theoretical insight into the mode-locking principle, discuss the parameters effect on soliton properties, and provide experimental guidelines for broadband soliton generation. We predict chirped bright dissipative soliton with flat-top spectral envelope in microresonators with normal dispersion, which is fundamentally forbidden for the externally driven case. Furthermore, we experimentally achieve soliton microcombs with large bandwidth of ~10 nm and high mode efficiency of 90.7%. Finally, by taking advantage of an ultrahigh-speed time magnifier, we study the real-time soliton formation and interaction dynamics and experimentally observe soliton Newton's cradle. Our study will benefit the design of the novel, high-efficiency and self-starting microcombs for real-world applications.

Multimodal Imaging Response after the Singular or Combination Treatments of Vascular Endothelial Growth Factor Inhibitor and Immune Checkpoint Inhibitor.

This study aims to dynamically assess tumor changes after variable treatments with vascular endothelial growth factor (VEGF) inhibitor and/or immune checkpoint inhibitor (ICI) using multimodal imaging of MRI and 18F-FDG PET/CT in a hepatocellular carcinoma (HCC) mice model. Based on different treatments, 24 mice were randomly divided into four groups: control (isotype-matched IgG antibody 10 mg/kg), VEGF inhibitor (sorafenib 50 mg/kg), ICI (anti-PD-L1 antibody 10 mg/kg), and combination groups (sorafenib 50 mg/kg + anti-PD-L1 antibody 10 mg/kg). Quantitative imaging assessments, including volume transfer constant (Ktrans), apparent diffusion coefficient (ADC), lactate/choline ratio, and the maximum standardized 18F-FDG uptake value ratio of tumor to muscle (SUVtumor/SUVmuscle ratio), were acquired at different time points (before treatment and 7, 14, and 21 days after treatment). Quantitative data were presented as the mean ± standard errors and two-way repeated-measure ANOVA tests were performed for intergroup and intertime point comparisons. After 21 days from the initiation of therapies, combination group showed the lowest tumor volume and weight, followed by ICI, VEGF inhibitor, and control group, with no significance between the VEGF inhibitor and control groups. In addition, Ktrans values significantly decreased, and the lactate/choline ratio and SUVtumor/SUVmuscle ratio were significantly elevated in the VEGF inhibitor group. ADC significantly increased in the ICI and combination groups, with no significant differences in ADC observed between the control and VEGF inhibitor groups, which showed a similar dynamic change to the tumor volume. Furthermore, Ktrans, lactate/choline ratio, and ADC were significantly correlated with CD31+ area, hypoxyprobe+ area, and apoptosis, respectively. Our results suggest that the singular treatment and combination of the VEGF inhibitor and ICI treatments for HCC present different multimodal imaging changes in accordance with the specific histopathological features. These findings might facilitate the formulation of better treatment response criteria; besides, we find ADC is probably an indicator easily to obtain for treatment response evaluation.

Spatial layout planning of intensive pig farms in the suburb: a case study of Nanyu, China.

A large number of livestock and poultry breeding were distributed in the suburbs, brought a strong environmental pressure to the cities. The issue of whether livestock and poultry breeding could be carried out in the suburbs was a key controversy in the present. To address this question, this study constructed an index system of suitability evaluation of spatial layout of intensive pig farms, calculated the average surface temperature from June to September, and obtained potential intensive pig farms in Nanyu Town. Combing above results and area index results of cultivated land spatial matched with intensive pig farm, spatial relation between cultivated land and potential intensive pig farm was built, the optimum potential intensive pig farm in Nanyu Town was determined, and its carrying capacity was calculated. Results showed that livestock and poultry breeding could be carried out in the suburbs. A total of 3403 and 3253 pieces of cultivated lands occupying 52.01% and 49.67% of the total cultivated lands had a spatial relation between potential intensive pig farms taking N and P as indices, respectively. Moreover, 14 and 15 potential intensive pig farms taking N and P as indices, respectively, in Nanyu Town were determined as optimum potential intensive pig farms. Results also indicated that most of the optimum potential intensive pig farms were suitable for constructing small- and medium-sized pig farms. Results would provide scientific basis for the planning of spatial arrangement of livestock and poultry breeding and the suburb environmental pollution control.

Spatial-temporal distribution of biogas production from agricultural waste per capita in rural China and its correlation with ground temperature.

Biogas production from agricultural waste has played a key role in recent years in reducing the environmental pollution risk of agricultural waste and alleviating energy shortage in rural China. However, few studies have focused on the effect of ground temperature on biogas production from agricultural waste from a quantitative point of view and the solution to increasing the temperature of biogas digesters in the cold season to improve biogas production from agricultural waste in rural areas at a provincial scale. Here, we calculated the spatial-temporal distribution of biogas production from agricultural waste per capita in rural China from 2001 to 2016 and agricultural waste per capita in rural China in 2016. Furthermore, we analyzed the correlation between biogas production from agricultural waste per capita in rural China and ground temperature. Finally, we proposed a solution to increase the temperature of biogas digesters in rural China in the cold season after analyzing its energy utilization. Results showed that the biogas production from agricultural waste per capita in rural China was correlated with the average and maximum ground temperature in January, February, March, November, and December from 2001 to 2016. The results also indicated that the suggested heating mode of biogas production from agricultural waste in rural China differed greatly among provinces. The provinces with high agricultural waste per capita in rural areas and low averaged biogas production from agricultural waste per capita are Inner Mongolia, Heilongjiang, and Xinjiang, which needed the suggested heating mode of biogas production from agricultural waste for increasing the temperature of biogas digesters in rural China in the cold season. Our findings provide a reference for biogas production from agricultural waste, greenhouse gas emission reduction, and the spatial layout of energy utilization in rural China.

Spatial layout planning of the pig northward movement based on GIS.

This study aimed to optimise the layout of pig breeding in the south water network area and guide the transfer of pig production capacity to the areas with large environmental capacity and the main maize-producing areas. Combining with the alarm value of equivalent pig manure load on cultivated land, the comprehensive advantage index of maize and GIS (Geographic Information System), this study analysed the spatial layout planning of the pig northward movement in China. Results showed that the alarm value of equivalent pig manure load on cultivated land in other parts of the study area exceeded 0.40, except in Jilin, Heilongjiang and the Inner Mongolia Autonomous Region. The highest alarm value of equivalent pig manure load on cultivated land value of 1.96 was observed in Fujian Province, followed by Jiangxi (1.09) and Hubei (0.42). A total of 573.996 million excess pig equivalents were present in the study area. In the provinces with potential pig equivalent, Jilin, Heilongjiang and the Inner Mongolia Autonomous Region can carry the potential pig equivalent of 306.270 million. The priority target areas of the pig northward movement were Jilin, Heilongjiang and the Inner Mongolia Autonomous Region according to the comprehensive advantage index of maize. Combining with the spatial analysis method of GIS, the scheme of the pig northward movement was obtained. According to the spatial layout planning of the pig northward movement, Jilin and Heilongjiang carried 15.339 and 135.36 million pig equivalents, respectively, thereby reaching the maximum number of pig equivalents they can carry, whereas the Inner Mongolia Autonomous Region can carry 80.086 million pig equivalents. The results can provide a scientific basis for the spatial layout planning of pig breeding and environmental pollution protection in China.

Driving Behavior Analysis of City Buses Based on Real-Time GNSS Traces and Road Information.

The driving behavior of bus drivers is related to the safety of all passengers and regulation of urban traffic. In order to analyze the relevant characteristics of speed and acceleration, accurate bus trajectories and patterns are essential for driver behavior analysis and development of effective intelligent public transportation. Exploiting real-time vehicle tracking, this paper develops a platform with vehicle-mounted terminals using differential global navigation satellite system (DGNSS) modules for driver behavior analysis. The DGNSS traces were used to derive the vehicle trajectories, which were then linked to road information to produce speed and acceleration matrices. Comprehensive field tests were undertaken on multiple bus routes in urban environments. The spatiotemporal results indicate that the platform can automatically and accurately extract the driving behavior characteristics. Furthermore, the platform's visual function can be used to effectively monitor driving risks, such as speeding and fierce acceleration, in multiple bus routes. The details of the platform's features are provided for intelligent transport system (ITS) design and applications.

Artifact Removal using Improved GoogLeNet for Sparse-view CT Reconstruction.

Sparse-view Reconstruction can be used to provide accelerated low dose CT imaging with both accelerated scan and reduced projection/back-projection calculation. Despite the rapid developments, image noise and artifacts still remain a major issue in the low dose protocol. In this paper, a deep learning based method named Improved GoogLeNet is proposed to remove streak artifacts due to projection missing in sparse-view CT reconstruction. Residual learning is used in GoogLeNet to study the artifacts of sparse-view CT reconstruction, and then subtracts the artifacts obtained by learning from the sparse reconstructed images, finally recovers a clear correction image. The intensity of reconstruction using the proposed method is very close to the full-view projective reconstructed image. The results indicate that the proposed method is practical and effective for reducing the artifacts and preserving the quality of the reconstructed image.

[Reconstruction of facial defects with frontal expanded flaps bipedicled by superficial temple vessels and supraorbital/supratrochlear neurovascular bundles].

OBJECTIVE: To investigate the therapeutic effect of reconstruction of facial defects with frontal expanded flaps bipedicled by superficial temple vessels and supraorbital/supratrochlear neurovascular bundles. METHODS: From June 2006 to Mar. 2013, the patients with mostly unilateral facial defects which affected temple area and crossed the facial midline, were treated with frontal expanded flaps. The expanders were implanted at first stage and the expanded frontal flaps were transferred at second stage. At third stage, pedicle division was performed and the pedicle skin tissue was used to repair the residue defect. RESULT: All the 18 flaps survived completely with satisfactory color and texture. Good results were achieved during the follow-up period of one year. CONCLUSION: The bipedicled frontal expanded flap has a reliable blood supply which is very suitable for large facial defect.

[Estimation of livestock manure nitrogen load and pollution risk evaluation of farmland in Daxing District].

Based on the livestock statistical data, the nutrient content of livestock manure was calculated and the nutrient transformation from livestock manure to farmland was realized by using the method of spatializing livestock manure nutrient. On this basis, this paper calculated nitrogen load of livestock manure combining with the area of farmland and realized the estimation of nitrogen load of livestock manure and potential pollution evaluation in landmass for unit taking Daxing District in Beijing as an example. The result showed that the average, minimum and maximum nitrogen loads of farmland were 214.02 kg/hm2, 10.64 kg/hm2 and 5996.26 kg/hm2 respectively and near half of farmland was threaten by nitrogen load of livestock manure, accounting for 42.14% of the total farmland. These farmland threaten to polluted had the characters of small area and few nutrient demand and mainly located nearby the inhabitant and the scale raising. The coefficients of variation and average of available nitrogen in topsoil and subsoil were 64.3%, 53.65% and 65.93 microg/g, 45.25 microg/g respectively and the enrichment coefficient was 1.46, which explained the existing pollution risk and the influence degree of livestock manure to soil environment pollution.