The Analysis of Key Factors Related to ADCs Structural Design

Antibody–drug conjugates (ADCs) have developed rapidly in recent decades. However, it is complicated to map out a perfect ADC that requires optimization of multiple parameters including antigens, antibodies, linkers, payloads, and the payload-linker linkage. The therapeutic targets of the ADCs are expected to express only on the surface of the corresponding target tumor cells. On the contrary, many antigens usually express on normal tissues to some extent, which could disturb the specificity of ADCs and limit their clinical application, not to mention the antibody is also difficult to choose. It requires to not only target and have affinity with the corresponding antigen, but it also needs to have a linkage site with the linker to load the payloads. In addition, the linker and payload are indispensable in the efficacy of ADCs. The linker is required to stabilize the ADC in the circulatory system and is brittle to release free payload while the antibody combines with antigen. Also, it is a premise that the dose of ADCs will not kill normal tissues and the released payloads are able to fulfill the killing potency in tumor cells at the same time. In this review, we mainly focus on the latest development of key factors affecting ADCs progress, including the selection of antibodies and antigens, the optimization of payload, the modification of linker, payload-linker linkage, and some other relevant parameters of ADCs

The relationship between aspirin consumption and hepatocellular carcinoma: a systematic review and meta-analysis

Abstract Background Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This meta-analysis aimed to investigate the correlation between aspirin consumption and HCC. Methods A systematic literature search was conducted on PubMed, Scopus, Cochrane Library, EMBASE, and Web of Science databases. The search period was from the establishment of the database to July 1, 2022 with no language restrictions. Results A total of 19 studies including three prospective studies and 16 retrospective ones with 2,217,712 patients were included. Compared with those who did not take aspirin, those who took aspirin had a 30% lower risk of HCC (hazard ratio [HR] = 0.70, 95% confidence interval [CI] 0.63–0.76, I 2 = 84.7%, P < 0.001). Subgroup analysis showed that aspirin significantly reduced the risk of HCC by 19% in Asia (HR = 0.81, 95% CI 0.80–0.82, I 2 = 85.2%, P < 0.001) and by 33% (HR = 0.67, 95% CI 0.61–0.73, I 2 = 43.6%, P = 0.150) in Europe and the U.S with no significant difference. Moreover, in patients with HBV or HCV infection, aspirin reduced 19% and 24% of the risk of HCC, respectively. However, aspirin administration might increase risks of gastrointestinal bleeding in patients with chronic liver disease (HR = 1.14, 95% CI 0.99–1.31, I 2 = 0.0%, P = 0.712). Sensitivity analysis showed no significant difference of results after excluding individual studies, suggesting that the results were robust. Conclusion Aspirin may reduce the risk of HCC in both healthy population and patients with chronic liver disease. However, attention should be paid to adverse events such as gastrointestinal bleeding in patients with chronic liver disease

Oil Flow Analysis in the Maritime Silk Road Region Using AIS Data

Monitoring maritime oil flow is important for the security and stability of energy transportation, especially since the &ldquo;21st Century Maritime Silk Road&rdquo; (MSR) concept was proposed. The U.S. Energy Information Administration (EIA) provides public annual oil flow data of maritime oil chokepoints, which do not reflect subtle changes. Therefore, we used the automatic identification system (AIS) data from 2014 to 2016 and applied the proposed technical framework to four chokepoints (the straits of Malacca, Hormuz, Bab el-Mandeb, and the Cape of Good Hope) within the MSR region. The deviations and the statistical values of the annual oil flow from the results estimated by the AIS data and the EIA data, as well as the general direction of the oil flow, demonstrate the reliability of the proposed framework. Further, the monthly and seasonal cycles of the oil flows through the four chokepoints differ significantly in terms of the value and trend but generally show an upward trend. Besides, the first trough of the oil flow through the straits of Hormuz and Malacca corresponds with the military activities of the U.S. in 2014, while the second is owing to the outbreak of the Middle East Respiratory Syndrome in 2015

A Concave Hull Methodology for Calculating the Crown Volume of Individual Trees Based on Vehicle-Borne LiDAR Data

Crown volume is an important tree factor used in forest surveys as a prerequisite for estimating biomass and carbon stocks. This study developed a method for accurately calculating the crown volume of individual trees from vehicle-borne laser scanning (VLS) data using a concave hull by slices method. CloudCompare, an open-source three-dimensional (3D) point cloud and mesh processing software package, was used with VLS data to segment individual trees from which single tree crowns were extracted by identifying the first branch point of the tree. The slice thickness and number to be fitted to the canopy point cloud were adaptively determined based on the change rate in area with height, with the area of each slice calculated using the concave hull algorithm with portions of the crown regarded as truncated cones. The overall volume was then calculated as the sum of all sub-volumes. The proposed method was experimentally validated on 30 urban trees by comparing the crown volumes calculated using the proposed method with those calculated using five existing methods (manual measurement, 3D convex hull, 3D alpha shape, convex hull by slices, and voxel-based). The proposed method produced the smallest average crown volume. Gaps and holes in the point cloud were regarded as part of the crown by the manual measurement, 3D convex hull, and convex hull by slices method, resulting in the calculated volume being higher than the true value; the proposed method reduced this effect. These results indicate that the concave hull by slices method can more effectively calculate the crown volume of a single tree from VLS data

Integrating Island Spatial Information and Integer Optimization for Locating Maritime Search and Rescue Bases: A Case Study in the South China Sea

Maritime search and rescue (SAR) operations are critical for ensuring safety at sea. Islands have been considered as feasible solutions for the construction of new maritime SAR bases to improve the capacity of SAR operations in remote sea areas. This paper proposes a new framework, based on island spatial information, for determining the optimal locations for maritime SAR bases. The framework comprises four steps. First, candidate islands for the construction of maritime SAR bases are selected. Second, the potential rescue demand is estimated by employing ship location data and marine incident data. In the third step, the response time from candidate islands to any site at sea is calculated, with explicit consideration of the impact of sea conditions on the ship&rsquo;s speed. Fourth, the final island locations are proposed by solving the maximal covering location problem (MCLP). The proposed framework was applied to the South China Sea. The results showed that there would be a decrease of 1.09 h in terms of the mean access time for the South China Sea if the six selected island bases were constructed, whilst the primary coverage increased from 62.63% to 80.02% when using a 6-hour threshold. This new framework is expected to contribute to improvements in safety at sea and should be applicable to any sea area where the construction of island rescue bases is being considered

Super-resolution reconstruction of GOSAT CO2 products using bicubic interpolation

Satellites provide global long-time series of spatio-temporal continuous CO2 observations. However, it is difficult to be applied to the study of small-scale carbon cycle because of its low spatial resolution. In this paper, the Greenhouse Gases Observing SATellite (GOSAT) XCO2 data are super-resolution reconstructed using bicubic interpolation, which improved the spatial resolution from 2.5° to 0.5°. CO2 measurements from ten selected TCCON sites are used to compare with the reconstructed GOSAT. Further, the high accuracy Orbiting Carbon Observatory-2 (OCO-2) data analysed by the combination of geographical grid statistics and kriging is used to evaluate the reconstructed data. The results show that compared with the original GOSAT data, the reconstructed GOSAT data not only improves the spatial resolution but also has little loss of the average accuracy. The mean error of original data has significant seasonal fluctuations with a peak from February to March and a trough from June to July

Assessment of soil erosion and its driving factors in the Huaihe region using the InVEST-SDR model

Aiming to provide a scientific basis for the prevention and control of soil erosion in the Huaihe region, this study uses the InVEST-SDR model to estimate the temporal and spatial changes of soil erosion and soil conservation in the Huaihe region in 2010, 2015 and 2020, and the driving factors are evaluated and quantified using Random Forest and Geodetector, respectively. The major findings are as follows: (1) From 2010 to 2020, soil loss and soil retention in the Huaihe region gradually intensified, while the spatial distribution trend was consistent from year to year. (2) The results from Random Forest and Geodetector show that changes in soil loss and soil retention are mainly influenced by slope and rainfall. (3) The steepness and length of slopes are the most influencing factors for soil erosion. Soil loss and soil retention vary widely between different land uses. Forests play an important role in soil conservation

The Verification of Land Cover Datasets with the Geo-Tagged Natural Scene Images

Land cover is important for global change studies, and its accuracy and reliability are usually verified by field sampling, which costs a lot. A method was proposed for the verification of land cover datasets with the geo-tagged natural scene images using a convolutional neural network. The nature scene images were firstly collected from the Land Use and Cover Area frame Survey (LUCAS) and global crowdsourcing images platform Flickr, then classified according to the Land Cover Classification System. The Nature Scene Image Classification (NSIC) model based on the GoogLeNet Inception network for recognition of natural scene images was then constructed. Finally, in the UK, as a verification area, the European Space Agency Climate Change Initiative Land Cover (ESA CCI-LC) datasets and the Global land-cover product with fine classification system (GLC-FCS) were verified using the NSIC-Inception model with the nature scene image set. The verification results showed that the overall accuracy verified by LUCAS was very close to the accuracy of the land cover product, which was 94.41% of CCI LC and 92.89% of GLC-FCS, demonstrating the feasibility of using geo-tagged images classified by the NSIC model. In addition, the VGG16 and ResNet50 were compared with GoogLeNet Inception. The differences in verification between LUCAS and Flickr images were discussed regarding the image&rsquo;s quantity, the spatial distribution, the representativeness, and so on. The uncertainties of verification arising from differences in the spatial resolution of the different datasets were explored by CCI LC and GCL-FCS. The application of the method has great potential to support and improve the efficiency of land cover verification

Unprecedented Boron-Functionalized Carborane Derivatives by Facile and Selective Cobalt-Induced B–H Activation

The 16-electron complex CpCoS₂C₂B₁₀H₁₀ (<b>1</b>) is found to react with the alkynes HCCC­(O)­R [R = methyl (Me), phenyl (Ph), styryl (St), ferrocenyl (Fc)] at ambient temperature to give two types of 17-electron cobalt complexes <b>2a</b>–<b>d</b> and <b>3a</b>–<b>d</b> containing unique B(3)/B(6)-norbornyl carborane moieties. A formation mechanism via a tandem sequence of metal-induced B–H activation, B–Cp formation, Cp delivery and Diels–Alder addition is proposed on the basis of DFT calculations. The reactivity of these paramagnetic 17-electron complexes has been studied: Exposed to a combination of air, moisture and silica, complexes <b>2a</b>–<b>d</b> undergo alkyl C–S cleavage to give 16-electron complexes <b>4a</b>–<b>c</b> containing a boron-norbornadienyl moiety, and simultaneous carboranyl C–S cleavage to afford cobalt-free carborane derivatives <b>5a</b>–<b>d</b> containing a boron-norbornyl unit. Both <b>2a</b>–<b>d</b> and <b>3a</b>–<b>d</b> allow further alkyne insertion into the Co–S bond to generate cobalt-free boron–norbornyl carborane derivatives (<i>Z</i>/<i>E</i>)-<b>7a</b>–<b>d</b> and (<i>Z</i>/<i>E</i>)-<b>8a</b>–<b>d</b>, both containing a vinyl sulfido group. Addition of AlCl₃ not only promotes the conversion of <b>2a</b>–<b>d</b>, but also leads predominantly to (<i>E</i>)-<b>9a</b>–<b>d</b> as retro-Diels–Alder products. Upon heating, the isomerization from <i>E</i> to <i>Z-</i>configuration of the vinyl group and reorganization of the norbornyl moiety of (<i>Z</i>/<i>E</i>)-<b>7a</b>–<b>d</b> occur to lead to (<i>Z</i>)-<b>9a</b>–<b>d</b> as well as the unexpected [1,2]-H shifted products (<i>Z</i>)-<b>10b</b>,<b>c</b>. Thus, the 17-electron complexes <b>2a</b>–<b>d</b> and <b>3a</b>–<b>d</b> serve as intermediates for synthesis of variety of boron-functionalized carborane derivatives. In this study, efficient routes have been developed through cobalt-mediated B–H activation to prepare boron-functionalized carborane derivatives that are unavailable by conventional routes