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ABSTRACTIntroductionHepatocellular carcinoma (HCC) accounts for 85% of liver cancer cases and is the third leading cause of cancer death. Regorafenib is a multi-target inhibitor that dramatically prolongs progression-free survival in HCC patients who have failed sorafenib therapy. However, one of the primary factors limiting regorafenib’s clinical utilization is toxicity. Using Clinical Trials.gov and PubMed, we gathered clinical data on regorafenib and conducted a extensive analysis of the medication’s adverse reactions and mechanisms. Next, we suggested suitable management techniques to improve regorafenib’s effectiveness.Areas coveredWe have reviewed the mechanisms by which regorafenib-induced toxicity occurs and general management strategies through clinical trials of regorafenib. Furthermore, by examining the literature on regorafenib and other tyrosine kinase inhibition, we summarized the mechanics of the onset of regorafenib toxicity and mechanism-based intervention strategies by reviewing the literature related to regorafenib and other tyrosine kinase inhibition.Expert opinionOne of the primary factors restricting regorafenib’s clinical utilization and combination therapy is its toxicity reactions. To optimize regorafenib treatment regimens, it is especially important to further understand the specific toxicity mechanisms of regorafenib as a multi-kinase inhibitor.

The α-Fe2O3@SiO2reddish pigments with core–shell structure were successfully prepared by hydrothermal and Stöber methods. The structure, morphology, and chromaticity of the synthesized pigments were characterized by XRD, SEM, TEM, FTIR, XPS, and colorimetry. The results indicated that the as-prepared pigments have the characteristics of narrow particle size distribution, high dispersion, and good sphericity. The α-Fe2O3@SiO2reddish pigments were uniform and well dispersed in solution. In addition, the pigments with different shell thickness were also prepared, and the effect of shell thickness on the color performance of the pigments was discussed.

Visceral adiposity is of greater risk than obesity in s.c. adipose tissue for diabetes and cardiovascular disease. Its pathogenesis remains unclear, but it is associated with extracellular matrix (ECM) remodeling. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are a family of secreted zinc-dependent metalloproteinases that play crucial roles in development and various diseases because of their ECM remodeling activity. ADAMTS18 is an orphan ADAMTS whose function and substrate remain unclear. Herein, we showed that Adamts18 mRNA was abundantly expressed in visceral (gonadal) white adipose tissue (vWAT) during the early stage of development after birth. Adamts18knockout (KO) mice showed increased body fat percentage and larger adipocyte size in vWAT relative to wild-type littermates. These findings may be partly attributed to ECM remodeling, especially increased expression of laminin 1 and adipokine thrombospondin 1 in vWAT. Attenuated extracellular signal–regulated kinase 1 and 2 activity, along with increased expression of adipocyte-specific transcription factors peroxisome proliferator-activated receptor-γ, CCAAT/enhancer binding protein β, and marker gene Fabp4, was detected in vWAT of Adamts18KO mice. Furthermore, Adamts18KO mice showed early metabolic syndrome, including hyperlipidemia, blood glucose metabolic disorder, and hypertension. ADAMTS18 deficiency promotes atherosclerosis in apolipoprotein E–deficient mice. These results indicate a novel function of ADAMTS18 in vWAT development and associated metabolic disorders.

Cadmium (Cd) is an important element for the assessment of environmental pollution. An accurate and high throughput method involving slurry sampling electrothermal atomic absorption spectrometry (ETAAS) was developed to detect trace Cd content in geological samples. After sonication of the sample with 0.5% v/v HNO3and 0.5% v/v Triton X-100 solution, the slurry was directly introduced into a graphite atomizer and detected by AAS. This simple method was shown to take 80% less time, and resulted in 90% less reagent waste than the conventional acid digestion method. Under optimized conditions (sample size ≤ 75 μm, sonication time: 20 min, pyrolysis temperature: 450 °C, and atomization temperature: 1600 °C), the characteristic mass and limit of detection for Cd were 0.8 pg and 0.002 μg g−1, respectively. The proposed method was applied to the determination of Cd in 86 soil, sediment, and rock standard reference materials (SRMs). The results for 78 of these materials were in good agreement with the reference values. The Cd levels in five limestone SRMs (GUI-1, GUI-2, DIAN-1, DIAN-2, and DIAN-3) and one clay SRM (GBW03103) were reported for the first time. The proposed method shows great potential for the direct determination of trace Cd in various geological samples.

Collaborative problem-solving (CPS) engages students in solving ill-structured problems, creating group knowledge, and developing self-regulation and collaboration skills. Different scaffoldings, such as minimal-guided, task-oriented, and idea-oriented, can be used to facilitate students’ CPS activities, but their effects have not been comprehensively explored. In this research, we use minimally-guided, task-oriented, and idea-oriented scaffoldings to promote Chinese university students’ online CPS activities and use a multi-method approach to analyze the effects of three scaffolding on collaboration. The results indicate relatively complicated collaborative processes and outcomes supported by three scaffoldings. It is initially shown that the idea-centered scaffolding strengthens students’ connections between idea contribution, metacognitive regulation, and knowledge artifact behaviors, which are critical factors for improving the CPS quality. Based on the empirical research results, we conclude that future instructional design should carefully consider the educational culture, time constraint, and student regulation to better facilitate CPS practices.