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Cancer is a top-ranked life-threatening disease with intratumor heterogeneity. Tumor heterogeneity is associated with metastasis, relapse, and therapy resistance. These factors contribute to treatment failure and an unfavorable prognosis. Personalized tumor models faithfully capturing the tumor heterogeneity of individual patients are urgently needed for precision medicine. Advances in stem cell culture have given rise to powerful organoid technology for the generation of in vitro three-dimensional tissues that have been shown to more accurately recapitulate the structures, specific functions, molecular characteristics, genomic alterations, expression profiles, and tumor microenvironment of primary tumors. Tumoroids in vitro serve as an important component of the pipeline for the discovery of potential therapeutic targets and the identification of novel compounds. In this review, we will summarize recent advances in tumoroid cultures as an excellent tool for accurate cancer modeling. Additionally, vascularization and immune microenvironment modeling based on organoid technology will also be described. Furthermore, we will summarize the great potential of tumor organoids in predicting the therapeutic response, investigating resistance-related mechanisms, optimizing treatment strategies, and exploring potential therapies. In addition, the bottlenecks and challenges of current tumoroids will also be discussed in this review.

Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) is a negative modulatory signaling pathway for activation of T cell. It is acknowledged that PD-1/PD-L1 axis plays a crucial role in the progression of tumor by altering status of immune surveillance. As one of the most promising immune therapy strategies, PD-1/PD-L1 inhibitor is a breakthrough for the therapy of some refractory tumors. However, response rate of PD-1/PD-L1 inhibitors in overall patients is unsatisfactory, which limits the application in clinical practice. Therefore, biomarkers which could effectively predict the efficacy of PD-1/PD-L1 inhibitors are crucial for patient selection. Biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, density of tumor infiltrating lymphocyte (TIL), tumor mutational burden, and mismatch-repair (MMR) deficiency, have been noticed to associate with treatment effect of anti-PD-1/anti-PD-L1 therapy. Furthermore, gut microbiota, circulating biomarkers, and patient previous history have been found as valuable predictors as well. Therefore establishing a comprehensive assessment framework involving multiple biomarkers would be meaningful to interrogate tumor immune landscape and select sensitive patients.

CD44, a complex transmembrane glycoprotein, exists in multiple molecular forms, including the standard isoform CD44s and CD44 variant isoforms. CD44 participates in multiple physiological processes, and aberrant expression and dysregulation of CD44 contribute to tumor initiation and progression. CD44 represents a common biomarker of cancer stem cells, and promotes epithelial-mesenchymal transition. CD44 is involved in the regulation of diverse vital signaling pathways that modulate cancer proliferation, invasion, metastasis and therapy-resistance, and it is also modulated by a variety of molecules in cancer cells. In addition, CD44 can serve as an adverse prognostic marker among cancer population. The pleiotropic roles of CD44 in carcinoma potentially offering new molecular target for therapeutic intervention. Preclinical and clinical trials for evaluating the pharmacokinetics, efficacy and drug-related toxicity of CD44 monoclonal antibody have been carried out among tumors with CD44 expression. In this review, we focus on current data relevant to CD44, and outline CD44 structure, the regulation of CD44, functional properties of CD44 in carcinogenesis and cancer progression as well as the potential CD44-targeting therapy for cancer management.

HighlightsThe size of metal organic frameworks (MOFs) derivatives was manipulated by a spatial confined growth strategy.Dielectric polarization is the dominant dissipation mechanism due to the phase hybridization based on size dependent oxidation motion.The specific reflection loss of synthesized Co/Co3O4 hollow carbon nanocages surpasses most reported MOFs derived counterparts for practical microwave absorption applications.Precisely reducing the size of metal-organic frameworks (MOFs) derivatives is an effective strategy to manipulate their phase engineering owing to size-dependent oxidation; however, the underlying relationship between the size of derivatives and phase engineering has not been clarified so far. Herein, a spatial confined growth strategy is proposed to encapsulate small-size MOFs derivatives into hollow carbon nanocages. It realizes that the hollow cavity shows a significant spatial confinement effect on the size of confined MOFs crystals and subsequently affects the dielectric polarization due to the phase hybridization with tunable coherent interfaces and heterojunctions owing to size-dependent oxidation motion, yielding to satisfied microwave attenuation with an optimal reflection loss of −50.6 dB and effective bandwidth of 6.6 GHz. Meanwhile, the effect of phase hybridization on dielectric polarization is deeply visualized, and the simulated calculation and electron holograms demonstrate that dielectric polarization is shown to be dominant dissipation mechanism in determining microwave absorption. This spatial confined growth strategy provides a versatile methodology for manipulating the size of MOFs derivatives and the understanding of size-dependent oxidation-induced phase hybridization offers a precise inspiration in optimizing dielectric polarization and microwave attenuation in theory.

During the past decade, the three-dimensional organoid technology has sprung up and become more and more popular among researchers. Organoids are the miniatures of in vivo tissues and organs, and faithfully recapitulate the architectures and distinctive functions of a specific organ. These amazing three-dimensional constructs represent a promising, near-physiological model for human cancers, and tremendously support diverse potential applications in cancer research. Up to now, highly efficient establishment of organoids can be achieved from both normal and malignant tissues of patients. Using this bioengineered platform, the links of infection-cancer progression and mutation-carcinogenesis are feasible to be modeled. Another potential application is that organoid technology facilitates drug testing and guides personalized therapy. Although organoids still fail to model immune system accurately, co-cultures of organoids and lymphocytes have been reported in several studies, bringing hope for further application of this technology in immunotherapy. In addition, the potential value in regeneration medicine might be another paramount branch of organoid technology, which might refine current transplantation therapy through the replacement of irreversibly progressively diseased organs with isogenic healthy organoids. In conclusion, organoids represent an excellent preclinical model for human tumors, promoting the translation from basic cancer research to clinical practice. In this review, we outline organoid technology and summarize its applications in cancer research.

Under the background of the new development concept, compared with the absolute impacts, the relative impacts of climate change on agricultural growth deserve more attention. Based on the data from China for years 1991 and 2018, this paper uses historical fluctuations in temperature within cities to identify the heterogeneous effects on aggregate agricultural outcomes during farming and fallow periods. The results show that: first, as temperature rises reduce the economic growth rate of each agricultural sector, and the areas that are relatively vulnerable (i.e., areas where disposable income of farm households is below the sample mean) are more significantly affected by the negative impact of temperature rise; second, the impact of temperature rise on agricultural economic growth is mainly concentrated in the farming period, while the marginal damage of temperature rise is on a decreasing trend; third, the heterogeneous impact of temperature rise on agricultural economic growth during the agricultural fallow period is also not negligible. At the same time, its impact on agricultural economy is still in the primary stage, that is, its marginal damage tends to increase with the increase in temperature fluctuation. These results inform identifying the climate’s role in agricultural development and provide a theoretical and operational perspective for further optimizing the adaptive policy systems. With wide coverage of adaptive technology, we should pay more attention to the even distribution of technological dividends and continuously improve the coping ability of vulnerable groups.

Immune checkpoint inhibitors (ICIs) therapy is a novel strategy for cancer treatments in recent years. However, it was observed that most patients treated with ICIs could not get benefit from the therapy, which led to the limitation of clinical application. Motivated by potent and durable efficacy of ICIs, oncologists endeavor to explore the mechanisms of resistance to ICIs and increase the drug sensitivity. It is known that heterogeneity of gut microbiome in populations may result in different outcomes of therapy. In xenograft model, bacteria in gut have been proved as a crucial factor regulating immunotherapy efficacy. And the similar phenomenon was obtained in patients. In this review, we summarized relevant advancements about gut microbiome and ICIs. Furthermore, we focused on modulatory function of gut microbiome in ICIs therapy and possible antitumor mechanism of specific commensals in ICIs treatment. We propose that gut microbiome is an important predictive factor, and manipulation of gut microbiome is feasible to elevate response rate in ICIs therapy.

It is known that there are no primary odors that can represent any other odors with their combination. Here, we propose an alternative approach: “quasi” primary odors. This approach comprises the following condition and method: (1) within a collected dataset and (2) by the machine learning-based endpoint detection. The quasi-primary odors are selected from the odors included in a collected odor dataset according to the endpoint score. While it is limited within the given dataset, the combination of such quasi-primary odors with certain ratios can reproduce any other odor in the dataset. To visually demonstrate this approach, the three quasi-primary odors having top three high endpoint scores are assigned to the vertices of a chromaticity triangle with red, green, and blue. Then, the other odors in the dataset are projected onto the chromaticity triangle to have their unique colors. The number of quasi-primary odors is not limited to three but can be set to an arbitrary number. With this approach, one can first find “extreme” odors (i.e., quasi-primary odors) in a given odor dataset, and then, reproduce any other odor in the dataset or even synthesize a new arbitrary odor by combining such quasi-primary odors with certain ratios.

Organoid technology bridges the gap between conventional two-dimensional cell line culture and in vivo models. The near-physiological technology can virtually recapitulates organ development and human diseases, such as infectious diseases, genetic abnormality and even cancers. In addition, organoids can more accurately predict drug responses, and serve as an excellent platform for drug development, including efficacy evaluation, toxicity testing and pharmacokinetics analysis. Furthermore, organoids can also be exploited to explore the possible optimized treatment strategies for each individual patient. Besides, organoid technology is a promising strategy for regeneration medicine and transplantation use, which can overcome the deficiency in the supply of healthy donor tissues and inherent immunological rejection through establishing isogenic organoids from minuscule amounts of patient biopsies. Collectively, organoids hold enormous potential for clinical applications and bring basic research closer to clinical practice. In this review, we described common organoid lines, summarized the potential clinical applications, and outlined the current limitations.

The complex formation process of reconstructed soil triggers the high spatial variability of soil physical properties, for which traditional soil sampling methods are not applicable due to the destructive and time-consuming modes. Ground penetrating radar (GPR) can collect continuous and high-resolution data flexibly, but the technology has rarely been employed to detect reconstructed soil properties in opencast coalmine regions. This study explored the applicability and accuracy of GPR in measuring reconstructed soil bulk density (RSBD) in southern dump, expanded western dump, and internal dump of the Antaibao open-pit mine, China. The variations of RSBD and the relationships between the dielectric constant and RSBD were analyzed based on ring knife sampling weighing, GPR detection, variance analysis, and fitting analysis. The results showed that (1) RSBD exhibited significant variations in different dumps and at different depths of the same profile. (2) RSBD differences in different dumps could be qualitatively analyzed based on the large-amplitude signals in GPR images. (3) When the soil volume moisture content ranged from 15 to 25%, RSBD was found to be negatively correlated with the dielectric constant. GPR has the potential to be widely employed to detect RSBD in reclaimed lands, which can contribute to the development of non-destructive quality testing of land reclamation.