Warburg effect is a dominant phenotype of most cancer cells. Here we show that this phenotype depends on its environment. When cancer cells are under regular culture condition, they show Warburg effect; whereas under lactic acidosis, they show a nonglycolytic phenotype, characterized by a high ratio of oxygen consumption rate over glycolytic rate, negligible lactate production and efficient incorporation of glucose carbon(s) into cellular mass. These two metabolic modes are intimately interrelated, for Warburg effect generates lactic acidosis that promotes a transition to a nonglycolytic mode. This dual metabolic nature confers growth advantage to cancer cells adapting to ever changing microenvironment.

Solid tumours are dependent on glucose, but are generally glucose-deprived due to poor vascularization. Nevertheless, cancer cells can generally survive glucose deprivation better than their normal counterparts. Thus, to render cancer cells sensitive to glucose depletion may potentially provide an effective strategy for cancer intervention. We propose that lactic acidosis, a tumour microenvironment factor, may allow cancer cells to develop resistance to glucose deprivation-induced death, and that disruption of lactic acidosis may resume cancer cells' sensitivity to glucose depletion. Lactic acidosis, lactosis, or acidosis was generated by adding pure lactic acid, sodium lactate, or HCl to the culture medium. Cell death, cell cycle, autophagy, apoptosis, and gene expression profiling of the surviving cancer cells under glucose deprivation with lactic acidosis were determined. Under glucose deprivation without lactic acidosis, 90% of 4T1 cancer cells died within a single day; in a sharp contrast, under lactic acidosis, 90% of 4T1 cells died in a period of 10 days, with viable cells identified even 65 days after glucose was depleted. Upon glucose restoration, surviving cells resumed proliferation. Lactic acidosis also significantly extended survival of other cancer cells under glucose deprivation. G1/G0 arrest, autophagy induction, and apoptosis inhibition were tightly associated with lactic acidosis-mediated resistance to glucose deprivation. Lactosis alone had no effect on cell survival under glucose deprivation; acidosis alone can prolong cell survival time but is not as potent as lactic acidosis. Thus, the ability of cancer cells to resist glucose deprivation-induced cell death is conferred, at least in part, by lactic acidosis, and we envision that disrupting the lactic acidosis may resume the sensitivity of cancer cells to glucose deprivation.

Metal–organic frameworks (MOFs) are promising hosts for catalytic active sites due to their adjustable porosity and framework chemistry. Strategies to improve synergistic effects between the installed sites and the parent MOF are highly desired. Herein, a facile and rapid method for the preparation of xAg@ZIF-8 materials was reported. The materials were systematically characterized and used as catalysts for carboxylation of terminal alkynes via direct insertion of CO2 to the C­(sp)–H bond (CTACO2). It was found that the integrity of the ZIF-8 structure could be retained upon Ag loading, but short-range crystalline ordering was modified. Two types Ag species could be installed, namely, highly dispersed Ag­(I) in the backbone (AgHD) and aggregated Ag(0) nanoparticles on the outer surface (AgNP). The AgNP sites are highly effective for the activation of terminal alkynes due to its high accessibility, while the AgHD-modified ZIF-8 framework worked as a CO2 reservoir with enhanced affinity. Combination of these factors translated to high activity in the CTACO2 process, the measured turnover frequency and time yield are among the highest among most heterogeneous catalysts.

PurposeCancer drug resistance is a major obstacle for the success of chemotherapy. Since most clinical anticancer drugs could induce drug resistance, it is desired to develop candidate drugs that are highly efficacious but incompetent to induce drug resistance. Numerous previous studies have proven that shikonin and its analogs not only are highly tumoricidal but also can bypass drug-transporter and apoptotic defect mediated drug resistance. The purpose of this study is to investigate if or not shikonin is a weak inducer of cancer drug resistance.Experimental DesignDifferent cell lines (K562, MCF-7, and a MDR cell line K562/Adr), after repeatedly treated with shikonin for 18 months, were assayed for drug resistance and gene expression profiling.ResultsAfter 18-month treatment, cells only developed a mere 2-fold resistance to shikonin and a marginal resistance to cisplatin and paclitaxel, without cross resistance to shikonin analogs and other anticancer agents. Gene expression profiles demonstrated that cancer cells did strongly respond to shikonin treatment but failed to effectively mobilize drug resistant machineries. Shikonin-induced weak resistance was associated with the up-regulation of βII-tubulin, which physically interacted with shikonin.ConclusionTaken together, apart from potent anticancer activity, shikonin and its analogs are weak inducers of cancer drug resistance and can circumvent cancer drug resistance. These merits make shikonin and its analogs potential candidates for cancer therapy with advantages of avoiding induction of drug resistance and bypassing existing drug resistance.

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CO2 capture, utilization, and storage (CCUS) technology is a rare option for the large-scale use of fossil fuels in a low-carbon way, which will definitely play a part in the journey towards carbon neutrality. Within the CCUS nexus, CCU is especially interesting because these processes will establish a new “atmosphere-to-atmosphere” carbon cycle and thus indirectly offer huge potential in carbon reduction. This study focuses on the new positioning of CCUS in the carbon neutrality scenario and aims to identify potential cutting-edge/disruptive CCU technologies that may find important application opportunities during the decarbonization of the energy and industrial system. To this end, direct air capture (DAC), flexible metal-framework materials (MOFs) for CO2 capture, integrated CO2 capture and conversion (ICCC), and electrocatalytic CO2 reduction (ECR) were selected, and their general introduction, the importance to carbon neutrality, and most up-to-date research progress are summarized.

Background Major adverse cardiac event (MACE) prediction plays a key role in providing efficient and effective treatment strategies for patients with acute coronary syndrome (ACS) during their hospitalizations. Existing prediction models have limitations to cope with imprecise and ambiguous clinical information such that clinicians cannot reach to reliable MACE prediction results for individuals. Methods To remedy it, this study proposes a hybrid method using Rough Set Theory (RST) and Dempster-Shafer Theory (DST) of evidence. In details, four state-of-the-art models, including one traditional ACS risk scoring model, i.e., GRACE, and three machine learning based models, i.e., Support Vector Machine, L 1 -Logistic Regression, and Classification and Regression Tree, are employed to generate initial MACE prediction results, and then RST is applied to determine the weights of the four single models. After that, the acquired prediction results are assumed as basic beliefs for the problem propositions and in this way, an evidential prediction result is generated based on DST in an integrative manner. Results Having applied the proposed method on a clinical dataset consisting of 2930 ACS patient samples, our model achieves 0.715 AUC value with competitive standard deviation, which is the best prediction results comparing with the four single base models and two baseline ensemble models. Conclusions Facing with the limitations in traditional ACS risk scoring models, machine learning models and the uncertainties of EHR data, we present an ensemble approach via RST and DST to alleviate this problem. The experimental results reveal that our proposed method achieves better performance for the problem of MACE prediction when compared with the single models.