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Abstract Non-small cell lung cancer (NSCLC) presents a global health challenge due to its low five-year survival rates, underscoring the need for novel therapeutic strategies. Our research explored the synergistic mechanisms of syrosingopine and UK-5099 in treating NSCLC. In vitro experiments showed that the combination of syrosingopine and UK-5099 significantly synergized to suppress NSCLC proliferation. Further experiments revealed that this combination induced cell cycle arrest and promoted apoptosis in NSCLC cells. In vivo experiments demonstrated that the combination of syrosingopine and UK-5099 markedly inhibited tumor growth. Mechanistic studies revealed that this drug combination promoted mitochondrial damage by inducing lactate accumulation and oxidative stress. Additionally, the combination triggered an integrated stress response (ISR) through the activation of heme-regulated inhibitor kinase (HRI). Importantly, our findings suggested that the synergistic suppression of NSCLC by syrosingopine and UK-5099 was dependent on ISR activation. In summary, our study proposed a promising therapeutic approach that involved the combination of Syrosingopine and UK-5099 to activate ISR, significantly hindering NSCLC growth and proliferation.

In view of the poisonous nature of Cr(VI), it is of great significance to explore an effective and environmentally friendly method to remove Cr(VI). The potential synergistic effects of Cr(VI) reduction by iron-rich biochar and Pseudomonas aeruginosa (PA) were systematically explored in this study. Significantly, in association with PA, the biochar produced by pyrolyzing iron-rich sludge at 300 °C (Fe-300) was more efficient at reducing Cr(VI) than that pyrolyzed at 800 °C (Fe-800), and the performance was always better than biochar or PA alone. For instance, upon an incubation for 20 days, the Cr(VI) removal efficiencies in the groups Cr + Fe-300 + PA, Cr + Fe-800 + PA, Cr + Fe-300, Cr + Fe-800 and Cr + PA were 80%, 19%, 51%, 0% and 35%, respectively. Through further analyses of phosphorus (P) and iron species as well as the cell extraction components of PA, the high Cr(VI) efficiency in Fe-300 + PA was mainly attributed to two aspects: (1) more P (mainly in the form of ortho phosphorus) was released from Fe-300 by PA compared to that from Fe-800, and the released P may react with Fe(II), Fe(III), Cr(VI) and Cr(III) ions to form precipitation; (2) cytoplasmic and periplasmic proteins as well as membrane proteins extracted from PA further helped to reduce Cr(VI). A novel approach for reducing Cr(VI) may be proposed by using the potential synergistic effects of iron-rich biochar and PA from this study.

Arsenic-alkali residue (AAR) from antimony smelting is highly hazardous due to its ready leachability of As, seeking for proper disposal such as stabilization treatment. However, As stabilization in AAR would be challenging due to the high content of coexisting soluble carbonate. This study conducted the stabilization treatments of AAR by ferrous sulfate and lime, respectively, and revealed the significant influence of coexisting carbonate. It was found that ferrous sulfate was more efficient than lime, which required only one-tenth of dosages of lime to reduce the As leaching concentration from 915 mg/L to a level below 2.5 mg/L to meet the Chinese regulatory limit. The combining qualitative and quantitative analyses based on XRD, SEM–EDS, and thermodynamic modeling suggested that the formation of insoluble arsenate minerals, ferrous arsenate or calcium arsenate, was the predominant mechanism for As stabilization in the two treatment systems, and their efficiency difference was primarily attributed to the coexisting carbonate, which had a slight effect on ferrous arsenate but severely obstructed calcium arsenate formation. Moreover, the examination of As leaching concentrations in 1-year-cured samples indicated that the long-term stability of ferrous sulfate treatment was far superior to that of lime treatment. This study provides ferrous salts as a promising and green scheme for stabilization treatment of AAR as well as other similar As-bearing solid wastes with coexisting soluble carbonate. Keywords: Arsenic-alkali residue, Arsenic stabilization, Ferrous sulfate, Lime, Arsenate minerals, Coexisting soluble carbonate

The prediction of toxicological interactions and hormesis of chemical mixtures is important because organisms are mostly exposed to numerous contaminants and typically to low dose of these mixtures, and it is still a challenge. Although many models have been developed to predict the mixture toxicities such as concentration addition (CA) and independent action (IA), they cannot solve these challenges perfectly. This study has developed an improved inverse distance weighted (IDW) interpolation for prediction of the mixture toxicities. IDW uses the mixture and the single compound as scatter points in space, and the space can be constructed by the concentration axes of various components in the mixture system. Some known mixtures (or the single compound) closest to the unknown mixture are selected as interpolation nodes. To be more accurate in calculation, a new normalization method for concentration has been proposed through dividing the concentration of the mixture and the single compound by the respective EC50 values. Sixteen binary mixture systems are selected for leave-one-out cross-validation and three binary mixture systems are selected for external validation. The results show that the accuracy of IDW is ≥95% for three types of mixtures including no hormetic component, one hormetic component (show no toxicological interaction), and two hormetic components. The IDW also show higher prediction accuracy than that of CA and IA. The IDW developed in this study can be used to predict the toxicity of various mixture systems, thus providing predictive information for chemical mixtures risk assessment. Keywords: Combined toxicity, Euclidean distance, Multi-component, Normalization, Cross validation

Microbial fuel cells (MFCs) are remarkable "green energy" devices that exploit microbes to generate electricity from organic compounds. MFC devices currently being used and studied do not generate sufficient power to support widespread and cost-effective applications. Hence, research has focused on strategies to enhance the power output of the MFC devices, including exploring more electrochemically active microbes to expand the few already known electricigen families. However, most of the MFC devices are not compatible with high throughput screening for finding microbes with higher electricity generation capabilities. Here, we describe the development of a microfabricated MFC array, a compact and user-friendly platform for the identification and characterization of electrochemically active microbes. The MFC array consists of 24 integrated anode and cathode chambers, which function as 24 independent miniature MFCs and support direct and parallel comparisons of microbial electrochemical activities. The electricity generation profiles of spatially distinct MFC chambers on the array loaded with Shewanella oneidensis MR-1 differed by less than 8%. A screen of environmental microbes using the array identified an isolate that was related to Shewanella putrefaciens IR-1 and Shewanella sp. MR-7, and displayed 2.3-fold higher power output than the S. oneidensis MR-1 reference strain. Therefore, the utility of the MFC array was demonstrated.