Broadband Tunable Optical Gain from Ecofriendly Semiconductor Quantum Dots with Near-Half-Exciton Threshold.

Optical gain in solution-processable quantum dots (QDs) has attracted intense interest toward next-generation optoelectronics; however, the development of optical gain in heavy-metal-free QDs remains challenging. Herein, we reveal that the ZnSe1-xTex-based QDs show excellent optical gain covering the violet to near-red regime. A new gain mechanism is established in the alloy QDs, which promotes a theoretically threshold-less optical gain thanks to the ultrafast carrier localization and suppression of ground-state absorption by the Te-derived isoelectronic state. Further, we disclose that the hot-carrier trapping represents the main culprit to exacerbate the gain performance. With the increase of Te-to-Se ratio, a sub-band-gap photoinduced absorption (PA) appears and extinguishes the optical gain. To overcome this issue, we modulate the inner ZnSe shell thickness, and the gain is recovered by reducing the overlap between the gain and PA regions in the Te-rich QDs. Our finding represents a significant step toward sustainable QD-based optoelectronics.

CD13 Induces Autophagy to Promote Hepatocellular Carcinoma Cell Chemoresistance Through the P38/Hsp27/CREB/ATG7 Pathway.

The chemoresistance of hepatocellular carcinoma (HCC) is a serious problem that directly hinders the effect of chemotherapeutic agents. We previously reported that Aminopeptidase N (CD13) inhibition can enhance the cytotoxic efficacy of chemotherapy agents. In the present study, we use liver cancer cells to explore the molecular mechanism accounting for the relationship between CD13 and chemoresistance. We demonstrate that CD13 overexpression activates the P38/heat shock protein 27/cAMP response element-binding protein (CREB) signaling pathway to limit the efficacy of cytotoxic agents. Moreover, blockade of P38 or CREB sensitizes HCC cells to 5-fluorouracil. Then we reveal that CREB binds to the autophagy related 7 (ATG7) promoter to induce autophagy and promote HCC cell chemoresistance. CD13 inhibition also downregulates the expression of ATG7, autophagy, and tumor cell growth in vivo. Overall, the combination a CD13 inhibitor and chemotherapeutic agents may be a potential strategy for overcoming drug resistance in HCC. SIGNIFICANCE STATEMENT: Our study demonstrates that Aminopeptidase N (CD13) promotes hepatocellular carcinoma (HCC) cell chemoresistance via the P38/heat shock protein 27/cAMP response element-binding protein (CREB) pathway. CREB regulates autophagy related 7 transcription and expression to induce autophagy. Our results collectively suggest that CD13 may serve as a potential target for overcoming HCC resistance.

Inhibition of the proliferation, migration, and invasion of human breast cancer cells by leucine aminopeptidase 3 inhibitors derived from natural marine products.

Leucine aminopeptidase 3 is involved in the progression and metastasis of several cancers. This study aimed to screen anti-tumor lead compounds targeting leucine aminopeptidase 3. The compounds' suppression effect on enzyme activity and anti-tumor activity were evaluated through a series of assays. Leucine aminopeptidase 3 overexpression K562 cells were used as an enzyme source to screen 43 natural marine compounds. Compounds 5 and 6 exhibited high suppression effect on leucine aminopeptidase 3 activity. Cell activity tests indicated that both compounds have an anti-proliferative effect on triple-negative breast cancer cells. Wound healing assay and transwell invasion assay showed that both compounds could inhibit the migration and invasion of breast cancer cells. Immunoblot analysis exhibited that both compounds could downregulate the expression of metastasis-related proteins fascin and matrix metalloproteinase-2/9. A molecular dynamic simulation process was applied to discover the key features of compounds 5 and 6 in binding to leucine aminopeptidase 3 active site. This study described the anti-tumor effects of two leucine aminopeptidase 3 small molecule inhibitors. Taken together, compounds 5 and 6 could be used as anti-tumor lead compounds targeting leucine aminopeptidase 3.

Biofluid biomarkers for Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease, with a complex pathogenesis and an irreversible course. Therefore, the early diagnosis of AD is particularly important for the intervention, prevention, and treatment of the disease. Based on the different pathophysiological mechanisms of AD, the research progress of biofluid biomarkers are classified and reviewed. In the end, the challenges and perspectives of future research are proposed.

Bio-organic fertilizer promoted phytoremediation using native plant leymus chinensis in heavy Metal(loid)s contaminated saline soil.

Heavy metal(loid)s (HMs) contaminated saline soil appeared around the world, however, remediation regarding these collected from field conditions remains unknown. Native plants cultivation and bio-organic fertilizer (BOF) application were two efficient tools for soil amelioration. Herein, a pot experiment was conducted to examine the feasibility of a native plant (Leymus chinensis) for phytoremediation, and investigate the impacts of lignite based bio-organic fertilizer (LBOF) and manure based bio-organic fertilizer (MBOF) on phytoremediation of the soil contaminated by Pb, Cd, As, Zn, Cu, Ca2+, and SO42-. The results demonstrated the effectiveness of L. chinensis and highlighted the positive impacts of BOF according to the improved plant growth, HMs phytostabilization, salt removal, and soil properties. LBOF and MBOF changed soil microbiome to assist phytoremediation in addition to physiological modulation. Having enhanced fungal and bacterial richness respectively, LBOF and MBOF recruited various plant growth promoting rhizobacteria with different functions, and shifted microbial co-occurrence networks and keystone taxa towards these different but beneficial forms. Structural equation models comprehensively reveled the strategy discrepancy of LBOF and MBOF to regulate the plant biomass, HMs uptake, and soil salt. In summary, L. chinensis coupled with BOF, especially LBOF, was a effective strategy to remediate HMs contaminated saline soil.

Vimentin plays an important role in the promotion of breast cancer cell migration and invasion by leucine aminopeptidase 3.

Breast cancer is a common type of cancer in females. Our previous studies indicated that leucine aminopeptidase 3 (LAP3) promotes migration and invasion of breast cancer cells. Vimentin is a mesenchymal marker, and its upregulation represents the promotion of epithelial-mesenchymal transition. In this study, we found that LAP3 and vimentin were highly expressed in breast cancer tissues, and the overexpression of LAP3 in breast cancer cells promoted the expression of vimentin. Western blot analysis indicated that the overexpression of LAP3 upregulated the phosphorylation of Erk1/2. MEK inhibitor PD98059 downregulated the expression of vimentin, matrix metalloproteinase-2/9 (MMP-2/9), and fascin through the inhibition of Erk1/2 activity. We hypothesized that LAP3 promoted tumor migration and invasion by upregulating vimentin. The knockdown of vimentin resulted in the inhibited migration and invasion of MDA-MB-231 and MDA-MB-468 cells. The expression of MMP-2/9 and fascin could also be downregulated. In conclusion, vimentin might play an important role in the promotion of breast cancer metastasis by LAP3.

A new method to evaluate the enzyme-suppressing activity of a leucine aminopeptidase 3 inhibitor.

The expression of leucine aminopeptidase 3 (LAP3) is associated with the prognosis for and malignant transformation of many types of tumors. Therefore, a LAP3 inhibitor may represent a new strategy for cancer therapy. Evaluating the suppression of enzyme activity by an LAP3 inhibitor is essential. Right now, leucine aminopeptidases (LAPs) purified from the porcine kidneys are the only enzymes that can be used to evaluate the suppression of enzyme activity by an LAP3 inhibitor. This approach cannot accurately reflect the suppression of human LAP3 by an inhibitor. The current study developed a new method with which to evaluate the suppression of enzyme activity by an LAP3 inhibitor. Total protein from K562 cells seldom catalyzed the LAP3 substrate. A lentivirus was used to induce K562 cells to overexpress LAP3 (K562-LAP3). After puromycin screening, flow cytometry data indicated that 98.8% of cells expressed green fluorescent protein. The expression of LAP3 in K562-LAP3 cells was also assessed using Western blotting. K562-LAP3 cells were lysed with ultrasonication. Total protein was used as an enzyme source and L-leucine p-nitroaniline hydrochloride was used as a substrate to measure enzyme activity. Total protein from K562-LAP3 cells catalyzed the substrate more than that from K562 cells did. The LAP3 inhibitor ubenimex was used as a positive control to evaluate the suppression of LAP3 enzyme activity. Results indicated that ubenimex significantly inhibited the enzyme activity of LAP3. This approach provides a convenient and accurate way to evaluate the suppression of enzyme activity by an LAP3 inhibitor.

Calcineurin/P-ERK/Egr-1 Pathway is Involved in Fear Memory Impairment after Isoflurane Exposure in Mice.

Isoflurane exposure adversely influences subsequent fear memory formation in mice. Calcineurin (CaN), a phosphatase, prevents the establishment of emotional memory by dephosphorylating substrates and inhibiting the expression of learning and memory related genes. We investigated whether isoflurane impairment of fear memory formation was associated with altered CaN activity and downstream phosphorylated-extracellular signal-regulated kinases (p-ERK) and early growth response gene-1 (Egr-1) expression in hippocampus and amygdala. We also tested whether memory performance can be rescued by the CaN inhibitor FK506. Adult C57BL/6 mice were injected FK506 or vehicle after being exposed to 1.3% isoflurane or air for 1 h. After a 1 h- recovery, mice underwent classical fear conditioning (FC) training. Fear memory were tested 30 min, 48 h and 7 days after training. The activity of CaN, and expression of p-ERK and Egr-1 in hippocampus and amygdala were analyzed. Isoflurane exposure reduced mice freezing time in contextual and tone FC tests 30 min and 48 h after training. Hippocampus and amygdala from isoflurane-exposed mice had enhanced CaN activity, reduced p-ERK/ERK and Egr-1 expression. All these changes in isoflurane-exposed mice were attenuated by FK506 treatment. These results indicate calcineurin/p-ERK/Egr-1 Pathway is involved in fear memory impairment after isoflurane exposure in mice.

Impaired acquisition of conditioned taste aversion memory induced by isoflurane is accompanied with calcineurin activation and Egr-1 down-regulation in amygdala in rats.

Compared to neutral memory, emotional memory is extremely strong and persistent immediately after acquisition, therefore it may recruit specific mechanisms during acquisition. The calcineurin-dependent mechanisms engaging early growth response 1 (Egr-1) have been proved to determine the strength of emotional memory during establishment. Isoflurane, a widely used inhalation anesthetic, can interfere with the acquisition of emotional memory. We hypothesized that isoflurane impairs the acquisition of conditioned taste aversion (CTA) memory in rats and the Egr-1 expression regulation via calcineurin (CaN) and ERK signaling pathway is involved in isoflurane-induced repression of CTA memory. To examine this, we investigated the influence of isoflurane on CTA memory and the expression and activity of CaN, the phosphorylation level of ERK and the expression of Egr-1 in amygdala in response to CTA training in rats. The results showed that isoflurane exposure (1.5%, 2h) before training impaired the acquisition of CTA memory in rats. Isoflurane exposure increased the CaN activity and decreased the p-ERK and Egr-1 in amygdala in rats. These findings suggest that isoflurane can disrupt the establishment of aversion memory, and CaN activation associating with p-ERK and Egr-1 down-regulation may contribute to the isoflurane induced impairment of aversion memory acquisition.