Nanomaterials are well known to possess excellent electrical, optical, thermal, catalytic properties and strong mechanical strength, which offer great opportunities to construct nanomaterials-based sensors or devices for monitoring environmental contaminations in air, water and soil. Various nanomaterials, such as carbon nanotubes, gold nanoparticles, silicon nanowires and quantum dots, have been extensively explored in detecting and measuring toxic metal ions, toxic gases, pesticides, and hazardous industrial chemicals with high sensitivity, selectivity and simplicity. In the feature article, we reviewed recent advances in this direction, by classifying nanomaterials into five categories to illustrate the applications of nanomaterials in environmental monitoring.

Hypoxia-inducible factor-1α (HIF-1α) is a master transcription factor that is critical for the regulation of a variety of cellular functions. HIF-1α is rapidly degraded under normoxic conditions by ubiquitin-mediated proteasome pathway controlled by the tumor suppressor von Hippel Lindau (VHL). Several recent studies reveal that heat-shock proteins (Hsp) can regulate HIF-1α protein degradation by a VHL-independent pathway. Here, we demonstrate that the stress kinase c-Jun NH₂-terminal kinase 1 (JNK1) is required for Hsp-dependent regulation of HIF-1α. Stabilization of HIF-1α was impaired in JNK1−/− cells but could be rescued by JNK1 reconstitution under hypoxic conditions. These effects could be phenocopied in other cell settings by JNK1 silencing. Accordingly, HIF-1 transcriptional activity and target gene expression were dramatically reduced in JNK1−/− cells. Further, decreased levels of endogenous Hsp90/Hsp70 proteins in JNK1−/− cells affected the protective roles of these chaperones in stabilizing newly synthesized HIF-1α, whereas enforced expression of Hsp90/Hsp70 in JNK1−/− cells increased HIF-1α stability relative to parental control cells. Furthering this connection, we also found that defective expression of the Hsp90 acetyltransferase HDAC6 in JNK1−/− cells was associated with reduced Hsp90 chaperone activity. Taken together, our studies define a novel function for JNK1 in regulating HIF-1α turnover by a VHL-independent mechanism. Cancer Res; 70(2); 813–23

Chimeric antigen receptor (CAR) technology has revolutionized cancer treatment, particularly in malignant hematological tumors. Currently, the BCMA-targeted second-generation CAR-T cells have showed impressive efficacy in the treatment of refractory/relapsed multiple myeloma (R/R MM), but up to 50% relapse remains to be addressed urgently. Here we constructed the BCMA-targeted fourth-generation CAR-T cells expressing IL-7 and CCL19 (i.e., BCMA-7 × 19 CAR-T cells), and demonstrated that BCMA-7 × 19 CAR-T cells exhibited superior expansion, differentiation, migration and cytotoxicity. Furthermore, we have been carrying out the first-in-human clinical trial for therapy of R/R MM by use of BCMA-7 × 19 CAR-T cells (ClinicalTrials.gov Identifier: NCT03778346), which preliminarily showed promising safety and efficacy in first two enrolled patients. The two patients achieved a CR and VGPR with Grade 1 cytokine release syndrome only 1 month after one dose of CAR-T cell infusion, and the responses lasted more than 12-month. Taken together, BCMA-7 × 19 CAR-T cells were safe and effective against refractory/relapsed multiple myeloma and thus warranted further clinical study.

Significance: The mechanistic or mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that integrates various environmental signals/cues to regulate cell growth, proliferation, metabolism, and survival. The promyelocytic leukemia zinc-finger transcription factor (PLZF) is known to be critical not only for invariant natural killer T ( i NKT)-cell development and effector program differentiation of lymphocytes, but also for many other developmental programs. Our study demonstrates that mTOR is a crucial regulator of PLZF via control of PLZF localization to special nuclear compartments, which is essential for i NKT-cell lineage development and effector function.