Long-Range Hot-Carrier Transport in Topologically Connected HgTe Quantum Dots.

The utilization of hot carriers as a means to surpass the Shockley-Queasier limit represents a promising strategy for advancing highly efficient photovoltaic devices. Quantum dots, owing to their discrete energy states and limited multi-phonon cooling process, are regarded as one of the most promising materials. However, in practical implementations, the presence of numerous defects and discontinuities in colloidal quantum dot (CQD) films significantly curtails the transport distance of hot carriers. In this study, the harnessing of excess energies from hot-carriers is successfully demonstrated and a world-record carrier diffusion length of 15 µm is observed for the first time in colloidal systems, surpassing existing hot-carrier materials by more than tenfold. The observed phenomenon is attributed to the specifically designed honeycomb-like topological structures in a HgTe CQD superlattice, with its long-range periodicity confirmed by High-Resolution Transmission Electron Microscopy(HR-TEM), Selected Area Electron Diffraction(SAED) patterns, and low-angle X-ray diffraction (XRD). In such a superlattice, nonlocal hot carrier transport is supported by three unique physical properties: the wavelength-independent responsivity, linear output characteristics and microsecond fast photoresponse. These findings underscore the potential of HgTe CQD superlattices as a feasible approach for efficient hot carrier collection, thereby paving the way for practical applications in highly sensitive photodetection and solar energy harvesting.

RGCC-mediated PLK1 activity drives breast cancer lung metastasis by phosphorylating AMPKα2 to activate oxidative phosphorylation and fatty acid oxidation.

BACKGROUND: More than 90% of the mortality of triple-negative breast cancer (TNBC) patients is attributed to cancer metastasis with organotropism. The lung is a frequent site of TNBC metastasis. However, the precise molecular mechanism for lung-specific metastasis of TNBC is not well understood. METHODS: RNA sequencing was performed to identify patterns of gene expression associated with lung metastatic behavior using 4T1-LM3, MBA-MB-231-LM3, and their parental cells (4T1-P, MBA-MB-231-P). Expressions of RGCC, called regulator of cell cycle or response gene to complement 32 protein, were detected in TNBC cells and tissues by qRT-PCR, western blotting, and immunohistochemistry. Kinase activity assay was performed to evaluate PLK1 kinase activity. The amount of phosphorylated AMP-activated protein kinase α2 (AMPKα2) was detected by immunoblotting. RGCC-mediated metabolism was determined by UHPLC system. Oxidative phosphorylation was evaluated by JC-1 staining and oxygen consumption rate (OCR) assay. Fatty acid oxidation assay was conducted to measure the status of RGCC-mediated fatty acid oxidation. NADPH and ROS levels were detected by well-established assays. The chemical sensitivity of cells was evaluated by CCK8 assay. RESULTS: RGCC is aberrantly upregulated in pulmonary metastatic cells. High level of RGCC is significantly related with lung metastasis in comparison with other organ metastases. RGCC can effectively promote kinase activity of PLK1, and the activated PLK1 phosphorylates AMPKα2 to facilitate TNBC lung metastasis. Mechanistically, the RGCC/PLK1/AMPKα2 signal axis increases oxidative phosphorylation of mitochondria to generate more energy, and promotes fatty acid oxidation to produce abundant NADPH. These metabolic changes contribute to sustaining redox homeostasis and preventing excessive accumulation of potentially detrimental ROS in metastatic tumor cells, thereby supporting TNBC cell survival and colonization during metastases. Importantly, targeting RGCC in combination with paclitaxel/carboplatin effectively suppresses pulmonary TNBC lung metastasis in a mouse model. CONCLUSIONS: RGCC overexpression is significantly associated with lung-specific metastasis of TNBC. RGCC activates AMPKα2 and downstream signaling through RGCC-driven PLK1 activity to facilitate TNBC lung metastasis. The study provides implications for RGCC-driven OXPHOS and fatty acid oxidation as important therapeutic targets for TNBC treatment.

Hypoxia-induced circSTT3A enhances serine synthesis and promotes H3K4me3 modification to facilitate breast cancer stem cell formation.

Hypoxia is a key feature of tumor microenvironment that contributes to the development of breast cancer stem cells (BCSCs) with strong self-renewal properties. However, the specific mechanism underlying hypoxia in BCSC induction is not completely understood. Herein, we provide evidence that a novel hypoxia-specific circSTT3A is significantly upregulated in clinical breast cancer (BC) tissues, and is closely related to the clinical stage and poor prognosis of patients with BC. The study revealed that hypoxia-inducible factor 1 alpha (HIF1α)-regulated circSTT3A has a remarkable effect on mammosphere formation in breast cancer cells. Mechanistically, circSTT3A directly interacts with nucleotide-binding domain of heat shock protein 70 (HSP70), thereby facilitating the recruitment of phosphoglycerate kinase 1 (PGK1) via its substrate-binding domain, which reduces the ubiquitination and increases the stability of PGK1. The enhanced levels of PGK1 catalyze 1,3-diphosphoglycerate (1,3-BPG) into 3-phosphoglycerate (3-PG) leading to 3-PG accumulation and increased serine synthesis, S-adenosylmethionine (SAM) accumulation, and trimethylation of histone H3 lysine 4 (H3K4me3). The activation of the H3K4me3 contributes to BCSCs by increasing the transcriptional level of stemness-related factors. Especially, our work reveals that either loss of circSTT3A or PGK1 substantially suppresses tumor initiation and tumor growth, which dramatically increases the sensitivity of tumors to doxorubicin (DOX) in mice. Injection of PGK1-silenced spheroids with 3-PG can significantly reverse tumor initiation and growth in mice, thereby increasing tumor resistance to DOX. In conclusion, our study sheds light on the functional role of hypoxia in the maintenance of BCSCs via circSTT3A/HSP70/PGK1-mediated serine synthesis, which provides new insights into metabolic reprogramming, tumor initiation and growth. Our findings suggest that targeting circSTT3A alone or in combination with chemotherapy has potential clinical value for BC management.

Colloidal Quantum Dots in Very-Long-Wave Infrared Detection: Progress, Challenges, and Opportunities.

The very long wave infrared (VLWIR) is an electromagnetic wave with a wavelength range of 15-30 µm, which plays an important role in missile defense and weather monitoring. This paper briefly introduces the development of intraband absorption of colloidal quantum dots (CQDs) and investigates the possibility of using CQDs to produce VLWIR detectors. We calculated the detectivity of CQDs for VLWIR. The results show that the detectivity is affected by parameters such as quantum dot size, temperature, electron relaxation time, and distance between quantum dots. The theoretical derivation results, combined with the current development status, show that the detection of VLWIR by CQDs is still in the theoretical stage.

Erratum: FOSL2 promotes VEGF-independent angiogenesis by transcriptionnally activating Wnt5a in breast cancer-associated fibroblasts: Erratum.

[This corrects the article DOI: 10.7150/thno.55074.].

A PrEP Demonstration Project Using eHealth and Community Outreach to Justice-Involved Cisgender Women and Their Risk Networks.

Women involved in criminal justice systems (WICJ) are a key population at risk for HIV, and pre-exposure prophylaxis (PrEP) is critical for HIV prevention. This project was designed to evaluate the feasibility and acceptability of delivering PrEP via eHealth to WICJ and members of their risk network (RN). We recruited HIV-negative cisgender WICJ index participants (n = 38) and risk network (RN) members (n = 67) using modified respondent-driven sampling. TDF/FTC was initiated for PrEP in participants meeting clinical criteria and dispensed through eHealth using a community-based, low barrier-to-care outreach model. Key steps in the PrEP care continuum were measured over 12 months. Enrolled participants (n = 105) had high current and lifetime justice-involvement and were predominantly cisgender women and non-Hispanic white with a mean age of 40.9y (SD 9.6). Despite most having primary care providers and medical insurance, PrEP awareness was low, and participants experienced high levels of medical, psychiatric, substance use, social, and economic need. Fifty-two participants (50%) were PrEP-eligible, of whom 24 (46%) initiated PrEP. TDF/FTC was safe and well-tolerated throughout follow-up and 13 individuals chose to remain on PrEP following study conclusion. In this novel PrEP demonstration project for WICJ and RN members, despite high medical, psychiatric, and social comorbidity, PrEP was positively received and effectively delivered using a community outreach model via eHealth.Registered on clinicaltrials.gov under trial registration number NCT03293290.

A novel lncRNA ROPM-mediated lipid metabolism governs breast cancer stem cell properties.

BACKGROUND: Cancer stem cells (CSCs) are considered as the major cause to tumor initiation, recurrence, metastasis, and drug resistance, driving poor clinical outcomes in patients. Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in cancer development and progression. However, limited lncRNAs involved in CSCs have been reported. METHODS: The novel lncROPM (a regulator of phospholipid metabolism) in breast CSCs (BCSCs) was identified by microarray and validated by qRT-PCR in BCSCs from breast cancer cells and tissues. The clinical significance of lncROPM was evaluated in two breast cancer cohorts and TANRIC database (TCGA-BRCA, RNAseq data). Gain- and loss-of-function assays were performed to examine the role of lncROPM on BCSCs both in vitro and in vivo. The regulatory mechanism of lncROPM was investigated by bioinformatics, RNA FISH, RNA pull-down, luciferase reporter assay, and actinomycin D treatment. PLA2G16-mediated phospholipid metabolism was determined by UHPLC-QTOFMS system. Cells' chemosensitivity was assessed by CCK8 assay. RESULTS: LncROPM is highly expressed in BCSCs. The enhanced lncROPM exists in clinic breast tumors and other solid tumors and positively correlates with malignant grade/stage and poor prognosis in breast cancer patients. Gain- and loss-of-function studies show that lncROPM is required for the maintenance of BCSCs properties both in vitro and in vivo. Mechanistically, lncROPM regulates PLA2G16 expression by directly binding to 3'-UTR of PLA2G16 to increase the mRNA stability. The increased PLA2G16 significantly promotes phospholipid metabolism and the production of free fatty acid, especially arachidonic acid in BCSCs, thereby activating PI3K/AKT, Wnt/ß-catenin, and Hippo/YAP signaling, thus eventually involving in the maintenance of BCSCs stemness. Importantly, lncROPM and PLA2G16 notably contribute to BCSCs chemo-resistance. Administration of BCSCs using clinic therapeutic drugs such as doxorubicin, cisplatin, or tamoxifen combined with Giripladib (an inhibitor of cytoplasmic phospholipase A2) can efficiently eliminate BCSCs and tumorigenesis. CONCLUSIONS: Our study highlights that lncROPM and its target PLA2G16 play crucial roles in sustaining BCSC properties and may serve as a biomarker for BCSCs or other cancer stem cells. Targeting lncROPM-PLA2G16 signaling axis may be a novel therapeutic strategy for patients with breast cancer.

Hypoxia-stimulated ATM activation regulates autophagy-associated exosome release from cancer-associated fibroblasts to promote cancer cell invasion.

Cancer-associated fibroblasts (CAFs) as a predominant cell component in the tumour microenvironment (TME) play an essential role in tumour progression. Our earlier studies revealed oxidized ATM activation in breast CAFs, which is independent of DNA double-strand breaks (DSBs). Oxidized ATM has been found to serve as a redox sensor to maintain cellular redox homeostasis. However, whether and how oxidized ATM in breast CAFs regulates breast cancer progression remains poorly understood. In this study, we found that oxidized ATM phosphorylates BNIP3 to induce autophagosome accumulation and exosome release from hypoxic breast CAFs. Inhibition of oxidized ATM kinase by KU60019 (a small-molecule inhibitor of activated ATM) or shRNA-mediated knockdown of endogenous ATM or BNIP3 blocks autophagy and exosome release from hypoxic CAFs. We also show that oxidized ATM phosphorylates ATP6V1G1, a core proton pump in maintaining lysosomal acidification, leading to lysosomal dysfunction and autophagosome fusion with multi-vesicular bodies (MVB) but not lysosomes to facilitate exosome release. Furthermore, autophagy-associated GPR64 is enriched in hypoxic CAFs-derived exosomes, which stimulates the non-canonical NF-κB signalling to upregulate MMP9 and IL-8 in recipient breast cancer cells, enabling cancer cells to acquire enhanced invasive abilities. Collectively, these results provide novel insights into the role of stromal CAFs in promoting tumour progression and reveal a new function of oxidized ATM in regulating autophagy and exosome release.