Caring for Dementia Caregivers: Psychosocial Factors Related to Engagement in Self-Care Activities.

Caregivers often prioritize the needs of the care recipient and neglect their own health needs. It is imperative to understand the factors related to their self-care practices and engagement in self-care activities. The present study examined the extent to which dementia caregivers engaged in self-care activities, how this varied depending on caregiver characteristics, and whether self-care engagement mediated the relationship between social support and caregiver outcomes. The study utilized baseline data from a diverse sample of dementia caregivers (N = 243) who participated in a randomized trial evaluating a psychosocial technology-based caregiver intervention. Results showed that the dementia caregivers engaged in low levels of self-care activities and that their engagement varied based on the caregivers' background characteristics (age, gender, race/ethnicity, relationship to the care recipient, and employment status). Less caregiver involvement (e.g., less ADL/IADL help provided and more caregiver preparedness) and more social support predicted higher self-care activity engagement. Self-care activity engagement served as a mediator, such that more social support predicted more self-care activities, which, in turn, were associated with more positive perceptions of caregiving and less caregiver burden and depression. The findings suggest a need for interventions that promote self-care engagement among dementia caregivers and underscore the importance of social support and caregiver preparedness to caregivers' well-being.

Erratum: N6-methyladenosine-induced ERRγ triggers chemoresistance of cancer cells through upregulation of ABCB1 and metabolic reprogramming: Erratum.

[This corrects the article DOI: 10.7150/thno.40144.].

Electrochemiluminescence resonance energy transfer between Ru(bpy)32+@Cu3(HHTP)2 and GO-Au composites for C-reactive protein detection.

Designing innovative electrochemiluminescence (ECL) immunosensors is critical for the detection of biomarkers with a low concentration and the precise evaluation of clinical diseases. Herein, a Cu3(hexahydroxytriphenylene)2 (Cu3(HHTP)2) nanoflake-based sandwich-type ECL immunosensor was constructed for C-Reactive Protein (CRP) detection. The Cu3(HHTP)2 nanoflake, an electronically conductive metal-organic framework (MOF), has a periodically arranged porous structure with a cavity size of 2 nm, which not only accommodates a large amount of Ru(bpy)32+ but also confines the spatial diffusion of active species. Therefore, the Ru(bpy)32+-loaded Cu3(HHTP)2 nanocomplex (Ru@CuMOF) as an ECL emitter exhibits an enhanced ECL efficiency. The ECL resonance energy transfer (ECL-RET) was accomplished by combining Ru@CuMOF used as a donor with gold nanoparticles-functionalized graphene oxide nanosheets (GO-Au) utilized as an acceptor. This should be ascribed to the fact that the ECL emission spectrum of Ru@CuMOF shows the strongest signal intensity at 615 nm, overlapping with the absorption spectrum of GO-Au at 580-680 nm. Targeted detection of CRP in human serum samples was achieved by the sandwich-type immunosensor based on the ECL-RET mechanism with a 0.26 pg mL-1 detection limit. The electro-activated hybrids of Cu3(HHTP)2 and ECL emitters provide a new sensing strategy for the high-sensitivity detection of disease markers.

RNA m6A methylation regulates dissemination of cancer cells by modulating expression and membrane localization of ß-catenin.

N6-methyladenosine (m6A) methylation, which is modified by the METTL3/METTL14 complex, is a dominant internal modification in mammalian RNA and tightly linked to cancer progression. Here we reveal that METTL3-promoted cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) are associated with expression and membrane localization of ß-catenin (encoded by CTNNB1), as opposed to Wnt signaling activation in various types of cancer cells, including cervical, lung, and liver cancer. Specifically, METTL3 regulates the transcription, mRNA decay, translation, and subcellular localization of ß-catenin. For CTNNB1 expression, METTL3 indirectly suppresses CTNNB1 transcription by stabilizing its transcription suppressor E2F1 mRNA； deposition of 5'UTR m6A in CTNNB1 promotes its decay in a content-dependent manner via YTHDF2 recognition; 5'UTR m6A in CTNNB1 suppresses its translation efficiency, whereas the global METTL3 level controls the canonical and non-canonical translation of CTNNB1, which is probably associated with the interaction between YTHDF1 and eIF4E1/eIF4E3. For ß-catenin translocation, METTL3 represses membrane localization of ß-catenin and its interaction with E-cadherin by downregulating c-Met kinase, leading to inhibition of cell motility. In vitro, in vivo, and clinical analyses confirm the essential role of ß-catenin and its expression regulators in cancer cell dissemination. The findings not only expand our understanding of m6A modification and its roles in gene expression and subcellular localization of targets but also suggest that the METTL3/ß-catenin axis might be a potential target to inhibit cancer metastasis.

N6-methyladenosine-induced ERRγ triggers chemoresistance of cancer cells through upregulation of ABCB1 and metabolic reprogramming.

Background: Drug resistance severely reduces treatment efficiency of chemotherapy and leads to poor prognosis. However, regulatory factors of chemoresistant cancer cells are largely unknown. Methods: The expression of estrogen receptor related receptors (ERRs) in chemoresistant cancer cells are checked. The roles of ERRγ in chemoresistance are confirmed by in vitro and in vivo studies. The mechanisms responsible for ERRγ-regulated expression of ABCB1 and CPT1B are investigated. Results: The expression of ERRγ is upregulated in chemoresistant cancer cells. Targeted inhibition of ERRγ restores the chemosensitivity. ERRγ can directly bind to the promoter of ABCB1 to increase its transcription. An elevated interaction between ERRγ and p65 in chemoresistant cells further strengthens transcription of ABCB1. Further, ERRγ can increase the fatty acid oxidation (FAO) in chemoresistant cells via regulation of CPT1B, the rate-limiting enzyme of FAO. The upregulated ERRγ in chemoresistant cancer cells might be due to increased levels of N6-methyladenosine (m6A) can trigger the splicing of precursor ESRRG mRNA. Conclusions: m6A induced ERRγ confers chemoresistance of cancer cells through upregulation of ABCB1 and CPT1B.

N6-Methyladenosine Regulates the Expression and Secretion of TGFß1 to Affect the Epithelial-Mesenchymal Transition of Cancer Cells.

N6-methyladenosine (m6A) is the most abundant modification on eukaryotic mRNA, which regulates all steps of the mRNA life cycle. An increasing number of studies have shown that m6A methylation plays essential roles in tumor development. However, the relationship between m6A and the progression of cancers remains to be explored. Here, we reported that transforming growth factor-ß (TGFß1)-induced epithelial-mesenchymal transition (EMT) was inhibited in methyltransferase-like 3 (METTL3) knockdown (Mettl3Mut/-) cells. The expression of TGFß1 was up-regulated, while self-stimulated expression of TGFß1 was suppressed in Mettl3Mut/- cells. We further revealed that m6A promoted TGFB1 mRNA decay, but impaired TGFB1 translation progress. Besides this, the autocrine of TGFß1 was disrupted in Mettl3Mut/- cells via interrupting TGFß1 dimer formation. Lastly, we found that Snail, which was down-regulated in Mettl3Mut/- cells, was a key factor responding to TGFß1-induced EMT. Together, our research demonstrated that m6A performed multi-functional roles in TGFß1 expression and EMT modulation, suggesting the critical roles of m6A in cancer progression regulation.

Inhibition of BRD4 suppresses the malignancy of breast cancer cells via regulation of Snail.

The mechanistic action of bromodomain-containing protein 4 (BRD4) in cancer motility, including epithelial-mesenchymal transition (EMT), remains largely undefined. We found that targeted inhibition of BRD4 reduces migration, invasion, in vivo growth of patient-derived xenograft (PDX), and lung colonization of breast cancer (BC) cells. Inhibition of BRD4 rapidly decreases the expression of Snail, a powerful EMT transcription factor (EMT-TF), via diminishing its protein stability and transcription. Protein kinase D1 (PRKD1) is responsible for BRD4-regulated Snail protein stability by triggering phosphorylation at Ser11 of Snail and then inducing proteasome-mediated degradation. BRD4 inhibition also suppresses the expression of Gli1, a key transductor of Hedgehog (Hh) required to activate the transcription of SNAI1, in BC cells. The GACCACC sequence (-341 to -333) in the SNAI1 promoter is responsible for Gli1-induced transcription of SNAI1. Clinically, BRD4 and Snail levels are increased in lung-metastasized, estrogen receptor-negative (ER-), and progesterone receptor-negative (PR-) breast cancers and correlate with the expression of mesenchymal markers. Collectively, BRD4 can regulate malignancy of breast cancer cells via both transcriptional and post-translational regulation of Snail.

RNA m6A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail.

N6-Methyladenosine (m6A) modification has been implicated in the progression of several cancers. We reveal that during epithelial-mesenchymal transition (EMT), one important step for cancer cell metastasis, m6A modification of mRNAs increases in cancer cells. Deletion of methyltransferase-like 3 (METTL3) down-regulates m6A, impairs the migration, invasion and EMT of cancer cells both in vitro and in vivo. m6A-sequencing and functional studies confirm that Snail, a key transcription factor of EMT, is involved in m6A-regulated EMT. m6A in Snail CDS, but not 3'UTR, triggers polysome-mediated translation of Snail mRNA in cancer cells. Loss and gain functional studies confirm that YTHDF1 mediates m6A-increased translation of Snail mRNA. Moreover, the upregulation of METTL3 and YTHDF1 act as adverse prognosis factors for overall survival (OS) rate of liver cancer patients. Our study highlights the critical roles of m6A on regulation of EMT in cancer cells and translation of Snail during this process.

64 Gb/s PAM4 VCSEL-based FSO link.

A 64 Gb/s four-level pulse amplitude modulation (PAM4) vertical-cavity surface-emitting laser (VCSEL)-based free-space optical (FSO) link with an external light injection scheme is proposed and successfully demonstrated. Experimental results show that the 11.2 GHz VCSEL with an external light injection scheme is sufficiently powerful for 64 Gb/s PAM4 FSO links. This study is the first one that adopts a 1550-nm VCSEL transmitter with an external light injection scheme in a 64 Gb/s PAM4 FSO link. The link performances of the proposed PAM4 VCSEL-based FSO links have been analyzed in real-time in terms of eye diagrams and offline processed by Matlab in terms of bit error rate (BER) performances. Good BER performance and clear eye diagrams are acquired over a 100-m free-space link. Such a proposed 64 Gb/s PAM4 VCSEL-based FSO link with an external light injection scheme is a promising one for providing high transmission rate and long transmission distance.

45 Gb/s PAM4 transmission based on VCSEL with light injection and optoelectronic feedback techniques.

A 45 Gb/s four-level pulse amplitude modulation (PAM4) transmission based on an 850 nm/7.4 GHz vertical cavity surface emitting laser (VCSEL) with light injection and optoelectronic feedback techniques is proposed. Experimental results show that such an 850 nm/7.4 GHz VCSEL with light injection and optoelectronic feedback techniques is powerful enough for a 45 Gb/s PAM4 signal transmission. To the best of our knowledge, this Letter is the first to adopt a VCSEL transmitter with light injection and optoelectronic feedback techniques in a 45 Gb/s PAM4 transmission system. Good bit error rate performance and three independent clear eye diagrams are achieved over a 200-m OM4 multimode fiber transport. This proposed 45 Gb/s PAM4 VCSEL-based transmission system has great potential for providing effective bandwidth in short-reach optical data communications.

Bidirectional fiber-wireless and fiber-IVLLC integrated system based on polarization-orthogonal modulation scheme.

A bidirectional fiber-wireless and fiber-invisible laser light communication (IVLLC) integrated system that employs polarization-orthogonal modulation scheme for hybrid cable television (CATV)/microwave (MW)/millimeter-wave (MMW)/baseband (BB) signal transmission is proposed and demonstrated. To our knowledge, it is the first one that adopts a polarization-orthogonal modulation scheme in a bidirectional fiber-wireless and fiber-IVLLC integrated system with hybrid CATV/MW/MMW/BB signal. For downlink transmission, carrier-to-noise ratio (CNR), composite second-order (CSO), composite triple-beat (CTB), and bit error rate (BER) perform well over 40-km single-mode fiber (SMF) and 10-m RF/50-m optical wireless transport scenarios. For uplink transmission, good BER performance is obtained over 40-km SMF and 50-m optical wireless transport scenario. Such a bidirectional fiber-wireless and fiber-IVLLC integrated system for hybrid CATV/MW/MMW/BB signal transmission will be an attractive alternative for providing broadband integrated services, including CATV, Internet, and telecommunication services. It is shown to be a prominent one to present the advancements for the convergence of fiber backbone and RF/optical wireless feeder.