Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) ...progression and could be a potential therapeutic target.
We screened highly expressed lncRNAs in human CRC samples compared with their matched adjacent normal tissues. The proteins that interact with LINRIS (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The proliferation and metabolic alteration of CRC cells with LINRIS inhibited were tested in vitro and in vivo.
LINRIS was upregulated in CRC tissues from patients with poor overall survival (OS), and LINRIS inhibition led to the impaired CRC cell line growth. Moreover, knockdown of LINRIS resulted in a decreased level of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a newly found N
-methyladenosine (m
A) 'reader'. LINRIS blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). Therefore, knockdown of LINRIS attenuated the downstream effects of IGF2BP2, especially MYC-mediated glycolysis in CRC cells. In addition, the transcription of LINRIS could be inhibited by GATA3 in CRC cells. In vivo experiments showed that the inhibition of LINRIS suppressed the proliferation of tumors in orthotopic models and in patient-derived xenograft (PDX) models.
LINRIS is an independent prognostic biomarker for CRC. The LINRIS-IGF2BP2-MYC axis promotes the progression of CRC and is a promising therapeutic target.
Ferroptosis regulates cell death through reactive oxygen species (ROS)‐associated lipid peroxide accumulation, which is expected to affect the structure and polarity of lipid droplets (LDs), but with ...no clear evidence. Herein, we report the first example of an LD/nucleus dual‐targeted ratiometric fluorescent probe, CQPP, for monitoring polarity changes in the cellular microenvironment. Due to the donor–acceptor structure of CQPP, it offers ratiometric fluorescence emission and fluorescence lifetime signals that reflect polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model. This LD/nucleus dual‐targeted fluorescent probe shows the great potential of using fluorescence imaging to study ferroptosis and ferroptosis‐related diseases.
The first lipid droplet (LD)/nucleus dual‐targeted ratiometric fluorescence probe, CQPP, for monitoring polarity change was developed. CQPP offers ratiometric fluorescence and fluorescence lifetime imaging of LD polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model.
Smart nanorobots have emerged as novel drug delivery platforms in nanomedicine, potentially improving anti‐cancer efficacy and reducing side effects. In this study, an intelligent tumor ...microenvironment‐responsive nanorobot is developed that effectively delivers CpG payloads to Toll‐like receptor 9 (TLR9)‐positive tumors to induce autophagy‐mediated cell death for immunotherapy. The nanorobots are fabricated by co‐self‐assembly of two amphiphilic triblock polymer peptides: one containing the matrix metallopeptidase 2 (MMP2)‐cleaved GPLGVRGS motif to control the mechanical opening of the nanorobots and provide targeting capability for TLR‐9‐positive tumors and the other consisting of an arginine‐rich GRRRDRGRS sequence that can condense nuclear acid payloads through electrostatic interactions. Using multiple tumor‐bearing mouse models, it is investigated whether the intravenous injection of CpG‐loaded nanorobots could effectively deliver CpG payloads to TLR‐9‐positive tumors and elicit anti‐tumor immunity through TLR9 signaling and autophagy. Therefore, besides being a commonly used adjuvant for tumor vaccination, CpG‐loaded nanorobots can effectively reprogram the tumor immunosuppressive microenvironment and suppress tumor growth and recurrence. This nanorobot‐based CpG immunotherapy can be considered a feasible approach to induce anti‐tumor immunity, showing great therapeutic potential for the future treatment of TLR9‐positive cancers.
In this study, an intelligent tumor microenvironment‐responsive nanorobot is developed that effectively delivers CpG payloads to Toll‐like receptor 9 (TLR9)‐positive tumors to induce autophagy‐mediated cell death for immunotherapy.
Motivated by the concept of energy-optimized air/space vehicles, the design of more-electric and all-electric vehicles has become increasingly popular. With the advance of micro-electro-mechanical ...systems, on-board electronic/electrical devices become more integrated and miniaturized. It means that these highly-advanced devices should rely on a high heat-flux dissipation method to maintain an effective and safe operation. Spray cooling, universally recognized as the next-generation cooling scheme, has been extensively utilized in the thermal protection of the ground-based electric/electronic equipment. In contrast, the aerospace-oriented spray cooling (AOSC) application is extremely rare. It can be attributed to the fact that the research into the space/air-oriented spray cooling technologies is still in its infancy, which leads to a lack in the knowledge of alternations of flow patterns and heat transfer behaviors caused by the complicated space or high-altitude space. This paper presents a comprehensive review of the up-to-date published articles on AOSC and divides these published articles into four categories: 1) investigation into the effect of gravity on the cooling performance; 2) investigation into the effect of environmental pressure on the cooling performance; 3) study of the effect of acceleration and vibration on the cooling performance; 4) investigation of the aerospace spray cooling system. Additionally, comments, perspectives, and orientations are provided, in which several promising contributions are highlighted. This paper aims to promote the practical application of the AOSC system which could facilitate the development of the energy-optimized green air/space vehicle.
•A review of aerospace-oriented spray cooling technology is performed.•Gravity plays a significant role in the flow pattern and heat & mass transfer.•A heat transfer enhancement can be gained by flash Boiling/evaporation.•Gravity-immune spray cooling systems promote its practical aerospace application.•Affordable ground-based research method for aerospace application is imperative.
A
bstract
We apply machine learning techniques to solve a specific classification problem in 4D F-theory. For a divisor
D
on a given complex threefold base, we want to read out the non-Higgsable ...gauge group on it using local geometric information near
D
. The input features are the triple intersection numbers among divisors near
D
and the output label is the non-Higgsable gauge group. We use decision tree to solve this problem and achieved 85%-98% out-of-sample accuracies for different classes of divisors, where the data sets are generated from toric threefold bases without (4,6) curves. We have explicitly generated a large number of analytic rules directly from the decision tree and proved a small number of them. As a crosscheck, we applied these decision trees on bases with (4,6) curves as well and achieved high accuracies. Additionally, we have trained a decision tree to distinguish toric (4,6) curves as well. Finally, we present an application of these analytic rules to construct local base configurations with interesting gauge groups such as SU(3).
This paper presents a review of the current state-of-the-art in micropumping technology for biomedical applications. The review focuses particularly on the actuation schemes, flow directing methods ...and liquid chamber configurations used in the devices proposed over the past five years. A comparative study is presented of the various mechanical and non-mechanical micropumps proposed for biomedical applications. The performance of the various devices is compared in terms of their actuation voltage, power consumption, operating frequency range, flow rate, backpressure, and so forth. The basic operating principles and advantages of each method are introduced, and their limitations described where appropriate. The review provides a useful source of reference for selecting micropumping schemes capable of meeting the specific flow rate requirements of different biomedical applications. In general, the review is expected to be of interest to both seasoned researchers and practitioners in the micropumping and biomedical technology fields and those entering the field for the first time.
•Micropumps are one of the most powerful approaches for biomedical applications.•The review focuses on proposals for operating principles and performance of two types of micropump.•A comprehensive review of the main applications of micropumps over the past five years.
Bio-inspired self-healing materials hold great promise for applications in wearable electronics, artificial muscles and soft robots, etc. However, self-healing at subzero temperatures remains a great ...challenge because the reconstruction of interactions will experience resistance of the frozen segments. Here, we present an ultrarobust subzero healable glassy polymer by incorporating polyphenol nano-assemblies with a large number of end groups into polymerizable deep eutectic solvent elastomers. The combination of multiple dynamic bonds and rapid secondary relaxations with low activation energy barrier provides a promising method to overcome the limited self-healing ability of glassy polymers, which can rarely be achieved by conventional dynamic cross-linking. The resulted material exhibits remarkably improved adhesion force at low temperature (promotes 30 times), excellent mechanical properties (30.6 MPa) and desired subzero healing efficiencies (85.7% at -20 °C). We further demonstrated that the material also possesses reliable cryogenic strain-sensing and functional-healing ability. This work provides a viable approach to fabricate ultrarobust subzero healable glassy polymers that are applicable for winter sports wearable devices, subzero temperature-suitable robots and artificial muscles.
2D organic-inorganic lead iodide perovskites have recently received tremendous attention as promising light absorbers for solar cells, due to their excellent optoelectronic properties, structural ...tunability, and environmental stability. However, although great efforts have been made, no 2D lead iodide perovskites have been discovered as ferroelectrics, in which the ferroelectricity may improve the photovoltaic performance. Here, by incorporating homochiral cations, 2D lead iodide perovskite ferroelectrics R-1-(4-chlorophenyl)ethylammonium
PbI
and S-1-(4-chlorophenyl)ethylammonium
PbI
are successfully obtained. The vibrational circular dichroism spectra and crystal structural analysis reveal their homochirality. They both crystalize in a polar space group P1 at room temperature, and undergo a 422F1 type ferroelectric phase transition with transition temperature as high as 483 and 473.2 K, respectively, showing a multiaxial ferroelectric nature. They also possess semiconductor characteristics with a direct bandgap of 2.34 eV. Nevertheless, their racemic analogue adopts a centrosymmetric space group P2
/c at room temperature, exhibiting no high-temperature phase transition. The homochirality in 2D lead iodide perovskites facilitates crystallization in polar space groups. This finding indicates an effective way to design high-performance 2D lead iodide perovskite ferroelectrics with great application prospects.
A
bstract
Applying the Ashok-Denef-Douglas estimation method to elliptic Calabi-Yau fourfolds suggests that a single elliptic fourfold
ℳ
max
gives rise to
O
10
272
,
000
F-theory flux vacua, and that ...the sum total of the numbers of flux vacua from all other F-theory geometries is suppressed by a relative factor of
O
10
−
3000
. The fourfold
ℳ
max
arises from a generic elliptic fibration over a specific toric threefold base
B
max
, and gives a geometrically non-Higgsable gauge group of
E
8
9
×
F
4
8
× (
G
2
× SU(2))
16
, of which we expect some factors to be broken by G-flux to smaller groups. It is not possible to tune an SU(5) GUT group on any further divisors in
ℳ
max
, or even an SU(2) or SU(3), so the standard model gauge group appears to arise in this context only from a broken
E
8
factor. The results of this paper can either be interpreted as providing a framework for predicting how the standard model arises most naturally in F-theory and the types of dark matter to be found in a typical F-theory compactification, or as a challenge to string theorists to explain why other choices of vacua are not exponentially unlikely compared to F-theory compactifications on
ℳ
max
.
A photothermal bacterium (PTB) is reported for tumor‐targeted photothermal therapy (PTT) by using facultative anaerobic bacterium Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to biomineralize ...palladium nanoparticles (Pd NPs) on its surface without affecting bacterial activity. It is found that PTB possesses superior photothermal property in near infrared (NIR) regions, as well as preferential tumor‐targeting capacity. Zeolitic imidazole frameworks‐90 (ZIF‐90) encapsulating photosensitizer methylene blue (MB) are hybridized on the surface of living PTB to further enhance PTT efficacy. MB‐encapsulated ZIF‐90 (ZIF‐90/MB) can selectively release MB at mitochondria and cause mitochondrial dysfunction by producing singlet oxygen (1O2) under light illumination. Mitochondrial dysfunction further contributes to adenosine triphosphate (ATP) synthesis inhibition and heat shock proteins (HSPs) down‐regulated expression. The PTB‐based therapeutic platform of PTB@ZIF‐90/MB demonstrated here will find great potential to overcome the challenges of tumor targeting and tumor heat tolerance in PTT.
A bacteria‐based photothermal therapeutic platform comprising PTB@ZIF‐90/MB is developed, which reveals great potential to augment photothermal therapy efficacy by tackling the challenges of tumor targeting and heat resistance.
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