An on-field colorimetric sensing strategy employing gold nanoparticles (AuNPs) and a paper-based analytical platform was investigated for mercury ion (Hg2+) detection at water sources. By utilizing ...thymine–Hg2+–thymine (T–Hg2+–T) coordination chemistry, label-free detection oligonucleotide sequences were attached to unmodified gold nanoparticles to provide rapid mercury ion sensing without complicated and time-consuming thiolated or other costly labeled probe preparation processes. Not only is this strategy’s sensing mechanism specific toward Hg2+, rather than other metal ions, but also the conformational change in the detection oligonucleotide sequences introduces different degrees of AuNP aggregation that causes the color of AuNPs to exhibit a mixture variance. To eliminate the use of sophisticated equipment and minimize the power requirement for data analysis and transmission, the color variance of multiple detection results were transferred and concentrated on cellulose-based paper analytical devices, and the data were subsequently transmitted for the readout and storage of results using cloud computing via a smartphone. As a result, a detection limit of 50 nM for Hg2+ spiked pond and river water could be achieved. Furthermore, multiple tests could be performed simultaneously with a 40 min turnaround time. These results suggest that the proposed platform possesses the capability for sensitive and high-throughput on-site mercury pollution monitoring in resource-constrained settings.
Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely used for treating ...hypercholesterolemia, is associated with improved disease-free survival. Here, we show that cholesterol mediates the metastatic effects of a high-fat diet via its oxysterol metabolite, 27-hydroxycholesterol. Ablation or inhibition of CYP27A1, the enzyme responsible for the rate-limiting step in 27-hydroxycholesterol biosynthesis, significantly reduces metastasis in relevant animal models of cancer. The robust effects of 27-hydroxycholesterol on metastasis requires myeloid immune cell function, and it was found that this oxysterol increases the number of polymorphonuclear-neutrophils and γδ-T cells at distal metastatic sites. The pro-metastatic actions of 27-hydroxycholesterol requires both polymorphonuclear-neutrophils and γδ-T cells, and 27-hydroxycholesterol treatment results in a decreased number of cytotoxic CD8
T lymphocytes. Therefore, through its actions on γδ-T cells and polymorphonuclear-neutrophils, 27-hydroxycholesterol functions as a biochemical mediator of the metastatic effects of hypercholesterolemia.High cholesterol is a risk factor for breast cancer recurrence. Here the authors show that cholesterol promotes breast cancer metastasis via its metabolite 27-hydroxycholesterol (27HC) that acts on immune myeloid cells residing at the distal metastatic sites, thus promoting an immune suppressive environment.
Long noncoding RNAs (lncRNAs) have been implicated in hypoxia/HIF-1-associated cancer progression through largely unknown mechanisms. Here we identify MIR31HG as a hypoxia-inducible lncRNA and ...therefore we name it LncHIFCAR (long noncoding HIF-1α co-activating RNA); we describe its oncogenic role as a HIF-1α co-activator that regulates the HIF-1 transcriptional network, crucial for cancer development. Extensive analyses of clinical data indicate LncHIFCAR level is substantially upregulated in oral carcinoma, significantly associated with poor clinical outcomes and representing an independent prognostic predictor. Overexpression of LncHIFCAR induces pseudo-hypoxic gene signature, whereas knockdown of LncHIFCAR impairs the hypoxia-induced HIF-1α transactivation, sphere-forming ability, metabolic shift and metastatic potential in vitro and in vivo. Mechanistically, LncHIFCAR forms a complex with HIF-1α via direct binding and facilitates the recruitment of HIF-1α and p300 cofactor to the target promoters. Our results uncover an lncRNA-mediated mechanism for HIF-1 activation and establish the clinical values of LncHIFCAR in prognosis and potential therapeutic strategy for oral carcinoma.
Diabetes mellitus (DM) has significant effects on cardiac calcium (Ca
) and sodium (Na⁺) regulation. Clinical studies have shown that empagliflozin (Jardiance™) has cardiovascular benefits, however ...the mechanisms have not been fully elucidated. This study aimed to investigate whether empagliflozin modulates cardiac electrical activity as well as Ca
/Na⁺ homeostasis in DM cardiomyopathy. Electrocardiography, echocardiography, whole-cell patch-clamp, confocal microscopic examinations, and Western blot, were performed in the ventricular myocytes of control and streptozotocin-induced DM rats, with or without empagliflozin (10 mg/kg for 4 weeks). The results showed that the control and empagliflozin-treated DM rats had smaller left ventricular end-diastolic diameters and shorter QT intervals than the DM rats. In addition, the prolonged action potential duration in the DM rats was attenuated in the empagliflozin-treated DM rats. Moreover, the DM rats had smaller sarcoplasmic reticular Ca
contents, intracellular Ca
transients, L-type Ca
, reverse mode Na⁺-Ca
exchanger currents, lower protein expressions of sarcoplasmic reticulum ATPase, ryanodine receptor 2 (RyR2), but higher protein expressions of phosphorylated RyR2 at serine 2808 than the control and empagliflozin-treated DM rats. The incidence and frequency of Ca
sparks, cytosolic and mitochondrial reactive oxygen species, and late Na⁺ current and Na⁺/hydrogen-exchanger currents were greater in the DM rats than in the control and empagliflozin-treated DM rats. Empagliflozin significantly changed Ca
regulation, late Na⁺ and Na⁺/hydrogen-exchanger currents and electrophysiological characteristics in DM cardiomyopathy, which may contribute to its cardioprotective benefits in DM patients.
The coronavirus disease 2019 (COVID‑19) outbreak, which has caused >46 millions confirmed infections and >1.2 million coronavirus related deaths, is one of the most devastating worldwide crises in ...recent years. Infection with COVID‑19 results in a fever, dry cough, general fatigue, respiratory symptoms, diarrhoea and a sore throat, similar to those of acute respiratory distress syndrome. The causative agent of COVID‑19, SARS‑CoV‑2, is a novel coronavirus strain. To date, remdesivir has been granted emergency use authorization for use in the management of infection. Additionally, several efficient diagnostic tools are being actively developed, and novel drugs and vaccines are being evaluated for their efficacy as therapeutic agents against COVID‑19, or in the prevention of infection. The present review highlights the prevalent clinical manifestations of COVID‑19, characterizes the SARS‑CoV‑2 viral genome sequence and life cycle, highlights the optimal methods for preventing viral transmission, and discusses possible molecular pharmacological mechanisms and approaches in the development of anti‑SARS‑CoV‑2 therapeutic agents. In addition, the use of traditional Chinese medicines for management of COVID‑19 is discussed. It is expected that novel anti‑viral agents, vaccines or an effective combination therapy for treatment/management of SARS‑CoV‑2 infection and spread therapy will be developed and implemented in 2021, and we would like to extend our best regards to the frontline health workers across the world in their fight against COVID‑19.
Green valley galaxies represent the population that is likely to transition from star-forming to quiescent phases. To investigate the role of the environment in quenching star formation, we use the ...wide-field data from the Hyper Suprime-Cam Strategic Subaru Proposal survey to quantify the frequency of green valley galaxies in different environments and their redshift evolution. We find that the green valley fraction, in general, is less than 20% in any redshift and environment. The green valley fraction, when normalized to the total population, is higher in the field than that in groups or clusters and decreases with decreasing redshift and increasing mass. The lower fraction of transitional galaxies in denser environments could be a consequence of the lack of star-forming galaxies, which could be the progenitors of green valley galaxies. To assess the effect of the environment on star formation quenching, we define the effective green valley fraction as the ratio of the number of green valley galaxies to that of nonquiescent galaxies only. The effective green valley fraction for field galaxies is lower than that for group or cluster galaxies, which reveals a strong positive mass dependence and mild redshift evolution. Moreover, the specific star formation rate is reduced by 0.1-0.3 dex in groups or clusters. Our results thus imply that an ongoing slow quenching process has been acting in the dense environment since z ∼ 1.
Membrane proteins play a crucial role in various cellular processes and are essential components of cell membranes. Computational methods have emerged as a powerful tool for studying membrane ...proteins due to their complex structures and properties that make them difficult to analyze experimentally. Traditional features for protein sequence analysis based on amino acid types, composition, and pair composition have limitations in capturing higher‐order sequence patterns. Recently, multiple sequence alignment (MSA) and pre‐trained language models (PLMs) have been used to generate features from protein sequences. However, the significant computational resources required for MSA‐based features generation can be a major bottleneck for many applications. Several methods and tools have been developed to accelerate the generation of MSAs and reduce their computational cost, including heuristics and approximate algorithms. Additionally, the use of PLMs such as BERT has shown great potential in generating informative embeddings for protein sequence analysis. In this review, we provide an overview of traditional and more recent methods for generating features from protein sequences, with a particular focus on MSAs and PLMs. We highlight the advantages and limitations of these approaches and discuss the methods and tools developed to address the computational challenges associated with features generation. Overall, the advancements in computational methods and tools provide a promising avenue for gaining deeper insights into the function and properties of membrane proteins, which can have significant implications in drug discovery and personalized medicine.
Abstract
We present ALMA 870
μ
m and JCMT/SCUBA2 850
μ
m dust continuum observations of a sample of optically dark and strongly lensed galaxies in cluster fields. The ALMA and SCUBA2 observations ...reach a median rms of ∼0.11 mJy and 0.44 mJy, respectively, with the latter close to the confusion limit of the data at 850
μ
m. This represents one of the most sensitive searches for dust emission in optically dark galaxies. We detect the dust emission in 12 out of 15 galaxies at >3.8
σ
, corresponding to a detection rate of 80%. Thanks to the gravitational lensing, we reach a deeper limiting flux than previous surveys in blank fields by a factor of ∼3. We estimate delensed infrared luminosities in the range 2.9 × 10
11
–4.9 × 10
12
L
⊙
, which correspond to dust-obscured star formation rates of ∼30–520
M
⊙
yr
−1
. Stellar population fits to the optical-to-NIR photometric data yield a median redshift
z
= 4.26 and delensed stellar mass 6.0 × 10
10
M
⊙
. They contribute a lensing-corrected star formation rate density at least an order of magnitude higher than that of equivalently massive UV-selected galaxies at
z
> 3. The results suggest that there is a missing population of massive star-forming galaxies in the early Universe, which may dominate the SFR density at the massive end (
M
⋆
> 10
10.3
M
⊙
). Five optically dark galaxies are located within
r
< 50″ in one cluster field, representing a potential overdensity structure that has a physical origin at a confidence level >99.974% from Poisson statistics. Follow-up spectroscopic observations with ALMA and/or JWST are crucial to confirm whether it is associated with a protocluster at similar redshifts.
ABSTRACT We combine Sloan Digitital Sky Survey (SDSS) and WISE photometry for the full SDSS spectroscopic galaxy sample, creating spectral energy distributions (SEDs) that cover λ = 0.4-22 m for an ...unprecedentedly large and comprehensive sample of 858,365 present-epoch galaxies. Using MAGPHYS, we then simultaneously and consistently model both the attenuated stellar SED and the dust emission at 12 and 22 m, producing robust new calibrations for monochromatic mid-IR star formation rate (SFR) proxies. These modeling results provide the first mid-IR-based view of the bimodality in star formation activity among galaxies, exhibiting the sequence of star-forming galaxies ("main sequence") with a slope of 0.80 and a scatter of 0.39 dex. We find that these new SFRs along the SF main sequence are systematically lower by a factor of 1.4 than those derived from optical spectroscopy. We show that for most present-day galaxies, the 0.4-22 m SED fits can exquisitely predict the fluxes measured by Herschel at much longer wavelengths. Our analysis also illustrates that the majority of stars in the present-day universe are formed in luminous galaxies ( ) in and around the "green valley" of the color-luminosity plane. We make publicly available the matched photometry catalog and SED modeling results.
Abstract
We investigate the performance of machine-learning techniques in classifying active galactic nuclei (AGNs), including X-ray-selected AGNs (XAGNs), infrared-selected AGNs (IRAGNs), and ...radio-selected AGNs (RAGNs). Using the known physical parameters in the Cosmic Evolution Survey (COSMOS) field, we are able to create quality training samples in the region of the Hyper Suprime-Cam (HSC) survey. We compare several Python packages (e.g.,
scikit-learn
,
Keras
, and
XGBoost
) and use
XGBoost
to identify AGNs and show the performance (e.g., accuracy, precision, recall, F1 score, and AUROC). Our results indicate that the performance is high for bright XAGN and IRAGN host galaxies. The combination of the HSC (optical) information with the Wide-field Infrared Survey Explorer band 1 and band 2 (near-infrared) information performs well to identify AGN hosts. For both type 1 (broad-line) XAGNs and type 1 (unobscured) IRAGNs, the performance is very good by using optical-to-infrared information. These results can apply to the five-band data from the wide regions of the HSC survey and future all-sky surveys.
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