Cascades of systemic and intracellular obstacles, including low stability in blood, little tumor accumulation, weak tumor penetration, poor cellular uptake, inefficient endosomal escape and deficient ...disassembly in the cytoplasm, must be overcome in order to deliver nucleic acid drugs for cancer therapy. Nanocarriers that are sensitive to a variety of physiological stimuli, such as pH, redox status, and cell enzymes, are substantially changing the landscape of nucleic acid drug delivery by helping to overcome cascaded systemic and intracellular barriers. This review discusses nucleic acid-based therapeutics, systemic and intracellular barriers to efficient nucleic acid delivery, and nanocarriers responsive to extracellular and intracellular biological stimuli to overcome individual barriers. In particular, responsive nanocarriers for the cascaded delivery of nucleic acids in vivo are highlighted. Developing novel cascaded nanocarriers that transform their physicochemical properties in response to various stimuli in a timely and spatially controlled manner for nucleic acid drug delivery holds great potential for translating the promise of nucleic acid drugs and achieving clinically successful cancer therapy.
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The deep learning method has developed very fast as a tool for data analysis in recent years. Moreover, as a technique, it is quite promising as a way to analyze gravitational-wave detection data. ...Multiple works in the literature have already used deep learning to process simulated gravitational-wave data. In this paper, we apply deep learning to LIGO data. In order to improve the weak signal recognition, we design a new structure of the convolutional neural network (CNN). The key feature of our new CNN structure is the sensing layer. This layer mimics matched filtering but is different from the usual matched-filtering technique. Usually, the matched-filtering technique uses a full template bank to match the data. However, our sensing layer only uses tens of waveforms. Our new convolutional neural network admits comparable accuracy and efficiency of signal recognition compared to other deep learning works published in the literature. Based on our new CNN, we can clearly recognize the 11 confirmed gravitational-wave events included in O1 and O2. In addition, we find about 2000 gravitational-wave triggers in O1 data.
Transglutaminase (EC 2.3.2.13) initially attracted interest because of its ability to reconstitute small pieces of meat into a ‘steak’. The extremely high cost of transglutaminase of animal origin ...has hampered its wider application and has initiated efforts to find an enzyme of microbial origin. Since the early 1990s, many microbial transglutaminase-producing strains have been found, and production processes have been optimized. This has resulted in a rapidly increasing number of applications of transglutaminase in the food sector. However, applications of microbial transglutaminase in other sectors have been explored to a much lesser extent. Here, we will present the wider potential of transglutaminases and discuss recent efforts that could contribute to the realization of their potential.
Mushrooms in the basidiomycete family Amanitaceae are very important both economically and ecologically. However, the delimitation of the family is still controversial, in part due to limited taxon ...sampling and in part because of insufficient gene fragment employed for molecular phylogenetic analyses. Furthermore, species diversity in the family is likely to have been largely underestimated, due to morphological similarity between taxa and phenotypic plasticity. In this study, we examined 1190 collections, including 1008 Chinese and 182 external ones, and performed the first comprehensive phylogenetic analyses of Amanitaceae using multi-locus sequence data. To test the monophyly of the Amanitaceae, a concatenated (nrLSU,
rpb
1, and
rpb
2) dataset of 200 taxa of the order Agaricales was analyzed. To infer the phylogeny of Amanitaceae, a concatenated nrLSU,
tef1
-
α
,
rpb
2 and
β
-
tubulin
dataset (3010 sequences from ca. 890 samples with 2309 newly generated sequences) was used. In this dataset, 252 sequences from the types of 77 species were provided. Our results indicate that Amanitaceae is a monophyletic group, and consists of five genera, namely
Amanita
,
Catatrama
,
Limacella
,
Limacellopsis
and
Myxoderma
. It is clear that
Catatrama
is closely related to
Limacella
, however, the phylogenetic relationships among these genera remain largely unresolved.
Amanita
contains 95% of the species in the family, and is here divided into three subgenera and eleven sections (subgen.
Amanita
, containing: sect.
Amanita
, sect.
Amarrendiae
, sect.
Caesareae
and sect.
Vaginatae
; subgen.
Amanitina
, containing: sect.
Amidella
, sect.
Arenariae
, sect.
Phalloideae
, sect.
Roanokenses
, sect.
Strobiliformes
and sect.
Validae
; and subgen.
Lepidella
, containing sect.
Lepidella
). Subgen.
Lepidella
occupies the basal position in the genus. One-hundred and sixty-two species of Amanitaceae known from China are treated in this study, including 50 novel species and 112 known taxa.
Amanita gleocystidiosa
,
A. pyriformis
,
A. atrofusca
,
A. subjunquillea
var.
alba
and
A. areolata
are treated as synonyms of
A. sychnopyramis
f.
subannulata
,
A. orientigemmata
,
A. umbrinolutea
,
A. subjunquillea
and
A. zangii
, respectively. 26 extralimital taxa including a novel species, namely
Catatrama indica
, were included in our study to allow us to make comparisons between these and the Chinese taxa. DNA sequence data for all the species of Amanitaceae in China and keys for identification of the species are provided.
Brightly red fluorescent carbon dots are synthesized hydrothermally and dissolved in diluted hydrochloric acid solution. Such carbon dots exhibit excitation-independent emission at about 620 nm with ...quantum yield over 10%, which is visible in daylight. After the carbon dots solution is sprayed to the fingerprints on various solid substrates and dried in air, clear fingerprints can be seen under an ultraviolet lamp and stay stable for 1 day. Detailed characterizations suggest that during the drying process, the coffee-ring effect and the electrostatic interactions between the carbon dots and the fingerprint residues prevent the typical aggregation-induced fluorescence quenching of carbon dots.
Boron compound BOMes2 containing an internal B−O bond undergoes highly efficient photoisomerization, followed by sequential structural transformations, resulting in a rare eight‐membered B, ...O‐heterocycle (S. Wang, et al. Org. Lett. 2019, 21, 5285–5289). In this work, the detailed reaction mechanisms of such a unique carbonyl‐supported tetracoordinate boron system in the first excited singlet (S1) state and the ground (S0) state were investigated by using the complete active space self‐consistent field and its second‐order perturbation (MS‐CASPT2//CASSCF) method combined with time‐dependent density functional theory (TD‐DFT). Moreover, an imine‐substituted tetracoordinated organic boron system (BNMes2) was selected for comparative study to explore the intrinsic reasons for the difference in reactivity between the two types of compounds. Steric factor was found to influence the photoisomerization activity of BNMes2 and BOMes2. These results rationalize the experimental observations and can provide helpful insights into understanding the excited‐state dynamics of heteroatom‐doped tetracoordinate organoboron compounds, which facilitates the rational design of boron‐based materials with superior photoresponsive performances.
MS‐CASPT2//CASSCF calculations reveal detailed mechanisms for the photoisomerization of boron compounds, showing that the steric hindrance influences their photoisomerization activity.
Cancer stem cells (CSCs) are crucial components of the tumor microenvironment that take part in tumor initiation, progression, recurrence, metastasis, and resistance to chemotherapy. This study ...explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal cancer (CRC), which thus far remain uncertain. Our findings indicated that the expression of miR‐20b‐5p is negatively correlated with that of metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1, r = −0.928, p = 0.023) and Oct4 (r = −0.894, p = 0.041) in CRC cells. We hypothesized that there may be some targeted regulatory relationships among MALAT1, miR‐20b‐5p, and Oct4. We proceeded to show that both si‐MALAT1 and miR‐20b‐5p‐mimic attenuated microsphere formation and self‐renewal capacity, decreased the proportion of CSCs, and downregulated the expression of proteins associated with tumor cell stemness maintenance (Oct4, Nanog, sex‐determining region Y‐box 2, and Notch1) and cellular metabolism (glucose transporter 1, lactate dehydrogenase B, hexokinase 2, and pyruvate kinase isozyme M2) in HCT‐116 cells in vitro. In addition, a xenograft model based on Balb/c mice demonstrated that the administration of either si‐MALAT1 or miR‐20b‐5p‐mimic suppressed the tumorigenicity of HCT‐116 cells in vivo. The underlying mechanisms may involve the targeting of the tumor cell stemness maintenance‐related factor Oct4 by miR‐20b‐5p. For the first time, we present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of CRC cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated.
We present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of colorectal cancer cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated.
A method for generation of S
VI
sulfones from β-sulfinyl esters (S
IV
) under transition-metal-free non-oxidative mild conditions is presented. Various sulfones have been achieved with moderate to ...excellent yields. The advantage of using β-sulfinyl esters as masked aryl sulfinates has also been exemplified using brominated substrates. Oxygen isotope-labeling experiments indicated that the oxygen atoms incorporated into the sulfone product come from the sulfoxide of the β-sulfinyl ester. Successive β-elimination/
O
-addition/sulfinate esterification/β-elimination processes are proposed for the mechanism of generating S
VI
from S
IV
.
A method for generation of S
VI
sulfones from β-sulfinyl esters (S
IV
) under transition-metal-free non-oxidative mild conditions is presented.
Fungal species of Armillaria, which can act as plant pathogens and/or symbionts of the Chinese traditional medicinal herb Gastrodia elata ("Tianma"), are ecologically and economically important and ...have consequently attracted the attention of mycologists. However, their taxonomy has been highly dependent on morphological characterization and mating tests. In this study, we phylogenetically analyzed Chinese Armillaria samples using the sequences of the internal transcribed spacer region, translation elongation factor-1 alpha gene and beta-tubulin gene. Our data revealed at least 15 phylogenetic lineages of Armillaria from China, of which seven were newly discovered and two were recorded from China for the first time. Fourteen Chinese biological species of Armillaria, which were previously defined based on mating tests, could be assigned to the 15 phylogenetic lineages identified herein. Seven of the 15 phylogenetic lineages were found to be disjunctively distributed in different continents of the Northern Hemisphere, while eight were revealed to be endemic to certain continents. In addition, we found that seven phylogenetic lineages of Armillaria were used for the cultivation of Tianma, only two of which had been recorded to be associated with Tianma previously. We also illustrated that G. elata f. glauca ("Brown Tianma") and G. elata f. elata ("Red Tianma"), two cultivars of Tianma grown in different regions of China, form symbiotic relationships with different phylogenetic lineages of Armillaria. These findings should aid the development of Tianma cultivation in China.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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