Abstract
N6-methyladenosine (m
6
A) is one of the most common RNA modifications in eukaryotes, mainly in messenger RNA (mRNA). Increasing evidence shows that m
6
A methylation modification acts an ...essential role in various physiological and pathological bioprocesses. Noncoding RNAs (ncRNAs), including miRNAs, lncRNAs and circRNAs, are known to participate in regulating cell differentiation, angiogenesis, immune response, inflammatory response and carcinogenesis. m
6
A regulators, such as METTL3, ALKBH5 and IGF2BP1 have been reported to execute a m
6
A-dependent modification of ncRNAs involved in carcinogenesis. Meanwhile, ncRNAs can target or modulate m
6
A regulators to influence cancer development. In this review, we provide an insight into the interplay between m
6
A modification and ncRNAs in cancer.
Abstract
Dimethylsulfoniopropionate (DMSP) is an important marine osmolyte. Aphotic environments are only recently being considered as potential contributors to global DMSP production. Here, ...our Mariana Trench study reveals a typical seawater DMSP/dimethylsulfide (DMS) profile, with highest concentrations in the euphotic zone and decreased but consistent levels below. The genetic potential for bacterial DMSP synthesis via the
dsyB
gene and its transcription is greater in the deep ocean, and is highest in the sediment.s DMSP catabolic potential is present throughout the trench waters, but is less prominent below 8000 m, perhaps indicating a preference to store DMSP in the deep for stress protection. Deep ocean bacterial isolates show enhanced DMSP production under increased hydrostatic pressure. Furthermore, bacterial
dsyB
mutants are less tolerant of deep ocean pressures than wild-type strains. Thus, we propose a physiological function for DMSP in hydrostatic pressure protection, and that bacteria are key DMSP producers in deep seawater and sediment.
Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to co-target alternative pathways and ...select optimal patients. Herein, we investigated patient subpopulations more likely to benefit from immunotherapy and inform more effective combination regimens for TNBC patients.
We conducted exploratory analyses in the FUSCC cohort to characterize a novel patient selection method and actionable targets for TNBC immunotherapy. We investigated this in vivo and launched a phase 2 trial to assess the clinical value of such criteria and combination regimen. Furthermore, we collected clinicopathological and next-generation sequencing data to illustrate biomarkers for patient outcomes.
CD8-positivity could identify an immunomodulatory subpopulation of TNBCs with higher possibilities to benefit from immunotherapy, and angiogenesis was an actionable target to facilitate checkpoint blockade. We conducted the phase II FUTURE-C-Plus trial to assess the feasibility of combining famitinib (an angiogenesis inhibitor), camrelizumab (a PD-1 monoclonal antibody) and chemotherapy in advanced immunomodulatory TNBC patients. Within 48 enrolled patients, the objective response rate was 81.3% (95% CI, 70.2-92.3), and the median progression-free survival was 13.6 months (95% CI, 8.4-18.8). No treatment-related deaths were reported. Patients with CD8- and/or PD-L1- positive tumors benefit more from this regimen. PKD1 somatic mutation indicates worse progression-free and overall survival.
This study confirms the efficacy and safety of the triplet regimen in immunomodulatory TNBC and reveals the potential of combining CD8, PD-L1 and somatic mutations to guide clinical decision-making and treatments.
ClinicalTrials.gov: NCT04129996 . Registered 11 October 2019.
Platinum‐catalyzed formal 5+2 and 4+2 annulations of isoxazoles with heterosubstituted alkynes enabled the atom‐economical synthesis of valuable 1,3‐oxazepines and 2,5‐dihydropyridines, respectively. ...Importantly, this Pt catalysis not only led to unique reactivity dramatically divergent from that observed under Au catalysis, but also proceeded via unprecedented α‐imino platinum carbene intermediates.
Gold's deviant relative: Platinum‐catalyzed formal 5+2 and 4+2 annulations of isoxazoles and heterosubstituted alkynes provided valuable 1,3‐oxazepines and 2,5‐dihydropyridines (see scheme). This reactivity deviates dramatically from that observed under gold catalysis and involves the generation of an α‐imino platinum carbene. A computational study provided evidence for the proposed mechanism of this unusual tandem sequence.
Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral ...composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements.
We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated.
These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.
The point process is a solid framework to model sequential data, such as videos, by exploring the underlying relevance. As a challenging problem for high-level video understanding, weakly supervised ...action recognition and localization in untrimmed videos have attracted intensive research attention. Knowledge transfer by leveraging the publicly available trimmed videos as external guidance is a promising attempt to make up for the coarse-grained video-level annotation and improve the generalization performance. However, unconstrained knowledge transfer may bring about irrelevant noise and jeopardize the learning model. This article proposes a novel adaptability decomposing encoder-decoder network to transfer reliable knowledge between the trimmed and untrimmed videos for action recognition and localization by bidirectional point process modeling, given only video-level annotations. By decomposing the original features into the domain-adaptable and domain-specific ones based on their adaptability, trimmed-untrimmed knowledge transfer can be safely confined within a more coherent subspace. An encoder-decoder-based structure is carefully designed and jointly optimized to facilitate effective action classification and temporal localization. Extensive experiments are conducted on two benchmark data sets (i.e., THUMOS14 and ActivityNet1.3), and the experimental results clearly corroborate the efficacy of our method.
G‐quadruplex DNA show structural polymorphism, leading to challenges in the use of selective recognition probes for the accurate detection of G‐quadruplexes in vivo. Herein, we present a tripodal ...cationic fluorescent probe, NBTE, which showed distinguishable fluorescence lifetime responses between G‐quadruplexes and other DNA topologies, and fluorescence quantum yield (Φf) enhancement upon G‐quadruplex binding. We determined two NBTE‐G‐quadruplex complex structures with high Φf values by NMR spectroscopy. The structures indicated NBTE interacted with G‐quadruplexes using three arms through π–π stacking, differing from that with duplex DNA using two arms, which rationalized the higher Φf values and lifetime response of NBTE upon G‐quadruplex binding. Based on photon counts of FLIM, we detected the percentage of G‐quadruplex DNA in live cells with NBTE and found G‐quadruplex DNA content in cancer cells is 4‐fold that in normal cells, suggesting the potential applications of this probe in cancer cell detection.
G4 imaging: A tripodal cationic fluorescence probe, NBTE, was used for the visualization (based on fluorescence lifetime) and quantification (based on photon counts) of G‐quadruplex DNA in live cells by fluorescence lifetime imaging microscopy (FLIM). Structural studies provided a structural basis for the DNA‐topology‐based fluorescence response of NBTE.
Ubiquitous contamination of microplastics and arsenic in soil ecosystems can induce many health issues to nontarget soil organisms, and will also cause many potential threats to the gut bacterial ...communities of soil fauna. However, the changes in the gut bacterial communities of soil fauna after exposure to both microplastics and arsenic remain unknown. In this study, the toxicity and effects on the gut microbiota of earthworm Metaphire californica caused by the combined exposure of microplastics and arsenic were examined by using arsenic species analysis and high throughput sequencing of gut microbiota. Results showed that total arsenic and arsenic species in the earthworm gut and body tissues after exposure to combination of microplastics with arsenate (As(V)) were significantly different from that treated with As(V) alone. Microplastics lessened the accumulation of total arsenic and the transformation rate of As(V) to arsenite (As(III)). Microplastics alleviated the effect of arsenic on the gut microbiota possibly via adsorbing/binding As(V) and lowering arsenic bioavailability, thus prevented the reduction of As(V) and accumulation of total arsenic in the gut which resulted in a lower toxicity on the earthworm. The study broadens our understanding of the ecotoxicity of microplastics with other pollutants on the soil animals and on their gut microbiota.
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•Arsenic exposure prominently altered the gut bacterial communities of earthworm.•Microplastics reduced arsenic accumulation in the earthworm gut and body tissues by inhibiting As(V) reduction.•Microplastics alleviated the effect of arsenic on the gut microbiota.
Exposure to microplastics lowers arsenic accumulation in the gut and body tissues of earthworm, and alters gut bacterial communities of Metaphire californica.
The scarcity of reliable methods for synthesizing chiral gem‐diarylmethine borons limits their applications. Herein, we report a method for highly enantioselective dirhodium‐catalyzed B−H bond ...insertion reactions with diaryl diazomethanes as carbene precursors. These reactions afforded chiral gem‐diarylmethine borane compounds in high yield (up to 99 % yield), high activity (turnover numbers up to 14 300), high enantioselectivity (up to 99 % ee) and showed unprecedented broad functional group tolerance. The borane compounds synthesized by this method could be efficiently transformed into diaryl methanol, diaryl methyl amine, and triaryl methane derivatives with good stereospecificity. Mechanistic studies suggested that the borane adduct coordinated to the rhodium catalyst and thus interfered with decomposition of the diazomethane, and that insertion of a rhodium carbene (generated from the diaryl diazomethane) into the B−H bond was most likely the rate‐determining step.
We report highly enantioselective dirhodium‐catalyzed B−H bond insertion reactions with diaryl diazomethanes as carbene precursors. These reactions afforded chiral gem‐diarylmethine borane compounds in high yield (up to 99 % yield), high activity (turnover numbers up to 14 300), high enantioselectivity (up to 99 % ee) and showed unprecedented broad functional group tolerance.
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