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A changing climate is altering many ocean properties that consequently will modify marine productivity. Previous phytoplankton manipulation studies have focused on individual or subsets of these properties. Here, we investigate the cumulative effects of multi-faceted change on a subantarctic diatom Pseudonitzschia multiseries by concurrently manipulating five stressors (light/nutrients/CO 2 /temperature/iron) that primarily control its physiology, and explore underlying reasons for altered physiological performance. Climate change enhances diatom growth mainly owing to warming and iron enrichment, and both properties decrease cellular nutrient quotas, partially offsetting any effects of decreased nutrient supply by 2100. Physiological diagnostics and comparative proteomics demonstrate the joint importance of individual and interactive effects of temperature and iron, and reveal biased future predictions from experimental outcomes when only a subset of multi-stressors is considered. Our findings for subantarctic waters illustrate how composite regional studies are needed to provide accurate global projections of future shifts in productivity and distinguish underlying species-specific physiological mechanisms. Investigation of multiple stressors on a subantarctic diatom reveals the importance of considering individual and interactive effects. Experiments show that temperature and iron enrichment enhance growth and help overcome nutrient depletion.

Several recent observational studies have shown organic carbon aerosols to be a significant source of absorption of solar radiation. The absorbing part of organic aerosols is referred to as \"brown\" carbon (BrC). Using a global chemical transport model and a radiative transfer model, we estimate for the first time the enhanced absorption of solar radiation due to BrC in a global model. The simulated wavelength dependence of aerosol absorption, as measured by the absorption Ångström exponent (AAE), increases from 0.9 for non-absorbing organic carbon to 1.2 (1.0) for strongly (moderately) absorbing BrC. The calculated AAE for the strongly absorbing BrC agrees with AERONET spectral observations at 440–870 nm over most regions but overpredicts for the biomass burning-dominated South America and southern Africa, in which the inclusion of moderately absorbing BrC has better agreement. The resulting aerosol absorption optical depth increases by 18% (3%) at 550 nm and 56% (38%) at 380 nm for strongly (moderately) absorbing BrC. The global simulations suggest that the strongly absorbing BrC contributes up to +0.25 W m−2 or 19% of the absorption by anthropogenic aerosols, while 72% is attributed to black carbon, and 9% is due to sulfate and non-absorbing organic aerosols coated on black carbon. Like black carbon, the absorption of BrC (moderately to strongly) inserts a warming effect at the top of the atmosphere (TOA) (0.04 to 0.11 W m−2), while the effect at the surface is a reduction (−0.06 to −0.14 W m−2). Inclusion of the strongly absorption of BrC in our model causes the direct radiative forcing (global mean) of organic carbon aerosols at the TOA to change from cooling (−0.08 W m−2) to warming (+0.025 W m−2). Over source regions and above clouds, the absorption of BrC is higher and thus can play an important role in photochemistry and the hydrologic cycle.

Cardiac progenitor cells derived from adult heart have emerged as one of the most promising stem cell types for cardiac protection and repair. Exosomes are known to mediate cell–cell communication by transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we investigated the cardiac progenitor cell (CPC)-derived exosomal miRNAs on protecting myocardium under oxidative stress. Sca1 + CPCs-derived exosomes were purified from conditional medium, and identified by nanoparticle trafficking analysis (NTA), transmission electron microscopy and western blotting using CD63, CD9 and Alix as markers. Exosomes production was measured by NTA, the result showed that oxidative stress-induced CPCs secrete more exosomes compared with normal condition. Although six apoptosis-related miRNAs could be detected in two different treatment-derived exosomes, only miR-21 was significantly upregulated in oxidative stress-induced exosomes compared with normal exosomes. The same oxidative stress could cause low miR-21 and high cleaved caspase-3 expression in H9C2 cardiac cells. But the cleaved caspase-3 was significantly decreased when miR-21 was overexpressed by transfecting miR-21 mimic. Furthermore, miR-21 mimic or inhibitor transfection and luciferase activity assay confirmed that programmed cell death 4 (PDCD4) was a target gene of miR-21, and miR-21/PDCD4 axis has an important role in anti-apoptotic effect of H9C2 cell. Western blotting and Annexin V/PI results demonstrated that exosomes pre-treated H9C2 exhibited increased miR-21 whereas decreased PDCD4, and had more resistant potential to the apoptosis induced by the oxidative stress, compared with non-treated cells. These findings revealed that CPC-derived exosomal miR-21 had an inhibiting role in the apoptosis pathway through downregulating PDCD4. Restored miR-21/PDCD4 pathway using CPC-derived exosomes could protect myocardial cells against oxidative stress-related apoptosis. Therefore, exosomes could be used as a new therapeutic vehicle for ischemic cardiac disease.

The traditional view of genome organization has been upended in the last decade with the discovery of vast amounts of non-protein-coding transcription. After initial concerns that this \"dark matter\" of the genome was transcriptional noise, it is apparent that a subset of these noncoding RNAs are functional. Long noncoding RNA (lncRNA) genes resemble protein-coding genes in several key aspects, and they have myriad molecular functions across many cellular pathways and processes, including oncogenic signaling. The number of lncRNA genes has recently been greatly expanded by our group to triple the number of protein-coding genes; therefore, lncRNAs are likely to play a role in many biological processes. Based on their large number and expression specificity in a variety of cancers, lncRNAs are likely to serve as the basis for many clinical applications in oncology.

Norway rats (Rattus norvegicus) and black rats (Rattus rattus) are among the most prolific and widespread urban pest species in the world. Yet despite their ubiquity, a unified understanding of the ecology of these species in urban habitats eludes us. A comprehensive understanding of urban rat ecology is important for managing rat populations and mitigating the harmful effects that they may have on urban ecosystems (e.g., structural damage, food contamination, and disease spread). The objective of this systematic review and narrative synthesis is to collate, compare, and contrast data from the published literature regarding the ecology of Norway and black rats in urban centers. Themes emerging from the synthesis process, and discussed in detail, include population dynamics, behavior, movement, and environmental influences on rat populations.

Experiments on man-made flawed rock-like materials are applied extensively to study the mechanical behaviour of rock masses as well as crack initiation modes and crack coalescence types. A large number of experiments on specimens containing two or three pre-existing flaws were previously conducted. In the present work, experiments on rock-like materials (formed from a mixture of sand, plaster, limestone and water at mass ratio of 126:9:9:16) containing multiple flaws subjected to uniaxial compression were conducted to further research the effects of the layout of pre-existing flaws on mechanical properties, crack initiation modes and crack coalescence types. Compared with previous experiments in which only three types of cracks were found, the present experiments on specimens containing multiple flaws under uniaxial compression revealed five types of cracks, including wing cracks, quasi-coplanar secondary cracks, oblique secondary cracks, out-of-plane tensile cracks and out-of-plane shear cracks. Ten types of crack coalescence occurred through linkage among wing cracks, quasi-coplanar secondary cracks, oblique secondary cracks, out-of-plane shear cracks and out-of-plane tensile cracks. Moreover, the effects of the non-overlapping length and flaw angle on the complete stress–strain curves, the stress of crack initiation, the peak strength, the peak strain and the elastic modulus were also investigated in detail.

The purposes of this study were to compare Young’s modulus values determined by shear wave ultrasound elastography (SWUE) with stiffness index obtained using a hand-held MyotonPRO device on the resting stiffness of gastrocnemius muscle belly and Achilles tendon; and to examine the test-retest reliability of those stiffness measurement using hand-held MyotonPRO. Twenty healthy volunteers participated in the study. The measurement values of muscle and tendon was determined in dominant legs. Each marker point was assessed using MyotonPRO and SWUE, respectively. Intra-operator reliability of MyotonPRO was established in 10 of the subjects. The correlation coefficients between the values of muscle and tendon stiffness indices determined by MyotonPRO and SWUE were calculated. Significant correlations were found for muscle and tendon stiffness and Young’s modulus ranged from 0.463 to 0.544 (all P  < 0.05). The intra-operator reliability ranged from good to excellent (ICC (3,1)  = 0.787~0.928). These results suggest that the resting stiffness of gastrocnemius muscle belly and Achilles tendon measured by MyotonPRO is related to the Young’s modulus of those quantified by SWUE. The MyotonPRO shows good intra-operator repeatability. Therefore, the present study shows that MyotonPRO can be used to assess mechanical properties of gastrocnemius muscle belly and Achilles tendon with a resting condition.

Remdesivir (GS-5734) is a 1′-cyano-substituted adenosine nucleotide analogue prodrug that shows broad-spectrum antiviral activity against several RNA viruses. This compound is currently under clinical development for the treatment of Ebola virus disease (EVD). While antiviral effects have been demonstrated in cell culture and in non-human primates, the mechanism of action of Ebola virus (EBOV) inhibition for remdesivir remains to be fully elucidated. The EBOV RNA-dependent RNA polymerase (RdRp) complex was recently expressed and purified, enabling biochemical studies with the relevant triphosphate (TP) form of remdesivir and its presumptive target. In this study, we confirmed that remdesivir-TP is able to compete for incorporation with adenosine triphosphate (ATP). Enzyme kinetics revealed that EBOV RdRp and respiratory syncytial virus (RSV) RdRp incorporate ATP and remdesivir-TP with similar efficiencies. The selectivity of ATP against remdesivir-TP is ~4 for EBOV RdRp and ~3 for RSV RdRp. In contrast, purified human mitochondrial RNA polymerase (h-mtRNAP) effectively discriminates against remdesivir-TP with a selectivity value of ~500-fold. For EBOV RdRp, the incorporated inhibitor at position i does not affect the ensuing nucleotide incorporation event at position i+1. For RSV RdRp, we measured a ~6-fold inhibition at position i+1 although RNA synthesis was not terminated. Chain termination was in both cases delayed and was seen predominantly at position i+5. This pattern is specific to remdesivir-TP and its 1′-cyano modification. Compounds with modifications at the 2′-position show different patterns of inhibition. While 2′-C-methyl-ATP is not incorporated, ara-ATP acts as a non-obligate chain terminator and prevents nucleotide incorporation at position i+1. Taken together, our biochemical data indicate that the major contribution to EBOV RNA synthesis inhibition by remdesivir can be ascribed to delayed chain termination. The long distance of five residues between the incorporated nucleotide analogue and its inhibitory effect warrant further investigation.

We report the first detection of polarization angle orthogonal jumps, a phenomenon previously only observed from radio pulsars, from a fast radio burst (FRB) source FRB 20201124A. We find three cases of orthogonal jumps in over 2000 bursts, all resembling those observed in pulsar single pulses. We propose that the jumps are due to the superposition of two orthogonal emission modes that could only be produced in a highly magnetized plasma, and they are caused by the line of sight sweeping across a rotating magnetosphere. The shortest jump timescale is of the order of 1 millisecond, which hints that the emission modes come from regions smaller than the light cylinder of most pulsars or magnetars. This discovery provides convincing evidence that FRB emission originates from the complex magnetosphere of a magnetar, suggesting an FRB emission mechanism that is analogous to radio pulsars despite a huge luminosity difference between two types of objects.

Natural products have proven to have significant curative effects and are increasingly considered as potential candidates for clinical prevention, diagnosis, and treatment. Compared with synthetic drugs, natural products not only have diverse structures but also exhibit a range of biological activities against different disease states and molecular targets, making them attractive for development in the field of medicine. Despite advancements in the use of natural products for clinical purposes, there remain obstacles that hinder their full potential. These challenges include issues such as limited solubility and stability when administered orally, as well as short durations of effectiveness. To address these concerns, nano-drug delivery systems have emerged as a promising solution to overcome the barriers faced in the clinical application of natural products. These systems offer notable advantages, such as a large specific surface area, enhanced targeting capabilities, and the ability to achieve sustained and controlled release. Extensive in vitro and in vivo studies have provided further evidence supporting the efficacy and safety of nanoparticle-based systems in delivering natural products in preclinical disease models. This review describes the limitations of natural product applications and the current status of natural products combined with nanotechnology. The latest advances in nano-drug delivery systems for delivery of natural products are considered from three aspects: connecting targeting warheads, self-assembly, and co-delivery. Finally, the challenges faced in the clinical translation of nano-drugs are discussed.