Abstract
Copper electrocatalysts have been shown to selectively reduce carbon dioxide to hydrocarbons. Nevertheless, the absence of a systematic study based on time-resolved spectroscopy renders the ...functional agent—either metallic or oxidative Copper—for the selectivity still undecidable. Herein, we develop an operando seconds-resolved X-ray absorption spectroscopy to uncover the chemical state evolution of working catalysts. An oxide-derived Copper electrocatalyst is employed as a model catalyst to offer scientific insights into the roles metal states serve in carbon dioxide reduction reaction (CO
2
RR). Using a potential switching approach, the model catalyst can achieve a steady chemical state of half-Cu(0)-and-half-Cu(I) and selectively produce asymmetric C
2
products - C
2
H
5
OH. Furthermore, a theoretical analysis reveals that a surface composed of Cu-Cu(I) ensembles can have dual carbon monoxide molecules coupled asymmetrically, which potentially enhances the catalyst’s CO
2
RR product selectivity toward C
2
products. Our results offer understandings of the fundamental chemical states and insights to the establishment of selective CO
2
RR.
Organic light-emitting diodes (OLEDs) based on thermally activated delayed fluorescence (TADF) materials are promising for the realization of highly efficient light emitters. However, such devices ...have so far suffered from efficiency roll-off at high luminance. Here, we report the design and synthesis of two diboron-based molecules, CzDBA and tBuCzDBA, which show excellent TADF properties and yield efficient OLEDs with very low efficiency roll-off. These donor–acceptor–donor (D–A–D) type and rod-like compounds concurrently generate TADF with a photoluminescence quantum yield of ~100% and an 84% horizontal dipole ratio in the thin film. A green OLED based on CzDBA exhibits a high external quantum efficiency of 37.8 ± 0.6%, a current efficiency of 139.6 ± 2.8 cd A−1 and a power efficiency of 121.6 ± 3.1 lm W−1 with an efficiency roll-off of only 0.3% at 1,000 cd m−2. The device has a peak emission wavelength of 528 nm and colour coordinates of the Commission International de l´Eclairage (CIE) of (0.31, 0.61), making it attractive for colour-display applications.
Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. ...Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPRmt) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPRmt-responsive transcription factor. Furthermore, the mitochondrial changes and longevity effects induced by CA are conserved across different species. Together, our results identified molecular targets for developing pro-longevity microbes and a bacterial metabolite acting on host mitochondria to promote longevity.
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•Systematic analysis of longevity-promoting microbial genetic variations•Colanic acid as a pro-longevity natural compound effective in different species•Bacterial metabolites regulate host mitochondrial dynamics and UPRmit
The genetic composition of gut microbes controls the production of metabolites that impact host longevity.
Some oral probiotics have been shown to prevent necrotizing enterocolitis (NEC) and decrease mortality effectively in preterm very low birth weight (PVLBW) infants. However, it is unclear whether a ...single probiotic or a mixture of probiotics is most effective for the prevention of NEC.
A meta-analysis was conducted by reviewing the most up to date literature to investigate whether multiple strains probiotics are more effective than a single strain in reducing NEC and death in PVLBW infants.
Relevant studies were identified by searches of the MEDLINE, EMBASE, and Cochrane CENTRAL databases, from 2001 to 2016.
The inclusion criteria were randomized controlled trials of any enteral probiotic supplementation that was initiated within the first 7 days and continued for at least 14 days in preterm infants (≤ 34 weeks' gestation) and/or those of a birth weight ≤1500 g.
A total of 25 trials (n = 7345 infants) were eligible for inclusion in the meta-analysis using a fixed-effects model. Multiple strains probiotics were associated with a marked reduction in the incidence of NEC, with a pooled OR of 0.36 (95% CI, 0.24-0.53; P < .00001). Single strain probiotic using Lactobacillus species had a borderline effect in reducing NEC (OR of 0.60; 95% CI 0.36-1.0; P = .05), but not mortality. Multiple strains probiotics had a greater effectiveness in reducing mortality and were associated with a pooled OR of 0.58 (95% CI, 0.43-0.79; P = .0006). Trials using single strain of Bifidobacterium species and Saccharomyces boulardii did not reveal any beneficial effects in terms of reducing NEC or mortality.
This updated report found that multiple strains probiotics appear to be the most feasible and effective strategy for the prevention of NEC and reduction of mortality in PVLBW neonates. Further clinical trials should focus on which probiotic combinations are most effective.
Mitochondria play crucial roles in regulating metabolism and longevity. A body of recent evidences reveals that the gut microbiome can also exert significant effects on these activities in the host. ...Here, by summarizing the currently known mechanisms underlying these regulations, and by comparing mitochondrial fission–fusion dynamics with bacterial interactions such as quorum sensing, we hypothesize that the microbiome impacts the host by communicating with their intracellular relatives, mitochondria. We highlight recent discoveries supporting this model, and these new findings reveal that metabolite molecules derived from bacteria can fine‐tune mitochondrial dynamics in intestinal cells and hence influence host metabolic fitness and longevity. This perspective mode of chemical communication between bacteria and mitochondria may help us understand complex and dynamic environment–microbiome–host interactions regarding their vital impacts on health and diseases.
Gut microbiome orchestrates biological processes in the host by communicating with mitochondria, intracellular organelles that originated from bacteria. Reciprocating to environmental challenges, bacteria produce metabolites that can modulate mitochondrial dynamics to adjust intracellular activities. Together, the interplay between microbiome and mitochondria provides new insights into the regulation of host metabolic health and longevity.
Abstract Previously, gold nanoshells were shown to be able to effectively convert photon energy to heat, leading to hyperthermia and suppression of tumor growths in mice. Herein, we show that in ...addition to the nanomaterial-mediated photothermal effects (NmPTT), gold nanoshells (including, nanocages, nanorod-in-shell and nanoparticle-in-shell) not only are able to absorb NIR light, but can also emit fluorescence, sensitize formation of singlet oxygen and exert nanomaterial-mediated photodynamic therapeutic (NmPDT) complete destruction of solid tumors in mice. The modes of NmPDT and NmPTT can be controlled and switched from one to the other by changing the excitation wavelength. In the in vitro experiments, gold nanocages and nanorod-in-shell show larger percentage of cellular deaths originating from NmPDT along with the minor fraction of NmPTT effects. In contrast, nanoparticle-in-shell exhibits larger fraction of NmPTT-induced cellular deaths together with minor fraction of NmPDT-induced apoptosis. Fluorescence emission spectra and DPBF quenching studies confirm the generation of singlet O2 upon NIR photoirradiation. Both NmPDT and NmPTT effects were confirmed by measurements of reactive oxygen species (ROS) and subsequent sodium azide quenching, heat shock protein expression (HSP 70), singlet oxygen sensor green (SOSG) sensing, changes in mitochondria membrane potential and apoptosis in the cellular experiments. In vivo experiments further demonstrate that upon irradiation at 980 nm under ultra-low doses (∼150 mW/cm2 ), gold nanocages mostly exert NmPDT effect to effectively suppress the B16F0 melanoma tumor growth. The combination of NmPDT and NmPTT effects on destruction of solid tumors is far better than pure NmPTT effect by 808 nm irradiation and also doxorubicin. Overall, our study demonstrates that gold nanoshells can serve as excellent multi-functional theranostic agents (fluorescence imaging + NmPDT + NmPTT) upon single photon NIR light excitation under ultra-low laser doses.
Abnormal tumour vasculature has a significant impact on tumour progression and response to therapy. Nitric oxide (NO) regulates angiogenesis and maintains vascular homeostasis and, thus, can be ...delivered to normalize tumour vasculature. However, a NO-delivery system with a prolonged half-life and a sustained release mechanism is currently lacking. Here we report the development of NanoNO, a nanoscale carrier that enables sustained NO release to efficiently deliver NO into hepatocellular carcinoma. Low-dose NanoNO normalizes tumour vessels and improves the delivery and effectiveness of chemotherapeutics and tumour necrosis factor-related, apoptosis-inducing, ligand-based therapy in both primary tumours and metastases. Furthermore, low-dose NanoNO reprogrammes the immunosuppressive tumour microenvironment toward an immunostimulatory phenotype, thereby improving the efficacy of cancer vaccine immunotherapy. Our findings demonstrate the ability of nanoscale NO delivery to efficiently reprogramme tumour vasculature and immune microenvironments to overcome resistance to cancer therapy, resulting in a therapeutic benefit.
While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder the broader application of cancer ...immunotherapy. Here, we report a combinatorial immunotherapy approach that uses a highly efficient and tumor-selective gene carrier to improve anticancer efficacy and circumvent the systemic toxicity. In this study, we engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers that exhibit not only enhanced gene delivery capacity but also immune adjuvant properties by activating the stimulator of interferon genes (STING)-cGAS pathway. TT-LDCP NPs delivered siRNA against immune checkpoint ligand PD-L1 and immunostimulatory IL-2-encoding plasmid DNA to hepatocellular carcinoma (HCC), increased tumoral infiltration and activation of CD8
T cells, augmented the efficacy of cancer vaccine immunotherapy, and suppressed HCC progression. Our work presents nanotechnology-enabled dual delivery of siRNA and plasmid DNA that selectively targets and reprograms the immunosuppressive tumor microenvironment to improve cancer immunotherapy.
Sensitive and specific visualization of small biomolecules in living systems is highly challenging. We report stimulated Raman-scattering imaging of alkyne tags as a general strategy for studying a ...broad spectrum of small biomolecules in live cells and animals. We demonstrate this technique by tracking alkyne-bearing drugs in mouse tissues and visualizing de novo synthesis of DNA, RNA, proteins, phospholipids and triglycerides through metabolic incorporation of alkyne-tagged small precursors.
Microorganisms and their hosts share the same environment, and microbial metabolic molecules (metabolites) exert crucial effects on host physiology. Environmental factors not only shape the ...composition of the host's resident microorganisms, but also modulate their metabolism. However, the exact molecular relationship among the environment, microbial metabolites and host metabolism remains largely unknown. Here, we discovered that environmental methionine tunes bacterial methyl metabolism to regulate host mitochondrial dynamics and lipid metabolism in Caenorhabditis elegans through an endocrine crosstalk involving NR5A nuclear receptor and Hedgehog signalling. We discovered that methionine deficiency in bacterial medium decreases the production of bacterial metabolites that are essential for phosphatidylcholine synthesis in C. elegans. Reductions of diundecanoyl and dilauroyl phosphatidylcholines attenuate NHR-25, a NR5A nuclear receptor, and release its transcriptional suppression of GRL-21, a Hedgehog-like protein. The induction of GRL-21 consequently inhibits the PTR-24 Patched receptor cell non-autonomously, resulting in mitochondrial fragmentation and lipid accumulation. Together, our work reveals an environment-microorganism-host metabolic axis regulating host mitochondrial dynamics and lipid metabolism, and discovers NR5A-Hedgehog intercellular signalling that controls these metabolic responses with critical consequences for host health and survival.
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