A photothermal bacterium (PTB) is reported for tumor‐targeted photothermal therapy (PTT) by using facultative anaerobic bacterium Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to biomineralize ...palladium nanoparticles (Pd NPs) on its surface without affecting bacterial activity. It is found that PTB possesses superior photothermal property in near infrared (NIR) regions, as well as preferential tumor‐targeting capacity. Zeolitic imidazole frameworks‐90 (ZIF‐90) encapsulating photosensitizer methylene blue (MB) are hybridized on the surface of living PTB to further enhance PTT efficacy. MB‐encapsulated ZIF‐90 (ZIF‐90/MB) can selectively release MB at mitochondria and cause mitochondrial dysfunction by producing singlet oxygen (1O2) under light illumination. Mitochondrial dysfunction further contributes to adenosine triphosphate (ATP) synthesis inhibition and heat shock proteins (HSPs) down‐regulated expression. The PTB‐based therapeutic platform of PTB@ZIF‐90/MB demonstrated here will find great potential to overcome the challenges of tumor targeting and tumor heat tolerance in PTT.
A bacteria‐based photothermal therapeutic platform comprising PTB@ZIF‐90/MB is developed, which reveals great potential to augment photothermal therapy efficacy by tackling the challenges of tumor targeting and heat resistance.
By leveraging the ability of Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to anaerobically catabolize lactate through the transfer of electrons to metal minerals for respiration, a lactate‐fueled ...biohybrid (Bac@MnO2) was constructed by modifying manganese dioxide (MnO2) nanoflowers on the S. oneidensis MR‐1 surface. The biohybrid Bac@MnO2 uses decorated MnO2 nanoflowers as electron receptor and the tumor metabolite lactate as electron donor to make a complete bacterial respiration pathway at the tumor sites, which results in the continuous catabolism of intercellular lactate. Additionally, decorated MnO2 nanoflowers can also catalyze the conversion of endogenous hydrogen peroxide (H2O2) into generate oxygen (O2), which could prevent lactate production by downregulating hypoxia‐inducible factor‐1α (HIF‐1α) expression. As lactate plays a critical role in tumor development, the biohybrid Bac@MnO2 could significantly inhibit tumor progression by coupling bacteria respiration with tumor metabolism.
MnO2 nanoflowers were modified on the cell surface of electrochemically active bacteria, S. oneidensis MR‐1. The biohybrids, which couple bacterial respiration with tumor metabolism, can catabolize intercellular lactate and prevent intracellular lactate production in the tumor, thereby inducing significant tumor inhibition.
Synthetic biology based on bacteria has been displayed in antitumor therapy and shown good performance. In this study, an engineered bacterium Escherichia coli MG1655 is designed with NDH‐2 enzyme ...(respiratory chain enzyme II) overexpression (Ec‐pE), which can colonize in tumor regions and increase localized H2O2 generation. Following from this, magnetic Fe3O4 nanoparticles are covalently linked to bacteria to act as a catalyst for a Fenton‐like reaction, which converts H2O2 to toxic hydroxyl radicals (•OH) for tumor therapy. In this constructed bioreactor, the Fenton‐like reaction occurs with sustainably synthesized H2O2 produced by engineered bacteria, and severe tumor apoptosis is induced via the produced toxic •OH. These results show that this bioreactor can achieve effective tumor colonization, and realize a self‐supplied therapeutic Fenton‐like reaction without additional H2O2 provision.
A Fenton‐like bioreactor based on bacteria is reported for tumor therapy without exogenous H2O2 provision. It is found that this bioreactor can achieve effective tumor colonization, and realize a self‐supplied therapeutic Fenton‐like reaction without additional H2O2 provision.
Synthetic biology based on bacteria has been displayed in antitumor therapy and shown good performance. In this study, an engineered bacterium Escherichia coli MG1655 is designed with NDH-2 enzyme ...(respiratory chain enzyme II) overexpression (Ec-pE), which can colonize in tumor regions and increase localized H
O
generation. Following from this, magnetic Fe
O
nanoparticles are covalently linked to bacteria to act as a catalyst for a Fenton-like reaction, which converts H
O
to toxic hydroxyl radicals (•OH) for tumor therapy. In this constructed bioreactor, the Fenton-like reaction occurs with sustainably synthesized H
O
produced by engineered bacteria, and severe tumor apoptosis is induced via the produced toxic •OH. These results show that this bioreactor can achieve effective tumor colonization, and realize a self-supplied therapeutic Fenton-like reaction without additional H
O
provision.
Recognition of viral RNA by the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) initiates innate antiviral immune response. How the binding of viral RNA to and activation of the RLRs are ...regulated remains enigmatic. In this study, we identified ZCCHC3 as a positive regulator of the RLRs including RIG-I and MDA5. ZCCHC3 deficiency markedly inhibited RNA virus-triggered induction of downstream antiviral genes, and ZCCHC3-deficient mice were more susceptible to RNA virus infection. ZCCHC3 was associated with RIG-I and MDA5 and functions in two distinct processes for regulation of RIG-I and MDA5 activities. ZCCHC3 bound to dsRNA and enhanced the binding of RIG-I and MDA5 to dsRNA. ZCCHC3 also recruited the E3 ubiquitin ligase TRIM25 to the RIG-I and MDA5 complexes to facilitate its K63-linked polyubiquitination and activation. Thus, ZCCHC3 is a co-receptor for RIG-I and MDA5, which is critical for RLR-mediated innate immune response to RNA virus.
•ZCCHC3 mediates viral RNA-triggered innate immune response•ZCCHC3 binds to viral RNA•ZCCHC3 acts as a co-receptor for RIG-I and MDA5•ZCCHC3 mediates polyubiquitination and activation of RIG-I and MDA5 by TRIM25
Recognition of viral RNA by RIG-I-like receptors (RLRs) initiates innate antiviral response. Lian et al. demonstrate that ZCCHC3 is a co-receptor for RLRs, thereby acting as an important modulator of innate antiviral response.
Cyclic GMP-AMP synthase (cGAS) senses double-strand (ds) DNA in the cytosol and then catalyzes synthesis of the second messenger cGAMP, which activates the adaptor MITA/STING to initiate innate ...antiviral response. How cGAS activity is regulated remains enigmatic. Here, we identify ZCCHC3, a CCHC-type zinc-finger protein, as a positive regulator of cytosolic dsDNA- and DNA virus-triggered signaling. We show that ZCCHC3-deficiency inhibits dsDNA- and DNA virus-triggered induction of downstream effector genes, and that ZCCHC3-deficient mice are more susceptible to lethal herpes simplex virus type 1 or vaccinia virus infection. ZCCHC3 directly binds to dsDNA, enhances the binding of cGAS to dsDNA, and is important for cGAS activation following viral infection. Our results suggest that ZCCHC3 is a co-sensor for recognition of dsDNA by cGAS, which is important for efficient innate immune response to cytosolic dsDNA and DNA virus.
Bacteria can act as a promising anti‐tumor platform due to their specific targeting capacity to the tumor microenvironment. In this study, it is discovered that intravenous administration of ...Escherichia coli TOP10 induces rapid and intense blood coagulation in tumor tissues instead of normal tissues. It is demonstrated that E. coli TOP10 can act as an activator of a coagulation cascade to trigger abnormal hemorrhage, blood coagulation, and inflammation with abundant macrophages recruitment in tumors. In addition, the recruited macrophages are principally polarized by lipopolysaccharide in the bacterial wall to the anti‐tumor M1‐like phenotype. Based on the above finding, coagulation‐tropism blood platelets decorated with CD47 antibodies (Anti‐CD47), which possess tropism for bacteria‐treated tumors are further prepared. As a result, Anti‐CD47 blocks the “don't eat me” signal from tumor cells, consequently promoting the phagocytosis of polarized M1‐like phenotype macrophages for tumor cells. This manipulation of local blood coagulation in tumors may find great potential for accurately delivering immune checkpoint inhibitors and facilitating tumor immunotherapy.
Living Escherichia coli TOP10 is demonstrated to induce rapid and intense blood coagulation specifically in tumors, along with macrophages recruitment and polarization. The coagulation‐tropism blood platelets decorated with CD47 antibodies (Anti‐CD47) are prepared for promoting the phagocytosis of polarized macrophages for tumor cells.
To develop a lipophilic bulk polymer capable of self-healing and recycling for future structural applications in different aquatic environments, hyperbranched polyurethane containing a few ...hydrophilic quaternary ammonium salts and abundant dynamic reversible catechol-B3+ crosslinkages is synthesized as our first step in this direction. The compositional and structural design ensures dynamicity of the polymer networks as well as effective interdiffusion and interaction of dangling chains on the damaged surface in water. More importantly, the boronic ester bonds become not easily hydrolyzed at lower pH due to the electron attracting effect of quaternary ammonium cations from catechol-B3+ bonds. Qualitative visual inspection and quantitative tensile tests demonstrate that the proposed idea works, and the target polymer is allowed to be self-healed and reprocessed in waters at pH 7 and 9 at room temperature. Reshuffling and rearrangement of the polymer networks via dynamic reversible coordination of catechol-B3+ bonds helps to re-bond the interface. The technical route provides an effective solution to stabilizing catechol-B3+ bonds at lower pH, and obviously reduces the pH sensitivity of boronic ester bonds, which is the objective of the current work. As a result, the adaptivity and serviceable range of the underwater intrinsic self-healing polymer are expanded.
In this work, water triggered dynamic catechol-Fe
coordinate bonds are revealed and studied at atomic, molecular and macroscopic levels using Mössbauer spectroscopy, rheological analysis,
DOPA-iron ...complexation is found to be dynamic in the presence of water, and this dynamic manner is immobilized after removing water. Accordingly, a water saturated lipophilic polymer containing catechol-Fe
crosslinks, rather than the dry version, exhibits dynamic coordination-dissociation behavior. In addition, a migration of iron proves to be enabled in the catechol-Fe
crosslinked polymer immersed in seawater. Rearrangement of the dynamic catechol-Fe
coordinate bonds among different molecules is thus favored. Based on these results, we develop a bulk lipophilic polymer solid capable of repeated autonomic recovery of strength in seawater without manual intervention. When the polymer is damaged in seawater, reshuffling of the mobile hyperbranched polymer networks across the crack interface, owing to the dynamic catechol-Fe
crosslinkages activated by the alkaline circumstances, rebinds the damaged site. By taking advantage of the same mechanism, the polymer can be remolded with the help of seawater and this recycled polymer is still self-healable in seawater. Unlike in the case of conventional polymers where water would shield macromolecules from interacting, here, seawater is a necessary environmental assistant for the material interaction to take effect. The outcomes are beneficial for deepening the understanding of coordinate bonds, and the development of robust underwater self-healing lipophilic polymers.
According to epidemiological studies, particulate matter 2.5 (PM2.5) is a significant contributor to cardiovascular disease (CVD). However, making causal inferences is difficult due to the ...methodological constraints of observational studies. In this study, we used two-sample Mendelian randomization (MR) to examine the causal relationship between PM 2.5 and the risk of CVD.
Genome-wide association study (GWAS) statistics for PM2.5 and CVD were collected from the FinnGen and UK Biobanks. Mendelian randomization analyses were applied to explore the causal effects of PM2.5 on CVD by selecting single-nucleotide polymorphisms(SNP) as instrumental variables.
The results revealed that a causal effect was observed between PM2.5 and coronary artery disease(IVW: OR 2.06, 95% CI 1.35, 3.14), and hypertension(IVW: OR 1.07, 95% CI 1.03, 1.12). On the contrary, no causal effect was observed between PM2.5 and myocardial infarction(IVW: OR 0.73, 95% CI 0.44, 1.22), heart failure(IVW: OR 1.54, 95% CI 0.96, 2.47), atrial fibrillation(IVW: OR 1.03, 95% CI 0.71, 1.48), and ischemic stroke (IS)(IVW: OR 0.98, 95% CI 0.54, 1.77).
We discovered that there is a causal link between PM2.5 and coronary artery disease and hypertension in the European population, using MR methods. Our discovery may have the significance of public hygiene to improve the understanding of air quality and CVD risk.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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