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.
Poly(N-isopropylacrylamide-co-3-(trimethoxysilyl)propyl methacrylate)-b-poly(2-(diethylamino)ethyl methacrylate) (P(NIPAAm-co-MPMA)-b-P(DEA)) copolymer was synthesized by reversible ...addition−fragmentation chain transfer (RAFT) polymerization. The temperature and pH responsive schizophrenic micellization behaviors of P(NIPAAm-co-MPMA)-b-P(DEA) and the cross-linking of P(NIPAAm-co-MPMA) blocks using inorganic silica-based cross-linking strategy were investigated in detail. Transmission electron microscopy (TEM) showed that the resultant core cross-linked (CCL) and shell cross-linked (SCL) micelles displayed regular spherical shapes with different sizes in N,N′-dimethylformamide (DMF) and aqueous media. The structure changes of CCL and SCL micelles at different pHs and temperatures were characterized by 1H NMR. Optical absorption measurements showed that the lower critical solution temperatures (LCSTs) of the CCL and SCL micelles were 37.5 and 40.5 °C, respectively. In vitro drug release study showed that the drug-loaded CCL and SCL micelles displayed thermoresponsive and pH double responsive release behaviors.
Cancer cells, with unique their metabolism, frequently exhibit a high level of redox homeostasis, which could be a feasible target for cancer treatment. Here, liquid metal (LM) nanoparticles are used ...as a template to guide the growth of yolk‐shell structured LM@MnO2 (LMN). With yolk‐shell structures, LMNs is applied to load with cinnamaldehyde (CA) (CLMN) and further coated with hyaluronic acid (HA) to construct the CA&LM@MnO2‐HA nanoflowers (CLMNF) for cancer targeted treatment. Owing to the urchin‐like structured shell, it is found that the obtained CLMNF particles rapidly deplete glutathione (GSH) and produce manganese ions, which further facilitate hydrogen peroxide converting into hydroxyl radical (·OH) for cancer cell killing. Accompanying the depletion of GSH, the balance of intracellular redox homeostasis tilts towards oxidation, resulting in amplified oxidative damage caused by CA, eventually, leading to the apoptosis of cancer cells. Combined with the remarkable near infrared (NIR) photothermal conversion properties, the novel structured CLMNF exhibits favorable inhibition of tumors in vivo, indicating that using nanoflowers to induce intracellular oxidative/thermal stress damage could be a promising strategy for anticancer treatment.
Yolk‐shell structured nanoflowers induce intracellular oxidative/thermal stress damage for cancer treatment. By using liquid metal as a template, the yolk‐shell structured manganese dioxide nanoflowers are rapidly constructed through an in situ surface reduction process. Benefiting from the guidance of multimode imaging, the nanoparticles exhibit satisfactory inhibition of tumor growth in vivo.
The proton’s tensor charges are calculated at leading order in a symmetry-preserving truncation of all matter-sector equations relevant to the associated bound-state and scattering problems. In ...particular, the nucleon three-body bound-state equation is solved without using a diquark approximation of the two-body scattering kernel. The computed charges are similar to those obtained in contemporary simulations of lattice-regularized quantum chromodynamics, an outcome which increases the tension between theory and phenomenology. Curiously, the theoretical calculations produce a value of the scale-invariant ratio (−δTd/δTu) which matches that obtained in simple quark models, even though the individual charges are themselves different. The proton’s tensor charges can be used to constrain extensions of the Standard Model using empirical limits on nucleon electric dipole moments.
Mass spectra and wave functions of the
J
P
=
1
2
+
(
bcq
) baryons are calculated by the relativistic Bethe–Salpeter equation (BSE) with considering the mixing effects between the
1
+
and
0
+
(
bc
...)-diquarks inside. Based on the diquark picture, the three-body problem of baryons is transformed into two two-body problems. The BSE and wave functions of the
0
+
diquark are given, and then solved numerically to obtain the effective mass spectra and form factors. Also we present the wave functions at zero point for the (
bc
)-diquark. Considering the obtained diquark form factors, the (
bcq
) baryons are then described by the BSE as the bound state of a diquark and a light quark, where the interaction kernel includes the inner transitions between the
0
+
and
1
+
diquarks. The general wave function of the
1
2
+
(
bcq
) baryons is constructed and solved to obtain the corresponding mass spectra. Especially, by using the obtained wave functions, the mixing effects between
Ξ
bc
(
Ω
bc
)
and
Ξ
bc
′
(
Ω
bc
′
)
in ground states are computed and determined to be small (
∼
1
%
). The numerical results indicate that it is a good choice to take
Ξ
bc
and
Ξ
bc
′
as the baryon states with the inside (
bc
)-diquarks occupying the definite spin.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The chronic rejection responses and side effects of the systematic administration of immunosuppressants are the main obstacles to heart allograft and patient survival. The development of ...xenotransplantation also urgently requires more efficient immune regulation strategies. Herein, it is demonstrated that lymph‐node (LN)‐targeted drug delivery can realize LN‐specific immunomodulation with attenuated immune suppression on distant peripheral immune organs to effectively prolong long‐term survival after heart transplantation in a chronic murine heart transplantation model. A chemokine C‐C motif ligand 21 (CCL21) specific aptamer for LN targeting is decorated onto the surface of the hybrid nanoparticular delivery vector mainly composed of CaCO3/CaP/heparin. The targeting delivery system can dramatically enhance accumulation of the loaded immunosuppressant, fingolimod hydrochloride (FTY720), in draining lymph nodes (dLNs) for inducing powerful immune suppression. By promoting the generation of endogenous regulatory T cells (Tregs) and decreasing the proportion of effector T cells (Teffs) in dLNs after heart transplantation, the LN‐targeting strategy can effectively regulate local immune responses instead of systemic immunity, which reduces the incidence of long‐term complications. This study provides an efficient strategy to improve the survival rate after organ transplantation by precise and localized immunoregulation with minimized side effects of immunosuppression.
A targeting drug delivery system decorated by a chemokine C‐C motif ligand 21 (CCL21) specific aptamer can realize lymph‐node‐targeted immunomodulation with attenuated immune suppression on distant peripheral immune organs, resulting in effectively prolonged long‐term survival after heart transplantation. This study provides an efficient strategy to achieve precise and localized immunoregulation with minimized side effects of immunosuppression.
A considerable number of deep engineering cases show that strain rockbursts occur on both sidewalls of circular caverns and ultimately form a symmetrical V-shaped notch. To investigate the occurrence ...process and mechanism of strain rockbursts in deep circular cavern under high stresses, simulation experiments under four different three-dimensional (3D) stress conditions were conducted on cubic granite specimens with a prefabricated circular hole using the true-triaxial electro-hydraulic servo mutagenesis testing system. The rock bursting process was monitored on the sidewalls of the hole and recorded in real-time with a wireless microcamera. The results show that the entire rock bursting process on the sidewalls can be divided into four distinct periods for every 3D stress condition: calm period, pellet ejection period, rock fragment exfoliation period, and rock bursting period. Under the conditions that the vertical stress is constant and the horizontal radial stress is equal to the horizontal axial stress, the rockburst severity of the sidewalls clearly decreases with increasing horizontal stress. When the vertical stress is constant and the horizontal axial stress is low, the rockburst severity clearly decreases with the increase of horizontal radial stress. In contrast, when the horizontal axial stress is high, the rockburst severity becomes more serious with increasing horizontal radial stress. During the process of rock fracture and bursting, the damage zones on both sidewalls form two symmetrical V-shaped notches, and the line connecting the centres of the two V-shaped notches is perpendicular to the maximum principal stress direction. The symmetrical V-shaped failure modes on both sidewalls under the four stress conditions are in line with the statistical relationship of the far-field stress state and failure mode of a deep circular cavern without support (Martin et al. in Can Geotech J 36(1):136–151, 1999).
The effects of high-intensity ultrasound on the emulsifying properties of chicken myofibrillar protein (MP) and the rheological properties and stability of the emulsion stabilized by ...ultrasound-treated MP were investigated. MP suspensions (0.6 M NaCl) were subjected to ultrasound treatments (frequency 20 kHz, power 450 W, intensity 30 W/cm2) for 0, 3 and 6 min. Ultrasound treatment significantly increased (p < 0.05) the emulsion activity index and emulsion stability index of MP and yielded a more stable emulsion. The frequency sweep and temperature sweep of emulsions indicated that ultrasound treatment of MP enhanced the elasticity and viscosity of MP-stabilized emulsion. Ultrasound significantly reduced the particle size of MP (p < 0.05) and promoted the formation of smaller and more uniform emulsion droplets. Ultrasound treatment increased the absorbed protein concentration (p < 0.05), while SDS-PAGE of adsorbed proteins recovered from the emulsion layer showed that the band intensity of myosin heavy chains and actin were increased. Ultrasound significantly increased the unfolding of MP, showing an increase in the reactive sulfhydryl content, surface hydrophobicity and intrinsic fluorescence intensity. Ultrasound significantly reduced (p < 0.05) the α-helical content and increased the content of β-sheet, β-turn and random coil contents. High-intensity ultrasound induced structural changes in MP and increased interfacial proteins around oil droplets, contributing to an improvement in the emulsifying properties of MP and enhancement in the rheological properties and storage ability of the O/W emulsion. High-intensity ultrasound has important potential for directly enhancing emulsifying characteristics of lean meat proteins on emulsion-type products.
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•High-intensity ultrasound (20 kHz, 450 W, 6 min, 30 W/cm2) improved emulsifying properties of myofibrillar protein (MP).•Ultrasound-treated MP enhanced the G′ and G″ of emulsion and emulsion stability.•Ultrasound-treated MP contributed to form smaller and more uniform emulsion droplets.•Ultrasound-treated MP increased the interfacial proteins surrounding oil droplets.
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