Enhancing tissue imaging contrast in photoacoustic tomography using the ultrasound thermal effect.

Photoacoustic imaging is a powerful technique for obtaining high-resolution images of vascular distribution and physiological information about blood by utilizing the light absorption coefficient as an imaging contrast. However, visualizing weakly light-absorbing components without specific contrast agents or multi-wavelength techniques presents a challenge due to significant differences in light absorption between these components and blood. In this study, we propose a novel method that leverages the thermal effect of ultrasound to induce temperature differences and enhance the contrast of photoacoustic imaging. We conducted phantom experiments to verify the feasibility of our method. Our method effectively highlighted weakly light-absorbing components with strong acoustic absorption, even in the presence of highly light-absorbing components such as blood or melanin. Furthermore, it enabled the differentiation of components with similar light absorption but different acoustic absorption.

Establishing Ohmic Contact of a Radial Compressed CNT Bundle with High Work Function Metal.

Establishing low-resistance ohmic contact is critical for developing electronic devices based on traditional silicon and new low-dimensional materials. Due to unprecedented electronic and mechanical properties, the one-dimensional carbon nanotubes (CNTs) have been used as source/drain, gate, or tunnel to fabricate transistors. However, the mechanism causing low-resistance ohmic contact is not clear yet. Here, the hybrid atomic force microscopy-scanning electron microscopy (AFM-SEM) instrument was developed to establish lower-resistance ohmic contact between a radial compressed deformed multiwalled CNT bundle and high work function metal (platinum and gold). The radial compression structure under strong van der Waals attraction was in situ characterized through the SEM image to obtain the diameter and width and through AFM to get height and to perform nanoindentation, indicating that Pt has the smaller radial compression deformation. Molecular dynamics simulations exhibit that compared to Pt, a wider ribbon-like graphene layer formed when the radial compressed CNTs contacted with Au. The bond forming and electron orbital overlapping between C atoms of deformed CNTs and the high work function metal atom is beneficial for good electrical contact.

Netrin-1 Role in Nociceptive Neuron Sprouting through Activation of DCC Signaling in a Rat Model of Bone Cancer Pain.

BACKGROUND: Bone cancer pain (BCP) is a common primary or metastatic bone cancer complication. Netrin-1 plays an essential role in neurite elongation and pain sensitization. This study aimed to determine the role of netrin-1 from the metastatic bone microenvironment in BCP development and identify the associated signaling pathway for the strategy of BCP management. METHODS: The rat BCP model was established by intratibial implantation of Walker 256 cells. Von Frey filaments measured the mechanical pain threshold. Movement-induced pain was assessed using limb use scores. Expressions of associated molecules in the affected tibias or dorsal root ganglia (DRG) were measured by immunofluorescence, immunohistochemistry, real-time quantitative polymerase chain reaction, or western blotting. Transduction of deleted in colorectal cancer (DCC) signaling was inhibited by intrathecal injection of DCC-siRNA. RESULTS: In BCP rats, the presence of calcitonin gene-related peptide (CGRP)-positive nerve fibers increased in the metastatic bone lesions. The metastatic site showed enrichment of well-differentiated osteoclasts and expressions of netrin-1 and its attractive receptor DCC. Upregulation of DCC and increased phosphorylation levels of focal adhesion kinase (FAK) and Rac family small GTPase 1/Cell division cycle 42 (Rac1/Cdc42) were found in the DRG. Intrathecal administration of DCC-siRNA led to a significant reduction in FAK and Rac1/Cdc42 phosphorylation levels in the DRG, decreased nociceptive nerve innervation, and improved pain behaviors. CONCLUSIONS: Netrin-1 may contribute to the activation of the BCP by inducing nociceptive nerve innervation and improving pain behaviors.

Activation of the STING pathway induces peripheral sensitization via neuroinflammation in a rat model of bone cancer pain.

BACKGROUND: Neuroinflammation in the peripheral nervous system has been linked to cancer metastasis-induced bone pain. The stimulator of interferon genes (STING), an innate immune sensor for cytosolic DNA, plays an important role in inflammation and cancer metastasis and is reported to be a critical regulator of nociception. Here, we examined the role of STING in primary nociceptive neurons and chronic pain to determine if it could be a new target for treating bone cancer pain (BCP). METHODS: Walker 256 cancer cells were injected intratibially to induce bone cancer pain in rats. STING and its downstream inflammatory factors in dorsal root ganglia (DRG) were detected using western blotting and immunofluorescent staining. Transmission electron microscopy and the BCL2-associated X (Bax) expression were used to detect the mitochondrial stress in DRG neurons. C-176, a specific inhibitor of STING, was used to block STING activation and to test the pain behavior. RESULTS: Mechanical hyperalgesia and spontaneous pain were observed in BCP rats, accompanied by the upregulation of the STING expression in the ipsilateral L4-5 DRG neurons which showed significant mitochondrion stress. The STING/TANK-binding kinase 1 (TBK1)/nuclear factor-kappa B (NF-κB) pathway activation was observed in the DRGs of BCP rats as well as increased IL-1ß, IL-6, and TNF-α expression. C-176 alleviated bone cancer pain and reduced the STING and its downstream inflammatory pathway. CONCLUSION: We provide evidence that STING pathway activation leads to neuroinflammation and peripheral sensitization. Pharmacological blockade of STING may be a promising novel strategy for preventing BCP.

A General Picture of Cucurbit[8]uril Host-Guest Binding: Recalibrating Bonded Interactions.

Atomic-level understanding of the dynamic feature of host-guest interactions remains a central challenge in supramolecular chemistry. The remarkable guest binding behavior of the Cucurbiturils family of supramolecular containers makes them promising drug carriers. Among Cucurbit[n]urils, Cucurbit[8]uril (CB8) has an intermediate portal size and cavity volume. It can exploit almost all host-guest recognition motifs formed by this host family. In our previous work, an extensive computational investigation of the binding of seven commonly abused and structurally diverse drugs to the CB8 host was performed, and a general dynamic binding picture of CB8-guest interactions was obtained. Further, two widely used fixed-charge models for drug-like molecules were investigated and compared in great detail, aiming at providing guidelines in choosing an appropriate charge scheme in host-guest modelling. Iterative refitting of atomic charges leads to improved binding thermodynamics and the best root-mean-squared deviation from the experimental reference is 2.6 kcal/mol. In this work, we focus on a thorough evaluation of the remaining parts of classical force fields, i.e., the bonded interactions. The widely used general Amber force fields are assessed and refitted with generalized force-matching to improve the intra-molecular conformational preference, and thus the description of inter-molecular host-guest interactions. The interaction pattern and binding thermodynamics show a significant dependence on the modelling parameters. The refitted system-specific parameter set improves the consistency of the modelling results and the experimental reference significantly. Finally, combining the previous charge-scheme comparison and the current force-field refitting, we provide general guidelines for the theoretical modelling of host-guest binding.

Comprehensive evaluation of end-point free energy techniques in carboxylated-pillar[6]arene host-guest binding: II. regression and dielectric constant.

End-point free energy calculations as a powerful tool have been widely applied in protein-ligand and protein-protein interactions. It is often recognized that these end-point techniques serve as an option of intermediate accuracy and computational cost compared with more rigorous statistical mechanic models (e.g., alchemical transformation) and coarser molecular docking. However, it is observed that this intermediate level of accuracy does not hold in relatively simple and prototypical host-guest systems. Specifically, in our previous work investigating a set of carboxylated-pillar[6]arene host-guest complexes, end-point methods provide free energy estimates deviating significantly from the experimental reference, and the rank of binding affinities is also incorrectly computed. These observations suggest the unsuitability and inapplicability of standard end-point free energy techniques in host-guest systems, and alteration and development are required to make them practically usable. In this work, we consider two ways to improve the performance of end-point techniques. The first one is the PBSA_E regression that varies the weights of different free energy terms in the end-point calculation procedure, while the second one is considering the interior dielectric constant as an additional variable in the end-point equation. By detailed investigation of the calculation procedure and the simulation outcome, we prove that these two treatments (i.e., regression and dielectric constant) are manipulating the end-point equation in a somehow similar way, i.e., weakening the electrostatic contribution and strengthening the non-polar terms, although there are still many detailed differences between these two methods. With the trained end-point scheme, the RMSE of the computed affinities is improved from the standard ~ 12 kcal/mol to ~ 2.4 kcal/mol, which is comparable to another altered end-point method (ELIE) trained with system-specific data. By tuning PBSA_E weighting factors with the host-specific data, it is possible to further decrease the prediction error to ~ 2.1 kcal/mol. These observations along with the extremely efficient optimized-structure computation procedure suggest the regression (i.e., PBSA_E as well as its GBSA_E extension) as a practically applicable solution that brings end-point methods back into the library of usable tools for host-guest binding. However, the dielectric-constant-variable scheme cannot effectively minimize the experiment-calculation discrepancy for absolute binding affinities, but is able to improve the calculation of affinity ranks. This phenomenon is somehow different from the protein-ligand case and suggests the difference between host-guest and biomacromolecular (protein-ligand and protein-protein) systems. Therefore, the spectrum of tools usable for protein-ligand complexes could be unsuitable for host-guest binding, and numerical validations are necessary to screen out really workable solutions in these 'prototypical' situations.

Enhanced electrochemical removal of sulfadiazine using stainless steel electrode coated with activated algal biochar.

With the increasingly discharging and inappropriately disposing of antibiotics from human disease treatment and breeding industry, extensive development of antibiotic resistance in bacteria raised serious public health concern. In this work, algal biochar was coated onto the stainless steel mesh, and was employed as cathodic electrode for the degradation of sulfadiazine (SDZ) in an electro-Fenton (EF) system. It was found that algal biochar pyrolyzed at 600 °C with 1:1 KOH achieved best catalytic performance to generate H2O2 via oxygen reduction. Moreover, removal efficiency of SDZ reached 96.11% in 4 h with an initial concentration of 25 µg/mL, under the optimized condition as: initial pH at 3, 50 mM of Na2SO4 as electrolyte and an applied current of 20 mA/cm2. In addition, it was found that the SDZ removal kept at about 96.99% even after four repeated degradation process. Moreover, four possible SDZ degradative pathways during the EF process were proposed according to determined intermediates, model optimization and density functional theory calculation. Finally, acute and chronic biotoxicity of the degradative products against fish and green algae was evaluated, to further elaborate the environmental impact of SDZ after electrochemical degradation.

Commutator Matrix in Phase Space Mapping Models for Nonadiabatic Quantum Dynamics.

We show that a novel, general phase space mapping Hamiltonian for nonadiabatic systems, which is reminiscent of the renowned Meyer-Miller mapping Hamiltonian, involves a commutator variable matrix rather than the conventional zero-point-energy parameter. In the exact mapping formulation on constraint space for phase space approaches for nonadiabatic dynamics, the general mapping Hamiltonian with commutator variables can be employed to generate approximate trajectory-based dynamics. Various benchmark model tests, which range from gas phase to condensed phase systems, suggest that the overall performance of the general mapping Hamiltonian is better than that of the conventional Meyer-Miller Hamiltonian.

Absorption matrix of multi-site systems calculated by a hybrid quantum-classical Liouville equation.

The linear absorption spectrum of a multisite system can be written as a weighted accumulation of elements of an absorption matrix. In the framework of the quantum-classical Liouville equation (QCLE), a mean-field approximation is introduced to simplify the calculation of the absorption matrix. The classical bath oscillators are propagated under partially shifted potentials, which reflects an averaged behavior after considering quantum jumps of the system states. For a specified initial condition, the time-dependent shifting possibility of each bath potential is given by the time evolution of site population estimated by the Redfield equation or the noninteracting blip approximation. The two hybrid QCLE approaches are tested in various models, including biased and unbiased two-site models, a subnetwork and the whole monomer of Fenna-Matthews-Olson, and harmonic and anharmonic baths. With numerically excellent results, the numerical studies show reliability and flexibility of the hybrid QCLE in calculating the absorption matrix and spectrum.

Dynamical scaling in the Ohmic spin-boson model studied by extended hierarchical equations of motion.

Through a decomposition of the bath correlation function, the hierarchical equations of motion are extended to the Ohmic spin-boson model at zero temperature. For two typical cutoff functions of the bath spectral density, the rate kernel of spin dynamics is numerically extracted by a time-convolution equation of the average magnetic moment. A characteristic time is defined accordingly as the inverse of the zeroth-order moment of the rate kernel. For a given Kondo parameter in the incoherent regime, the time evolution of average magnetic moments gradually collapses onto a master curve after rescaling the time variable with the characteristic time. The rescaled spin dynamics is nearly independent of the cutoff frequency and the form of cutoff functions. For a given cutoff frequency, the characteristic time with the change of the Kondo parameter is fitted excellently as a function of the renormalized tunneling amplitude. Despite a significant difference in definition, our result is in good agreement with the characteristic time of the noninteracting blip approximation.

Quantum kinetic expansion in the spin-boson model: Implemented by the quantum-classical Liouville equation in an anharmonic bath.

In the framework of the quantum-classical Liouville equation (QCLE), the quantum kinetic expansion (QKE) of the spin-boson model is extended to an arbitrary combination of the bath potential and the system-bath interaction. The mixed quantum-classical estimation of the QKE rate kernels and modification functions are transformed into averages of deterministic classical trajectories over the Wigner initial distribution. For the standard spin-boson model, the QCLE-QKE method produces exactly the same result as that from full quantum dynamics and the numerical applicability of the approximate action-angle initial distribution is verified. For an anharmonic bath with the quartic potential, the QCLE-QKE calculation under the action-angle initial distribution illustrates the influence of this specific anharmonicity. With the increase of the quartic parameter, the fourth order QKE corrections are suppressed and the short-time population transfer is accelerated together with an enhanced quantum oscillation.

Quantum kinetic expansion in the spin-boson model: Matrix formulation and system-bath factorized initial state.

Within the framework of the hierarchy equation of motion (HEOM), the quantum kinetic expansion (QKE) method of the spin-boson model is reformulated in the matrix representation. The equivalence between the two formulations (HEOM matrices and quantum operators) is numerically verified from the calculation of the time-integrated QKE rates. The matrix formulation of the QKE is extended to the system-bath factorized initial state. Following a one-to-one mapping between HEOM matrices and quantum operators, a quantum kinetic equation is rederived. The rate kernel is modified by an extra term following a systematic expansion over the site-site coupling. This modified QKE is numerically tested for its reliability by calculating the time-integrated rate and non-Markovian population kinetics. For an intermediate-to-strong dissipation strength and a large site-site coupling, the population transfer is found to be significantly different when the initial condition is changed from the local equilibrium to system-bath factorized state.

Generalized quantum kinetic expansion: Time scale separation between intra-cluster and inter-cluster kinetics.

For a general two-cluster network, a new methodology of the cluster-based generalized quantum kinetic expansion (GQKE) is developed in the matrix formalism under two initial conditions: the local cluster equilibrium and system-bath factorized states. For each initial condition, the site population evolution follows exactly a distinct closed equation, where all the four terms involved are systematically expanded over inter-cluster couplings. For the system-bath factorized initial state, the numerical investigation of the two models, a biased (2, 1)-site system and an unbiased (2, 2)-site system, verifies the reliability of the GQKE and the relevance of higher-order corrections. The time-integrated site-to-site rates and the time evolution of site population reveal the time scale separation between intra-cluster and inter-cluster kinetics. The population evolution of aggregated clusters can be quantitatively described by the approximate cluster Markovian kinetics.

Generalized quantum kinetic expansion: Higher-order corrections to multichromophoric Förster theory.

For a general two-cluster energy transfer network, a new methodology of the generalized quantum kinetic expansion (GQKE) method is developed, which predicts an exact time-convolution equation for the cluster population evolution under the initial condition of the local cluster equilibrium state. The cluster-to-cluster rate kernel is expanded over the inter-cluster couplings. The lowest second-order GQKE rate recovers the multichromophoric Förster theory (MCFT) rate. The higher-order corrections to the MCFT rate are systematically included using the continued fraction resummation form, resulting in the resummed GQKE method. The reliability of the GQKE methodology is verified in two model systems, revealing the relevance of higher-order corrections.

Extended hierarchy equation of motion for the spin-boson model.

An extended hierarchy equation of motion (HEOM) is proposed and applied to study the dynamics of the spin-boson model. In this approach, a complete set of orthonormal functions are used to expand an arbitrary bath correlation function. As a result, a complete dynamic basis set is constructed by including the system reduced density matrix and auxiliary fields composed of these expansion functions, where the extended HEOM is derived for the time derivative of each element. The reliability of the extended HEOM is demonstrated by comparison with the stochastic Hamiltonian approach under room-temperature classical ohmic and sub-ohmic noises and the multilayer multiconfiguration time-dependent Hartree theory under zero-temperature quantum ohmic noise. Upon increasing the order in the hierarchical expansion, the result obtained from the extended HOEM systematically converges to the numerically exact answer.

A continued fraction resummation form of bath relaxation effect in the spin-boson model.

In the spin-boson model, a continued fraction form is proposed to systematically resum high-order quantum kinetic expansion (QKE) rate kernels, accounting for the bath relaxation effect beyond the second-order perturbation. In particular, the analytical expression of the sixth-order QKE rate kernel is derived for resummation. With higher-order correction terms systematically extracted from higher-order rate kernels, the resummed quantum kinetic expansion approach in the continued fraction form extends the Pade approximation and can fully recover the exact quantum dynamics as the expansion order increases.

Decoding of Salty/Saltiness-Enhancing Peptides Derived from Goose Hemoglobin and the Interaction Mechanism with TMC4 Receptor.

Amid the growing concern for health-oriented food choices, salt reduction has received widespread attention, particularly in the exploitation of salt alternatives. Peptides with a saltiness-enhancing effect may provide an alternative method for salt reduction. The objective of this study was to isolate and extract novel peptides with salt-reducing effects by fermenting goose blood using a Lactobacillus plantarum strain. Five potential target peptides were screened by a virtual database prediction and molecular docking. Sensory evaluation and E-tongue analysis showed that five peptides (NEALQRM, GDAVKNLD, HAYNLRVD, PEMHAAFDK, and AEEKQLITGL) were identified as target peptides. Particularly, the results of E-tongue showed that GDAVKNLD can increase the saltiness intensity (2.87 ± 0.02) in the complex system. The sensory evaluation results also indicated an increase in saltiness intensity (46.67 ± 4.67 mmol/L NaCl) after adding GDAVKNLD. The results of molecular dynamics simulation indicated that five peptides have good ability to bind tightly to TMC4 receptor, thereby stimulating it to exert an active effect. And these peptides interacted with the TMC4 receptor via hydrogen bonding, hydrophobic interactions, and electrostatic interactions. This research lays a theoretical foundation for discovering novel salty/saltiness-enhancing peptides and provides meaningful contributions to efforts in salt reduction.

Activation of the BMP2-SMAD1-CGRP pathway in dorsal root ganglia contributes to bone cancer pain in a rat model.

Peripheral nerve remodeling and sensitization are involved in cancer-related bone pain. As a member of the transforming growth factor-ß class, bone morphogenetic protein 2 (BMP2) is recognized to have a role in the development of the neurological and skeletal systems. Our previous work showed that BMP2 is critical for bone cancer pain (BCP) sensitization. However, the mechanism remains unknown. In the current study, we demonstrated a substantial increase in BMP2 expression in the dorsal root ganglia (DRG) in a rat model of BCP. Knockdown of BMP2 expression ameliorated BCP in rats. Furthermore, the DRG neurons of rats with BCP expressed higher levels of calcitonin gene-related peptide (CGRP), and BCP was successfully suppressed by intrathecal injection of a CGRP receptor blocker (CGRP8-37). Downregulation of BMP2 expression reduced the expression of CGRP in the DRG of rats with BCP and relieved pain behavior. Moreover, we revealed that upregulation of CGRP expression in the DRG may be induced by activation of the BMPR/Smad1 signaling pathway. These findings suggest that BMP2 contributes to BCP by upregulating CGRP in DRG neurons via activating BMPR/Smad1 signaling pathway and that therapeutic targeting of the BMP2-Smad1-CGRP pathway may ameliorate BCP in the context of advanced cancer.

Potential role of remimazolam in alleviating bone cancer pain in mice via modulation of translocator protein in spinal astrocytes.

Bone cancer pain (BCP) is a complex clinical challenge, with current treatments often falling short of providing adequate relief. Remimazolam, a benzodiazepine receptor agonist recognized for its anxiolytic effects, has emerged as a potential agent in managing BCP. This study explores the analgesic properties of remimazolam and its interaction with the translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, in spinal astrocytes. In the context of BCP, previous research has indicated that TSPO expression in spinal astrocytes may serve a protective regulatory function in neuropathic pain models. Building on this, the BCP mice received various doses of remimazolam on the 15th day post-inoculation, and pain behavior was assessed over time. The results showed that BCP induced an upregulation of TSPO and astrocyte activation in the spinal dorsal horn, alongside increased extracellular signal-regulated kinase (ERK) signaling and inflammatory cytokine expression. Remimazolam administration resulted in a dose-dependent reduction of pain behaviors, which corresponded with a decrease in both ERK pathway activation and inflammatory factor expression. This suggests that remimazolam's analgesic effects are mediated through its action as a TSPO agonist, leading to the attenuation of neuroinflammation and pain signaling pathways. Importantly, the analgesic effects of remimazolam were reversed by the TSPO antagonist PK11195, underscoring the pivotal role of TSPO in the drug's mechanism of action. This reversal also reinstated the heightened levels of ERK activity and inflammatory mediators, further confirming the involvement of TSPO in the modulation of these pain-related processes. These findings open new avenues for the therapeutic management of bone cancer pain, positioning remimazolam as a promising candidate for further investigation and development.