Challenges and advances in two-dimensional photoacoustic computed tomography: a review.

Significance: Photoacoustic computed tomography (PACT), a hybrid imaging modality combining optical excitation with acoustic detection, has rapidly emerged as a prominent biomedical imaging technique. Aim: We review the challenges and advances of PACT, including (1) limited view, (2) anisotropy resolution, (3) spatial aliasing, (4) acoustic heterogeneity (speed of sound mismatch), and (5) fluence correction of spectral unmixing. Approach: We performed a comprehensive literature review to summarize the key challenges in PACT toward practical applications and discuss various solutions. Results: There is a wide range of contributions from both industry and academic spaces. Various approaches, including emerging deep learning methods, are proposed to improve the performance of PACT further. Conclusions: We outline contemporary technologies aimed at tackling the challenges in PACT applications.

Berberine ameliorates nonalcoholic fatty liver disease-induced bone loss by inhibiting ferroptosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) may contribute to osteoporosis. Berberine is a traditional Chinese medicine and was recently shown to be beneficial in NAFLD. However, little is known about its impact on bone loss induced by NAFLD. AIM: We aimed to explore the role of berberine in bone loss and determine its underlying mechanisms in NAFLD. METHODS: C57BL/6 mice were fed a high-fat high-fructose high-glucose diet (HFFGD) for 16 weeks to establish a NAFLD mouse model. The mice were administered berberine (300 mg/kg/d) by gavage, and fatty liver levels and bone loss indicators were tested. RESULTS: Berberine significantly improved HFFGD-induced weight gain, hepatic lipid accumulation and increases in serum liver enzymes, thereby alleviating NAFLD. Berberine increased trabecular number (Tb. N), trabecular thickness (Tb. Th), bone volume to tissue volume ratio (BV/TV), and decreased trabecular separation (Tb. Sp) and restored bone loss in NAFLD. Mechanistically, berberine significantly inhibited ferroptosis and 4-hydroxynonenal (4-HNE), prostaglandin-endoperoxide synthase 2 (PTGS2), and transferrin (TF) levels and increased ferritin heavy chain (FTH) levels in the femurs of HFFGD-fed mice. Moreover, berberine also activated the solute carrier family 7 member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) signaling pathway. CONCLUSION: Berberine significantly ameliorates bone loss induced by NAFLD by activating the SLC7A11/GSH/GPX4 signaling pathway and inhibiting ferroptosis. Therefore, berberine may serve as a therapeutic agent for NAFLD-induced bone loss.

Embedding Quantum Many-Body Scars into Decoherence-Free Subspaces.

Quantum many-body scars are nonthermal excited eigenstates of nonintegrable Hamiltonians, which could support coherent revival dynamics from special initial states when scars form an equally spaced tower in the energy spectrum. For open quantum systems, engineering many-body scarred dynamics by a controlled coupling to the environment remains largely unexplored. Here, we provide a general framework to exactly embed quantum many-body scars into the decoherence-free subspaces of Lindblad master equations. The dissipative scarred dynamics manifest persistent periodic oscillations for generic initial states, and can be practically utilized to prepare scar states with potential quantum metrology applications. We construct the Liouvillian dissipators with the local projectors that annihilate the whole scar towers, and utilize the Hamiltonian part to rotate the undesired states out of the null space of dissipators. We demonstrate our protocol through several typical models hosting many-body scar towers and propose an experimental scheme to observe the dissipative scarred dynamics based on digital quantum simulations and resetting ancilla qubits.

Enhanced Tumor Targeting and Antitumor Activity of Methylated ß-Cyclodextrin-Threaded Polyrotaxanes by Conjugating Cyclic RGD Peptides.

We previously reported that acid-degradable methylated ß-cyclodextrins (Me-ß-CDs)-threaded polyrotaxanes (Me-PRXs) can induce autophagic cell death through endoplasmic reticulum (ER) stress-related autophagy, even in apoptosis-resistant cells. Hence, Me-PRXs show great potential as anticancer therapeutics. In this study, peptide-supermolecule conjugates were designed to achieve the targeted delivery of Me-PRX to malignant tumors. Arg-Gly-Asp peptides are well-known binding motifs of integrin αvß3, which is overexpressed on angiogenic sites and many malignant tumors. The tumor-targeted cyclic Arg-Gly-Asp (cRGD) peptide was orthogonally post-modified to Me-PRX via click chemistry. Surface plasmon resonance (SPR) results indicated that cRGD-Me-PRX strongly binds to integrin αvß3, whereas non-targeted cyclic Arg-Ala-Glu (cRGE) peptide conjugated to Me-PRX (cRGE-Me-PRX) failed to interact with integrins αvß3. In vitro, cRGD-Me-PRX demonstrated enhanced cellular internalization and antitumor activity in 4T1 cells than that of unmodified Me-PRX and non-targeted cRGE-Me-PRX, due to its ability to recognize integrin αvß3. Furthermore, cRGD-Me-PRX accumulated effectively in tumors, leading to antitumor effects, and exhibited excellent biocompatibility and safety in vivo. Therefore, cRGD conjugation to enhance selectivity for integrin αvß3-positive cancer cells is a promising design strategy for Me-PRXs in antitumor therapy.

Supramolecular nanoarchitectonics of propionylated polyrotaxanes with bulky nitrobenzyl stoppers for light-triggered drug release.

Cyclodextrin (CD)-based polyrotaxanes (PRXs) are supramolecular polymers comprising multiple CDs mechanically interlocked onto a linear polymer chain by capping the polymer ends with bulky stoppers. Among various PRX derivatives, propionylated PRXs (Pr-PRXs) composed of propionylated α-CD and high molecular-weight poly(ethylene glycol) (PEG) form self-assembled nanoparticles in aqueous solution through hydrophobic interactions. Although Pr-PRX nanoparticles can encapsulate hydrophobic drugs in their hydrophobic domains, their release rate is limited. To improve the efficiency of drug release from Pr-PRX nanoparticles, ultraviolet (UV) light-dissociable Pr-PRXs were designed using 4,5-dimethoxy 2-nitrobenzyl groups as UV-cleavable bulky stopper molecules to facilitate UV-induced drug release. Photodegradable Pr-PRX (Pr-PD-PRX) was synthesized, and its UV-induced dissociation was examined. Pr-PD-PRX was completely dissociated via UV irradiation (365 nm) for 30 min. Additionally, Pr-PD-PRX nanoparticles encapsulating hydrophobic drugs collapsed upon UV irradiation, which promoted the release of the encapsulated drugs compared to non-degradable Pr-PRX nanoparticles. UV irradiation of drug-loaded Pr-PD-PRX nanoparticles resulted in higher cytotoxicity than non-irradiated Pr-PD-PRX and non-degradable Pr-PRX. Consequently, designing photodegradable PRX-based nanoparticles provides new insights into developing photoresponsive drug carriers and smart biomedical materials.

Extracting Quantum Many-Body Scarred Eigenstates with Matrix Product States.

Quantum many-body scarred systems host nonthermal excited eigenstates immersed in a sea of thermal ones. In cases where exact expressions for these special eigenstates are not known, it is computationally demanding to distinguish them from their exponentially many thermal neighbors. We propose a matrix-product-state (MPS) algorithm, dubbed DMRG-S, to extract such states at system sizes far beyond the scope of exact diagonalization. Using this technique, we obtain scarred eigenstates in Rydberg-blockaded chains of up to 80 sites and perform a finite-size scaling study to address the lingering question of the stability for the Néel state revivals in the thermodynamic limit. Our method also provides a systematic way to obtain exact MPS representations for scarred eigenstates near the target energy without a priori knowledge. In particular, we find several new scarred eigenstates with exact MPS representations in kinetically constrained spin and clock models. The combination of numerical and analytical investigations in our work provides a new methodology for future studies of quantum many-body scars.

Ruxolitinib Alleviates Inflammation, Apoptosis, and Intestinal Barrier Leakage in Ulcerative Colitis via STAT3.

BACKGROUND: Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa with increasing prevalence and limited management. Ruxolitinib is a new anti- JAK/STAT3 biologic agent that has shown potential in protecting against colitis. METHODS: We first constructed an in vivo UC model and an in vitro colonic epithelial cell inflammation model. Ruxolitinib was administered via gavage in mice. After treatment, colon tissues, cells, and cell lysates were collected and prepared for histological evaluation, immunohistochemistry, immunofluorescence staining, quantitative reverse-transcriptase polymerase chain reaction, Western blotting, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining, and cytokine analysis. STAT3 expression was silenced and overexpressed via small interfering RNA and overexpression plasmid transfection, respectively, and quantitative reverse-transcriptase polymerase chain reaction was used to examine the downstream effects. RESULTS: Ruxolitinib administration significantly alleviated colitis both in vivo and in vitro, as manifested by reduced body weight loss, shortened colon lengths, relieved disease activity (measured by the disease activity index), and prolonged survival. A mechanistic study showed that ruxolitinib attenuated nuclear factor kappa B-induced inflammation, reduced apoptosis, and ameliorated epithelial barrier leakage, and thereby reduced colitis activity in vivo. STAT3 knockdown partially reversed the protective effect of ruxolitinib against colitis, while STAT3 overexpression exaggerated the reductions in proinflammatory cytokine levels upon ruxolitinib treatment. CONCLUSIONS: We demonstrate that ruxolitinib alleviates colitis by inhibiting nuclear factor kappa B-related inflammation and apoptosis in addition to restoring epithelial barrier function via STAT3, providing a new strategy for UC treatment.

We studied the effect and mechanism of ruxolitinib on ulcerative colitis. We discovered that ruxolitinib administration significantly alleviated murine colitis by relieving disease activity and prolonged survival through intestinal epithelial cell nuclear factor kappa B­induced inflammation, reduced apoptosis, and ameliorated epithelial barrier leakage via STAT3.

Mitigating RANKL-induced cholesterol overload in macrophages with ß-cyclodextrin-threaded polyrotaxanes suppresses osteoclastogenesis.

Free cholesterol acts as an endogenous agonist for estrogen-related receptor α (ERRα), a nuclear receptor that regulates osteoclastogenesis. Because stimulation of macrophages with receptor activator of nuclear factor κB ligand (RANKL) induces an overload of free cholesterol and activates ERRα, we hypothesized that direct removal of cellular cholesterol would suppress osteoclastogenesis. In this study, the effect of 2-hydroxypropyl ß-cyclodextrin (HP-ß-CD), a highly water-soluble cyclic glucopyranose, and ß-CD-threaded polyrotaxanes (PRXs), supramolecular polymers designed to release threaded ß-CDs in acidic lysosomes, on RANKL-induced cholesterol overload and osteoclast differentiation of murine macrophage-like RAW264.7 cells were investigated. PRXs suppressed RANKL-induced cholesterol overload. Additionally, RANKL-induced osteoclast differentiation of RAW264.7 cells was inhibited by PRXs. In contrast, HP-ß-CD did not reduce cholesterol levels or inhibit osteoclast differentiation in RAW264.7 cells. Gene expression analysis of osteoclast markers suggested that PRXs suppress only the early stage of osteoclast differentiation, as PRXs cannot be internalized into multinucleated osteoclasts. However, modification of PRXs with cell-penetrating peptides facilitated their cellular uptake into multinucleated osteoclasts and inhibited osteoclast maturation. Thus, PRXs are promising candidates for inhibiting osteoclast differentiation by suppressing cholesterol overload and may be useful for treating osteoporosis or other bone defects caused by the overactivity of osteoclasts.

A Retrospective Study of Parietal Lobe Epilepsy: Functional Anatomy and Surgical Treatment.

Context: Parietal lobe epilepsy (PLE) accounts for approximately 5% of all focal epilepsies worldwide,1 and few PLE patients have undergone epilepsy surgery in the past. With the introduction of functional neuroimaging methods, such as interictal fluorodeoxyglucose-positron emission tomography (FDG-PET), stereotactic electroencephalograms (SEEGs), and high-resolution magnetic resonance imaging (MRI), more patients with intractable neocortical epilepsy have been considered for surgical treatment. Objective: The study intended to characterize the clinical features, aura, and presurgical evaluations of patients with PLE, by investigating their demographic and clinical characteristics, and to evaluate the prognostic value of the four diagnostic modalities-MRI, FDG-PET, scalp EEG, and SEEG-in terms of the localization of epileptogenic area. Design: The research team performed a retrospective analysis of outcomes for PLE patients who underwent resistive brain surgery. Setting: The study took place in the Neurosurgery Department of Epilepsy at the Second Hospital of Hebei Medical University in Shijiazhuang, China. Participants: Participants were 9 PLE patients, 4 males and 5 females, who underwent epilepsy surgery at the hospital between 2017 and 2019. Outcome Measures: The measures included demographic data, seizure data, electroencephalogram (EEG) recordings, magnetic resonance imaging (MRI) of the brain, positron emission tomography (PET), and stereotactic electroencephalogram (SEEG). The pathological findings were reviewed. Results: The five participants who had a PET all had positive results. Eight participants who had parietal lobe lesions had an MRI, and four had a stereotactic electroencephalogram (SEEG) that localized the epileptogenic zone. The interictal scalp EEG recordings for seven participants showed an abnormality, and six participants who had ictal surface EEG recordings showed parietal ictal EEG onset. Conclusions: Surgical excision of epileptogenic foci is the main treatment for drug-resistant PLE. Parietal functional anatomy is the basis for understanding and diagnosing PLE. Aura, semiology, interictal EEG, and PET are an important foundation for evaluation of PLE patients, and the SEEG is the most valuable tool, allowing localization of the epileptogenic zone.

Calcium phosphate-adsorbable and acid-degradable carboxylated polyrotaxane consisting of ß-cyclodextrins suppresses osteoclast resorptive activity.

Recently, the potential of ß-cyclodextrin-thread acid-degradable polyrotaxane (AdPRX) has been emphasized as a therapeutic agent for cholesterol-related metabolic disorders. In this study, we investigated whether carboxymethyl carbamate-modified AdPRX (CMC-AdPRX) can be used for adsorption to calcium phosphate to treat bone diseases. We first synthesized CMC-AdPRX and used it to coat the calcium phosphate plate. RAW264.7 cells were then differentiated into osteoclasts via a receptor activator of nuclear factor-κB ligand, and the number of osteoclasts and the area of absorption lacunae were determined. The number of tartrate-resistant acid phosphatase-positive multinucleated cells was reduced on the CMC-AdPRX-coated plate. The area of the absorption lacunae was smaller with CMC-AdPRX than with AdPRX, which was not carboxy-modified. Our results suggest that CMC-AdPRX can adsorb to calcium phosphate and act on differentiated osteoclasts to suppress their functional expression.

Cografting of Zwitterionic Sulfobetaines and Cationic Amines on ß-Cyclodextrin-Threaded Polyrotaxanes Facilitates Cellular Association and Tissue Accumulation with High Biocompatibility.

ß-Cyclodextrins (ß-CDs) and ß-CD-containing polymers have attracted considerable attention as potential candidates for the treatment of cholesterol-related metabolic and intractable diseases. We have advocated the use of ß-CD-threaded acid-degradable polyrotaxanes (PRXs) as intracellular delivery carriers for ß-CDs. As unmodified PRXs are insoluble in aqueous solutions, chemical modification of PRXs is an essential process to improve their solubility and impart novel functionalities. In this study, we investigated the effect of the modification of zwitterionic sulfobetaines on PRXs due to their excellent solubility, biocompatibility, and bioinert properties. Sulfobetaine-modified PRXs were synthesized by converting the tertiary amino groups of precursor 2-(N,N-dimethylamino)ethyl carbamate-modified PRXs (DMAE-PRXs) using 1,3-propanesultone. The resulting sulfobetaine-modified PRXs showed high solubility in aqueous solutions and no cytotoxicity, while their intracellular uptake levels were low. To further improve this system, we designed PRXs cografted with zwitterionic sulfobetaine and cationic DMAE groups via partial betainization of the DMAE groups. Consequently, the interaction with proteins, intracellular uptake levels, and liver accumulation of partly betainized PRXs were found to be higher than those of completely betainized PRXs. Additionally, partly betainized PRXs showed no toxicity in vitro or in vivo despite the presence of residual cationic DMAE groups. Furthermore, partly betainized PRXs ameliorated the abnormal free cholesterol accumulation in Niemann-Pick type C disease patient-derived cells at lower concentrations than ß-CD derivatives and previously designed PRXs. Overall, the cografting of sulfobetaines and amines on PRXs is a promising chemical modification for therapeutic applications due to the high cholesterol-reducing ability and biocompatibility of such modified PRXs. In addition, modification with both zwitterionic and cationic groups can be used for the design of various polymeric materials exhibiting both bioinert and bioactive characteristics.

m6A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability.

N6-methyladenosine (m6A) has been identified to exert critical roles in human cancer; however, the regulation of m6A modification on glioblastoma multiforme (GBM) and long non-coding RNA (lncRNA) CASC9 (cancer susceptibility 9) is still unclear. Firstly, MeRIP-Seq revealed the m6A profile in the GBM. Moreover, the m6A-related lncRNA CASC9 expression was significantly elevated in the GBM tissue and its ectopic high expression was associated with poor survival, acting as an independent prognostic factor for GBM patients. Functionally, the aerobic glycolysis was promoted in the CASC9 overexpression transfection, which was inhibited in CASC9 knockdown in GBM cells. Mechanistically, m6A reader IGF2BP2 (insulin-like growth factor 2 mRNA binding protein 2) could recognize the m6A site of CASC9 and enhance its stability, then CASC9 cooperated with IGF2BP2, forming an IGF2BP2/CASC9 complex, to increase the HK2 (Hexokinase 2) mRNA stability. Our findings reveal that CASC9/IGF2BP2/HK2 axis promotes the aerobic glycolysis of GBM.

Neurosurgical robot-assistant stereoelectroencephalography system: Operability and accuracy.

BACKGROUND: Fine operation has been an eternal topic in neurosurgery. There were many problems in functional neurosurgery field with high precision requirements. Our study aims to explore the operability, accuracy and postoperative effect of robot-assisted stereoelectroencephalography (SEEG) in neurosurgery. METHODS: We conducted a retrospective analysis of patients with epilepsy who underwent electrode implantation in our hospital. From 2016 to 2019, the epilepsy center of Hebei people's hospital implanted electrodes in neurosurgery on 24 patients, including 20 with SINO robot-assisted SEEG system and eight with frame-SEEG technology. RESULT: Robot-assisted SEEG neurosurgery had higher accuracy, and the mean error of entry and target point was smaller than that of frame SEEG surgery. No bleeding or infection occurred postoperatively, and two patients who underwent robot-assisted SEEG neurosurgery had electrode displacement. Electrode displacement was observed in two patients, both the entry points were orbital frontal, one in the frame system and one in the robot assistant system. The average placement time of each electrode in robot assisted system surgery was less than that in frame system surgery. CONCLUSION: The SINO SEEG electrode implantation assisted by surgical robot-assistant system manufactured in China is safe, accurate and mature.

Weakly acidic carboxy group-grafted ß-cyclodextrin-threaded acid-degradable polyrotaxanes for modulating protein interaction and cellular internalization.

To improve the therapeutic potential of ß-cyclodextrin (ß-CD)-threaded acid-degradable polyrotaxanes (ß-CD PRXs) in cholesterol-related metabolic disorders, we investigated the effect of carboxylation of ß-CD PRXs on intracellular uptake. In this study, we established a synthetic method for the modification of carboxylalkyl carbamates on ß-CD PRXs without degradation and synthesized three series of carboxyalkyl carbamate group-modified ß-CD PRXs with different alkyl spacer lengths. The modification of carboxymethyl carbamate (CMC), carboxyethyl carbamate (CEC), and carboxypropyl carbamate (CPC) on the ß-CD PRXs slightly reduced the interaction of the PRXs with the lipid layer model compared with the modification of 2-(2-hydroxyethoxy)ethyl carbamate (HEE-PRX), which was used in our previous studies. However, all the carboxylated ß-CD PRXs showed a significantly stronger interaction with a protein model compared with HEE-PRX. The carboxylated ß-CD PRXs showed significantly high intracellular uptake, through macrophage scavenger receptor A (MSR-A)-mediated endocytosis, in MSR-A-positive RAW 264.7 cells compared with HEE-PRX. Interestingly, the carboxylated ß-CD PRXs also showed significantly higher intracellular uptake even in MSR-A-negative cells compared with HEE-PRX. Carboxylated ß-CD PRXs are considered to strongly interact with other membrane proteins, resulting in high intracellular uptake. The length of the alkyl spacer affected the intracellular uptake levels of carboxylated PRXs, however, this relationship was varied for different cell types. Furthermore, none of the carboxylated ß-CD PRXs exhibited cytotoxicity in the RAW 264.7 and NIH/3T3 cells. Altogether, carboxylation of ß-CD PRXs is a promising chemical modification approach for their therapeutic application because carboxylated ß-CD PRXs exhibit high cellular internalization efficiency in MSR-A-negative cells and negligible toxicity.

Exact dimer phase with anisotropic interaction for one dimensional magnets.

We report the exact dimer phase, in which the ground states are described by product of singlet dimer, in the extended XYZ model by generalizing the isotropic Majumdar-Ghosh model to the fully anisotropic region. We demonstrate that this phase can be realized even in models when antiferromagnetic interaction along one of the three directions. This model also supports three different ferromagnetic (FM) phases, denoted as x-FM, y-FM and z-FM, polarized along the three directions. The boundaries between the exact dimer phase and FM phases are infinite-fold degenerate. The breaking of this infinite-fold degeneracy by either translational symmetry breaking or [Formula: see text] symmetry breaking leads to exact dimer phase and FM phases, respectively. Moreover, the boundaries between the three FM phases are critical with central charge [Formula: see text] for free fermions. We characterize the properties of these boundaries using entanglement entropy, excitation gap, and long-range spin-spin correlation functions. These results are relevant to a large number of one dimensional magnets, in which anisotropy is necessary to isolate a single chain out from the bulk material. We discuss the possible experimental signatures in realistic materials with magnetic field along different directions and show that the anisotropy may resolve the disagreement between theory and experiments based on isotropic spin-spin interactions.

Sources of seasonal wetland methane emissions in permafrost regions of the Qinghai-Tibet Plateau.

In this study, systematic soil methane cycle geochemical monitoring was carried out in a typical gas hydrate region in the Qinghai-Tibet Plateau. Soil gas samples were collected for hydrocarbon components and carbon isotope analysis. Meanwhile, soil-methane fluxes from the upper active layer (20-30 cm) were monitored during six months of one year. The results of this research provide evidence of a new source of methane emission from wetland soils in permafrost regions: gas hydrate release. Sites with large methane emissions were found using flux monitoring, the characteristics of thermogenic methane were identified using carbon isotope tracing, and the relationship between emission by soils and effusion from gas hydrates was determined through correlation analyses of soil-adsorbed hydrocarbons. Seasonal variation of methane emissions are also discussed by considering the emission of bacterial methane, thermogenic methane, and the absorption of methane from the soil active layer. These comprehensive findings provide valuable information for carbon cycle research of wetlands in permafrost regions.

Long noncoding RNA CASC9/miR-519d/STAT3 positive feedback loop facilitate the glioma tumourigenesis.

Emerging evidence have illustrated the vital roles of long noncoding RNAs (lncRNAs) in glioma. Nevertheless, the majority of their roles and mechanisms in gliomagenesis are still largely unclear. In this study, we investigate the roles of lncRNA CASC9 on glioma tumourigenesis and authenticate its potential mechanisms. Results manifested that CASC9 was highly expressed in glioma specimens and cells, moreover, the ectopic overexpression was correlated with glioma patients' clinic. Functional studies found that siRNA-mediated CASC9 silencing inhibited the proliferative ability, invasion in vitro, and impaired the tumour growth in vivo. Mechanical studies revealed that miR-519d both targeted the 3'-UTR of CASC9 and STAT3 mRNA, which was identified by luciferase reporter assay and RNA immunoprecipitation (RIP). Moreover, chromatin immunoprecipitation (ChIP) and luciferase reporter assay revealed that STAT3, an oncogenic transcription factor, could bind with the promoter of CASC9 and activate its transcriptional level. In conclusion, our results concluded that CASC9 promotes STAT3 expression via sponging miR-519d, in return, STAT3 activate CASC9 transcription, forming a positive feedback loop of CASC9/miR-519d/STAT3. The novel finding provides a potential therapeutic target for glioma.