Superoxide is an intrinsic signaling molecule triggering muscle hypertrophy.

AIMS: Redox signaling plays a key role in skeletal muscle remodeling induced by exercise and prolonged inactivity, but it is unclear which oxidant triggers myofiber hypertrophy due to the lack of strategies to precisely regulate individual oxidants in vivo. In this study, we used tetrathiomolybdate (TM) to dissociate the link between superoxide and H2O2 and thereby to specifically explore the role of superoxide in muscle hypertrophy in C2C12 cells and mice. RESULTS: TM can linearly regulate intracellular superoxide levels by inhibition of superoxide dismutase 1 (SOD1). A 70% increase in superoxide levels in C2C12 myoblast cells and mice is necessary and sufficient for triggering hypertrophy of differentiated myotubes, and can enhance exercise performance by more than 50% in mice. SOD1 knockout blocks TM-induced superoxide increments and thereby prevents hypertrophy, whereas SOD1 restoration rescues all these effects. Scavenging superoxide with antioxidants abolishes TM-induced hypertrophy and the enhancement of exercise performance, while the restoration of superoxide levels with a superoxide generator promotes muscle hypertrophy independent of SOD1 activity. INNOVATION AND CONCLUSION: These findings suggest that superoxide is an endogenous initiator of myofiber hypertrophy, and that TM may be used to treat muscle wasting diseases. Our work not only suggests a novel druggable mechanism to increase muscle mass but also provides a tool for precisely regulating superoxide levels in vivo.

Correction for: Cornel iridoid glycoside exerts a neuroprotective effect on neuroinflammation in rats with brain injury by inhibiting NF-kB and STAT3.

[This corrects the article DOI: 10.1007/s13205-019-1697-5.].

Sn-based film electrodeposited on Ag foil for selective electrochemical CO2 reduction to CO.

Electrochemical CO2 reduction (ECR) to valuable chemicals and fuels using renewable energy is a promising way to reduce carbon emission. Herein, Sn-based films were electrodeposited on Ag foil surfaces (Sn/Ag-y) for selective ECR to CO, where y represented the concentration of SnCl2 in the electrodeposition bath. The Sn/Ag-20 electrode achieved a high CO faradaic efficiency of 96.0% with a current density of 69.3 mA cm-2. The enhanced catalytic performance could be attributed to appropriate superficial properties, large electrochemical active surface areas, low charge transfer resistance, efficient stabilization capacity of the CO2˙- intermediates, and suitable combination with electrolytes.

Electron scattering beyond the independent atom model: Quantum fluctuation of the Coulomb potential.

In the past century, electron scattering has mostly served as a powerful tool to measure the microscopic structure of gases, liquids, and solids in either a static or time-resolved manner. One common basis for these works is the independent atom model, which directly relates electron scattering signals to the atomic structure of matter. In this perspective, we explore the information content of electron scattering that goes beyond the independent atom model. We show that the small-angle limit of the electron scattering signal encodes the quantum mechanical fluctuation of the long-range Coulomb potential. This quantum fluctuation, described by the second moment of the dipole operator, is the root cause of the intermolecular van der Waals forces.

Transcranial alternating current stimulation improves quality of life in Parkinson's disease: study protocol for a randomized, double-blind, controlled trial.

BACKGROUND: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory. METHODS: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. DISCUSSION: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.

Establishment of a hybrid model of atherosclerosis and acute colitis in ApoE-/- mice.

Inflammatory bowel disease (IBD) and atherosclerosis (AS) are both common chronic inflammatory diseases with similar pathophysiological mechanisms. Some studies have shown that IBD patients are at increased risk for early atherosclerosis, myocardial infarction and venous thrombosis. Here we set up a hybrid mouse model associated with atherosclerosis and acute colitis in order to investigate the interplay of the two diseases. We fed ApoE-/- mice with high fat diet to establish atherosclerosis model, and used animal ultrasound machine to detect the artery of mice noninvasively. Then a new hybrid model of atherosclerosis and acute colitis was prepared by drinking water for 7 days. At the end of the experiment, the hybrid model mice showed typically pathological and intuitionistic changes of atherosclerosis and acute colitis. We found the shortened colon length, high histopathological scores of the colon with mucosal erosion and necrosis, hyperlipidemia, a plaque-covered mouse aorta and plaque with foam cells and lipid deposition in the hybrid model group, which proved that the hybrid model was successfully established. At the same time, ultrasonic detection showed that the end-diastolic blood flow velocity and the relative dilation value were decreased, while systolic time / diastolic time, the wall thickness, systolic diameters as well as diastolic diameters were gradually increased, and statistical significance appeared as early as 8 weeks. We clearly described the process of establishing a hybrid model of atherosclerosis and acute colitis, which might provide a repeatable platform for the interaction mechanism exploring and drug screening of atherosclerosis and inflammatory bowel disease in preclinical study.

Reactive lymphoid hyperplasia of the liver: A rare case report.

BACKGROUND: Hepatic reactive lymphoid hyperplasia (RLH) is a rare benign lymphoproliferative lesion and a poorly understood disease. It is usually asymptomatic and incidental, but it is difficult to distinguish from hepatocellular carcinoma and metastatic liver tumor on imaging, and percutaneous biopsy is not sufficient to distinguish from low-grade malignant lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), making diagnosis difficult. CASE SUMMARY: A 69-year-old woman came to our hospital for reexamination of pulmonary nodules followed by liver occupation. The lesions showed "wash-in and wash-out" on contrast-enhanced ultrasonography and magnetic resonance imaging. Enhanced magnetic resonance also showed annular envelope enhancement and limited diffusion on the ADC map during the delay period. Imaging revealed metastatic liver cancer, and the patient underwent a partial hepatectomy. However, the final histopathological diagnosis was RLH. CONCLUSION: If small isolated nodules are found in the liver of middle-aged and elderly female patients with no risk factors for liver malignancy, when the enhanced imaging suggests "wash-in and wash-out", further focus should be placed on whether the enhanced imaging shows perinodular enhancement and whether the DWI shows limited diffusion in MRI, in order to emphasize the possibility of liver RLH diagnosis.

Excessive linoleic acid induces muscle oxidative stress through 5-lipoxygenase-dependent peroxidation.

Oxidative stress in muscles is closely related to the occurrence of insulin resistance, muscle weakness and atrophy, age-related sarcopenia, and cancer. Aldehydes, a primary oxidation intermediate of polyunsaturated fatty acids, have been proven to be an important trigger for oxidative stress. However, the potential role of linoleic acid (LA) as a donor for volatile aldehydes to trigger oxidative stress has not been reported. Here, we reported that excessive dietary LA caused muscle redox imbalance and volatile aldehydes containing hexanal, 2-hexenal, and nonanal were the main metabolites leading to oxidative stress. Importantly, we identified 5-lipoxygenase (5-LOX) as a key enzyme mediating LA peroxidation in crustaceans for the first time. The inhibition of 5-LOX significantly suppressed the content of aldehydes produced by excessive LA. Mechanistically, the activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway facilitated the translocation of 5-LOX from the nucleus to the cytoplasm, where 5-LOX oxidized LA, leading to oxidative stress through the generation of aldehydes. This study suggests that 5-LOX is a potential target to prevent the production of harmful aldehydes.

Enhancing the water permeability of composite NF membranes through the incorporation of organic ions in the aqueous phase.

Composite nanofiltration (NF) membranes prepared using interfacial polymerization (IP) have gained significant attention in the field of wastewater treatment. In this study, sodium camphor sulfonate (CSA-Na) and tetraethylammonium chloride (TEAC) were employed as aqueous phase additives to regulate the diffusion of piperazine (PIP) molecules through electrostatic interactions. The dissociated CSA-Na and TEAC in the aqueous solution formed an organic structure at a certain concentration, restricting the interfacial transport behavior of PIP monomers. The results show that when the content of CSA-Na is 2% w/v, TEAC is 3.9% w/v, that is, the material dosage ratio is 1 : 3, and the NF membrane shows the best performance, with a water flux of 55.61 L m-2 h-1 (test pressure is 0.5 MPa), and MgSO4 rejection rate of more than 98%.

Acoustic Cell Patterning for Structured Cell-Laden Hydrogel Fibers/Tubules.

Cell-laden hydrogel fibers/tubules are one of the fundamentals of tissue engineering. They have been proven as a promising method for constructing biomimetic tissues, such as muscle fibers, nerve conduits, tendon and vessels, etc. However, current hydrogel fiber/tubule production methods have limitations in ordered cell arrangements, thus impeding the biomimetic configurations. Acoustic cell patterning is a cell manipulation method that has good biocompatibility, wide tunability, and is contact-free. However, there are few studies on acoustic cell patterning for fiber production, especially on the radial figure cell arrangements, which mimic many native tissue-like cell arrangements. Here, an acoustic cell patterning system that can be used to produce hydrogel fibers/tubules with tunable cell patterns is shown. Cells can be pre-patterned in the liquid hydrogel before being extruded as cross-linked hydrogel fibers/tubules. The radial patterns can be tuned with different complexities based on the acoustic resonances. Cell viability assays after 72 h confirm good cell viability and proliferation. Considering the biocompatibility and reliability, the present method can be further used for a variety of biomimetic fabrications.

Embedded bioprinted multicellular spheroids modeling pancreatic cancer bioarchitecture towards advanced drug therapy.

The desmoplastic bioarchitecture and microenvironment caused by fibroblasts have been confirmed to be closely related to the drug response behavior of pancreatic ductal adenocarcinoma (PDAC). Despite the extensive progress in developing PDAC models as in vitro drug screening platforms, developing efficient and controllable approaches for the construction of physiologically relevant models remains challenging. In the current study, multicellular spheroid models that emulate pancreatic cancer bioarchitecture and the desmoplastic microenvironment are bioengineered. An extrusion-based embedded dot bioprinting strategy was established to fabricate PDAC spheroids in a one-step process. Cell-laden hydrogel beads were directly deposited into a methacrylated gelatin (GelMA) suspension bath to generate spherical multicellular aggregates (SMAs), which further progressed into dense spheroids through in situ self assembly. By modulating the printing parameters, SMAs, even from multiple cell components, could be manipulated with tunable size and flexible location, achieving tunable spheroid patterns within the hydrogel bath with reproducible morphological features. To demonstrate the feasibility of this printing strategy, we fabricated desmoplastic PDAC spheroids by printing SMAs consisting of tumor cells and fibroblasts within the GelMA matrix bath. The produced hybrid spheroids were further exposed to different concentrations of the drug gemcitabine to verify their potential for use in cell therapy. Beyond providing a robust and facile bioprinting system that enables desmoplastic PDAC bioarchitecture bioengineering, this work introduces an approach for the scalable, flexible and rapid fabrication of cell spheroids or multi-cell-type spheroid patterns as platforms for advanced drug therapy or disease mechanism exploration.

Designing a use-error robust machine learning model for quantitative analysis of diffuse reflectance spectra.

Significance: Machine learning (ML)-enabled diffuse reflectance spectroscopy (DRS) is increasingly used as an alternative to the computation-intensive inverse Monte Carlo (MCI) simulation to predict tissue's optical properties, including the absorption coefficient, µa and reduced scattering coefficient, µs'. Aim: We aim to develop a use-error-robust ML algorithm for optical property prediction from DRS spectra. Approach: We developed a wavelength-independent regressor (WIR) to predict optical properties from DRS data. For validation, we generated 1520 simulated DRS spectra with the forward Monte Carlo model, where µa=0.44 to 2.45 cm-1, and µs'=6.53 to 9.58 cm-1. We introduced common use-errors, such as wavelength miscalibrations and intensity fluctuations. Finally, we collected 882 experimental DRS images from 170 tissue-mimicking phantoms and compared performances of the WIR model, a dense neural network, and the MCI model. Results: When compounding all use-errors on simulated data, the WIR model best balanced accuracy and speed, yielding errors of 1.75% for µa and 1.53% for µs', compared to the MCI's 50.9% for µa and 24.6% for µs'. Regarding experimental data, WIR model had mean errors of 13.2% and 6.1% for µa and µs', respectively. The errors for MCI were about eight times higher. Conclusions: The WIR model presents reliable use-error-robust optical property predictions from DRS data.

TEE-Graph: efficient privacy and ownership protection for cloud-based graph spectral analysis.

Introduction: Big graphs like social network user interactions and customer rating matrices require significant computing resources to maintain. Data owners are now using public cloud resources for storage and computing elasticity. However, existing solutions do not fully address the privacy and ownership protection needs of the key involved parties: data contributors and the data owner who collects data from contributors. Methods: We propose a Trusted Execution Environment (TEE) based solution: TEE-Graph for graph spectral analysis of outsourced graphs in the cloud. TEEs are new CPU features that can enable much more efficient confidential computing solutions than traditional software-based cryptographic ones. Our approach has several unique contributions compared to existing confidential graph analysis approaches. (1) It utilizes the unique TEE properties to ensure contributors' new privacy needs, e.g., the right of revocation for shared data. (2) It implements efficient access-pattern protection with a differentially private data encoding method. And (3) it implements TEE-based special analysis algorithms: the Lanczos method and the Nystrom method for efficiently handling big graphs and protecting confidentiality from compromised cloud providers. Results: The TEE-Graph approach is much more efficient than software crypto approaches and also immune to access-pattern-based attacks. Compared with the best-known software crypto approach for graph spectral analysis, PrivateGraph, we have seen that TEE-Graph has 103-105 times lower computation, storage, and communication costs. Furthermore, the proposed access-pattern protection method incurs only about 10%-25% of the overall computation cost. Discussion: Our experimentation showed that TEE-Graph performs significantly better and has lower costs than typical software approaches. It also addresses the unique ownership and access-pattern issues that other TEE-related graph analytics approaches have not sufficiently studied. The proposed approach can be extended to other graph analytics problems with strong ownership and access-pattern protection.

Carbon nanotube supported cobalt nickel sulphide nano-catalyst for degradation of chloroquine phosphate with peroxymonosulphate.

Carbon nanotubes supported cobalt nickel sulphide nanoparticles (nano-NiCo2S4@CNTs) were successfully prepared by a hydrothermal method as heterogeneous catalyst which can be used as an activator of peroxymonosulphate (PMS) for the degradation of chloroquine phosphate (CQP). Based on characterisation techniques, the prepared catalyst has excellent surface properties and structural stability. When different concentrations of CQP were treated with 0.2 g/L nano-NiCo2S4@CNTs and 1.0 mM PMS, the highest degradation rate could reach 99.86% after 30 min. Under the interference of pH, common anions and humic acid in the water environment, the reaction system can still achieve high degradation efficiency, showing excellent anti-interference ability and practical applicability. Furthermore, in the nano-NiCo2S4@CNTs/PMS system, according to the identification results of reactive oxygen species, the free radical and non-free radical pathway are responsible for the degradation of CQP, and the PMS mechanism activation was comprehensively proposed. Twelve intermediate products were detected in the degradation process, and the possible degradation pathways of CQP were proposed. This toxicity analysis demonstrates that the intermediate products formed during CQP degradation pose lower environmental risks compared to the original pollutant. In addition, after using the catalyst four cycles, the removal efficiency of CQP remains above 80%, indicating the excellent reusability and low metal ion leaching characteristics. Therefore, the nano-NiCo2S4@CNTs synthesised in this research has broad application prospects in activating PMS for wastewater treatment.

Three-Dimensional Acoustic Assembly Device for Mass Manufacturing of Cell Spheroids.

Cell spheroids are promising three-dimensional (3D) models that have gained wide applications in many biological fields. This protocol presents a method for manufacturing high-quality and high-throughput cell spheroids using a 3D acoustic assembly device through maneuverable procedures. The acoustic assembly device consists of three lead zirconate titanate (PZT) transducers, each arranged in the X/Y/Z plane of a square polymethyl methacrylate (PMMA) chamber. This configuration enables the generation of a 3D dot-array pattern of levitated acoustic nodes (LANs) when three signals are applied. As a result, cells in the gelatin methacryloyl (GelMA) solution can be driven to the LANs, forming uniform cell aggregates in three dimensions. The GelMA solution is then UV-photocured and crosslinked to serve as a scaffold that supports the growth of cell aggregates. Finally, masses of matured spheroids are obtained and retrieved by subsequently dissolving the GelMA scaffolds under mild conditions. The proposed new 3D acoustic cell assembly device will enable the scale-up fabrication of cell spheroids, and even organoids, offering great potential technology in the biological field.

Allogeneic hematopoietic stem cell transplantation corrects ligase IV deficiency.

BACKGROUND: Mutations in the DNA ligase IV (LIG4) gene cause a rare autosomal recessive disorder called LIG4 deficiency syndrome. The LIG4 deficiency is featured by severe disorders, including combined immunodeficiency disease, special face ("bird-head-like" face), developmental delays, pancytopenia, and radiosensitivity. Currently there are no curative treatment options except potentially by performing a hematopoietic stem cell transplantation (HSCT). CASE PRESENTATION: Here we reported the clinical course of a 4 and 1/2-year-old Chinese female with LIG4-deficiency featured with pancytopenia, severe growth retardation (weight of 13.5 kg, < 3rd percentile), length of 100 cm (<2d percentile), head circumference of 46 cm (<3rd percentile), and mild microcephaly. Despite regular IVIG administrations (5 g, once a month), the patient's thrombocytopenia had progressed. Eventually, the patient received HSCT that successfully normalized the LIG4 syndrome associated pancytopenia and corrected the LIG4 mutation. Despite progress the patient succumbed to thrombotic microangiopathy more than 3 months after HSCT. CONCLUSIONS: This case reports an example of partially successful HSCT as a treatment option for LIG4 syndrome. It is possible that individual factors influence the therapeutic effect of HSCT in LIG4 deficiency.

3D Bioprinting of an Endothelialized Liver Lobule-like Construct as a Tumor-Scale Drug Screening Platform.

3D cell culture models replicating the complexity of cell-cell interactions and biomimetic extracellular matrix (ECM) are novel approaches for studying liver cancer, including in vitro drug screening or disease mechanism investigation. Although there have been advancements in the production of 3D liver cancer models to serve as drug screening platforms, recreating the structural architecture and tumor-scale microenvironment of native liver tumors remains a challenge. Here, using the dot extrusion printing (DEP) technology reported in our previous work, we fabricated an endothelialized liver lobule-like construct by printing hepatocyte-laden methacryloyl gelatin (GelMA) hydrogel microbeads and HUVEC-laden gelatin microbeads. DEP technology enables hydrogel microbeads to be produced with precise positioning and adjustable scale, facilitating the construction of liver lobule-like structures. The vascular network was achieved by sacrificing the gelatin microbeads at 37 °C to allow HUVEC proliferation on the surface of the hepatocyte layer. Finally, we used the endothelialized liver lobule-like constructs for anti-cancer drug (Sorafenib) screening, and stronger drug resistance results were obtained when compared to either mono-cultured constructs or hepatocyte spheroids alone. The 3D liver cancer models presented here successfully recreate liver lobule-like morphology, and may have the potential to serve as a liver tumor-scale drug screening platform.

Fuzi polysaccharides improve immunity in immunosuppressed mouse models by regulating gut microbiota composition.

Rationale and objectives: Fuzi, the dried root of Aconitum carmichaelii Debx, is one of the widely used traditional Chinese medicines. Fuzi polysaccharides are considered the most bioactive compounds with immunomodulatory functions, however, the mechanisms have not been evaluated. This study aims to systematically investigate the effects of Fuzi polysaccharides on the gut microbiota and immune function using a mouse model immunosuppressed with cyclophosphamide. Methods: The short-chain fatty acid levels in cecal contents were measured by gas chromatography-mass spectrometry. The gut microbiota 16S rRNA gene were sequenced by next generation sequencing. The mRNA expression levels of NF-κB, IL-6, TNF-α, iNOS and COX-2 were measured using quantitative real-time polymerase chain reaction. The protein expression of occludin and zonula occludens-1 were analyzed by Western blot. The white blood cells were counted using automated hematology analyzer, and CD4+FOXP3+/CD4+ ratio was measured by flow cytometry. Results and Conclusions: Fuzi polysaccharides had the function of elevating the concentration of acetic acid, propionic acid, isobutyric acid, and n-butyric acid in the cecum. Meanwhile, Fuzi polysaccharides could decrease the relative abundance of Helicobacter, Anaerotruncus, Faecalibacterium, Lachnospira, Erysipelotrichaceae_UCG-003, Mucispirillum, and Mycoplasma, and increase the relative abundance of Rhodospirillales, Ruminococcaceae_UCG-013, Mollicutes_RF39, Ruminococcus_1, Christensenellaceae_R-7_group, and Muribaculaceae in the gut. Furthermore, Fuzi polysaccharides exhibited the function of increasing spleen and thymus indices and number of white blood cells and lymphocytes. Fuzi polysaccharides could reverse the decreased mRNA expression of NF-кB, IL-6, and iNOS, differentiation of CD4+FOXP3+ regulatory T cells as well as protein expression of occludin and zonula occludens-1 induced by cyclophosphamide. In addition, the mRNA and protein expression of cytokines were significantly correlated with the abundance of gut microbiota under Fuzi polysaccharides treatment. Collectively, the above results demonstrated that Fuzi polysaccharides could regulate inflammatory cytokines and gut microbiota composition of immunosuppressive mice to improve immunity, thereby shedding light on revealing the molecular mechanism of polysaccharides of traditional Chinese medicines in the future.

The construction of an efficient magnesium-lithium separation thin film composite membrane with dual aqueous-phase monomers (PIP and MPD).

A series of thin film composite (TFC) membranes was prepared with piperazine (PIP) and m-phenylenediamine (MPD) in different ratios, and the magnesium-lithium separation performance of TFC membranes in salt-lake brine with the magnesium-lithium ratio of 28 were systematically compared. The prepared TFC membranes exhibited high rejection of magnesium ions and negative rejection of lithium ions with high water flux, enabling high magnesium-lithium separation efficiency. The characterisation using FTIR spectroscopy, XPS, zeta potential measurements, and SEM techniques indicated that the composition and surface morphology of the membrane prepared with dual aqueous monomers were found to be different from those prepared with single aqueous monomers under the similar conditions. The interfacial polymerization process of different monomers and the structure-performance mechanism of TFC membranes were further discussed.