Sliding Ferroelectricity Engineered Coupling between Spin Hall Effect and Layertronics in 2D Lattice.

Coupling the spin Hall effect with novel degrees of freedom of electrons is central to the rich phenomena observed in condensed-matter physics. Here, using symmetry analysis and a low-energy k·p model, we report the sliding ferroelectricity engineered coupling between spin Hall effect and emerging layertronics, thereby generating the layer spin Hall effect (LSHE), in a 2D lattice. The physics is rooted in a pair of T-symmetry connected valleys, which experience spin splitting accompanied by large Berry curvature under spin-orbit coupling. The interaction between the out-of-plane ferroelectricity and electronic properties gives rise to the layer-locked Berry curvature and thus layer-polarized spin Hall effect (LP-SHE) in the bilayers. Such LP-SHE is strongly coupled with sliding ferroelectricity, enabling it to be ferroelectrically reversible. Using first-principles calculations, the mechanism is further demonstrated in a series of real bilayer systems, including MoS2, MoTe2, WSe2, MoSi2P4, and MoSi2As4. These phenomena and insights open a new direction for spin Hall effect.

Dorsal raphe neurons integrate the values of reward amount, delay, and uncertainty in multi-attribute decision-making.

The dorsal raphe nucleus (DRN) is implicated in psychiatric disorders that feature impaired sensitivity to reward amount, impulsivity when facing reward delays, and risk-seeking when confronting reward uncertainty. However, it has been unclear whether and how DRN neurons signal reward amount, reward delay, and reward uncertainty during multi-attribute value-based decision-making, where subjects consider these attributes to make a choice. We recorded DRN neurons as monkeys chose between offers whose attributes, namely expected reward amount, reward delay, and reward uncertainty, varied independently. Many DRN neurons signaled offer attributes, and this population tended to integrate the attributes in a manner that reflected monkeys' preferences for amount, delay, and uncertainty. After decision-making, in response to post-decision feedback, these same neurons signaled signed reward prediction errors, suggesting a broader role in tracking value across task epochs and behavioral contexts. Our data illustrate how the DRN participates in value computations, guiding theories about the role of the DRN in decision-making and psychiatric disease.

3D Poly (L-lactic acid) fibrous sponge with interconnected porous structure for bone tissue scaffold.

Large bone defects, often resulting from trauma and disease, present significant clinical challenges. Electrospun fibrous scaffolds closely resembling the morphology and structure of natural ECM are highly interested in bone tissue engineering. However, the traditional electrospun fibrous scaffold has some limitations, including lacking interconnected macropores and behaving as a 2D scaffold. To address these challenges, a sponge-like electrospun poly(L-lactic acid) (PLLA)/polycaprolactone (PCL) fibrous scaffold has been developed by an innovative and convenient method (i.e., electrospinning, homogenization, progen leaching and shaping). The resulting scaffold exhibited a highly porous structure (overall porosity = 85.9 %) with interconnected, regular macropores, mimicking the natural extracellular matrix. Moreover, the incorporation of bioactive glass (BG) particles improved the hydrophilicity (water contact angle = 79.7°) and biocompatibility and promoted osteoblast cell growth. In-vitro 10-day experiment revealed that the scaffolds led to high cell viability. The increment of the proliferation rates was 195.4 % at day 7 and 281.6 % at day 10. More importantly, Saos-2 cells could grow, proliferate, and infiltrate into the scaffold. Therefore, this 3D PLLA/PCL with BG sponge holds great promise for bone defect repair in tissue engineering applications.

Engineering Layertronics in Two-Dimensional Ferromagnetic Multiferroic Lattice.

Layertronics, rooted in the layer Hall effect (LHE), is an emerging fundamental phenomenon in condensed matter physics and spintronics. So far, several theoretical and experimental proposals have been made to realize LHE, but all are based on antiferromagnetic systems. Here, using symmetry and tight-binding model analysis, we propose a general mechanism for engineering layertronics in a two-dimensional ferromagnetic multiferroic lattice. The physics is related to the band geometric properties and multiferroicity, which results in the coupling between Berry curvature and layer degree of freedom, thereby generating the LHE. Using first-principles calculations, we further demonstrate this mechanism in bilayer (BL) TcIrGe2S6. Due to the intrinsic inversion and time-reversal symmetry breakings, BL TcIrGe2S6 exhibits multiferroicity with large Berry curvatures at both the center and corners of the Brillouin zone. These Berry curvatures couple with the layer physics, forming the LHE in BL TcIrGe2S6. Our work opens a new direction for research on layertronics.

Temporally Decoupled Ammonia Splitting by a Zn-NH3 Battery with an Ammonia Oxidation/Hydrogen Evolution Bifunctional Electrocatalyst as a Cathode.

Ammonia splitting to hydrogen is a decisive route for hydrogen economy but is seriously limited by the complex device and low efficiency. Here, we design and propose a new rechargeable Zn-NH3 battery based on temporally decoupled ammonia splitting to achieve efficient NH3-to-H2 conversion. In this system, ammonia is oxidized into nitrogen during cathodic charging (2NH3 + 6OH- → N2 + 6H2O + 6e-) with external electrical energy conversion and storage, while during cathodic discharging, water is reduced to hydrogen (2H2O + 2e- → H2 + 2OH-) with electrical energy generation. In this loop, continuous and efficient H2 production without separation and purification is achieved. With the help of the ammonia oxidation reaction (AOR) and hydrogen evolution reaction (HER) bifunctional catalyst of Mo2C/NiCu@C, a rechargeable Zn-NH3 battery is realized that exhibits a high NH3-to-H2 FE of 91.6% with outstanding durability for 900 cycles (300 h) at 20 mA/cm2, enabling efficient and continuous NH3-to-H2 conversion.

Sirt6 ablation in the liver causes fatty liver that increases cancer risky by upregulating Serpina12.

Non-alcoholic fatty liver disease is a chronic liver abnormality that exhibits high variability and can lead to liver cancer in advanced stages. Hepatic ablation of SIRT6 results in fatty liver disease, yet the potential mechanism of SIRT6 deficiency, particularly in relation to downstream mediators for NAFLD, remains elusive. Here we identify Serpina12 as a key gene regulated by Sirt6 that plays a crucial function in energy homeostasis. Specifically, Sirt6 suppresses Serpina12 expression through histone deacetylation at its promoter region, after which the transcription factor, Cebpα, binds to and regulates its expression. Sirt6 deficiency results in an increased expression of Serpina12 in hepatocytes, which enhances insulin signaling and promotes lipid accumulation. Importantly, CRISPR-Cas9 mediated Serpina12 knockout in the liver ameliorated fatty liver disease caused by Sirt6 ablation. Finally, we demonstrate that Sirt6 functions as a tumor suppressor in the liver, and consequently, deletion of Sirt6 in the liver leads to not only the spontaneous development of tumors but also enhanced tumorigenesis in response to DEN treatment or under conditions of obesity.

Broadband nonlinear optical response and sub-picosecond carrier dynamics in graphene-SnSe2 van der Waals heterostructures.

The van der Waals (vdWs) heterostructures, with vertical layer stacking structure of various two-dimensional (2D) materials, maintain the reliable photonic characteristics while compensating the shortcomings of the participating individual components. In this work, we combine the less-studied multilayer tin selenide (SnSe2) thin film with one of the traditional 2D materials, graphene, to fabricate the graphene-based vdWs optical switching element (Gr-SnSe2) with superior broadband nonlinear optical response. The transient absorption spectroscopy (TAS) measurement results verify that graphene acts as the recombination channel for the photogenerated carrier in the Gr-SnSe2 sample, and the fast recovery time can be reduced to hundreds of femtoseconds which is beneficial for the optical modulation process. The optical switching properties are characterized by the I-scan measurements, exhibiting a saturable energy intensity of 2.82 mJ·cm-2 (0.425 µJ·cm-2) and a modulation depth of 15.6% (22.5%) at the wavelength of 1030 nm (1980nm). Through integrating Gr-SnSe2 with a cladding waveguide, high-performance picosecond Q-switched operation in the near-infrared (NIR) and mid-infrared (MIR) spectral regions are both achieved. This work experimentally demonstrates the great potential of graphene-based vdWs heterostructures for applications in broadband ultrafast photonics.

The heterogeneity of signaling pathways and drug responses in intrahepatic cholangiocarcinoma with distinct genetic mutations.

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy among primary liver cancers, with an increasing overall incidence and poor prognosis. The intertumoral and intratumoral heterogeneity of ICC makes it difficult to find efficient drug therapies. Therefore, it is essential to identify tumor suppressor genes and oncogenes that induce ICC formation and progression. Here, we performed CRISPR/Cas9-mediated genome-wide screening in a liver-specific Smad4/Pten knockout mouse model (Smad4co/co;Ptenco/co;Alb-Cre, abbreviated as SPC), which normally generates ICC after 6 months, and detected that mutations in Trp53, Fbxw7, Inppl1, Tgfbr2, or Cul3 markedly accelerated ICC formation. To illustrate the potential mechanisms, we conducted transcriptome sequencing and found that multiple receptor tyrosine kinases were activated, which mainly upregulated the PI3K pathway to induce cell proliferation. Remarkably, the Cul3 mutation stimulated cancer progression mainly by altering the immune microenvironment, whereas other mutations promoted the cell cycle. Moreover, Fbxw7, Inppl1, Tgfbr2, and Trp53 also affect inflammatory responses, apelin signaling, mitotic spindles, ribosome biogenesis, and nucleocytoplasmic transport pathways, respectively. We further examined FDA-approved drugs for the treatment of liver cancer and performed high-throughput drug screening of the gene-mutant organoids. Different drug responses and promising drug therapies, including chemotherapy and targeted drugs, have been discovered for ICC.

A neural mechanism for conserved value computations integrating information and rewards.

Behavioral and economic theory dictate that we decide between options based on their values. However, humans and animals eagerly seek information about uncertain future rewards, even when this does not provide any objective value. This implies that decisions are made by endowing information with subjective value and integrating it with the value of extrinsic rewards, but the mechanism is unknown. Here, we show that human and monkey value judgements obey strikingly conserved computational principles during multi-attribute decisions trading off information and extrinsic reward. We then identify a neural substrate in a highly conserved ancient structure, the lateral habenula (LHb). LHb neurons signal subjective value, integrating information's value with extrinsic rewards, and the LHb predicts and causally influences ongoing decisions. Neurons in key input areas to the LHb largely signal components of these computations, not integrated value signals. Thus, our data uncover neural mechanisms of conserved computations underlying decisions to seek information about the future.

Dorsal raphe neurons signal integrated value during multi-attribute decision-making.

The dorsal raphe nucleus (DRN) is implicated in psychiatric disorders that feature impaired sensitivity to reward amount, impulsivity when facing reward delays, and risk-seeking when grappling with reward uncertainty. However, whether and how DRN neurons signal reward amount, reward delay, and reward uncertainty during multi-attribute value-based decision-making, where subjects consider all these attributes to make a choice, is unclear. We recorded DRN neurons as monkeys chose between offers whose attributes, namely expected reward amount, reward delay, and reward uncertainty, varied independently. Many DRN neurons signaled offer attributes. Remarkably, these neurons commonly integrated offer attributes in a manner that reflected monkeys' overall preferences for amount, delay, and uncertainty. After decision-making, in response to post-decision feedback, these same neurons signaled signed reward prediction errors, suggesting a broader role in tracking value across task epochs and behavioral contexts. Our data illustrate how DRN participates in integrated value computations, guiding theories of DRN in decision-making and psychiatric disease.

Production of high-energy 6-Ah-level Li | |LiNi0.83Co0.11Mn0.06O2 multi-layer pouch cells via negative electrode protective layer coating strategy.

Stable lithium metal negative electrodes are desirable to produce high-energy batteries. However, when practical testing conditions are applied, lithium metal is unstable during battery cycling. Here, we propose poly(2-hydroxyethyl acrylate-co-sodium benzenesulfonate) (PHS) as negative electrode protective layer. The PHS contains soft poly (2-hydroxyethyl acrylate) and poly(sodium p-styrene sulfonate), which improve electrode flexibility, connection with the Cu current collector and transport of Li ions. Transmission electron cryomicroscopy measurements reveal that PHS induces the formation of a solid electrolyte interphase with a fluorinated rigid and crystalline internal structure. Furthermore, theoretical calculations suggest that the -SO3- group of poly(sodium p-styrene sulfonate) promotes Li-ion motion towards interchain migration through cation-dipole interaction, thus, enabling uniform Li-ion diffusion. Electrochemical measurements of Li | |PHS-coated-Cu coin cells demonstrate an average Coulombic efficiency of 99.46% at 1 mA/cm2, 6 mAh/cm2 and 25 °C. Moreover, when the PHS-coated Li metal negative electrode is paired with a high-areal-capacity LiNi0.83Co0.11Mn0.06O2-based positive electrode in multi-layer pouch cell configuration, the battery delivers an initial capacity of 6.86 Ah (corresponding to a specific energy of 489.7 Wh/kg) and, a 91.1% discharge capacity retention after 150 cycles at 2.5 mA/cm2, 25 °C and 172 kPa.

Development, Essence, and Application of a Metal-Catalysis Battery.

ConspectusIn the pursuit of maximizing the energy supply and sustainable energy development, high-energy-density energy storage systems beyond lithium-ion batteries are surging. The metal-catalysis battery, composed of a metal anode, electrolyte, and redox-coupled electrocatalyst cathode with gas, liquid, or solid as active reactants, is regarded as a promising energy storage and conversion system due to its dual functions of energy storage and chemical production. In this system, with the assistance of a redox-coupled catalyst, during discharging, the reduction potential energy of the metal anode is converted into chemicals along with electrical energy generation, while the external electrical energy is translated to the reduction potential energy of the metal anode and the oxidation potential energy of the reactants during charging. In this loop, the electrical energy and sometimes chemicals can be generated simultaneously. Although intensive effort has been devoted to the exploration of redox-coupled catalysts, the essence of the metal-catalysis battery, which is the prerequisite for further development and application, has been overlooked.In this Account, we present the journey of the metal-catalysis battery from development to essence and application and propose that the metal-catalysis battery system, which combines energy storage and electrocatalytic redox reactions with the characteristics of temporal decoupling and spatial coupling and an energy-conversion paradigm from electrical energy to chemicals via electrochemical energy storage, is achieved. First, inspired by the Zn-air/Li-air battery, we developed and realized Li-CO2/Zn-CO2 batteries and enriched the functions of the metal-catalysis battery from energy storage to chemical production. Based on OER/ORR and OER/CDRR catalysts, we have further explored OER/NO3-RR and HzOR/HER coupled catalysts and developed Zn-nitrate and Zn-hydrazine batteries. By extending the redox-coupled electrocatalyst systems from O, C species to N species and others, the metal-catalysis battery systems would develop from metal-Ox, Cx to metal-Nx and other batteries. Then, from Zn-CO2 and Zn-hydrazine batteries, we found that the overall reaction is decoupled into two separate reduction and oxidation reactions via the cathodic discharge and charge processes, and we further extracted the essence of the metal-catalysis battery, namely, the temporal-decouple and spatial-couple (TD-SC) mechanism, which is completely opposite to the conventional temporal couple and spatial decouple in electrochemical water splitting. Based on the TD-SC mechanism, we developed various applications of metal-catalysis batteries for the green and efficient synthesis of fine chemicals by modifying the metal anode and redox-coupled catalysts and electrolytes, including the Li-N2/H2 battery for NH3 synthesis and the organic Li-N2 battery for fine chemical synthesis. Finally, the main challenges and the possible opportunities for the metal-catalysis battery are discussed, including the rational design of highly efficient redox-coupled electrocatalysts and green electrochemical synthesis. The deep insight into the metal-catalysis battery will provide an alternative approach to energy storage and chemical production.

Distributed MPC of vehicle platoons with guaranteed consensus and string stability.

Control of vehicle platoon can effectively reduce the traffic accidents caused by fatigue driving and misoperation, reduce air resistance by eliminating the inter-vehicle gap which will effectively reduce fuel consumption and exhaust emissions. A hierarchical control scheme for vehicle platoons is proposed in this paper. Considering safety, consistency, and passengers' comfort, a synchronous distributed model predictive controller is designed as an upper-level controller, in which a constraint guaranteeing string stability is introduced into the involved local optimization problem so as to guarantee that the inter-vehicle gap error gradually attenuates as it propagates downstream. A terminal equality constraint is added to guarantee asymptotic consensus of vehicle platoons. By constructing the vehicle inverse longitudinal dynamics model, a lower-level control scheme with feedforward and feedback controllers is designed to adjust the throttle angle and brake pressure of vehicles. A PID is used as the feedback controller to eliminate the influence of unmodeled dynamics and uncertainties. Finally, the performance of longitudinal tracking with the proposed control scheme is validated by joint simulations with PreScan, CarSim, and Simulink.

Enhancement of the immune response via the facilitation of dendritic cell maturation by CD-205 Receptor-mediated Long-circling liposomes acting as an antigen and astragalus polysaccharide delivery system.

CD-205 receptor-mediated dendritic cell (DC) targeting liposomes are commonly used as a delivery system for inducing a strong T-cell immune response or specific immune tolerance. This delivery system can carry both the antigen and adjuvant, thereby modulating DC maturation and also activating the T-cell response. In order to maximize the desired therapeutic effects of Astragalus polysaccharides (APS) and induce an efficient cellular and humoral immune response against the antigen, ovalbumin (OVA) and APS were encapsulated in long-circling liposomes conjugated with anti-CD-205 receptor antibodies to produce CD-205-targeted liposomes (iLPSM). We explored using a series of experiments evaluating the targeting efficiency of iLPSM. In vitro, iLPSM nanoparticles promoted the proliferation of macrophages, and the nanoparticles were rapidly phagocytized by macrophages. In vivo, iLPSM significantly improved the antibody titers of OVA-specific IgG and IgG, isotypes cytokine production, and T and B lymphocyte differentiation. Furthermore, iLPSM facilitated the maturation of DCs. In addition, iLPSM nanoparticles could prolong the retention time of nanoparticles at the injection site, leading to a strong, sustained immune response. These results show that the CD-205 antibody successfully binds to the corresponding cell receptor.

Layer Hall Effect in Multiferroic Two-Dimensional Materials.

The layer Hall effect (LHE) is of fundamental and practical importance in condensed-matter physics and material science; however, it was rarely observed and usually based on the paradigms of persistent electric field and sliding ferroelectricity. Here, a new mechanism of LHE is proposed by coupling layer physics with multiferroics using symmetry analysis and a low-energy k·p model. Due to time-reversal symmetry breaking and valley physics, the Bloch electrons on one valley will be subject to a large Berry curvature. This combined with inversion symmetry breaking gives rise to layer-polarized Berry curvature and can force the electrons to deflect in one direction of a given layer, thereby generating the LHE. We demonstrate that the resulting LHE is ferroelectrically controllable and reversible. Using first-principles calculations, this mechanism and predicted phenomena are verified in the multiferroic material of bilayer Co2CF2. Our finding opens a new direction for LHE and 2D materials research.

Coupled Solar Battery with 6.9 % Efficiency.

Solar-to-electrochemical energy storage in solar batteries is an important solar utilization technology comparable to solar-to-electricity (solar cells) and solar-to-fuel (photocatalytic cells) conversion. Unlike the indirect approach of integrated solar flow batteries combining photoelectrodes with redox-electrodes, coupled solar batteries enable direct solar energy storage, but are hampered by low efficiency due to rapid charge recombination of materials and misaligned energy levels between electrodes. Herein, we propose a design for a coupled solar battery that intercouples two photo-coupled ion transfer (PCIT) reactions through electron-ion transfer upon co-photo-pumping of photoelectrochemical storage cathode and anode. We used a representative covalent organic framework (COF) to achieve efficient charge separation and directional charge transfer between two band-matched photoelectrochemical storage electrodes, with a photovoltage sufficient for COF dual-redox reactions. By pumping these electrodes, the coupled solar battery stores solar energy via two synergistic PCIT reactions of electron-proton-relayed COF oxidation and reduction, and the stored solar energy is released as electrochemical energy during COF regeneration in discharge while interlocking the loops. A breakthrough in efficiency (6.9 %) was achieved, adaptive to a large-area (56 cm2 ) tandem device. The presented photo-intercoupled electron-ion transfer (PIEIT) mechanism provides expandable paths toward practical solar-to-electrochemical energy storage.

Solar utilization beyond photosynthesis.

Natural photosynthesis is an efficient biochemical process which converts solar energy into energy-rich carbohydrates. By understanding the key photoelectrochemical processes and mechanisms that underpin natural photosynthesis, advanced solar utilization technologies have been developed that may be used to provide sustainable energy to help address climate change. The processes of light harvesting, catalysis and energy storage in natural photosynthesis have inspired photovoltaics, photoelectrocatalysis and photo-rechargeable battery technologies. In this Review, we describe how advanced solar utilization technologies have drawn inspiration from natural photosynthesis, to find sustainable solutions to the challenges faced by modern society. We summarize the uses of advanced solar utilization technologies, such as converting solar energy to electrical and chemical energy, electrochemical storage and conversion, and associated thermal tandem technologies. Both the foundational mechanisms and typical materials and devices are reported. Finally, potential future solar utilization technologies are presented that may mimic, and even outperform, natural photosynthesis.

FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2.

BACKGROUND & AIMS: Metastasis remains the major reason for the high mortality of patients with hepatocellular carcinoma (HCC). This study was designed to investigate the role of E-twenty-six-specific sequence variant 4 (ETV4) in promoting HCC metastasis and to explore a new combination therapy strategy for ETV4-mediated HCC metastasis. METHODS: PLC/PRF/5, MHCC97H, Hepa1-6, and H22 cells were used to establish orthotopic HCC models. Clodronate liposomes were used to clear macrophages in C57BL/6 mice. Gr-1 monoclonal antibody was used to clear myeloid-derived suppressor cells (MDSCs) in C57BL/6 mice. Flow cytometry and immunofluorescence were used to detect the changes of key immune cells in the tumour microenvironment. RESULTS: ETV4 expression was positively related to higher tumour-node-metastasis (TNM) stage, poor tumour differentiation, microvascular invasion, and poor prognosis in human HCC. Overexpression of ETV4 in HCC cells transactivated PD-L1 and CCL2 expression, which increased tumour-associated macrophage (TAM) and MDSC infiltration and inhibited CD8+ T-cell accumulation. Knockdown of CCL2 by lentivirus or CCR2 inhibitor CCX872 treatment impaired ETV4-induced TAM and MDSC infiltration and HCC metastasis. Furthermore, FGF19/FGFR4 and HGF/c-MET jointly upregulated ETV4 expression through the ERK1/2 pathway. Additionally, ETV4 upregulated FGFR4 expression, and downregulation of FGFR4 decreased ETV4-enhanced HCC metastasis, which created a FGF19-ETV4-FGFR4 positive feedback loop. Finally, anti-PD-L1 combined with FGFR4 inhibitor BLU-554 or MAPK inhibitor trametinib prominently inhibited FGF19-ETV4 signalling-induced HCC metastasis. CONCLUSIONS: ETV4 is a prognostic biomarker, and anti-PD-L1 combined with FGFR4 inhibitor BLU-554 or MAPK inhibitor trametinib may be effective strategies to inhibit HCC metastasis. IMPACT AND IMPLICATIONS: Here, we reported that ETV4 increased PD-L1 and chemokine CCL2 expression in HCC cells, which resulted in TAM and MDSC accumulation and CD8+ T-cell inhibition to facilitate HCC metastasis. More importantly, we found that anti-PD-L1 combined with FGFR4 inhibitor BLU-554 or MAPK inhibitor trametinib markedly inhibited FGF19-ETV4 signalling-mediated HCC metastasis. This preclinical study will provide a theoretical basis for the development of new combination immunotherapy strategies for patients with HCC.

Ultrasonic Treatment Enhances the Antioxidant and Immune-Stimulatory Properties of the Polysaccharide from Sinopodophyllum hexandrum Fruit.

We aimed to assess the potential of ultrasonic treatment on the processing of polysaccharides as functional foods or food additives. The polysaccharide from Sinopodophyllum hexandrum fruit (SHP, 52.46 kDa, 1.91 nm) was isolated and purified. SHP was treated with various levels of ultrasound (250 W and 500 W), resulting in the formation of two polysaccharides, SHP1 (29.37 kD, 1.40 nm) and SHP2 (36.91 kDa, 0.987 nm). Ultrasonic treatment was found to reduce the surface roughness and molecular weight of the polysaccharides, leading to thinning and fracturing. The effect of ultrasonic treatment on polysaccharide activity was evaluated in vitro and in vivo. In vivo experiments showed that ultrasonic treatment improved the organ index. Simultaneously, it enhanced the activity of superoxide dismutase, total antioxidant capacity, and decreased the content of malondialdehyde in the liver. In vitro experiments demonstrated that ultrasonic treatment also promoted proliferation, nitric oxide secretion, phagocytic efficiency, costimulatory factors (CD80+, CD86+) expression, and cytokine(IL-6, IL-1ß) production of RAW264.7 macrophages.

Integrated analysis of genomic and transcriptomic data for the discovery of splice-associated variants in cancer.

Somatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools ( www.regtools.org ), a computationally efficient, free, and open-source software package designed to integrate somatic variants from genomic data with splice junctions from bulk or single cell transcriptomic data to identify variants that may cause aberrant splicing. We apply RegTools to over 9000 tumor samples with both tumor DNA and RNA sequence data. RegTools discovers 235,778 events where a splice-associated variant significantly increases the splicing of a particular junction, across 158,200 unique variants and 131,212 unique junctions. To characterize these somatic variants and their associated splice isoforms, we annotate them with the Variant Effect Predictor, SpliceAI, and Genotype-Tissue Expression junction counts and compare our results to other tools that integrate genomic and transcriptomic data. While many events are corroborated by the aforementioned tools, the flexibility of RegTools also allows us to identify splice-associated variants in known cancer drivers, such as TP53, CDKN2A, and B2M, and other genes.