ONC206 targeting ClpP induces mitochondrial dysfunction and protective autophagy in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for approximately 90 % of all cases. ONC201, a member of the imipridone drug family, has shown promising therapeutic potential and a good safety profile in both malignant pediatric central nervous system tumors (diffuse midline glioma [DMG]) and hematologic malignancies. ONC206 is a more potent analog of ONC201. However, the ONC206 potential and mechanism of action in HCC remain to be elucidated. We found that ONC206 hindered HCC growth by suppressing cell proliferation and inducing apoptosis. Moreover, ONC206 induced cytoprotective autophagy, and blocking autophagy enhanced the proapoptotic effect of ONC206. Additionally, ONC206 induced mitochondrial swelling, reduced the mitochondrial membrane potential (MMP), and led to the accumulation of mitochondrial ROS in HCC cells, ultimately resulting in mitochondrial dysfunction. The HCC patient samples exhibited notably elevated levels of caseinolytic protease proteolytic subunit (ClpP), which serves as a mediator of ONC206-induced mitochondrial dysfunction and the activation of protective autophagy. knockdown of ClpP reversed the cytotoxic effects of ONC206 on HCC cells. In summary, our results provide the first insight into the mechanism by which ONC206 exerts its anti-HCC effects and induces protective autophagy in HCC cells through ClpP.

One-Step Preparation of Magnetic Lipid Bubbles: Magnetothermal Effect Induces the Simultaneous Formation of Gas Nuclei and Self-Assembly of Phospholipids.

In recent years, enveloped micro-nanobubbles have garnered significant attention in research due to their commendable stability, biocompatibility, and other notable properties. Currently, the preparation methods of enveloped micro-nanobubbles have limitations such as complicated preparation process, large bubble size, wide distribution range, low yield, etc. There exists an urgent demand to devise a simple and efficient method for the preparation of enveloped micro-nanobubbles, ensuring both high concentration and a uniform particle size distribution. Magnetic lipid bubbles (MLBs) are a multifunctional type of enveloped micro-nanobubble combining magnetic nanoparticles with lipid-coated bubbles. In this study, MLBs are prepared simply and efficiently by a magneto internal heat bubble generation process based on the interfacial self-assembly of iron oxide nanoparticles induced by the thermogenic effect in an alternating magnetic field. The mean hydrodynamic diameter of the MLBs obtained was 384.9 ± 8.5 nm, with a polydispersity index (PDI) of 0.248 ± 0.021, a zeta potential of -30.5 ± 1.0 mV, and a concentration of (7.92 ± 0.46) × 109 bubbles/mL. Electron microscopy results show that the MLBs have a regular spherical stable core-shell structure. The superparamagnetic iron oxide nanoparticles (SPIONs) and phospholipid layers adsorbed around the spherical gas nuclei of the MLBs, leading the particles to demonstrate commendable superparamagnetic and magnetic properties. In addition, the effects of process parameters on the morphology of MLBs, including phospholipid concentration, phospholipid proportiona, current intensity, magnetothermal time, and SPION concentration, were investigated and discussed to achieve controlled preparation of MLBs. In vitro imaging results reveal that the higher the concentration of MLBs loaded with iron oxide nanoparticles, the better the in vitro ultrasound (US) imaging and magnetic resonance imaging (MRI) results. This study proves that the magneto internal heat bubble generation process is a simple and efficient technique for preparing MLBs with high concentration, regular structure, and commendable properties. These findings lay a robust foundation for the mass production and application of enveloped micro-nanobubbles, particularly in biomedical fields and other related domains.

Detoxification of DON-induced hepatotoxicity in mice by cold atmospheric plasma.

Deoxynivalenol (DON) is one of the most common mycotoxins distributed in food and feed, which causes severe liver injury in humans and animals. Cold atmospheric plasma (CAP) has received much attention in mycotoxin degradation due to the advantages of easy operation, high efficiency, and low temperature. So far, the majority of studies have focused on the degradation efficiency and mechanism of CAP on DON, while there is still little information available on the hepatotoxicity of DON after CAP treatment. Herein, this study aimed to investigate the effect of CAP on DON-induced hepatotoxicity both in vitro and in vivo and its underlying mechanisms. The results showed that 120-s CAP treatment achieved 97 % degradation of DON. The vitro hepatotoxicity of DON in L02 cells was significantly reduced with CAP treatment time. Meanwhile, CAP markedly alleviated DON-induced liver injury in mice including the balloon-like degeneration of liver tissues and elevation of AST and ALP level. The underlying mechanism for CAP detoxification of DON-induced hepatotoxicity was further elucidated. The results showed that DON caused severe oxidative stress in cells by suppressing the antioxidant signaling pathway of Nrf2/HO-1/NQO-1, consequently leading to mitochondrial dysfunction and cell apoptosis, accompanied by cellular senescence and inflammation. CAP blocked DON inhibition on the Nrf2/HO-1/NQO-1 signaling pathway through the efficient degradation of DON, accordingly alleviating the oxidative stress and liver injury induced by DON. Therefore, CAP is an effective method to eliminate DON hepatotoxicity, which can be applied in the detoxification of mycotoxin-contaminated food and feed to ensure human and animal health.

GhiPLATZ17 and GhiPLATZ22, zinc-dependent DNA-binding transcription factors, promote salt tolerance in upland cotton.

KEY MESSAGE: The utilization of transcriptome analysis, functional validation, VIGS, and DAB techniques have provided evidence that GhiPLATZ17 and GhiPLATZ22 play a pivotal role in improving the salt tolerance of upland cotton. PLATZ (Plant AT-rich sequences and zinc-binding proteins) are known to be key regulators in plant growth, development, and response to salt stress. In this study, we comprehensively analyzed the PLATZ family in ten cotton species in response to salinity stress. Gossypium herbaceum boasts 25 distinct PLATZ genes, paralleled by 24 in G. raimondii, 25 in G. arboreum, 46 in G. hirsutum, 48 in G. barbadense, 43 in G. tomentosum, 67 in G. mustelinum, 60 in G. darwinii, 46 in G. ekmanianum, and a total of 53 PLATZ genes attributed to G. stephensii. The PLATZ gene family shed light on the hybridization and allopolyploidy events that occurred during the evolutionary history of allotetraploid cotton. Ka/Ks analysis suggested that the PLATZ gene family underwent intense purifying selection during cotton evolution. Analysis of synteny and gene collinearity revealed a complex pattern of segmental and dispersed duplication events to expand PLATZ genes in cotton. Cis-acting elements and gene expressions revealed that GhiPLATZ exhibited salt stress resistance. Transcriptome analysis, functional validation, virus-induced gene silencing (VIGS), and diaminobenzidine staining (DAB) demonstrated that GhiPLATZ17 and GhiPLATZ22 enhance salt tolerance in upland cotton. The study can potentially advance our understanding of identifying salt-resistant genes in cotton.

Homogeneous and Heterogeneous Frustrated Lewis Pairs for the Activation and Transformation of CO2.

Due to the serious ecological problems caused by the high CO2 content in the atmosphere, reducing atmospheric CO2 has attracted widespread attention from academia and governments. Among the many ways to mitigate CO2 concentration, the capture and comprehensive utilization of CO2 through chemical methods have obvious advantages, whose key is to develop suitable adsorbents and catalysts. Frustrated Lewis pairs (FLPs) are known to bind CO2 through the interaction between unquenched Lewis acid sites/Lewis base sites with the O/C of CO2, simultaneously achieving CO2 capture and activation, which render FLP better potential for CO2 utilization. However, how to construct efficient FLP targeted for CO2 utilization and the mechanism of CO2 activation have not been systematically reported. This review firstly provides a comprehensive summary of the recent advances in the field of CO2 capture, activation, and transformation with the help of FLP, including the construction of homogeneous and heterogeneous FLPs, their interaction with CO2, reaction activity, and mechanism study. We also illustrated the challenges and opportunities faced in this field to shed light on the prospective research.

Application of atmospheric cold plasma for zearalenone detoxification in cereals: Kinetics, mechanisms, and cytotoxicity analysis.

INTRODUCTION: Zearalenone (ZEN) is one of the most widely contaminated mycotoxins in world, posing a severe threat to human and animal health. Atmospheric cold plasma (ACP) holds great penitential in mycotoxin degradation. OBJECTIVES: This study aimed to investigate the degradation efficiency and mechanisms of ACP on ZEN as well as the cytotoxicity of ZEN degradation products by ACP. Additionally, this study also investigated the degradation efficiency of ACP on ZEN in cereals and its effect on cereal quality. METHODS: The degradation efficiency and products of ZEN by ACP was analyzed by HPLC and LC-MS/MS. The human normal liver cells and mice were employed to assess the cytotoxicity of ZEN degradation products. The ZEN artificially contaminated cereals were used to evaluate the feasibility of ACP detoxification in cereals. RESULTS: The results showed that the degradation rate of ZEN was 96.18 % after 30-W ACP treatment for 180 s. The degradation rate was dependent on the discharge power, and treatment time and distance. Four major ZEN degradation products were produced after ACP treatment due to the oxidative destruction of CC double bond, namely C18H22O7 (m/z = 351.19), C18H22O8 (m/z = 367.14), C18H22O6 (m/z = 335.14), and C17H20O6 (m/z = 321.19). L02 cell viability was increased from 52.4 % to 99.76 % with ACP treatment time ranging from 0 to 180 s. Mice results showed significant recovery of body weight and depth of colonic crypts as well as mitigation of glomerular and liver damage. Additionally, ACP removed up to 50.55 % and 58.07 % of ZEN from wheat and corn. CONCLUSIONS: This study demonstrates that ACP could efficiently degrade ZEN in cereals and its cytotoxicity was significantly reduced. Therefore, ACP is a promising effective method for ZEN detoxification in cereals to ensure human and animal health. Future study needs to develop large-scale ACP device with high degradation efficiency.

Genome-Wide Identification, Characterization, and Expression Analysis of Four Subgroup Members of the GH13 Family in Wheat (Triticum aestivum L.).

The glycoside hydrolase 13 (GH13) family is crucial for catalyzing α-glucoside linkages, and plays a key role in plant growth, development, and stress responses. Despite its significance, its role in plants remains understudied. This study targeted four GH13 subgroups in wheat, identifying 66 GH13 members from the latest wheat database (IWGSC RefSeq v2.1), including 36 α-amylase (AMY) members, 18 1,4-α-glucan-branching enzyme (SBE) members, 9 isoamylase (ISA) members, and 3 pullulanase (PU) members. Chromosomal distribution reveals a concentration of wheat group 7 chromosomes. Phylogenetic analysis underscores significant evolutionary distance variations among the subgroups, with distinct molecular structures. Replication events shaped subgroup evolution, particularly in regard to AMY members. Subcellular localization indicates AMY member predominance in extracellular and chloroplast regions, while others localize solely in chloroplasts, confirmed by the heterologous expression of TaSEB16 and TaAMY1 in tobacco. Moreover, 3D structural analysis shows the consistency of GH13 across species. Promoter cis-acting elements are suggested to be involved in growth, stress tolerance, and starch metabolism signaling. The RNA-seq data revealed TaGH13 expression changes under drought and submergence stress, and significant expression variation was observed between strong and weak gluten varieties during seed germination using quantitative real-time PCR (qRT-PCR), correlating with seed starch content. These findings demonstrate the pivotal role of GH13 family gene expression in wheat germination, concerning variety preference and environmental stress. Overall, this study advances the understanding of wheat GH13 subgroups, laying the groundwork for further functional studies.

Titanium induces pro-inflammatory and tissue-destructive responses in primary human macrophages.

Implants and medical devices are efficient and practical therapeutic solutions for a multitude of pathologies. Titanium and titanium alloys are used in orthopedics, dentistry, and cardiology. Despite very good mechanical properties, and corrosion resistance titanium implants can fail due to inflammatory or tissue-degradation related complications. Macrophages are major immune cells that control acceptance of failure of the implant. In this study, for the first time, we have performed a systematic analysis of the response of differentially activated human macrophages (M(Control), M(IFNγ) and M(IL-4)) to the polished and porous titanium surfaces in order to identify the detrimental effect of titanium leading to the tissue destruction and chronic inflammation. Transcriptome analysis revealed that the highest number of differences between titanium and control settings are found in M(IL-4) that model healing type of macrophages. RT-qPCR analysis confirmed that both polished and porous titanium affected expression of cytokines, chitinases/chitinase-like proteins and matrix metalloproteinases. Titanium-induced release and activation of MMP7 by macrophages was enhanced by fibroblasts in both juxtacrine and paracrine cell interaction models. Production of titanium-induced MMPs and cytokines associated with chronic inflammation were independent of the presence of Staphylococcus aureus. MMP7, one of the most pronounced tissue-destroying factor and chitinase-like protein YKL-40 were expressed in CD68+ macrophages in peri-implant tissues of patients with orthopedic implants. In summary, we demonstrated that titanium induces pro-inflammatory and tissue-destructing responses mainly in healing macrophages, and the detrimental effects of titanium surfaces on implant-adjacent macrophages are independent on the bacterial contamination.

Recent advances in the degradation efficacy and mechanisms of mycotoxins in food by atmospheric cold plasma.

Food contaminated by mycotoxins has become a worldwide public problem with political and economic implications. Although a variety of traditional methods have been used to eliminate mycotoxins from agri-foods, the results have been somewhat less than satisfactory. As an emerging non-thermal processing technology, atmospheric cold plasma (ACP) has great potential for food decontamination. Herein, this review mainly presents the degradation efficiency of ACP on mycotoxins in vitro and agri-foods as well as its possible degradation mechanisms. Meanwhile, ACP effects on food quality, factors affecting the degradation efficiency and the toxicity of degradation products are also discussed. According to the literatures, ACP could efficiently degrade many mycotoxins (e.g., aflatoxin, deoxynivalenol, zearalenone, ochratoxin A, fumonisin, and T-2 toxin) both in vitro and various foods (e.g., hazelnut, peanut, maize, rice, wheat, barley, oat flour, and date palm fruit) with little effects on the nutritional and sensory properties of food. The degradation efficacy was dependent on many factors including ACP treatment parameter, working gas, mycotoxin property, and food substrate. The mycotoxin degradation by ACP was mainly attributed to the reactive oxygen and nitrogen species in ACP, which can damage the chemical bonds of mycotoxins, consequently reducing the toxicity of mycotoxins.

Efficient Production of Flavonoid Glucuronides in Escherichia coli Using Flavonoid O-Glucuronosyltransferases Characterized from Marchantia polymorpha.

As a model liverwort, Marchantia polymorpha contains various flavone glucuronides with cardiovascular-promoting effects and anti-inflammatory properties. However, the related glucuronosyltransferases have not yet been reported. In this study, two bifunctional UDP-glucuronic acid/UDP-glucose:flavonoid glucuronosyltransferases/glucosyltransferases, MpUGT742A1 and MpUGT736B1, were identified from M. polymorpha. Extensive enzymatic assays found that MpUGT742A1 and MpUGT736B1 exhibited efficient glucuronidation activity for flavones, flavonols, and flavanones and showed promiscuous regioselectivity at positions 3, 6, 7, 3', and 4'. These enzymes catalyzed the production of a variety of flavonoid glucuronides with medicinal value, including apigenin-7-O-glucuronide and scutellarein-7-O-glucuronide. With the use of MpUGT736B1, apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide were prepared by scaled-up enzymatic catalysis and structurally identified by NMR spectroscopy. MpUGT742A1 also displayed glucosyltransferase activity on the 7-OH position of the flavanones using UDP-glucose as the sugar donor. Furthermore, we constructed four recombinant strains by combining the pathway for increasing the UDP-glucuronic acid supply with the two novel UGTs MpUGT742A1 and MpUGT736B1. When apigenin was used as a substrate, the extracellular apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide production obtained from the Escherichia coli strain BB2 reached 598 and 81 mg/L, respectively. Our study provides new candidate genes and strategies for the biosynthesis of flavonoid glucuronides.

Function analysis and characterisation of a novel chitinase, MdCht9, in Musca domestica.

Insect chitinases have been proposed as potential targets for pest control. In this work, a novel group IV chitinase gene, MdCht9, from Musca domestica was found to have multiple functions in the physiological activity, including chitin regulation, development and antifungal immunity. The MdCht9 gene was cloned and sequenced, its phylogeny was analysed and its expression was determined in normal and 20E treated larvae. Subsequently, RNA interference (RNAi)-mediated MdCht9 knockdown was performed, followed by biochemical assays, morphological observations and transcriptome analysis. Finally, the recombinant protein MdCht9 (rMdCht9) was purified and tested for anti-microbial activity and enzyme characteristics. The results showed that MdCht9 consists of three domains, highly expressed in a larval salivary gland. RNAi silencing of MdCht9 resulted in significant down-regulation of chitin content and expression of 15 chitin-binding protein (CBP) genes, implying a new insight that MdCht9 might regulate chitin content by influencing the expression of CBPs. In addition, more than half of the lethality and partial wing deformity appeared due to the dsMdCht9 treatment. In addition, the rMdCht9 exhibited anti-microbial activity towards Candida albicans (fungus) but not towards Escherichia coli (G-) or Staphylococcus aureus (G+). Our work expands on previous studies of chitinase while providing a potential target for pest management.

Heterodimers of Aromadendrane Sesquiterpenoid with Benzoquinone from the Chinese Liverwort Mylia nuda.

Mylnudones A-G (1-7), unprecedented 1,10-seco-aromadendrane-benzoquinone-type heterodimers, and a highly rearranged aromadendrane-type sesquiterpenoid (8), along with four known analogs (9-12), were isolated from the liverwort Mylia nuda. Compounds 1-6 and 7, bearing tricyclo[6.2.1.02,7] undecane and tricyclo[5.3.1.02,6] undecane backbones, likely formed via a Diels-Alder reaction and radical cyclization, respectively. Their structures were determined by spectroscopic analysis, computational calculation, and single-crystal X-ray diffraction analysis. Dimeric compounds displayed cytoprotective effects against glutamic acid-induced neurological deficits.

Simulation of the expanding universe in hyperbolic metamaterials.

The particle horizon represents the boundary between observable and unobservable regions of the universe, which changes as the universe expands. Based on transformation optics, hyperbolic electromagnetic metamaterials can be utilized to simulate metrics with different signs due to their unique anisotropic properties. In this paper, we use hyperbolic metamaterials to visually depict the variation of the particle horizon under three models of an expanding universe (open, flat, and closed) by substituting one-dimensional time with one-dimensional space. The good agreement between theory and simulation confirms that hyperbolic metamaterials are excellent for simulating space-times, suggesting their potential as a new platform for cosmological analogies.

Composition and structural characteristics of compressed alkaline earth metal hydrides.

The metallization of alkaline earth metal hydrides offers a way to achieve near-room temperature superconductivity. In order to explore the metallization mechanism of these hydrides under pressure, a detailed understanding of the property changes of alkaline earth metal hydrides is required. Based on first-principles calculations, we have systematically investigated the dihydrides (XH2, X = Be, Mg, Ca, Sr, Ba) and tetrahydrides (XH4, X = Mg, Ca, Sr, Ba) of alkaline earth metals, respectively. By applying external pressure, we show that the structures of these alkaline earth metal hydrides undergo a series of phase transitions. Moreover, we investigate how the size of the bandgap decreases and eventually closes and reveal the role of electronegativity of metal elements in the critical pressure of hydride metallization. Remarkably, the hydrogen units (H6 or H8) formed in XH4 can accelerate the metallization process. The increase of the energy level difference in hydrogen units promotes the electroacoustic coupling effect, which is conducive to realization of high superconducting transition temperature (Tc). Our theoretical findings identify MgH4-I4/mmm as having potential to be a high-temperature superconductor and provide unusual ideas for the search of unknown high-temperature superconducting materials.

CD58 acts as a tumor promotor in hepatocellular carcinoma via activating the AKT/GSK-3ß/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide because of rapid progression and high incidence of metastasis or recurrence. Accumulating evidence shows that CD58-expressing tumor cell is implicated in development of various cancers. The present study aimed to reveal the functional significance of CD58 in HCC progression and the underlying mechanisms. METHODS: Immunohistochemical staining (IHC), and western blotting were used to detect the expression of CD58 in HCC tissues and cells. The levels of sCD58 (a soluble form of CD58) in the cell supernatants and serum were assessed by ELISA. CCK-8, colony formation, and xenograft assays were used to detect the function of CD58 on proliferation in vitro and in vivo. Transwell assay and sphere formation assay were performed to evaluate the effect of CD58 and sCD58 on metastasis and self-renewal ability of HCC cells. Western blotting, immunofluorescence (IF), TOP/FOP Flash reporter assay, and subcellular fractionation assay were conducted to investigate the molecular regulation between CD58/sCD58 and AKT/GSK-3ß/ß-catenin axis in HCC cells. RESULTS: CD58 was significantly upregulated in HCC tissues. Elevation of CD58 expression correlated with more satellite foci and vascular invasion, and poorer tumor-free and overall survival in HCC patients. Higher sCD58 levels were in HCC patients' serum compared to healthy individuals. Functionally, CD58 promotes the proliferation of HCC cells in vitro and in vivo. Meanwhile, CD58 and sCD58 induce metastasis, self-renewal and pluripotency in HCC cells in vitro. Mechanistically, CD58 activates the AKT/GSK-3ß/ß-catenin signaling pathway by increasing phosphorylation of AKT or GSK3ß signaling, promoting expression of Wnt/ß-catenin target proteins and TCF/LEF-mediated transcriptional activity. Furthermore, AKT activator SC-79 or inhibitor LY294002 abolished the inhibitory effect of CD58 silencing on the proliferation, metastasis, and stemness of HCC cells. CONCLUSIONS: Taken together, CD58 promotes HCC progression and metastasis via activating the AKT/GSK-3ß/ß-catenin pathway, suggesting that CD58 is a novel prognostic biomarker and therapeutic target for HCC.

Inhibition of Fungal Growth and Aflatoxin B1 Synthesis in Aspergillus flavus by Plasma-Activated Water.

The gaseous reactive oxygen/nitrogen species (RONS) generated by cold atmospheric plasma (CAP) can effectively inactivate Aspergillus flavus (A. flavus) and prolong the shelf-life of food. Plasma-activated water (PAW) is the extension of cold plasma sterilization technology. Without the limitation of a plasma device, PAW can be applied to more scenarios of food decontamination. However, the efficacy of PAW as a carrier of RONS for eradicating A. flavus or inhibiting its growth remains unclear. In this study, the immediate fungicidal effect and long-term inhibitory effect of PAW on A. flavus were investigated. The results demonstrated that 60-min instant-prepared PAW could achieve a 3.22 log reduction CFU/mL of A. flavus and the fungicidal efficacy of PAW gradually declined with the extension of storage time. Peroxynitrite (ONOO-/ONOOH) played a crucial role in this inactivation process, which could damage the cell wall and membrane structure, disrupt intracellular redox homeostasis, and impair mitochondrial function, ultimately leading to fungal inactivation. In addition to the fungicidal effect, PAW also exhibited fungistatic properties and inhibited the synthesis of aflatoxin B1 (AFB1) in A. flavus. By analyzing the cellular antioxidant capacity, energy metabolism, and key gene expression in the AFB1 synthesis pathway, it was discovered that PAW can significantly reduce ATP levels, while increasing SOD and CAT activity during 5-d cultivation. Meanwhile, PAW effectively suppressed the expression of genes related to AFB1 synthesis.

Ent-eudesmane sesquiterpenoids from the Chinese liverwort Chiloscyphus polyanthus.

- Seven previously undescribed ent-eudesmane sesquiterpenoids (1-7), as well as seven known analogs (8-14), were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis. Their structures were established based on comprehensive spectroscopy analysis, electronic circular dichroism calculations, as well as biosynthetic considerations. The cytotoxicity against HepG2 (Human hepatocellular carcinomas) cancer cell line, and antifungal activity against Candida albicans SC5314 of all isolated ent-eudesmane sesquiterpenoids were preliminarily tested, results showed that the tested compounds did not display obvious cytotoxicity and antifungal activities under the tested concentration.

Comparative analysis of helium and air surface micro-discharge plasma treatment on the microbial reduction and quality attributes of beef slices.

This work aimed to compare the effects of helium and air surface micro-discharge (SMD) plasma on the microbial safety and quality of beef tissues. For the beef tissue model, the concentration and diffusion depth of hydroxyl radical and ozone have different change patterns over plasma treatment time and distance in helium and air SMD plasma. The inactivation efficiency of helium plasma depended on the plasma treatment time and distance, while the inactivation efficiency of air plasma only depended on the treatment time. For the fresh beef slices, air SMD plasma treatment exhibited a higher antimicrobial activity against S. aureus and E. coli than helium SMD plasma treatment (1.5 versus 0.9; 0.9 versus 0.28 log CFU/g at 10 min). However, air SMD plasma treatment caused more adverse effects on beef quality, leading to a smooth surface, extensive lipid oxidation, protein structure damage, low pH and discoloration compared to helium SMD plasma treatment. This work provides valuable guidelines for the working gas choice in the practical application of plasma to meat decontamination.

A randomized trial of Trendelenburg position for acute moderate ischemic stroke.

We aim to explore the effect of head-down position (HDP), initiated within 24 hours of onset, in moderate anterior circulation stroke patients with probable large artery atherosclerosis (LAA) etiology. This investigator-initiated, multi-center trial prospective, randomized, open-label, blinded-endpoint, multi-center and phase-2 trial was conducted in China and completed in 2021. Eligible patients were randomly assigned (1:1) into the HDP group receiving -20° Trendelenburg, or control group receiving standard care according to national guideline. The primary endpoint was proportion of modified Rankin Scale (mRS) of 0 to 2 at 90 days, which is a scale for measuring the degree of disability after stroke. 90-day mRS was assessed by a certified staff member who was blinded to group assignment. A total of 96 patients were randomized (47 in HDP group and 49 in control group) and 94 (97.9%) patients were included in the final analysis: 46 in HDP group and 48 in control group. The proportion of favorable outcome was 65.2% (30/46) in the HDP group versus 50.0% (24/48) in the control group (unadjusted: OR 2.05 [95%CI 0.87-4.82], P = 0.099). No severe adverse event was attributed to HDP procedures. This work suggests that the head-down position seems safe and feasible, but does not improve favorable functional outcome in acute moderate stroke patients with LAA. This trial was registered with ClinicalTrials.gov, NCT03744533.

Pallamins A-C, ent-labdane and pallavicinin based dimers from the Chinese liverwort Pallavicinia ambigua (mitt.) stephani.

Three unprecedented ent-labdane and pallavicinin based dimers pallamins A-C formed via [4 + 2] Diels-Alder cycloaddition, together with eight biosynthetically related monomers were isolated from Pallavicinia ambigua. Their structures were determined by the extensive analysis of HRESIMS and NMR spectra. The absolute configurations of the labdane dimers were determined by single crystal X-ray diffraction of the homologous labdane units, and 13C NMR and ECD calculations. Moreover, a preliminary evaluation of the anti-inflammatory activities of the isolated compounds was performed using the zebrafish model. Three of the monomers demonstrated significant anti-inflammatory activity.