A Cost-Effective and Chemical-Recycling Approach for Facile Preparation of Regenerated Cellulose Materials.

Cellulose is difficult to melt or dissolve. The dissolution and regeneration process paves the way to convert cellulose into diverse forms but still suffers from high costs and environmental pollution. Here, we developed a method that uses aqueous alkali to efficiently dissolve cellulose at a temperature above 0 °C in minutes for fabricating regenerated cellulose. Cellulose was modified with minimal carboxymethyl groups to weaken the intermolecular interaction and improve its dissolution. The modified cellulose can be commercially obtained from carboxymethyl cellulose manufacturing with low cost and high quality. The use of only aqueous alkali reduces pollution and facilitates chemical recycling, and the moderate dissolving temperature reduces energy consumption. The regenerated cellulose materials display excellent mechanical properties and can be recycled or biodegraded after use. The method allows the use of diverse raw materials and modifications to broaden its applicability. The study develops a low-cost and eco-friendly method to fabricate regenerated cellulose.

Remarkable stability of γ - N 2 and its prevalence in the nitrogen phase diagram.

Solid nitrogen exhibits a panoply of phenomena ranging from complex molecular crystalline configurations to polymerization and closing band gap at higher densities. Among the elemental molecular solids, nitrogen stands apart for having phases, which can only be stabilized following particular pressure-temperature pathways, indicative of metastability and kinetic barriers. Here, through the combination of Raman spectroscopy and dynamic compression techniques, we find that the appearance of the whole nitrogen phase diagram is determined by the P-T paths taken below 2 GPa. We reveal the existence of the path- and phase-dependent triple point between the ß - N 2 , δ loc - N 2 and γ - or ϵ - N 2 . We further show that the ß - N 2 towards γ - N 2 path below the triple point, that evades δ ( δ loc )- N 2 , results in the formation of γ - N 2 , which in turn becomes a dominant phase. We then demonstrate, that the ß - N 2 through δ ( δ loc )- N 2 above the triple point path leads to the formation of ϵ - N 2 and the "well-established" phase diagram. An additional pathway, which by-passes the rotationally inhibited modifications δ ( δ loc )- N 2 , via rapid compression is found to produce γ - N 2 at higher temperatures. We argue that the pathway and phase sensitive triple point and the compression rate dependent phase formation challenge our understanding of this archetypal dense molecular solid.

A longitudinal investigation of mental health outcomes after the Henan floods in China: Examining predictors of resilience trajectories.

A heavy rainstorm struck Henan, China, in July 2021. Previous studies have indicated that natural disasters have a wide range of psychological sequelae, but little research has been done on the psychological effects of floods specifically. This study aimed to track the mental health trajectories of flood victims over time and identify associated protective and risk factors. People living in the areas most impacted by the flood (N = 376) were surveyed at four different time points: 3 weeks, 1 month, 2 months, and 3 months post-flood. Latent growth mixture modeling was utilized to delineate longitudinal patterns of depression, anxiety, and posttraumatic stress disorder (PTSD). Least absolute shrinkage and selection operator logistic regression, a supervised machine-learning approach, was employed to discern predictors among 49 assessed variables at both contextual and personal levels. Results revealed three classes of PTSD (resilience, recovery, moderate symptoms) and anxiety (resilience, chronicity, recovery) trajectories, along with two classes of depression trajectories (resilience, chronicity). Key factors predicting resilience in mental health included personality traits, media consumption habits, pre-existing health conditions at the individual level, and asset loss and ongoing adversities at the contextual level. In spite of the widespread impact of the flood, most victims displayed resilience in the face of adversity. Identifying critical factors across various psychological symptoms offers valuable insights for both pre-disaster preparation and post-disaster trans-diagnostic psychological interventions.

Atmospheric brown carbon in China haze is dominated by secondary formation.

Brown carbon (BrC) is a class of light-absorbing organic aerosols (OA) and has significant influence on atmospheric radiative forcing. However, the current limited understanding of the physicochemical properties of BrC restricts the accurate evaluation of its environmental effects. Here the optical characteristics and chemical composition of BrC during wintertime in the Yangtze River Delta (YRD) region, China were measured by using high-resolution aerosol mass spectrometry (HR-AMS) and UV-vis spectrometry. Our results showed that BrC in PM2.5 during the campaign was dominated by water-soluble organics, which consist of less oxidized oxygenated OA (LO-OOA), more oxidized oxygenated OA (MO-OOA), fossil fuel OA (FFOA) and biomass burning OA (BBOA). MO-OOA and BBOA were the strongest light absorbing BrC at 365 nm (Abs365), followed by LO-OOA and FFOA with a mass absorption coefficient (MAC) being 0.74 ± 0.04, 0.73 ± 0.03, 0.48 ± 0.04 and 0.39 ± 0.06 m2 g-1 during the campaign, respectively. In the low relative humidity (RH < 80 %) haze periods Abs365 of LO-OOA contributed to 44 % of the total light absorption at 365 nm, followed by MO-OOA (31 %), FFOA (21 %) and BBOA (4 %). In contrast, in the high-RH (RH > 80 %) haze periods Abs365 was dominated by MO-OOA, which accounted for 62 % of the total Abs365, followed by LO-OOA (17 %), BBOA (13 %) and FFOA (8 %). Chemical composition analysis further showed that LO-OOA and MO-OOA are produced from gas-phase photooxidation of VOCs and aerosol aqueous reactions, respectively, in which ammonia significantly enhanced the formation and light absorption of BrC in the high RH haze period. On average, >75 % of the total Abs365nm in the YRD region during the haze events was contributed by LO-OOA and MO-OOA, suggesting that atmospheric BrC in China haze periods is predominantly formed by secondary reactions.

Driving force of value reversal in Chinese overleveraged firms: The mechanism and path of private placement.

To stimulate economic growth, China has launched multiple economic stimulus plans in recent years, intensifying corporate debt financing and subsequently elevating the leverage levels. Addressing and effectively reducing the leverage levels of our country's enterprises has emerged as a pressing issue in the trajectory of our economic development. This paper primarily investigates the drivers, pathways, and mechanisms for reversing the over-leveraged values of enterprises. Key findings include: (1) Excessive indebtedness exerts a negative impact on corporate value, with the suppressing effect intensifying as the degree of over-leverage increases; (2) Over-leveraged enterprises can effectively decrease their debt levels and enhance their value through private placement. Further research suggests that this mechanism operates by amplifying the operational leverage of over-leveraged enterprises post private placement and alleviating financing constraints, thereby elevating corporate value. (3) Compared to non-state-owned enterprises, state-owned enterprises exhibit higher levels of indebtedness. Among over-leveraged firms, enhancements in corporate governance and increased investment efficiency can positively transform corporate value. This study offers valuable insights for the ongoing supply-side structural reforms and governance guidance from the regulatory bodies.

Impact of long-term white matter hyperintensity changes on mobility and dexterity.

White matter hyperintensities (WMH), a common feature of cerebral small vessel disease, are related to worse clinical outcomes after stroke. We assessed the impact of white matter hyperintensity changes over 1 year after minor stroke on change in mobility and dexterity, including differences between the dominant and non-dominant hands and objective in-person assessment versus patient-reported experience. We recruited participants with lacunar or minor cortical ischaemic stroke, performed medical and cognitive assessments and brain MRI at presentation and at 1 year. At both time points, we used the timed-up and go test and the 9-hole peg test to assess mobility and dexterity. At 1 year, participants completed the Stroke Impact Scale. We ran two linear mixed models to assess change in timed-up and go and 9-hole peg test, adjusted for age, sex, stroke severity (National Institutes of Health Stroke Scale), dependency (modified Rankin Score), vascular risk factor score, white matter hyperintensity volume (as % intracranial volume) and additionally for 9-hole peg test: Montreal cognitive assessment, hand (dominant/non-dominant), National Adult Reading Test (premorbid IQ), index lesion side. We performed ordinal logistic regression, corrected for age and sex, to assess relations between timed-up and go and Stroke Impact Scale mobility, and 9-hole peg test and Stroke Impact Scale hand function. We included 229 participants, mean age 65.9 (standard deviation = 11.13); 66% male. 215/229 attended 1-year follow-up. Over 1 year, timed-up and go time increased with aging (standardized ß [standardized 95% Confidence Interval]: 0.124[0.011, 0.238]), increasing National Institutes of Health Stroke Scale (0.106[0.032, 0.180]), increasing modified Rankin Score (0.152[0.073, 0.231]) and increasing white matter hyperintensity volume (0.176[0.061, 0.291]). Men were faster than women (-0.306[0.011, 0.238]). Over 1 year, slower 9-hole peg test was related to use of non-dominant hand (0.290[0.155, 0.424]), aging (0.102[0.012, 0.192]), male sex (0.182[0.008, 0.356]), increasing National Institutes of Health Stroke Scale (0.160 [0.094, 0.226]), increasing modified Rankin Score (0.100[0.032, 0.169]), decreasing Montreal cognitive assessment score (-0.090[-0.167, -0.014]) and increasing white matter hyperintensity volume (0.104[0.015, 0.193]). One year post-stroke, Stroke Impact Scale mobility worsened per second increase on timed-up and go, odds ratio 0.67 [95% confidence interval 0.60, 0.75]. Stroke Impact Scale hand function worsened per second increase on the 9-hole peg test for the dominant hand (odds ratio 0.79 [0.71, 0.86]) and for the non-dominant hand (odds ratio 0.88 [0.83, 0.93]). Decline in mobility and dexterity is associated with white matter hyperintensity volume increase, independently of stroke severity. Mobility and dexterity declined more gradually for stable and regressing white matter hyperintensity volume. Dominant and non-dominant hands might be affected differently. In-person measures of dexterity and mobility are associated with self-reported experience 1-year post-stroke.

Comparison of physical activity and physical fitness in children and adolescents of Chinese Han and Tibet ethnicity.

Background: Physical activity (PA) and physical fitness (PF) are important markers of health status in children and adolescents in different ethnicities. In this study, we aimed to compare the PA and PF indicators between Tibetan and Han children and adolescents. Methods: Children and adolescents of 4-9 grades were recruited in Shigatse (n = 963) and Shanghai (n = 2,525) respectively. The information related to demographic, PA, and PF was collected via a self-reported questionnaire. PA was assessed through the participation of moderate to vigorous PA (MVPA), muscle-strengthening exercise (MSE) and organized sport participation (OSP). PF was estimated using the International Fitness Scale containing components of overall fitness, cardiorespiratory fitness, speed and agility, muscular strength and flexibility. Results: Han (mean age = 13.45 ± 3.3 years; 49.7% girls) and Tibet (mean age = 13.8 ± 2.5 years; 48.3% girls) children and adolescents from Shanghai and Shigatse completed the questionnaire survey. It was revealed that Tibetan students had higher MVPA, MSE and OSP than children and adolescents of Han ethnicity (p < 0.01, small to medium effect size). A relatively higher percentage of student in Shanghai did not participate in any form of PA. On the other hand, less Tibetan students thought their PF indicators including overall fitness, cardiorespiratory fitness, speed and agility, muscular strength and flexibility were poor or very poor than their counterparts of Han ethnicity (p < 0.01, small to medium effect size). Conclusion: Tibetan children and adolescents have higher levels of PA and PF in comparison to their Han counterparts. More children and adolescents of Han ethnicity engage in no PA and think their PF indicators were poor.

Facilely Fabricating F-Doped Fe3N Nanoellipsoids Grown on 3D N-Doped Porous Carbon Framework as a Preeminent Negative Material.

Transition metal nitride negative electrode materials with a high capacity and electronic conduction are still troubled by the large volume change in the discharging procedure and the low lithium ion diffusion rate. Synthesizing the composite material of F-doped Fe3N and an N-doped porous carbon framework will overcome the foregoing troubles and effectuate a preeminent electrochemical performance. In this study, we created a simple route to obtain the composite of F-doped Fe3N nanoellipsoids and a 3D N-doped porous carbon framework under non-ammonia atmosphere conditions. Integrating the F-doped Fe3N nanoellipsoids with an N-doped porous carbon framework can immensely repress the problem of volume expansion but also substantially elevate the lithium ion diffusion rate. When utilized as a negative electrode for lithium-ion batteries, this composite bespeaks a stellar operational life and rate capability, releasing a tempting capacity of 574 mAh g-1 after 550 cycles at 1.0 A g-1. The results of this study will profoundly promote the evolution and application of transition metal nitrides in batteries.

Solibacillus ferritrahens sp. nov., a novel siderophore-producing bacterium isolated from Wumeng Mountain National Nature Reserve in Yunnan Province.

A gram-stain-positive, aerobic, rod-shaped bacterial strain capable of producing siderophores, named YIM B08730T, was isolated from a soil sample collected from Wumeng Mountain National Nature Reserve, Zhaotong City, Yunnan Province. Growth occurred at 10-45 °C (optimum, 35-40 â„ƒ), pH 7.0-9.0 (optimum, 7.0) and in the presence of 0-5 % (w/v) NaCl (optimum, 0-1 %, w/v). A comparative analysis of the 16S rRNA gene sequence (1558 bp) of strain YIM B08730T showed the highest similarity to Solibacillus isronensis JCM 13838T (96.2 %), followed by Solibacillus silvestris DSM 12223T (96.0 %) and Solibacillus kalamii ISSFR-015T (95.4 %). The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine and one unidentified lipid. The main respiratory quinone of strain YIM B08730T was menaquinone 7 (MK-7). The major fatty acids were iso-C15:0 and C16:1ω7c alcohol. The digital DNA-DNA hybridization and average nucleotide identity values between strain YIM B08730T and the reference strain S. isronensis JCM 13838T were 24.8 % and 81.2 %, respectively. The G + C content of the genomic DNA was 37.1 mol%. The genome of the novel strain contained genes associated with the production of siderophores, and it also revealed other functional gene clusters involved in plant growth promotion and soil bioremediation. Based on these phenotypic, chemotaxonomic and phylogenetic analyses, strain YIM B08730T is considered to be a novel species of the genus Solibacillus, for which the name Solibacillus ferritrahens sp. nov. is proposed. The type strain is YIM B08730T (= NBRC 116268T = CGMCC 1.60169T).

Identification of potential core genes in pseudoexfoliation using bioinformatics analysis and retrospective analysis of 84 patients with this disease.

BACKGROUND: Pseudoexfoliation (XFS) is a common cause of glaucoma in nowadays. Because of XFS causing irreversible blindness secondary to glaucoma (XFG), this study aims to identify the current prevalence of XFS among Xinjiang Province of China, and identify the hub genes involved in XFS. METHODS: A retrospective chart review was conducted from 2007 to 2019 for patients aged 50 and older. All patients with XFS or XFG diagnosed by slit lamp exam were identified through chart review. RESULTS: Of the 84 patient charts available for review, 50% of the patients identified as male, with a mean age of 67 years. The top ten genes evaluated by connectivity degree in the PPI network were identified. The results showed that Tyrobp was the most outstanding gene, followed by Ptprc, Fcgr3, Itgb2, Emr1, Cd68, Syk, Fcerlg, Hck, and Lyz2. All of these hub genes were downregulated in XFS. CONCLUSION: Our findings show a considerably biomarkers of XFS for diagnosis and treatment.

PKM2 induces mitophagy through the AMPK-mTOR pathway promoting CSFV proliferation.

Viruses exploit the host cell's energy metabolism system to support their replication. Mitochondria, known as the powerhouse of the cell, play a critical role in regulating cell survival and virus replication. Our prior research indicated that the classical swine fever virus (CSFV) alters mitochondrial dynamics and triggers glycolytic metabolic reprogramming. However, the role and mechanism of PKM2, a key regulatory enzyme of glycolytic metabolism, in CSFV replication remain unclear. In this study, we discovered that CSFV enhances PKM2 expression and utilizes PKM2 to inhibit pyruvate production. Using an affinity purification coupled mass spectrometry system, we successfully identified PKM as a novel interaction partner of the CSFV non-structural protein NS4A. Furthermore, we validated the interaction between PKM2 and both CSFV NS4A and NS5A through co-immunoprecipitation and confocal analysis. PKM2 was found to promote the expression of both NS4A and NS5A. Moreover, we observed that PKM2 induces mitophagy by activating the AMPK-mTOR signaling pathway, thereby facilitating CSFV proliferation. In summary, our data reveal a novel mechanism whereby PKM2, a metabolic enzyme, promotes CSFV proliferation by inducing mitophagy. These findings offer a new avenue for developing antiviral strategies. IMPORTANCE: Viruses rely on the host cell's material-energy metabolic system for replication, inducing host metabolic disorders and subsequent immunosuppression-a major contributor to persistent viral infections. Classical swine fever virus (CSFV) is no exception. Classical swine fever is a severe acute infectious disease caused by CSFV, resulting in significant economic losses to the global pig industry. While the role of the metabolic enzyme PKM2 (pyruvate dehydrogenase) in the glycolytic pathway of tumor cells has been extensively studied, its involvement in viral infection remains relatively unknown. Our data unveil a new mechanism by which the metabolic enzyme PKM2 mediates CSFV infection, offering novel avenues for the development of antiviral strategies.

Dronedarone Enhances the Antibacterial Activity of Polymyxin B and Inhibits the Quorum Sensing System by Interacting with LuxS.

Quorum sensing (QS) is considered an appealing target for interference with bacterial infections. ß-Adrenergic blockers are promising anti-QS agents but do not have antibacterial activity. We assessed the potential ability of adrenergic receptor inhibitors to enhance the antibacterial activity of polymyxin B (PB) against Klebsiella pneumoniae and determined that dronedarone has the most potent activity both in vitro and in vivo. We found that dronedarone increases the thermal stability of LuxS, decreases the production of AI-2, and affects the biofilm formation of K. pneumoniae. We also identified the direct binding of dronedarone to LuxS. However, the mechanism by which dronedarone enhances the antibacterial activity of PB has not been elucidated and is worthy of further exploration. Our study provides a basis for the future development of drug combination regimens.

Elucidating the Mechanism on the Transition-Metal Ion-Synergetic-Catalyzed Oxidation of SO2 with Implications for Sulfate Formation in Beijing Haze.

Currently, atmospheric sulfate aerosols cannot be predicted reliably by numerical models because the pathways and kinetics of sulfate formation are unclear. Here, we systematically investigated the synergetic catalyzing role of transition-metal ions (TMIs, Fe3+/Mn2+) in the oxidation of SO2 by O2 on aerosols using chamber experiments. Our results showed that the synergetic effect of TMIs is critically dependent on aerosol pH due to the solubility of Fe(III) species sensitive to the aqueous phase acidity, which is effective only under pH < 3 conditions. The sulfate formation rate on aerosols is 2 orders of magnitude larger than that in bulk solution and increases significantly on smaller aerosols, suggesting that such a synergetic-catalyzed oxidation occurs on the aerosol surface. The kinetic reaction rate can be described as R = k*[H+]-2.95[Mn(II)][Fe(III)][S(IV)] (pH ≤ 3.0). We found that TMI-synergetic-catalyzed oxidation is the dominant pathway of sulfate formation in Beijing when haze particles are very acidic, while heterogeneous oxidation of SO2 by NO2 is the most important pathway when haze particles are weakly acidic. Our work for the first time clarified the role and kinetics of TMI-synergetic-catalyzed oxidation of SO2 by O2 in haze periods, which can be parameterized into models for future studies of sulfate formation.

Oxidation-induced superelasticity in metallic glass nanotubes.

Although metallic nanostructures have been attracting tremendous research interest in nanoscience and nanotechnologies, it is known that environmental attacks, such as surface oxidation, can easily initiate cracking on the surface of metals, thus deteriorating their overall functional/structural properties1-3. In sharp contrast, here we report that severely oxidized metallic glass nanotubes can attain an ultrahigh recoverable elastic strain of up to ~14% at room temperature, which outperform bulk metallic glasses, metallic glass nanowires and many other superelastic metals hitherto reported. Through in situ experiments and atomistic simulations, we reveal that the physical mechanisms underpinning the observed superelasticity can be attributed to the formation of a percolating oxide network in metallic glass nanotubes, which not only restricts atomic-scale plastic events during loading but also leads to the recovery of elastic rigidity on unloading. Our discovery implies that oxidation in low-dimensional metallic glasses can result in unique properties for applications in nanodevices.

Rho GTPase-activating protein 1 promotes hepatocellular carcinoma progression via modulation by CircPIP5K1A/MiR-101-3p.

AIM: There has been an increased focus on regulating cell function with Rho family GTPases, including proliferation, migration/invasion, polarity, and adhesion. Due to the challenges involved in targeting Rho family GTPases directly, it may be more effective to target their regulators, such as Rho GTPase-activating protein 1 (ARHGAP1). This present research was performed to define the clinical significance of ARHGAP1 expression, as well as its regulatory mechanisms in hepatocellular carcinoma. METHODS: ARHGAP1 and miR-101-3p expression of liver cancer patients, and their relevance with clinicopathological characteristics and prognosis were analyzed by the Cancer Genome Atlas sequencing data, and verified using samples of hepatocellular carcinoma patients. The interactions between miR-101-3p and ARHGAP1 or circPIP5K1A were validated by bioinformatic analyses, as well as confirmed by quantitative reverse transcription polymerase chain reaction, western blotting, and dual-luciferase reporter analysis. Plate clonality assays, cell adhesion and migration experiments, and proliferation experiments were used for assessing the participation of the circPIP5K1A/miR-101-3p/ARHGAP1 pathway in cell proliferation and motility. RESULTS: Elevated ARHGAP1 and reduced miR-101-3p expression are related to poorer survival. MiR-101-3p targets ARHGAP1 to suppress hepatocellular carcinoma cell colony formation and invasion, whereas miR-101-3p inhibitor reverses liver cancer proliferation and metastasis suppression caused by ARHGAP1 knockdown. In addition, circPIP5K1A, which is mainly distributed in the cytosol, showed carcinogenic effects by sponging miR-101-3p, thus regulating ARHGAP1 expression. CONCLUSIONS: ARHGAP1 serves as an oncogenic gene in liver cancer, and the expression thereof is regulated by circPIP5K1A through sponging miR-101-3p.

Influence of threshold selection and image sequence in in-vivo segmentation of enlarged perivascular spaces.

BACKGROUND: Growing interest surrounds perivascular spaces (PVS) as a clinical biomarker of brain dysfunction given their association with cerebrovascular risk factors and disease. Neuroimaging techniques allowing quick and reliable quantification are being developed, but, in practice, they require optimisation as their limits of validity are usually unspecified. NEW METHOD: We evaluate modifications and alternatives to a state-of-the-art (SOTA) PVS segmentation method that uses a vesselness filter to enhance PVS discrimination, followed by thresholding of its response, applied to brain magnetic resonance images (MRI) from patients with sporadic small vessel disease acquired at 3 T. RESULTS: The method is robust against inter-observer differences in threshold selection, but separate thresholds for each region of interest (i.e., basal ganglia, centrum semiovale, and midbrain) are required. Noise needs to be assessed prior to selecting these thresholds, as effect of noise and imaging artefacts can be mitigated with a careful optimisation of these thresholds. PVS segmentation from T1-weighted images alone, misses small PVS, therefore, underestimates PVS count, may overestimate individual PVS volume especially in the basal ganglia, and is susceptible to the inclusion of calcified vessels and mineral deposits. Visual analyses indicated the incomplete and fragmented detection of long and thin PVS as the primary cause of errors, with the Frangi filter coping better than the Jerman filter. COMPARISON WITH EXISTING METHODS: Limits of validity to a SOTA PVS segmentation method applied to 3 T MRI with confounding pathology are given. CONCLUSIONS: Evidence presented reinforces the STRIVE-2 recommendation of using T2-weighted images for PVS assessment wherever possible. The Frangi filter is recommended for PVS segmentation from MRI, offering robust output against variations in threshold selection and pathology presentation.

CSFV restricts necroptosis to sustain infection by inducing autophagy/mitophagy-targeted degradation of RIPK3.

IMPORTANCE: CSFV infection in pigs causes persistent high fever, hemorrhagic necrotizing multi-organ inflammation, and high mortality, which seriously threatens the global swine industry. Cell death is an essential immune response of the host against pathogen invasion, and lymphopenia is the most typical clinical feature in the acute phase of CSFV infection, which affects the initial host antiviral immunity. As an "old" virus, CSFV has evolved mechanisms to evade host immune response after a long genetic evolution. Here, we show that necroptosis is a limiting host factor for CSFV infection and that CSFV-induced autophagy can subvert this host defense mechanism to promote its sustained replication. Our findings reveal a complex link between necroptosis and autophagy in the process of cell death, provide evidence supporting the important role for CSFV in counteracting host cell necrosis, and enrich our knowledge of pathogens that may subvert and evade this host defense.

Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

Virus-like particle vaccines with epitopes from porcine epidemic virus and transmissible gastroenteritis virus incorporated into self-assembling ADDomer platform provide clinical immune responses in piglets.

Introduction: Porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are major intestinal coronaviruses that cause vomiting, diarrhea, dehydration, and mortality in piglets. These viruses coexist and lead to significant economic losses in the swine industry. Virus-like particles (VLPs) have emerged as promising alternatives to conventional inactivated vaccines due to their exceptional safety, efficacy, and ability to provide multi-disease protection with a single dose. Methods: Our study focused on specific antigenic epitopes from the PEDV S protein (SS2 and 2C10 regions) and the TGEV S protein (A and D sites) as target candidates. These epitopes were integrated into the ADDomer framework, and we successfully generated recombinant proteins AD, AD-P, AD-T, and AD-PT using the baculovirus expression vector system (BEVS). By meticulously optimizing conditions in High Five cells, we successfully expressed and purified the recombinant proteins. Subsequently, we developed the recombinant ADDomer-VLP vaccine and conducted a comprehensive evaluation of its efficacy in piglets. Results: Following ultrafiltration concentration and sucrose gradient centrifugation purification, the recombinant proteins self-assembled into VLPs as observed by transmission electron microscopy (TEM). Administration of the vaccine did not result in any adverse reactions in the immunized piglets. Additionally, no significant instances of fever were detected in any of the experimental groups, and there were no notable changes in average daily weight gain compared to the control group that received PBS. The recombinant ADDomer-VLP vaccines demonstrated strong immunogenicity, effectively stimulating the production of neutralizing antibodies against both PEDV and TGEV. Moreover, the recombinant ADDomer-VLP vaccine induced elevated levels of IFN-γ, IL-2, and IL-4, and enhanced cytotoxic T lymphocyte (CTL) activity in the peripheral blood of piglets. Discussion: These recombinant VLPs have demonstrated the ability to induce strong cellular and humoral immune responses in piglets, making them an incredibly promising platform for the rapid and simplified development of epitope vaccines.

Exogenous myristate promotes the colonization of arbuscular mycorrhizal fungi in tomato.

Arbuscular mycorrhizal fungi (AMF) can establish symbiotic associations with the roots of most terrestrial plants, thereby improving the tolerance of the host plants to biotic and abiotic stresses. Although AMF cannot synthesize lipids de novo, they can obtain lipids from the root cells for their growth and development. A recent study reveals that AMF can directly take up myristate (C14:0 lipid) from the environment and produce a large amount of hyphae in asymbiotic status; however, the effect of environmental lipids on AM symbiosis is still unclear. In this study, we inoculated tomato (Solanum lycopersicum) with AMF in an in vitro dual culture system and a sand culture system, and then applied exogenous myristate to the substrate, in order to explore the effect of exogenous lipids on the mycorrhizal colonization of AMF. We investigated the hyphae growth, development, and colonization of AMF, and examined the gene expression involved in phosphate transport, lipid biosynthesis, and transport. Results indicate that exogenous lipids significantly stimulated the growth and branching of hyphae, and significantly increased the number of hyphopodia and mycorrhizal colonization of AMF, with arbuscular abundance and intraradical spores or vesicles being the most promoted. In contrast, exogenous myristate decreased the growth range and host tropism of the germ tubes, and largely inhibited the exchange of nutrition between symbionts. As a result, exogenous myristate did not affect the plant growth. This study suggests that lipids promote mycorrhizal colonization by enhancing the growth and development of AMF hyphae and increasing their contact opportunities with plant roots. To the best of our knowledge, this is the first report that shows that lipids promote the colonization of AMF. Our study highlights the importance of better understanding the roles of environmental lipids in the establishment and maintenance of AM symbiosis and, thus, in agricultural production.