Intra-arterial Pressure Enabled Drug Delivery Significantly Increases Penetration of Glass Microspheres in a Porcine Liver Tumor Model.

PURPOSE: To test the hypothesis that Pressure Enabled Drug Delivery (PEDD) with a TriNav device (TNV-21120-35, TriSalus Life Sciences, Westminster, CO) would improve the delivery of surrogate therapeutic glass microspheres (GM) via hepatic artery infusion (HAI) to liver tumors when compared to a conventional endhole microcatheter. MATERIALS AND METHODS: The study was conducted in transgenic pigs (Oncopigs) with induced liver tumors. Tumors were infused intra-arterially with fluorescently labeled GM. PEDD with a TriNav device was compared to conventional endhole delivery in both lobar and selective infusions. Near-Infrared (nearIR) imaging was used to detect GM fluorescent signal in tumors. Image analysis with a custom Deep Learning algorithm (Visiopharm A/S) was used to quantitate signal intensity in relation to the tumor border. RESULTS: With lobar infusions, significant increases in GM signal intensity were observed in and around tumors after PEDD (n=10) when compared to conventional delivery (n=7), with PEDD increasing penetration into the tumor by 117% (p = 0.004). In selective infusions, PEDD (n=9) increased penetration into the tumor by 39% relative to conventional delivery (n=8, p =0.032). Lobar PEDD delivery of GM to the tumor was statistically equivalent to conventional selective delivery (p=0.497). CONCLUSIONS: PEDD with a TriNav device significantly improved GM uptake in liver tumors relative to conventional infusion in both lobar and selective procedures. Lobar GM delivery with PEDD was equivalent to conventional selective delivery with an endhole device, suggesting that proximal PEDD infusions may enable effective delivery without selection of distal target vessels.

Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice.

ABSTRACT: Postoperative cognitive dysfunction is a severe complication of the central nervous system that occurs after anesthesia and surgery, and has received attention for its high incidence and effect on the quality of life of patients. To date, there are no viable treatment options for postoperative cognitive dysfunction. The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research. To identify the signaling mechanisms contributing to postoperative cognitive dysfunction, we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset, which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus 3 days after tibial fracture. The dataset was enriched in genes associated with the biological process "regulation of immune cells," of which Chill was identified as a hub gene. Therefore, we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fracture surgery. Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 1 24 hours post-surgery, and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests. In addition, protein expression levels of proinflammatory factors (interleukin-1ß and inducible nitric oxide synthase), M2-type macrophage markers (CD206 and arginase-1), and cognition-related proteins (brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B) were measured in hippocampus by western blotting. Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment, downregulated interleukin-1ß and nducible nitric oxide synthase expression, and upregulated CD206, arginase-1, pNR2B, and brain-derived neurotropic factor expression compared with vehicle treatment. Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1. Collectively, our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus. Therefore, recombinant chitinase-3-like protein 1 may have therapeutic potential for postoperative cognitive dysfunction.

The impact of compound drought and heatwave events from 1982 to 2022 on the phenology of Central Asian grasslands.

In the context of global warming, the occurrence and severity of extreme events like atmospheric drought (AD) and warm spell duration index (WSDI) have increased, causing significant impacts on terrestrial ecosystems in Central Asia's arid regions. Previous research has focused on single extreme events such as AD and WSDI, but the effect of compound hot and dry events (CHWE) on grassland phenology in the arid regions of Central Asia remains unclear. This study utilized structural equation modeling (SEM) and the Pettitt breakpoint test to quantify the direct and indirect responses of grassland phenology (start of season - SOS, length of season - LOS, and end of season - EOS) to AD, WSDI, and CHWE. Furthermore, this research investigated the threshold of grassland phenology response to compound hot and dry events. The research findings indicate a significant increasing trend in AD, WSDI, and CHWE in the arid regions of Central Asia from 1982 to 2022 (0.51 day/year, P < 0.01; 0.25 day/year, P < 0.01; 0.26 day/year, P < 0.01). SOS in the arid regions of Central Asia showed a significant advancement trend, while EOS exhibited a significant advance. LOS demonstrated an increasing trend (-0.23 day/year, P < 0.01; -0.12 day/year, P < 0.01; 0.56 day/year). The temperature primarily governs the variation in SOS. While higher temperatures promote an earlier SOS, they also offset the delaying effect of CHWE on SOS. AD, temperature, and CHWE have negative impacts on EOS, whereas WSDI has a positive effect on EOS. AD exhibits the strongest negative effect on EOS, with an increase in AD leading to an earlier EOS. Temperature and WSDI are positively correlated with LOS, indicating that higher temperatures and increased WSDI contribute to a longer LOS. The threshold values for the response of SOS, EOS, and LOS to CHWE are 16.14, 18.49, and 16.61 days, respectively. When CHWE exceeds these critical thresholds, there are significant changes in the response of SOS, EOS, and LOS to CHWE. These findings deepen our understanding of the mechanisms by which extreme climate events influence grassland phenology dynamics in Central Asia. They can contribute to better protection and management of grassland ecosystems and help in addressing the impacts of global warming and climate change in practice.

Aging aggravates aortic aneurysm and dissection via miR-1204-MYLK signaling axis in mice.

The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates ß-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-ß signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.

Subcutaneous checkpoint inhibition is equivalent to systemic delivery when combined with nelitolimod delivered via pressure-enabled drug delivery for depletion of intrahepatic myeloid-derived suppressor cells and control of liver metastases.

BACKGROUND: Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM). METHODS: The LM model was developed by injecting MC38-Luc cells via the spleen of 8-12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45+ cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b+Gr1+), B cells (B220+), dendritic cells (DC, CD11c+), T (CD3+) cells, and M1-like macrophages (F4/80+CD38+Egr2-) were quantified. RESULTS: Nelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route. CONCLUSION: The SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.

Integrated cell wall and transcriptomic analysis revealed the mechanism underlying zinc-induced alleviation of cadmium toxicity in Cosmos bipinnatus.

Plant growth is severely harmed by cadmium (Cd) contamination, while the addition of zinc (Zn) can reduce the toxic effects of Cd. However, the interaction between Cd and Zn on the molecular mechanism and cell wall of Cosmosbipinnatus is unclear. In this study, a transcriptome was constructed using RNA-sequencing. In C. bipinnatus root transcriptome data, the expression of 996, 2765, and 3023 unigenes were significantly affected by Cd, Zn, and Cd + Zn treatments, respectively, indicating different expression patterns of some metal transporters among the Cd, Zn, and Cd + Zn treatments. With the addition of Zn, the damage to the cell wall was reduced, both the proportion and content of polysaccharides in the cell wall were changed, and Cd accumulation was decreased by 32.34%. In addition, we found that Cd and Zn mainly accumulated in pectins, the content of which increased by 30.79% and 61.4% compared to the CK treatment. Thus, Zn could alleviate the toxicity of Cd to C. bipinnatus. This study revealed the interaction between Cd and Zn at the physiological and molecular levels, broadening our understanding of the mechanisms of tolerance to Cd and Zn stress in cosmos.

Modulation of cardiac resident macrophages immunometabolism upon high-fat-diet feeding in mice.

Background: A high-fat diet (HFD) contributes to various metabolic disorders and obesity, which are major contributors to cardiovascular disease. As an essential regulator for heart homeostasis, cardiac resident macrophages may go awry and contribute to cardiac pathophysiology upon HFD. Thus, to better understand how HFD induced cardiac dysfunction, this study intends to explore the transcriptional and functional changes in cardiac resident macrophages of HFD mice. Methods: C57BL/6J female mice that were 6 weeks old were fed with HFD or normal chow diet (NCD) for 16 weeks. After an evaluation of cardiac functions by echocardiography, mouse hearts were harvested and cardiac resident CCR2- macrophages were sorted, followed by Smart sequencing. Bioinformatics analysis including GO, KEGG, and GSEA analyses were employed to elucidate transcriptional and functional changes. Results: Hyperlipidemia and obesity were observed easily upon HFD. The mouse hearts also displayed more severe fibrosis and diastolic dysfunction in HFD mice. Smart sequencing and functional analysis revealed metabolic dysfunctions, especially lipid-related genes and pathways. Besides this, antigen-presentation-related gene such as Ctsf and inflammation, particularly for NF-κB signaling and complement cascades, underwent drastic changes in cardiac resident macrophages. GO cellular compartment analysis was also performed and showed specific organelle enrichment trends of the involved genes. Conclusion: Dysregulated metabolism intertwines with inflammation in cardiac resident macrophages upon HFD feeding in mice, and further research on crosstalk among organelles could shed more light on potential mechanisms.

Bilayer Scaffolds of PLLA/PCL/CAB Ternary Blend Films and Curcumin-Incorporated PLGA Electrospun Nanofibers: The Effects of Polymer Compositions and Solvents on Morphology and Molecular Interactions.

Tissue engineering scaffolds have been dedicated to regenerating damaged tissue by serving as host biomaterials for cell adhesion, growth, differentiation, and proliferation to develop new tissue. In this work, the design and fabrication of a biodegradable bilayer scaffold consisting of a ternary PLLA/PCL/CAB blend film layer and a PLGA/curcumin (CC) electrospun fiber layer were studied and discussed in terms of surface morphology, tensile mechanical properties, and molecular interactions. Three different compositions of PLLA/PCL/CAB-60/15/25 (TBF1), 75/10/15 (TBF2), and 85/5/10 (TBF3)-were fabricated using the solvent casting method. The electrospun fibers of PLGA/CC were fabricated using chloroform (CF) and dimethylformamide (DMF) co-solvents in 50:50 and 60:40 volume ratios. Spherical patterns of varying sizes were observed on the surfaces of all blend films-TBF1 (17-21 µm) > TBF2 (5-9 µm) > TBF3 (1-5 µm)-caused by heterogeneous surfaces inducing bubble nucleation. The TBF1, TBF2, and TBF3 films showed tensile elongation at break values of approximately 170%, 94%, and 43%, respectively. The PLGA/CC electrospun fibers fabricated using 50:50 CF:DMF had diameters ranging from 100 to 400 nm, which were larger than those of the PLGA fibers (50-200 nm). In contrast, the PLGA/CC electrospun fibers fabricated using 60:40 CF:DMF had diameters mostly ranging from 200 to 700 nm, which were larger than those of PLGA fibers (200-500 nm). Molecular interactions via hydrogen bonding were observed between PLGA and CC. The surface morphology of the bilayer scaffold demonstrated adhesion between these two solid surfaces resembling "thread stitches" promoted by hydrophobic interactions, hydrogen bonding, and surface roughness.

Off-axis telescope misalignment correction based on defocus spot moment features.

Optical mirror misalignments, which are caused by assembly mistakes and changes in the surrounding environment (such as gravity, temperature, and atmosphere), degrade the system's imaging performance. Therefore, active misalignment correction is essential for ensuring the image quality of the off-axis telescope. In this paper, a novel misalignment correction method without wavefront sensors is proposed. The point spread functions (PSFs) of the system are analytically related to the optical mirror misalignments. On this basis, a fully connected neural network (FCNN) is used to establish the mapping relationship between the misalignments and the discrete orthogonal unbiased finite impulse response (UFIR) moment features, which can effectively characterize changes of intensity and geometric of the spot image. The simulation and experimental results in this paper justify the effectiveness and practicality of the proposed method. This approach offers a low-cost and straightforward technical method for achieving high imaging quality throughout the alignment and observation phases. This approach can prevent the accumulation of errors caused by wavefront detection and the high delay of multiple iterations.

Conjugation through Si-O-Si bonds, silsesquioxane (SQ) half cage copolymers, extended examples via SiO0.5/SiO1.5 units: multiple emissive states in violation of Kasha's rule.

We previously reported that phenyl- and vinyl-silsesquioxanes (SQs), [RSiO1.5]8,10,12 (R = Ph or vinyl) functionalized with three or more conjugated moieties show red-shifted absorption- and emission features suggesting 3-D conjugation via a cage centered LUMOs. Corner missing [PhSiO1.5]7(OSiMe3)3 and edge opened, end capped [PhSiO1.5]8(OSiMe2)2 (double decker, DD) analogs also offer red shifted spectra again indicating 3-D conjugation and a cage centered LUMO. Copolymerization of DD [PhSiO1.5]8(OSiMevinyl)2 with multiple R-Ar-Br gives copolymers with emission red-shifts that change with degree of polymerization (DP), exhibit charge transfer to F4TNCQ and terpolymer averaged red-shifts suggesting through chain conjugation even with two (O-Si-O) end caps possibly via a cage centered LUMO. Surprisingly, ladder (LL) SQ, (vinylMeSiO2)[PhSiO1.5]4(O2SiMevinyl) copolymers offer emission red-shifts even greater for analogous copolymers requiring a different explanation. Here we assess the photophysical behavior of copolymers of a more extreme SQ form: the half cage [PhSiO1.5]4(OSiMe2Vinyl)4, Vy4HC SQs. We again see small red-shifted absorptions coupled with significant red-shifted emissions, even with just a half cage, thus further supporting the existence of pπ-dπ and/or σ*-π* conjugation through Si-O-Si bonds and contrary to most traditional views of Si-O-Si linked polymers. These same copolymers donate an electron to F4TCNQ generating the radical anion, F4TCNQ-. as further proof of conjugation. Column chromatographic separation of short from longer chain oligomers reveals a direct correlation between DP and emission λmax red-shifts as another indication of conjugation. Further, one- and two-photon absorption and emission spectroscopy reveals multiple excited fluorescence-emitting states in a violation of Kasha's rule wherein emission occurs only from the lowest excited state. Traditional modeling studies again find HOMO LUMO energy levels residing only on the aromatic co-monomers rather than through Si-O-Si bonds as recently found in related polymers.

An efficient rare-earth free deep red-emitting GdGeSbO6:Mn4+ phosphor for white light-emitting diodes.

Red phosphors play an important role in improving the light quality and color rendering index of white light-emitting diodes (WLEDs) for lighting. In this paper, we report the transition ion Mn4+-activated deep red phosphor GdGeSbO6:x%Mn4+ and analyze its crystal structure, composition and luminescence behavior in detail. Its optimal doping concentration of Mn4+ is 0.3%. Under ultraviolet (UV) excitation, GdGeSbO6:0.3%Mn4+ produces a narrow emission peak centred at 682 nm in the range of 650-800 nm with a full width at half maximum (FWHM) of 25 nm, which is attributed to the spin-prohibited 2Eg → 4A2g transition of Mn4+ ions. Notably, the optimal phosphor GdGeSbO6:0.3%Mn4+ has a high internal quantum efficiency (IQE ≈ 65%) and excellent thermal stability performance (I423 K/I303 K ≈ 62%). The synthesis of high-performance warm WLEDs and full-spectrum WLEDs was achieved by combining and coating GdGeSbO6:0.3%Mn4+ phosphors with commercial phosphors on the surface of a 365 nm UV chip.

Immobilized Dipeptidase in Manganese Ion-Loaded Polyethylenimine-Induced Calcium Phosphate Nanocrystals for Carnosine Synthesis.

Carnosine is a natural bioactive dipeptide with important physiological functions widely used in food and medicine. Dipeptidase (PepD) from Serratia marcescens can catalyze the reverse hydrolytic reaction of ß-alanine with l-histidine to synthesize carnosine in the presence of Mn2+. However, it remains challenging to practice carnosine biosynthesis due to the low activity and high cost of the enzyme. Therefore, the development of biocatalysts with high activity and stability is of significance for carnosine synthesis. Here, we proposed to chelate Mn2+ to polyethylenimine (PEI) that induced rapid formation of calcium phosphate nanocrystals (CaP), and Mn-PEI@CaP was used for PepD immobilization via electrostatic interaction. Mn-PEI@CaP as the carrier enhanced the stability of the immobilized enzyme. Moreover, Mn2+ loaded in the carrier acted as an in situ activator of the immobilized PepD for facilitating the biocatalytic process of carnosine synthesis. The as-prepared immobilized enzyme (PepD-Mn-PEI@CaP) kept similar activity with free PepD plus Mn2+ (activity recovery, 102.5%), while exhibiting elevated thermal stability and pH tolerance. Moreover, it exhibited about two times faster carnosine synthesis than the free PepD system. PepD-Mn-PEI@CaP retained 86.8% of the original activity after eight cycles of batch catalysis without the addition of free Mn2+ ions during multiple cycles. This work provides a new strategy for the co-immobilization of PepD and Mn2+, which greatly improves the operability of the biocatalysis and demonstrates the potential of the immobilized PepD system for efficient carnosine synthesis.

HVEM in acute lymphocytic leukemia facilitates tumour immune escape by inhibiting CD8+ T cell function.

PURPOSE: Leukaemia remains a major contributor to global mortality, representing a significant health risk for a substantial number of cancer patients. Despite notable advancements in the field, existing treatments frequently exhibit limited efficacy or recurrence. Here, we explored the potential of abolishing HVEM (herpes virus entry mediator, TNFRSF14) expression in tumours as an effective approach to treat acute lymphoblastic leukaemia (ALL) and prevent its recurrence. METHODS: The clinical correlations between HVEM and leukaemia were revealed by public data analysis. HVEM knockout (KO) murine T cell lymphoblastic leukaemia cell line EL4 were generated using CRISPR-Cas9 technology, and syngeneic subcutaneous tumour models were established to investigate the in vivo function of HVEM. Immunohistochemistry (IHC), RNA-seq and flow cytometry were used to analyse the tumour immune microenvironment (TIME) and tumour draining lymph nodes (dLNs). Immune functions were investigated by depletion of immune subsets in vivo and T cell functional assays in vitro. The HVEM mutant EL4 cell lines were constructed to investigate the functional domain responsible for immune escape. RESULTS: According to public databases, HVEM is highly expressed in patients with ALL and acute myeloid leukemia (AML) and is negatively correlated with patient prognosis. Genetic deletion of HVEM in EL4 cells markedly inhibited tumour progression and prolonged the survival of tumour-bearing mice. Our experiments proved that HVEM exerted its immunosuppressive effect by inhibiting antitumour function of CD8+ T cell through CRD1 domain both in vivo and in vitro. Additionally, we identified a combination therapy capable of completely eradicating ALL tumours, which induces immune memory toward tumour protection. CONCLUSIONS: Our study reveals the potential mechanisms by which HVEM facilitates ALL progression, and highlights HVEM as a promising target for clinical applications in relapsed ALL therapy.

The influencing factors of game brand loyalty.

Our research aims to investigate the impact mechanism of brand loyalty among gamers during the gaming process within the framework of brand loyalty theory and cognitive theory. We surveyed game players from Zhejiang Province, China. The research methods include a questionnaire survey and structural equation modelling. Results show that game experience, interaction, and impression are positively correlated with game trust, while game trust is positively correlated with game brand loyalty. Game trust, as a mediator variable, plays a complete mediation role. The clustering results of player gender and age as moderating effects are not significant. Based on the analysis results, we have suggested corresponding policy recommendations and reflections. Our research contributes to the analysation of impact mechanism of brand loyalty during the gaming process through the establishment of a structural equation model and provides suggestions and reflections on the development of the gaming industry.

Transcriptomic profiling and regulatory pathways of cardiac resident macrophages in aging.

Cardiovascular diseases are an array of age-related disorders, and accumulating evidence suggests a link between cardiac resident macrophages (CRMs) and the age-related disorders. However, how does CRMs alter with aging remains elusive. In the present study, aged mice (20 months old) have been employed to check for their cardiac structural and functional alterations, and the changes in the proportion of CRM subsets as well, followed by sorting of CRMs, including C-C Motif Chemokine Receptor 2 (CCR2)+ and CCR2- CRMs, which were subjected to Smart-Seq. Integrated analysis of the Smart-Seq data with three publicly available single-cell RNA-seq datasets revealed that inflammatory genes were drastic upregulated for both CCR2+ and CCR2- CRMs with aging, but genes germane to wound healing were downregulated for CCR2- CRMs, suggesting the differential functions of these two subsets. More importantly, inflammatory genes involved in damage sensing, complement cascades, and phagocytosis were largely upregulated in CCR2- CRMs, implying the imbalance of inflammatory response upon aging. Our work provides a comprehensive framework and transcriptional resource for assessing the impact of aging on CRMs with a potential for further understanding cardiac aging.

Genomic identification and expression analysis of acid invertase (AINV) gene family in Dendrobium officinale Kimura et Migo.

BACKGROUND: Dendrobium officinale Kimura et Migo, a renowned traditional Chinese orchid herb esteemed for its significant horticultural and medicinal value, thrives in adverse habitats and contends with various abiotic or biotic stresses. Acid invertases (AINV) are widely considered enzymes involved in regulating sucrose metabolism and have been revealed to participate in plant responses to environmental stress. Although members of AINV gene family have been identified and characterized in multiple plant genomes, detailed information regarding this gene family and its expression patterns remains unknown in D. officinale, despite their significance in polysaccharide biosynthesis. RESULTS: This study systematically analyzed the D. officinale genome and identified four DoAINV genes, which were classified into two subfamilies based on subcellular prediction and phylogenetic analysis. Comparison of gene structures and conserved motifs in DoAINV genes indicated a high-level conservation during their evolution history. The conserved amino acids and domains of DoAINV proteins were identified as pivotal for their functional roles. Additionally, cis-elements associated with responses to abiotic and biotic stress were found to be the most prevalent motif in all DoAINV genes, indicating their responsiveness to stress. Furthermore, bioinformatics analysis of transcriptome data, validated by quantitative real-time reverse transcription PCR (qRT-PCR), revealed distinct organ-specific expression patterns of DoAINV genes across various tissues and in response to abiotic stress. Examination of soluble sugar content and interaction networks provided insights into stress release and sucrose metabolism. CONCLUSIONS: DoAINV genes are implicated in various activities including growth and development, stress response, and polysaccharide biosynthesis. These findings provide valuable insights into the AINV gene amily of D. officinale and will aid in further elucidating the functions of DoAINV genes.

Gene Amplification of Mediator Subunit 30 Redirects the MYC Transcriptional Program and Oncogenesis.

Understanding the molecular mechanisms underlying tumorigenesis is crucial for developing effective cancer therapies. Here, we investigate the co-amplification of MED30 and MYC across diverse cancer types and its impact on oncogenic transcriptional programs. Transcriptional profiling of MYC and MED30 single or both overexpression/amplification revealed the over amount of MED30 lead MYC to a new transcriptional program that associate with poor prognosis. Mechanistically, MED30 overexpression/amplification recruits other Mediator components and binding of MYC to a small subset of novel genomic regulatory sites, changing the epigenetic marks and inducing the formation of new enhancers, which drive the expression of target genes crucial for cancer progression. In vivo studies in pancreatic ductal adenocarcinoma (PDAC) further validate the oncogenic potential of MED30, as its overexpression promotes tumor growth and can be attenuated by knockdown of MYC. Using another cancer type as an example, MED30 knockdown reduces tumor growth particularly in MYC high-expressed glioblastoma (GBM) cell lines. Overall, our study elucidates the critical role of MED30 overexpression in orchestrating oncogenic transcriptional programs and highlights its potential as a therapeutic target for MYC-amplified cancer.

Temperature fluctuation in soil alters the nanoplastic sensitivity in wheat.

Despite the wide acknowledgment that plastic pollution and global warming have become serious agricultural concerns, their combined impact on crop growth remains poorly understood. Given the unabated megatrend, a simulated soil warming (SWT, +4 °C) microcosm experiment was carried out to provide a better understanding of the effects of temperature fluctuations on wheat seedlings exposed to nanoplastics (NPs, 1 g L-1 61.71 ± 0.31 nm polystyrene). It was documented that SWT induced oxidative stress in wheat seedlings grown in NPs-contaminated soil, with an 85.56 % increase in root activity, while decreasing plant height, fresh weight, and leaf area by 8.72 %, 47.68 %, and 15.04 % respectively. The SWT also resulted in reduced photosynthetic electron-transfer reaction and Calvin-Benson cycle in NPs-treated plants. Under NPs, SWT stimulated the tricarboxylic acid (TCA) metabolism and bio-oxidation process. The decrease in photosynthesis and the increase in respiration resulted in an 11.94 % decrease in net photosynthetic rate (Pn). These results indicated the complicated interplay between climate change and nanoplastic pollution in crop growth and underscored the potential risk of nanoplastic pollution on crop production in the future climate.

Monitoring and influencing factors of grassland livestock overload in Xinjiang from 1982 to 2020.

It is crucial to estimate the theoretical carrying capacity of grasslands in Xinjiang to attain a harmonious balance between grassland and livestock, thereby fostering sustainable development in the livestock industry. However, there has been a lack of quantitative assessments that consider long-term, multi-scale grass-livestock balance and its impacts in the region. This study utilized remote sensing and empirical models to assess the theoretical livestock carrying capacity of grasslands. The multi-scale spatiotemporal variations of the theoretical carrying capacity in Xinjiang from 1982 to 2020 were analyzed using the Sen and Mann-Kendall tests, as well as the Hurst index. The study also examined the county-level grass-livestock balance and inter-annual trends. Additionally, the study employed the geographic detector method to explore the influencing factors. The results showed that: (1) The overall theoretical livestock carrying capacity showed an upward trend from 1982 to 2020; The spatial distribution gradually decreased from north to south and from east to west. In seasonal scale from large to small is: growing season > summer > spring > autumn > winter; at the monthly scale, the strongest livestock carrying capacity is in July. The different grassland types from largest to smallest are: meadow > alpine subalpine meadow > plain steppe > desert steppe > alpine subalpine steppe. In the future, the theoretical livestock carrying capacity of grassland will decrease. (2) From 1988 to 2020, the average grass-livestock balance index in Xinjiang was 2.61%, showing an overall increase. At the county level, the number of overloaded counties showed an overall increasing trend, rising from 46 in 1988 to 58 in 2020. (3) Both single and interaction factors of geographic detectors showed that annual precipitation, altitude and soil organic matter were the main drivers of spatiotemporal dynamics of grassland load in Xinjiang. The results of this study can provide scientific guidance and decision-making basis for achieving coordinated and sustainable development of grassland resources and animal husbandry in the region.