Clinical Assessment of Magnetic Resonance Spectroscopy and Diffusion-Weighted Imaging in Diffuse Glioma: Insights Into Histological Grading and IDH Classification.

PURPOSE: To assess the diagnostic utility of clinical magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) in distinguishing between histological grading and isocitrate dehydrogenase (IDH) classification in adult diffuse gliomas. METHODS: A retrospective analysis was conducted on 247 patients diagnosed with adult diffuse glioma. Experienced radiologists evaluated DWI and MRS images. The Kruskal-Wallis test examined differences in DWI and MRS-related parameters across histological grades, while the Mann-Whitney U test assessed molecular classification. Receiver Operating Characteristic (ROC) curves evaluated parameter effectiveness. Survival curves, stratified by histological grade and IDH classification, were constructed using the Kaplan-Meier test. RESULTS: The cohort comprised 141 males and 106 females, with ages ranging from 19 to 85 years. The Kruskal-Wallis test revealed significant differences in ADC mean, Cho/NAA, and Cho/Cr concerning glioma histological grade (P < .01). Subsequent application of Dunn's test showed significant differences in ADC mean among each histological grade (P < .01). Notably, Cho/NAA exhibited a marked distinction between grade 2 and grade 3/4 gliomas (P < .01). The Mann-Whitney U test indicated that only ADC mean showed statistical significance for IDH molecular classification (P < .01). ROC curves were constructed to demonstrate the effectiveness of the specified parameters. Survival curves were also delineated to portray survival outcomes categorized by histological grade and IDH classification. Conclusions: Clinical MRS demonstrates efficacy in glioma histological grading but faces challenges in IDH classification. Clinical DWI's ADC mean parameter shows significant distinctions in both histological grade and IDH classification.

Comparative transcriptome analysis reveals nicotine metabolism is a critical component for enhancing stress response intensity of innate immunity system in tobacco.

The pyridine alkaloid nicotine acts as one of best-studied plant resistant traits in tobacco. Previous research has shown that NtERF199 and NtERF189, acting as master regulators within the NIC1 and NIC2 locus, quantitatively contribute to nicotine accumulation levels in N. tabacum. Genome editing-created Nic1(Nterf199) and Nic2 (Nterf189) double mutant provides an ideal platform for precisely dissecting the defensive role of nicotine and the connection between the nicotine biosynthetic pathway with other putative metabolic networks. Taking this advantage, we performed a comparative transcriptomic analysis to reevaluate the potential physiological and metabolic changes in response to nicotine synthesis defect by comparing the nic1nic2 and NIC1NIC2 plants. Our findings revealed that nicotine reduction could systematically diminishes the expression intensities of genes associated with stimulus perception, signal transduction and regulation, as well as secondary metabolic flux. Consequently, this global expression reduction might compromise tobacco adaptions to environmental fitness, herbivore resistances, and plant growth and development. The up-regulation of a novel set of stress-responsive and metabolic pathway genes might signify a newly established metabolic reprogramming to tradeoff the detrimental effect of nicotine loss. These results offer additional compelling evidence regarding nicotine's critical defensive role in nature and highlights the tight link between nicotine biosynthesis and gene expression levels of quantitative resistance-related genes for better environmental adaptation.

RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling.

Objectives: To investigate the potential role of Ribosomal protein L35 (RPL35) in regulating chondrocyte catabolic metabolism and to examine whether osteoarthritis (OA) progression can be delayed by overexpressing RPL35 in a mouse compression loading model. Methods: RNA sequencing analysis was performed on chondrocytes treated with or without 20 % elongation strain loading for 24 h. Experimental OA in mice was induced by destabilization of the medial meniscus and compression loading. Mice were randomly assigned to a sham group, an intra-articular adenovirus-mediated overexpression of the negative group, and an intra-articular adenovirus-mediated overexpression of the RPL35 operated group. The Osteoarthritis Research Society International score was used to evaluate cartilage degeneration. Immunostaining and western blot analyses were conducted to detect relative protein levels. Primary mouse chondrocytes were treated with 20 % elongation strain loading for 24 h to investigate the role of RPL35 in modulating chondrocyte catabolic metabolism and regulating cellular senescence in chondrocytes. Results: The protein expression of RPL35 in mouse chondrocytes was significantly reduced when excessive mechanical loading was applied, while elevated protein levels of RPL35 protected articular chondrocytes from degeneration. In addition, the RPL35 knockdown alone induced chondrocyte senescence, decreased the expression of anabolic markers, and increased the expression of catabolic markers in vitro in part through the hedgehog (Hh) pathway. Conclusions: These findings demonstrated a functional pathway important for OA development and identified intra-articular injection of RPL35 as a potential therapy for OA prevention and treatment. The translational potential of this article: It is necessary to develop new targeted drugs for OA due to the limitations of conventional pharmacotherapy. Our study explores and demonstrates the protective effect of RPL35 against excessive mechanical stress in OA models in vivo and in vitro in animals. These findings might provide novel insights into OA pathogenesis and show its translational potential for OA therapy.

Local CO Generator Enabled by a CO-Producing Core for Kinetically Enhancing Electrochemical CO2 Reduction to Multicarbon Products.

CO plays a crucial role as an intermediate in electrochemical CO2 conversion to generate multicarbon (C2+) products. However, optimizing the coverage of the CO intermediate (*CO) to improve the selectivity of C2+ products remains a great challenge. Here, we designed a hierarchically structured double hollow spherical nanoreactor featuring atomically dispersed nickel (Ni) atoms as the core and copper (Cu) nanoparticles as the shell, which can greatly improve the catalytic activity and selectivity for C2+ compounds. Within this configuration, CO generated at the active Ni sites on the inner layer accumulates in the cavity before spilling over neighboring Cu sites on the outer layer, thus enhancing CO dimerization within the cavity. Notably, this setup achieves a sustained faradaic efficiency of 74.4% for C2+ production, with partial current densities reaching 337.4 mA cm-2. In situ Raman spectroscopy and finite-element method (FEM) simulations demonstrate that the designed local CO generator can effectively increase the local CO concentration and restrict CO evolution, ultimately boosting C-C coupling. The hierarchically ordered architectural design represents a promising solution for achieving highly selective C2+ compound production in the electroreduction of CO2.

Establishment of a prognosis predictive model for liver cancer based on expression of genes involved in the ubiquitin-proteasome pathway.

BACKGROUND: The ubiquitin-proteasome pathway (UPP) has been proven to play important roles in cancer. AIM: To investigate the prognostic significance of genes involved in the UPP and develop a predictive model for liver cancer based on the expression of these genes. METHODS: In this study, UPP-related E1, E2, E3, deubiquitylating enzyme, and proteasome gene sets were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, aiming to screen the prognostic genes using univariate and multivariate regression analysis and develop a prognosis predictive model based on the Cancer Genome Atlas liver cancer cases. RESULTS: Five genes (including autophagy related 10, proteasome 20S subunit alpha 8, proteasome 20S subunit beta 2, ubiquitin specific peptidase 17 like family member 2, and ubiquitin specific peptidase 8) were proven significantly correlated with prognosis and used to develop a prognosis predictive model for liver cancer. Among training, validation, and Gene Expression Omnibus sets, the overall survival differed significantly between the high-risk and low-risk groups. The expression of the five genes was significantly associated with immunocyte infiltration, tumor stage, and postoperative recurrence. A total of 111 differentially expressed genes (DEGs) were identified between the high-risk and low-risk groups and they were enriched in 20 and 5 gene ontology and KEGG pathways. Cell division cycle 20, Kelch repeat and BTB domain containing 11, and DDB1 and CUL4 associated factor 4 like 2 were the DEGs in the E3 gene set that correlated with survival. CONCLUSION: We have constructed a prognosis predictive model in patients with liver cancer, which contains five genes that associate with immunocyte infiltration, tumor stage, and postoperative recurrence.

Study on the Preparation and Process Parameter-Mechanical Property Relationships of Carbon Fiber Fabric Reinforced Poly(Ether Ether Ketone) Thermoplastic Composites.

Carbon fiber fabric-reinforced poly(ether ether ketone) (CFF-PEEK) composites exhibit exceptional mechanical properties, and their flexibility and conformability make them a promising alternative to traditional prepregs. However, the formation of the CFF-PEEK composite is trapped in the high viscosity of PEEK, the smooth surface, and tightly interwoven bundles of CFF. It is more difficult for the resin to flow through the fibers of complex textile structures. Here, a simple film stacking method using the hot-pressing process of plain-woven CFF-PEEK thermoplastic composites is discussed. The uniform distribution of PEEK resin between each layer of CFF reduces the flow distance during the molding process, preventing defects in the composite material effectively. Four process parameters, including molding temperature (370, 385, 400, and 415 °C), molding pressure (1, 2, 4, 8, and 10 MPa), molding time (10, 20, 30, 40, 60, and 90 min), and pre-compaction process, are considered. Interlaminar shear strength (ILSS), tensile strength, and flexural strength of CFF/PEEK composites are evaluated to optimize the process parameters. Moreover, ultrasonic scanning microscopy and scanning electron microscopy are employed to observe the formation quality and microscopic failure modes of CFF/PEEK composites, respectively. The ultimate process parameters are a molding temperature of 410 °C, molding pressure of 10 MPa, molding time of 60 min, and the need for the pre-compaction process. Under the best process parameters, the ILSS is 62.5 MPa, the flexural strength is 754.4 MPa, and the tensile strength is 796.1 MPa. This work provides valuable insight for studying the process parameters of fiber fabric-reinforced thermoplastic polymer composites and revealing their impact on mechanical properties.

Lethal Immune Myocarditis and Myasthenia Gravis Due to Anti-PD-1 Treatment for a Bladder Cancer Patient: A Case Report and Possible Treatment Inspiration.

Immune checkpoint inhibitors (ICI) have become a new hope for many patients with advanced cancer by blocking tumor immune escape. Bladder cancer is a common malignant tumor of the urinary tract epithelium that often relapses and metastasizes after surgery, chemotherapy, and radiotherapy. Immunotherapy has dramatically improved patient survival rates and clinical benefits as a new, potentially effective therapy. However, avoidance of various immune-related adverse events (irAEs) remains an implausible idea. ICI-induced myocarditis is different from viral myocarditis, and mortality is still high with the current treatment. We report the case of an 82-year-old female patient with ICI-induced fulminant myocarditis and myasthenia gravis. Although she actively accepted the current mainstream treatment for immune-related myocarditis and myasthenia, she died of heart and respiratory failure. Analyzing and reporting the patient's disease development process and the changes in related indicators may help peers gain a deeper understanding of immune-related adverse events and reduce the mortality of immune-related myocarditis.

Effects of soil pH on the growth, soil nutrient composition, and rhizosphere microbiome of Ageratina adenophora.

Ageratina adenophora is an invasive weed species found in many countries. Methods to control the spread of this weed have been largely unsuccessful. Soil pH is the most important soil factor affecting the availability of nutrients for plant and impacting its growth. Understanding the mechanisms of the influence of soil pH on the growth of A. adenophora may help to develop effective control measures. In this study, we artificially changed the soil pH in pot experiments for A. adenophora. We studied the effects of acidic (pH 5.5), weakly acidic (pH 6.5), neutral (pH 7.2), and alkaline (pH 9.0) soils on the growth, availability of soil nutrients, activity of antioxidant enzymes, levels of redox markers in the leaves, and the structure and diversity of the rhizosphere microbiome. Soil with a pH 7.2 had a higher (47.8%) below-ground height versus soils of pH 5.5 at day 10; plant had a higher (11.3%) above-ground height in pH 7.2 soils than pH 9.0 soils at day 90; no differences in the fresh and dry weights of its above- and belowground parts, plant heights, and root lengths were observed in plants growing in acid, alkaline, or neutral pH soil were observed at day 180. Correspondingly, the antioxidant enzymes SOD (superoxide dismutase), POD (peroxidase), CAT (catalase) and redox markers GSH (glutathione) and MDA (malondialdehyde) were measured in the leaves. Significant differences existed in the activities of CAT and the levels of GSH between those growing in acidic and alkaline soils and those in neutral pH soil at day 90; however, only lower (36.8%) CAT activities in those grown at pH 5.5 than those grown at pH 7.2 were found at day 180. Similarly, significant differences in available P (16.89 vs 3.04 mg Kg-1) and total K (3.67 vs 0.96 mg Kg-1), total P (0.37 vs 0.25 g Kg-1) and total N (0.45 vs 1.09 g Kg-1) concentrations were found between the rhizosphere soils of A. adenophora grown at pH 9.0 and 7.2 at day 90; no such differences were seen at day 180. High throughput analyses of the 16S rRNA and ITS fragments showed that the rhizosphere microbiome diversity and composition under different soil pH conditions changed over 180 days. The rhizosphere microbiomes differed in diversity, phylum, and generic composition and population interactions under acid and alkaline conditions versus those grown in neutral soils. Soil pH had a greater impact on the diversity and composition of the prokaryotic rhizosphere communities than those of the fungal communities. A. adenophora responded successfully to pH stress by changing the diversity and composition of the rhizosphere microbiome to maintain a balanced nutrient supply to support its normal growth. The unusual pH tolerance of A. adenophora may be one crucial reason for its successful invasion. Our results suggest that attempts use soil pH to control its invasion by changing the soil pH (for example, using lime) will fail.

Human skeletal muscle aging atlas.

Skeletal muscle aging is a key contributor to age-related frailty and sarcopenia with substantial implications for global health. Here we profiled 90,902 single cells and 92,259 single nuclei from 17 donors to map the aging process in the adult human intercostal muscle, identifying cellular changes in each muscle compartment. We found that distinct subsets of muscle stem cells exhibit decreased ribosome biogenesis genes and increased CCL2 expression, causing different aging phenotypes. Our atlas also highlights an expansion of nuclei associated with the neuromuscular junction, which may reflect re-innervation, and outlines how the loss of fast-twitch myofibers is mitigated through regeneration and upregulation of fast-type markers in slow-twitch myofibers with age. Furthermore, we document the function of aging muscle microenvironment in immune cell attraction. Overall, we present a comprehensive human skeletal muscle aging resource ( https://www.muscleageingcellatlas.org/ ) together with an in-house mouse muscle atlas to study common features of muscle aging across species.

Universal Sublimation Strategy to Stabilize Single-Metal Sites on Flexible Single-Wall Carbon-Nanotube Films with Strain-Enhanced Activities for Zinc-Air Batteries and Water Splitting.

Single-metal-site catalysts have recently aroused extensive research in electrochemical energy fields such as zinc-air batteries and water splitting, but their preparation is still a huge challenge, especially in flexible catalyst films. Herein, we propose a sublimation strategy in which metal phthalocyanine molecules with defined isolated metal-N4 sites are gasified by sublimation and then deposited on flexible single-wall carbon nanotube (SWCNT) films by means of π-π coupling interactions. Specifically, iron phthalocyanine anchored on the SWCNT film prepared was directly used to boost the cathodic oxygen reduction reaction of the zinc-air battery, showing a high peak power density of 247 mW cm-2. Nickel phthalocyanine and cobalt phthalocyanine were, respectively, stabilized on SWCNT films as the anodic and cathodic electrocatalysts for water splitting, showing a low potential of 1.655 V at 10 mA cm-2. In situ Raman spectra and theoretical studies demonstrate that highly efficient activities originate from strain-induced metal phthalocyanine on SWCNTs. This work provides a universal preparation method for single-metal-site catalysts and innovative insights for electrocatalytic mechanisms.

Ursolic acid alleviates meiotic abnormalities induced by 3-nitropropionic acid in mouse oocytes.

3-nitropropionic acid (3-NPA), a toxic metabolite produced by mold, is mainly found in moldy sugarcane. 3-NPA inhibits the activity of succinate dehydrogenase that can induce oxidative stress injury in cells, reduce ATP production and induce oxidative stress in mouse ovaries to cause reproductive disorders. Ursolic acid (UA) has a variety of biological activities and is a pentacyclic triterpene compound found in many plants. This experiment aimed to investigate the cytotoxicity of 3-NPA during mouse oocyte in vitro maturation and the protective effects of UA on oocytes challenged with 3-NPA. The results showed that UA could alleviate 3-NPA-induced oocyte meiotic maturation failure. Specifically, 3-NPA induced a decrease in the first polar body extrusion rate of oocytes, abnormal distribution of cortical granules, and an increase in the proportion of spindle abnormalities. In addition, 3-NPA caused mitochondrial dysfunction and induced oxidative stress, including decreases in the GSH, mitochondrial membrane potential and ATP levels, and increases in the ROS levels, and these effects led to apoptosis and autophagy. The addition of UA could significantly improve the adverse effects caused by 3-NPA. In general, our data show that 3-NPA affects the normal development of oocytes during the in vitro culture, and the addition of UA can effectively repair the damage caused by 3-NPA to oocytes.

New multi-source waste co-incineration and clustering park operating model for small- and medium-sized city: A case study in China.

With improvements in urban waste management to promote sustainable development, an increasing number of waste types need to be sorted and treated separately. Due to the relatively low amount of waste generated in small- and medium-sized cities, separate treatment facilities for each waste type lack scale, waste is treated at a high cost and low efficiency. Therefore, industrial symbiosis principles are suggested to be used to guide collaborative waste treatment system of multi-source solid wastes, and co-incineration is the most commonly used technology. Most existing studies have focused on co-incineration of one certain waste type (such as sludge or medical waste) with municipal solid waste (MSW), but the systematic design and the comprehensive benefits on a whole city and park level have not been widely studied. Taking the actual operation of a multi-source waste co-incineration park in south-central China as an example, this study conducted a detailed analysis of the waste-energy-water metabolism process of MSW, sludge, food waste, and medical waste co-incineration. The environmental and economic benefits were evaluated and compared with the single decentralized waste treatment mode. The results showed that the multi-source waste co-incineration and clustering park operating model was comprehensively superior to the single treatment mode, greenhouse gases and human toxicity indicators were decreased by 11.87% and 295.74%, respectively, and the internal rate of return of the project was increased by 29.35%. This mainly benefits from the synergy of technical system and the economies of scale. Finally, this research proposed policy suggestions from systematic planning and design, technical route selection, and an innovative management mode in view of the potential challenges.

Impact on early outcome after endovascular repair of type B dissection without proximal landing zone using Castor single-branched stent graft-a retrospective cohort study.

Background: The early safety and efficacy of Castor branch stents have been demonstrated. However, the effect of aortic arch morphology on endovascular therapy remains an unresolved issue. This study aims to assess the impact of aortic arch morphology on the early outcomes of endovascular repair using Castor stent graft in patients who have acute type B aortic dissection involving the left subclavian artery (LSA). Methods: This is a retrospective cohort study. From January 2019 to December 2021, forty-one patients scheduled for thoracic endovascular aortic repair (TEVAR) of TBADs from Beijing Anzhen Hospital were enrolled in this retrospective cohort study and divided into two groups based on the length of the proximal landing zone left common carotid artery-LSA (PLZ LCCA-LSA), specifically the distance between the LCCA and the LSA (group A ≤10 mm and group B >10 mm). The study recorded technical success, mortality and aortic-related post-operative adverse events. Morphological indices were analyzed including the bird-beak configuration. The bird-beak configuration refers to the wedge-shaped gap between the undersurface of the endograft and the lesser curvature of the arch. The relationship between the risk of bird-beak configuration and PLZ was assessed with logistic regression analysis. Meanwhile, the relationship between the risk of aortic-related adverse events and bird-beak configuration was assessed with logistic regression analysis. Follow-up data were analyzed by Kaplan-Meier life table analysis. Results: The study included 41 patients with a mean age of 63.1±9.2 years, of which 80.5% were male. 18 patients from group A and 23 patients from group B were included in the comparative analysis. There were no significant differences in aortic-related adverse events, bird-beak phenomenon and re-intervention between groups A and B in 30-day outcomes. Six-month outcomes: aortic-related adverse events and the bird-beak phenomenon were observed in 11 (26.8%) and 12 (29.3%) patients, respectively. There was a significant difference in the occurrence of aortic-related adverse events (P=0.036) and bird-beak phenomenon (P=0.002) between groups A and B. In comparison to group B, the aortic-related adverse event rate was significantly higher in group A, with event-free rates of 83.3%, 83.3%, and 72.2% at 1, 3, and 6 months, respectively (P=0.020). Multivariable logistic regression analyses revealed that PLZ LCCA-LSA length [odds ratio (OR) 0.79; 95% CI: 0.64 to 0.97; P=0.026] was significantly associated with the occurrence of the bird-beak configuration, and bird-beak (OR 17.19; 95% CI: 2.24 to 131.81; P=0.006) was a significant risk factor for aortic-related adverse events. Conclusions: TEVAR with LSA revascularization has good early outcomes. However, it is more susceptible to aortic adverse events when the PLZ LCCA-LSA is less than 10 mm in length. This should be carefully considered, taking into account the risks and benefits.

Discrimination models with radiomics features derived from cardiovascular magnetic resonance images for distinguishing hypertensive heart disease from hypertrophic cardiomyopathy.

Background: Discriminating hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) is challenging, because both are characterized by left ventricular hypertrophy (LVH). Radiomics might be effective to differentiate HHD from HCM. Therefore, this study aimed to investigate discriminators and build discrimination models between HHD and HCM using multiparametric cardiac magnetic resonance (CMR) findings and radiomics score (radscore) derived from late gadolinium enhancement (LGE) and cine images. Methods: In this single center, retrospective study, 421 HCM patients [median and interquartile range (IQR), 50.0 (38.0-59.0) years; male, 70.5%] from January 2017 to September 2021 and 200 HHD patients [median and IQR, 44.5 (35.0-57.0) years; male, 88.5%] from September 2015 to July 2022 were consecutively included and randomly stratified into a training group and a validation group at a ratio of 6:4. Multiparametric CMR findings were obtained using cvi42 software and radiomics features using Python software. After dimensional reduction, the radscore was calculated by summing the remaining radiomics features weighted by their coefficients. Multiparametric CMR findings and radscore that were statistically significant in univariate logistic regression were used to build combined discrimination models via multivariate logistic regression. Results: After multivariate logistic regression, the maximal left ventricular end diastolic wall thickness (LVEDWT), left ventricular ejection fraction (LVEF), presence of LGE, cine radscore and LGE radscore were identified as significant characteristics and used to build a combined discrimination model. This model achieved an area under the receiver operator characteristic curve (AUC) of 0.979 (0.968-0.990) in the training group and 0.981 (0.967-0.995) in the validation group, significantly better than the model using multiparametric CMR findings alone (P<0.001). Conclusions: Radiomics features derived from cardiac cine and LGE images can effectively discriminate HHD from HCM.

Hierarchical blind phase search for correcting imperfect phase rotation in QAM signals synthesized via optical coherent superposition.

Coherent superposition has been proposed to synthesize high-order quadrature amplitude modulation (QAM) by coherently superposing low-order QAMs in the optical domain. These approaches could effectively relax the digital-to-analog converter resolution and reduce the complexity of the driving electronics. However, in the superposition process, imperfect phase rotations (IPRs) in low-order QAMs will be transferred to the resultant high-order QAM. Importantly, the induced IPR cannot be compensated for by conventional linear equalizers and carrier recovery methods. To combat the induced IPR, herein, we propose a hierarchical blind phase search (HBPS) algorithm to compensate for the IPRs in synthesized high-order QAMs. The proposed HBPS can match the generation mechanism of the IPRs in coherent superposition, by tracing back and estimating the IPR in the QPSK-like constellation of each hierarchy and finally correcting the induced IPRs. Simulation and experimental results verify that this algorithm could effectively compensate for the IPR in the resultant 16-QAMs synthesized using coherent superposition approaches. The proposed HBPS shows significant optical signal-to-noise ratio (OSNR) gains compared to the conventional blind phase search (BPS) method for high-order QAMs coherently superposed using optical signal processing (OSP) and tandem modulators (TMs). Specifically, at the BER of 2.4e-2, the HBPS achieves a 1.5-dB OSNR sensitivity enhancement over the BPS in either OSP or TMs-based schemes, even with an imperfection rotation of up to 20∘.

Latest Developments in Magnetic Resonance Imaging for Evaluating the Molecular Microenvironment of Gliomas.

The 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System has brought a transformative shift in the categorization of adult gliomas. Departing from traditional histological subtypes, the new classification system is guided by molecular genotypes, particularly the Isocitrate Dehydrogenase (IDH) mutation. This alteration reflects a pivotal change in understanding tumor behavior, emphasizing the importance of molecular profiles over morphological characteristics. Gliomas are now categorized into IDH-mutant and IDH wildtype, with significant prognostic implications. For IDH-mutant gliomas, the concurrent presence of Alpha-Thalassemia/mental retardation syndrome X-linked (ATRX) gene expression and co-deletion of 1p19q genes further refine classification. In the absence of 1p19q co-deletion, further categorization depends on the phenotypic expression of CDKN2A/B. Notably, IDH wildtype gliomas exhibit a poorer prognosis, particularly when associated with TERT promoter mutations, EGFR amplification, and +7/-10 co-deletion. Although not part of the new guidelines, the methylation status of the MGMT gene is crucial for guiding alkylating agent treatment. The integration of structural and functional Magnetic Resonance Imaging (MRI) techniques may play a vital role in evaluating these genetic phenotypes, offering insights into tumor microenvironment changes. This multimodal approach may enhance diagnostic precision, aid in treatment planning, and facilitate effective prognosis evaluation of glioma patients.

Functional divergence of two arginine decarboxylase genes in tropane alkaloid biosynthesis and root growth in Atropa belladonna.

Putrescine, produced via the arginine decarboxylase (ADC)/ornithine decarboxylase (ODC)-mediated pathway, is an initial precursor for polyamines metabolism and the root-specific biosynthesis of medicinal tropane alkaloids (TAs). These alkaloids are widely used as muscarinic acetylcholine antagonists in clinics. Although the functions of ODC in biosynthesis of polyamines and TAs have been well investigated, the role of ADC is still poorly understood. In this study, enzyme inhibitor treatment showed that ADC was involved in the biosynthesis of putrescine-derived metabolites and root growth in Atropa belladonna. Further analysis found that there were six ADC unigenes in the A. belladonna transcriptome, with two of them, AbADC1 and AbADC2, exhibiting high expression in the roots. To investigate their roles in TAs/polyamines metabolism and root growth, RNA interference (RNAi) was used to suppress either AbADC1 or AbADC2 expression in A. belladonna hairy roots. Suppression of the AbADC1 expression resulted in a significant reduction in the putrescine content and hairy root biomass. However, it had no noticeable effect on the levels of N-methylputrescine and the TAs hyoscyamine, anisodamine, and scopolamine. On the other hand, suppression of AbADC2 expression markedly reduced the levels of putrescine, N-methylputrescine, and TAs, but had no significant effect on hairy root biomass. According to ß-glucuronidase (GUS) staining assays, AbADC1 was mainly expressed in the root elongation and division region while AbADC2 was mainly expressed in the cylinder of the root maturation region. These differences in expression led to functional divergence, with AbADC1 primarily regulating root growth and AbADC2 contributing to TA biosynthesis.

A three-dimensional (3D) liver-kidney on a chip with a biomimicking circulating system for drug safety evaluation.

The liver and kidney are the major detoxifying organs in the human body and play an important role in pharmacokinetics. Drug-induced hepatotoxicity and nephrotoxicity can cause irreversible damage to the liver and kidney and are a major cause of drug failure in later stages. Both animal models and conventional cell culture have a number of limitations, such as animal ethics and gene mismatching and there is an urgent need to develop a new drug toxicity evaluation approach. In this paper, a 3D liver-kidney on a chip with a biomimicking circulating system (LKOCBCS) was constructed to obtain kidney and liver models in vitro for drug safety evaluation. LKOCBCS, which has a parallel circulating system mimicking biological circulation, consists of 3D biomimetic tissue of liver lobules similar to that of the human liver constructed by 3D bioprinting and renal proximal tubule barriers fabricated by ultrafast laser assisted etching. The proposed LKOCBCS facilitates the communication between the liver and the kidney, including the exchange of nutrients, compounds, and metabolites. The results revealed that the glucose concentration and cell metabolism stabilized after 7 days. A dynamically repeated low-dose administration of cyclosporine A (CsA) was fed to the system, and hepatotoxicity and nephrotoxicity were observed on day 3 according to the changes in toxicity markers. The high levels of drug induced biomarkers expressed in LKOCBCS indicate that this system is more sensitive than the monoculture liver chip and it is highly potential in replacing animal models for effective drug toxicity screening.

Weak transport of atmospheric water-insoluble particulate carbon from South Asia to the inner Tibetan Plateau in the monsoon season.

Carbonaceous particles play a crucial role in atmospheric radiative forcing. However, our understanding of the behavior and sources of carbonaceous particles in remote regions remains limited. The Tibetan Plateau (TP) is a typical remote region that receives long-range transport of carbonaceous particles from severely polluted areas such as South Asia. Based on carbon isotopic compositions (Δ14C/δ13C) of water-insoluble particulate carbon (IPC) in total suspended particle (TSP), PM2.5, and precipitation samples collected during 2020-22 at the Nam Co Station, a remote site in the inner TP, the following results were achieved: First, fossil fuel contributions (ffossil) to IPC in TSP samples (28.60 ± 9.52 %) were higher than that of precipitation samples (23.11 ± 8.60 %), and it is estimated that the scavenging ratio of IPC from non-fossil fuel sources was around 2 times that from fossil fuel combustion during the monsoon season. The ffossil of IPC in both TSP and PM2.5 samples peaked during the monsoon season. Because heavy precipitation during the monsoon season scavenges large amounts of long-range transported carbonaceous particles, the contribution of local emissions from the TP largely outweighs that from South Asia during this season. The results of the IPC source apportionment based on Δ14C and δ13C in PM2.5 samples showed that the highest contribution of liquid fossil fuel combustion also occurred in the monsoon season, reflecting increased human activities (e.g., tourism) on the TP during this period. The results of this study highlight the longer lifetime of fossil fuel-sourced IPC in the atmosphere than that of non-fossil fuel sources in the inner TP and the importance of local emissions from the TP during the monsoon season. The findings provide new knowledge for model improvement and mitigation of carbonaceous particles.