Molecular basis of phenotypic plasticity in a marine ciliate.

Phenotypic plasticity, which involves phenotypic transformation in the absence of genetic change, may serve as a strategy for organisms to survive in complex and highly-fluctuating environments. However, its reaction norm, molecular basis, and evolution remain unclear in most organisms, especially microbial eukaryotes. In this study, we explored these questions by investigating the reaction norm, regulation, and evolution of phenotypic plasticity in the cosmopolitan marine free-living ciliates Glauconema spp., which undergo significant phenotypic changes in response to food shortages. This study led to the de novo assembly of macronuclear genomes using long-read sequencing, identified hundreds of differentially expressed genes associated with phenotypic plasticity in different life stages, validated the function of two of these genes, and revealed that the reaction norm of body shape in response to food density follows a power-law distribution. Purifying selection may be the dominant evolutionary force acting on the genes associated with phenotypic plasticity, and the overall data support the hypothesis that phenotypic plasticity is a trait maintained by natural selection. This study provides novel insight into the developmental genetics of phenotypic plasticity in non-model unicellular eukaryotes, and sheds light on the complexity and long evolutionary history of this important survival strategy.

Pancreatic stellate cells and the interleukin family: Linking fibrosis and immunity to pancreatic ductal adenocarcinoma (Review).

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive form of cancer with a low survival rate. A successful treatment strategy should not be limited to targeting cancer cells alone, but should adopt a more comprehensive approach, taking into account other influential factors. These include the extracellular matrix (ECM) and immune microenvironment, both of which are integral components of the tumor microenvironment. The present review describes the roles of pancreatic stellate cells, differentiated cancer­associated fibroblasts and the interleukin family, either independently or in combination, in the progression of precursor lesions in pancreatic intraepithelial neoplasia and PDAC. These elements contribute to ECM deposition and immunosuppression in PDAC. Therapeutic strategies that integrate interleukin and/or stromal blockade for PDAC immunomodulation and fibrogenesis have yielded inconsistent results. A deeper comprehension of the intricate interplay between fibrosis, and immune responses could pave the way for more effective treatment targets, by elucidating the mechanisms and causes of ECM fibrosis during PDAC progression.

Integrative analyses on the ciliates Colpoda illuminate the life history evolution of soil microorganisms.

Microorganisms play a central role in sustaining soil ecosystems and agriculture, and these functions are usually associated with their complex life history. Yet, the regulation and evolution of life history have remained enigmatic and poorly understood, especially in protozoa, the third most abundant group of organisms in the soil. Here, we explore the life history of a cosmopolitan species-Colpoda steinii. Our analysis has yielded a high-quality macronuclear genome for C. steinii, with size of 155 Mbp and 37,123 protein-coding genes, as well as mean intron length of ~93 bp, longer than most other studied ciliates. Notably, we identify two possible whole-genome duplication events in C. steinii, which may account for its genome being about twice the size of C. inflata's, another co-existing species. We further resolve the gene expression profiles in diverse life stages of C. steinii, which are also corroborated in C. inflata. During the resting cyst stage, genes associated with cell death and vacuole formation are upregulated, and translation-related genes are downregulated. While the translation-related genes are upregulated during the excystment of resting cysts. Reproductive cysts exhibit a significant reduction in cell adhesion. We also demonstrate that most genes expressed in specific life stages are under strong purifying selection. This study offers a deeper understanding of the life history evolution that underpins the extraordinary success and ecological functions of microorganisms in soil ecosystems.IMPORTANCEColpoda species, as a prominent group among the most widely distributed and abundant soil microorganisms, play a crucial role in sustaining soil ecosystems and promoting plant growth. This investigation reveals their exceptional macronuclear genomic features, including significantly large genome size, long introns, and numerous gene duplications. The gene expression profiles and the specific biological functions associated with the transitions between various life stages are also elucidated. The vast majority of genes linked to life stage transitions are subject to strong purifying selection, as inferred from multiple natural strains newly isolated and deeply sequenced. This substantiates the enduring and conservative nature of Colpoda's life history, which has persisted throughout the extensive evolutionary history of these highly successful protozoa in soil. These findings shed light on the evolutionary dynamics of microbial eukaryotes in the ever-fluctuating soil environments. This integrative research represents a significant advancement in understanding the life histories of these understudied single-celled eukaryotes.

Genomic analyses reveal the stepwise domestication and genetic mechanism of curd biogenesis in cauliflower.

Cauliflower (Brassica oleracea L. var. botrytis) is a distinctive vegetable that supplies a nutrient-rich edible inflorescence meristem for the human diet. However, the genomic bases of its selective breeding have not been studied extensively. Herein, we present a high-quality reference genome assembly C-8 (V2) and a comprehensive genomic variation map consisting of 971 diverse accessions of cauliflower and its relatives. Genomic selection analysis and deep-mined divergences were used to explore a stepwise domestication process for cauliflower that initially evolved from broccoli (Curd-emergence and Curd-improvement), revealing that three MADS-box genes, CAULIFLOWER1 (CAL1), CAL2 and FRUITFULL (FUL2), could have essential roles during curd formation. Genome-wide association studies identified nine loci significantly associated with morphological and biological characters and demonstrated that a zinc-finger protein (BOB06G135460) positively regulates stem height in cauliflower. This study offers valuable genomic resources for better understanding the genetic bases of curd biogenesis and florescent development in crops.

Comparison of the Global Leadership Initiative on Malnutrition and the Patient-Generated Subjective Global Assessment for diagnosing malnutrition in patients undergoing surgery for hepatobiliary and pancreatic malignancies.

OBJECTIVE: to analyse the differences in malnutrition assessment between the Global Leadership Initiative on Malnutrition (GLIM) criteria and the Patient-Generated Subjective Global Assessment (PG-SGA) among patients with hepatobiliary and pancreatic malignancies. METHOD: this study was a cross-sectional study and included 126 hospitalised patients who underwent surgery for hepatobiliary and pancreatic malignancies between November 1, 2019 and August 1, 2020. The patients' clinical data were collected, and malnutrition assessments were completed using the different nutritional assessment tools. The consistency of both tools was analysed using Cohen's kappa coefficient. RESULTS: the prevalence of malnutrition showed a difference in diagnosis results between the GLIM criteria (36.51 %) and the PG-SGA (55.56 %). The two methods had moderate consistency (kappa = 0.590, p < 0.01). The sensitivity of a malnutrition diagnosis using a combination of GLIM and PG-SGA was 65.7 % (53.3 % and 76.4 %, respectively), and specificity was 100 % (92 % and 100 %, respectively). When malnutrition was evaluated using only PG-SGA, sensitivity was 88.9 % (95 % confidence interval (CI) 63.9 % to 98.1 %), whereas when only the GLIM score was used for malnutrition evaluation, sensitivity was 98.2 % (95 % CI, 92.8 % to 99.7 %). In addition, the PG-SGA score and the GLIM score had significant correlations. CONCLUSION: GLIM performed better than PG-SGA in the correlation analysis of nutritional indicators. GLIM is more suitable for patients with hepatobiliary and pancreatic malignancies than PG-SGA.

Deciphering the role of transcription factors in glioblastoma cancer stem cells.

Glioblastoma (GBM), the most aggressive and fatal brain malignancy, is largely driven by a subset of tumor cells known as cancer stem cells (CSCs). CSCs possess stem cell-like properties, including self-renewal, proliferation, and differentiation, making them pivotal for tumor initiation, invasion, metastasis, and overall tumor progression. The regulation of CSCs is primarily controlled by transcription factors (TFs) which regulate the expressions of genes involved in maintaining stemness and directing differentiation. This review aims to provide a comprehensive overview of the role of TFs in regulating CSCs in GBM. The discussion encompasses the definitions of CSCs and TFs, the significance of glioma stem cells (GSCs) in GBM, and how TFs regulate GSC self-renewal, proliferation, differentiation, and transformation. The potential for developing TF-targeted GSC therapies is also explored, along with future research directions. By understanding the regulation of GSCs by TFs, we may uncover novel diagnostic and therapeutic strategies against this devastating disease of GBM.

Investigation of Microstructure and Mechanical Properties of High-Depth-to-Width-Ratio Horizontal NG-GMAW Joint for S500Q Steel.

A novel high depth-to-width ratio of 15:1 narrow-gap gas metal arc welding technique was developed for the welding of S500Q steel in a horizontal butt joint. The bead arrangement of the I groove was optimized to produce a high-quality connection with the upper sidewall of the joint. The microstructure and mechanical properties were observed and evaluated by optical microscopy, scanning electron microscopy, tensile testing, and micro-hardness and impact toughness testing at 1/5, 2/5, 3/5, and 4/5 thickness of the joint. The 3/5 T position exhibited the highest strength, which was attributed to the presence of finer carbide precipitates. The highest micro-hardness appeared at 4/5 T. The highest impact toughness appeared at 3/5 T. The formation of coarse granular bainite was the major reason for the decrease in impact toughness in other regions. A microscopic fracture at 1/5 T and 3/5 T was further analyzed. It was observed that the width of the fibrous zone at 3/5 T was significantly larger than that at 1/5 T. The radial zones at 1/5 T were observed to exhibit cleavage, with secondary cracks on the fracture surface.

Exploring global symmetry-breaking superradiant phase via phase competition.

Superradiant phase transitions play a fundamental role in understanding the mechanism of collective light-matter interaction at the quantum level. Here we investigate multiple superradiant phases and phase transitions with different symmetry-breaking patterns in a two-mode V-type Dicke model. Interestingly, we show that there exists a quadruple point where one normal phase, one global symmetry-breaking superradiant phase, and two local symmetry-breaking superradiant phases meet. Such a global phase results from the phase competition between two local superradiant phases and cannot occur in the standard Λ- and Ξ-type three-level configurations in quantum optics. Moreover, we exhibit a sequential first-order quantum phase transition from one local to the global again to the other local superradiant phase. Our study opens up a perspective of exploring multilevel quantum critical phenomena with global symmetry breaking.

Long-term outcomes of survivors with influenza A H1N1 virus-induced severe pneumonia and ARDS: a single-center prospective cohort study.

Introduction: Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS). Method: This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument. Result: A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn't continue improving after 3 months. Health-related quality of life didn't change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening. Conclusion: The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.

Advances in understanding bioaerosol release characteristics and potential hazards during aerobic composting.

Bioaerosol emissions and their associated risks are attracting increasing attention. Bioaerosols are generated during the pretreatment, fermentation, and screening of mature compost when processing various types of solid waste at composting plants (e.g., municipal sludge and animal manure). In this review, we summarize research into bioaerosols at different types of composting plants by focusing on the methods used for sampling bioaerosols, stages when emissions potentially occur, major components of bioaerosols, survival and diffusion factors, and possible control strategies. The six-stage Andersen impactor is the main method used for sampling bioaerosols in composting plants. In addition, different composting management methods mainly affect bioaerosol emissions from composting plants. Studies of the components of bioaerosols produced by composting plants mainly focused on bacteria and fungi, whereas few considered others such as endotoxin. The survival and diffusion of bioaerosols are influenced by seasonal effects due to changes in environmental factors, such as temperature and relative humidity. Finally, three potential strategies have been proposed for controlling bioaerosols in composting plants. Improved policies are required for regulating bioaerosol emissions, as well as bioaerosol concentration diffusion models and measures to protect human health.

Construction of carbon nanospheres: A rational design based on BS-12 @ LiCl.

Nanocarbons have potential applications in almost all areas of materials science. While we have appreciated the various discoveries and applications of many nanocarbons, we recognize that the field remains challenging in terms of tunability. In this research, we report a new strategy for the self-assembly of surfactant @ salt from the concept of carbon nanostructure design, and introduce the concept of "separator". On the one hand, it allows the core and shell to be formed in one step. On the other hand, it allows the ordered aggregates to remain in their original shape under thermal action. The surface morphology, degree of graphitization, elemental composition and surface chemical state, formation mechanism, and specific luminescent properties of carbon nanomaterials were investigated. TEM reveals that (dodecyldimethyl betaine) BS-12 @ LiCl carbon nanospheres with tunable size (from 55 nm to 70 nm) can be successfully synthesized. Raman and XRD show that the structure of carbon nanospheres has some defects and disordered carbon. XPS and FTIR analyses indicate that the defects present in the carbon nanosphere structure are related to the N and O elements. The detailed growth mechanism shows that the micelle structure in the system can be well adjusted by changing the concentration of surfactant. PL research demonstrates that the synthesized carbon nanospheres have UV luminescent properties. Most importantly, the method can be further developed into a general strategy for self-assembly using a variety of surfactants and "separators" as promising candidates for future practical applications of nanocarbon materials.

Biochar improves the humification process during pig manure composting: Insights into roles of the bacterial community and metabolic functions.

Biochar could promote humification in composting, nevertheless, its mechanism has not been fully explored from the perspective of the overall bacterial community and its metabolism. This study investigated the effects of bamboo charcoal (BC) and wheat straw biochar (WSB) on the humic acid (HA) and fulvic acid (FA) contents during pig manure composting. The results showed that BC enhanced humification more than WSB, and significantly increased the HA content and HA/FA ratio. The bacterial community structure under BC differed from those under the other treatments, and BC increased the abundance of bacteria associated with the transformation of organic matter compared with the other treatments. Furthermore, biochar enhanced the metabolism of carbohydrates and amino acids in the thermophilic and cooling phases, especially BC. Through Mantel tests and network analysis, we found that HA was mainly related to carbon source metabolism and the bacterial community, and BC might change the interaction patterns among carbohydrates, amino acid metabolism, Bacillales, Clostridiales, and Lactobacillales with HA and FA to improve the humification process during composting. These results are important for understanding the mechanisms associated with the effects of biochar on humification during composting.

Study on material basis and anti-hypertensive metabolomics of Zhengan-Xifeng-Tang(ZXT): A comparison between ZXT decoction and granules.

High blood pressure is a serious human health problem and one of the leading risk factors for fatal complications in cardiovascular disease. The ZXT granules were prepared based on the Zhengan-Xifeng-Tang (ZXT) decoction. However, the therapeutic effects of ZXT granules on spontaneous hypertension and the metabolic pathways in which they may intervene are unclear. The aim of this study was to investigate the antihypertensive effect of ZXT granules on spontaneously hypertensive rats (SHR) and to analyze the metabolic pathway of intervention through chemical composition characterization, pharmacodynamics, and serum metabolomics analysis. After eight weeks of administration, serum and aortic arch samples were collected for biochemical, histopathology and serum metabolomics analysis to assess the effect of ZXT granules on SHR. The results showed that ZXT granules reduced aortic arch injury and blood pressure in SHR rats. Serum data from rats in each group was collected using LC-MS and 74 potential biomarkers were identified that showed significant differences between the model and control groups. Of these, 18 potential biomarkers were found to be deregulated after intervention with ZXT granules. These 18 potential differential metabolic markers are primarily involved in bile acid biosynthesis, arachidonic acid metabolism pathway, and fatty acid degradation. The results demonstrated that ZXT granules significantly affected blood lipids, aortic arch, and metabolic disorders in SHR rats. ZXT granules offer a new possibility for effective and convenient treatment of hypertensive patients.

Constructing a Hydrophilic Microsensor for High-Antifouling Neurotransmitter Dopamine Sensing.

Real-time sensing of dopamine is essential for understanding its physiological function and clarifying the pathophysiological mechanism of diseases caused by impaired dopamine systems. However, severe fouling from nonspecific protein adsorption, for a long time, limited conventional neural recording electrodes concerning recording stability. This study reported a high-antifouling nanocrystalline boron-doped diamond microsensor grown on a carbon fiber substrate. The antifouling properties of this diamond sensor were strongly related to the grain size (i.e., nanocrystalline and microcrystalline) and surface terminations (i.e., oxygen and hydrogen terminals). Experimental observations and molecular dynamics calculations demonstrated that the oxygen-terminated nanocrystalline boron-doped diamond microsensor exhibited enhanced antifouling characteristics against protein adsorption, which was attributed to the formation of a strong hydration layer as a physical and energetic barrier that prevents protein adsorption on the surface. This finally allowed for in vivo monitoring of dopamine in rat brains upon potassium chloride stimulation, thus presenting a potential solution for the design of next-generation antifouling neural recording sensors. Experimental observations and molecular dynamics calculations demonstrated that the oxygen-terminated nanocrystalline boron-doped diamond (O-NCBDD) microsensor exhibited ultrahydrophilic properties with a contact angle of 4.9°, which was prone to forming a strong hydration layer as a physical and energetic barrier to withstand the adsorption of proteins. The proposed O-NCBDD microsensor exhibited a high detection sensitivity of 5.14 µA µM-1 cm-2 and a low detection limit of 25.7 nM. This finally allowed for in vivo monitoring of dopamine with an average concentration of 1.3 µM in rat brains upon 2 µL of potassium chloride stimulation, thus presenting a potential solution for the design of next-generation antifouling neural recording sensors.

Quantitative analysis of low-content impurity crystal forms in canagliflozin tablets by NIR solid-state analysis technique.

Canagliflozin (CFZ) tablets was a commercially new class of anti-diabetic drug, CFZ had various anhydrate crystal forms and two hydrate crystal forms (Canagliflozin hemihydrate (Hemi-CFZ) and Canagliflozin monohydrate (Mono-CFZ) crystal form). The active pharmaceutical ingredients (APIs) of commercially available CFZ tablets were Hemi-CFZ, was easily convert to CFZ or Mono-CFZ under the influence of temperature, pressure, humidity and other factors in tablets processing, storage, and transportation, thus affected bioavailability and efficacy of tablets. Therefore, quantitative analysis of low-content CFZ and Mono-CFZ in tablets was essential to control tablets' quality. The main objective of this study was to explore the feasibility and in-depth explain its quantitative analysis mechanism of NIR for quantitative analysis of low-content CFZ/Mono-CFZ in CFZ tablets. PLSR models for low-content CFZ/Mono-CFZ were established by NIR solid-state analysis technique in different resolutions with different wavenumber regions combined with various pretreatments methods (such as Multiplicative Scatter Correction (MSC), Standard Normal Variate (SNV), Savitzky-Golay First Derivative (SG1st), Savitzky-Golay Second Derivative (SG2nd) and Wavelet Transform (WT)), and the PLSR models were verified. The feasibility of NIR spectroscopy for quantitative analysis of low-content CFZ and Mono-CFZ in CFZ tablets was discussed and analyzed from multiple perspectives, which included the distribution of effective information on the spectrum, the influence of resolution on PLSR models performance, the variance contribution/cumulative variance contribution of PLSR model principal components (PCs), the relation of PCI loadings, scores of the spectra and CFZ/Mono-CFZ content, and the mechanism of quantitative analysis was in-depth explained simultaneously. Eventually the most suitable PLSR models in 0.0000-10.0000 % w/w % obtained. That can provide theoretical support for quantitative analysis of low-content impurity crystal during the production, storage and transportation of CFZ tablets, thus provide reference methods for quality control of CFZ tablets and a reliable reference method for quantitative analysis of impurity crystal forms and quality control of similar drugs.

Fatal Case of Pneumocystis Jirovecii Pneumonia (PJP) During Treatment for Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an acute, rare and potentially fatal drug reaction. To date, limited studies have reported secondary Pneumocystis jirovecii pneumonia (PJP) infection during the treatment of DRESS syndrome. A 53-year-old man was admitted to the hospital due to a persistent fever lasting for 5 days. He had a medical history of hypertension, psoriasis, urticaria, and had recently been treated with carbamazepine for nerve spasm two weeks ago. After admission, the patient presented with a high fever accompanied by chills, abdominal pain, bilateral upper limb muscle pain, and generalized lymph nodes enlargement. Laboratory tests revealed elevated eosinophils and atypical lymphocytes. Subsequently, the patient developed multiple internal organ complications, including oliguria, elevated serum creatinine, liver enzymes, and cardiac troponin I. Based on diagnostic criteria, the patient was diagnosed with DRESS syndrome. To manage the DRESS syndrome, the patient was successively or simultaneously prescribed methylprednisolone, cyclosporin and intravenous immunoglobulin, resulting in an improvement of the condition. However, during the treatment, the patient was infected with Pneumocystis jirovecii. Despite targeted therapy with trimethoprim/sulfamethoxazole, primaquine and clindamycin successively, no remission was observed. Chest CT scans exhibited multiple exudations in both lungs, indicative of interstitial pneumonia. Unfortunately, the patient's oxygenation progressively declined, leading to his untimely demise. This rare case further highlights the need for clinicians to be aware of the risk of Pneumocystis jirovecii infection in DRESS syndrome patients treated with long-term and high-dose glucocorticoid therapy.

Bacteria-Based Double-Stranded RNA Production to Develop Cost-Effective RNA Interference Application for Insect Pest Management.

Since the discovery of the RNA interference (RNAi) mechanism, it has been widely used in the fields of gene function, biomedicine, and crop pest control. In the direction of agricultural application, this technology is highly expected, especially in the field of pest control, which is called "the third revolution in the history of pesticides". Currently, RNA biopesticides are developing rapidly all over the world. A genetically modified product (MON87411) has been approved for marketing, and a large number of agricultural companies are developing products based on direct spraying RNA biopesticides and submitting them for regulatory approval. The biggest problem that has emerged for spray RNA biopesticides is the technology for large-scale and low-cost production of dsRNA. At present, the bacterial fermentation production technology can realize large-scale dsRNA production with a yield of 4.23~182 mg/L bacterial solution. This article describes the experimental protocol for dsRNA production technology based on bacterial fermentation.

Mitogenomic architecture and evolution of the soil ciliates Colpoda.

Colpoda are cosmopolitan unicellular eukaryotes primarily inhabiting soil and benefiting plant growth, but they remain one of the least understood taxa in genetics and genomics within the realm of ciliated protozoa. Here, we investigate the architecture of de novo assembled mitogenomes of six Colpoda species, using long-read sequencing and involving 36 newly isolated natural strains in total. The mitogenome sizes span from 43 to 63 kbp and typically contain 28-33 protein-coding genes. They possess a linear structure with variable telomeres and central repeats, with one Colpoda elliotti strain isolated from Tibet harboring the longest telomeres among all studied ciliates. Phylogenomic analyses reveal that Colpoda species started to diverge more than 326 million years ago, eventually evolving into two distinct groups. Collinearity analyses also reveal significant genomic divergences and a lack of long collinear blocks. One of the most notable features is the exceptionally high level of gene rearrangements between mitochondrial genomes of different Colpoda species, dominated by gene loss events. Population-level mitogenomic analysis on natural strains also demonstrates high sequence divergence, regardless of geographic distance, but the gene order remains highly conserved within species, offering a new species identification criterion for Colpoda species. Furthermore, we identified underlying heteroplasmic sites in the majority of strains of three Colpoda species, albeit without a discernible recombination signal to account for this heteroplasmy. This comprehensive study systematically unveils the mitogenomic structure and evolution of these ancient and ecologically significant Colpoda ciliates, thus laying the groundwork for a deeper understanding of the evolution of unicellular eukaryotes.IMPORTANCEColpoda, one of the most widespread ciliated protozoa in soil, are poorly understood in regard to their genetics and evolution. Our research revealed extreme mitochondrial gene rearrangements dominated by gene loss events, potentially leading to the streamlining of Colpoda mitogenomes. Surprisingly, while interspecific rearrangements abound, our population-level mitogenomic study revealed a conserved gene order within species, offering a potential new identification criterion. Phylogenomic analysis traced their lineage over 326 million years, revealing two distinct groups. Substantial genomic divergence might be associated with the lack of extended collinear blocks and relaxed purifying selection. This study systematically reveals Colpoda ciliate mitogenome structures and evolution, providing insights into the survival and evolution of these vital soil microorganisms.

Serum-based metabolomics reveals the mechanism of action of isorhynchophylline in the intervention of atherosclerosis in ApoE-/- mice.

Atherosclerosis (AS) is a chronic inflammatory disease with disorders of lipid metabolism. Metabolic disorders, inflammation and lipid deposition are prominent pathological features of atherosclerosis. Isorhynchophylline (IRN) has pharmacological effects such as protection of vascular endothelial cells, anti-inflammatory, anti-thrombotic, and anti-smooth muscle cell proliferation. However, it is unclear whether IRN is efficacious in atherosclerosis. In the present study, we verified the pharmacological efficacy and hepatoprotective effects of IRN in intervening in AS. LC-MS-based serum untargeted metabolomics was performed to search for potential biomarkers and related pathways in IRN-treated AS in ApoE-/- mice. Fifty-eight biomarkers were metabolically disturbed in the model mice compared to controls. Thirteen biomarkers showed optimal recovery methods after IRN-40 mg ml-1 intervention. We identified three metabolic pathways involved in IRN: glycerophospholipid metabolism, linoleic acid metabolism, and alpha-linolenic acid metabolism. These findings provide a research basis for the intervention of IRN in atherosclerosis.

Clinical features and outcomes of small airway disease in ANCA-associated vasculitis.

BACKGROUND AND OBJECTIVE: To clarify the prevalence, features and outcomes of small airway disease (SAD) in a Chinese cohort with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) related pulmonary involvement. METHODS: SAD was recorded when the manifestations of either centrilobular nodules or air trapping were observed according to CT scans, except for infection or other airway-related comorbidities. Baseline and follow-up data were collected retrospectively. RESULTS: Of the 359 newly diagnosed AAV patients with pulmonary involvement, 92 (25.6%) had SAD, including 79 (85.9%) cases of anti-MPO-ANCA positive, 9 (9.8%) cases of anti-PR3-ANCA positive and 2 (2.2%) cases of double positive. Patients with SAD were more likely to be younger, female, non-smokers, have more ear-nose-throat (ENT) involvement, and have higher baseline Birmingham Vasculitis Activity Score (BVAS) compared to patients without SAD. Several AAV-related SAD patients have improved lung function and CT scans after immunosuppressive therapy. Patients with SAD had a better prognosis compared to those without SAD. When dividing all patients into three groups: isolated SAD (only small airway involvements), SAD with other lower airway involvements, and non-SAD, patients in the SAD with other lower airway involvements group had the highest risk of infection, while patients in the non-SAD group had the worst long-term outcomes. Similar results were observed in anti-MPO-ANCA positive patients when performing subgroup analyses. CONCLUSION: SAD is a unique manifestation of AAV-related lung involvement and exhibits distinct clinical features. It is vital to focus on SAD because of its association with prognosis and infection in AAV patients, especially in anti-MPO-ANCA positive patients. Moreover, SAD might represent a better response to immunosuppressors.