Significant spatiotemporal pattern of nitrous oxide emission and its influencing factors from a shallow eutropic lake in Inner Mongolia, China.

Eutrophic shallow lakes are generally considered as a contributor to the emission of nitrous oxide (N2O), while regional and global estimates have remained imprecise. This due to a lack of data and insufficient understanding of the multiple contributing factors. This study characterized the spatiotemporal variability in N2O concentrations and N2O diffusive fluxes and the contributing factors in Lake Wuliangsuhai, a typical shallow eutrophic and seasonally frozen lake in Inner Mongolia with cold and arid climate. Dissolved N2O concentrations of the lake exhibited a range of 4.5 to 101.2 nmol/L, displaying significant spatiotemporal variations. The lowest and highest concentrations were measured in summer and winter, respectively. The spatial distribution of N2O flux was consistent with that of N2O concentrations. Additionally, the hotspots of N2O emissions were detected within close to the main inflow of lake. The wide spatial and temporal variation in N2O emissions indicate the complexity and its relative importance of factors influencing emissions. N2O emissions in different lake zones and seasons were regulated by diverse factors. Factors influencing the spatial and temporal distribution of N2O concentrations and fluxes were identified as WT, WD, DO, Chl-a, SD and COD. Interestingly, the same factor demonstrated opposing effects on N2O emission in various seasons or zones. This research improves our understanding of N2O emissions in shallow eutrophic lakes in cold and arid areas.

Selection of indigenous Saccharomyces cerevisiae strains with good oenological and aroma characteristics for winemaking in Ningxia China.

Ningxia is one of the well-known wine producing regions in China. However, the oenological and aroma characteristics of indigenous yeasts remains hidden. The fermentative and oenological properties including stress resistance, hydrogen sulfide, foam production levels; killer phenotype, and flocculation of 89 Ningxia indigenous Saccharomyces cerevisiae isolates and ten commercial yeasts were evaluated. The fermentative and oenological properties of the tested strains varied significantly. They could resist 500 g/L glucose, 300 mg/L SO2, 14% (v/v) ethanol and pH 2.8, and produce more esters. They also produce low levels of ethanol and could conduct fermentations vigorously and at a high rate. Cabernet Sauvignon wines made with NXU 21-24 showed the high intensity of tropical fruit, dry fruit, temperate fruit, and spicy flavor. The floral flavor in NXU 21-102 fermented wine is very intense. The indigenous S. cerevisiae strains of NXU 21-102 and NXU 21-24 exhibited potential use as starter cultures in wine production.

Selective Clearance of Circulating Histones Based on Dodecapeptide-Grafted Copolymer Material for Sepsis Blood Purification.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Research indicates that circulating histones, as pathogenic factors, may represent a therapeutic target for sepsis. However, effectively clearing circulating histones poses a challenge due to their structural similarity to normal blood proteins, their low abundance in the bloodstream, and serious interference from other blood biomacromolecules. Here we design a dodecapeptide-based functional polymer that can selectively adsorb circulating histones from the blood. The peptide, named P1 (HNHHQLALVESY), was discovered through phage display screening and demonstrated a strong affinity for circulating histones while exhibiting negligible affinities for common proteins in the blood, such as human serum albumin (HSA), immunoglobulin G (IgG), and transferrin (TRF). Furthermore, the P1 peptide was incorporated into a functional polymer design, poly(PEGMA-co-P1), which was immobilized onto a silica gel surface through reversible addition-fragmentation chain transfer polymerization. The resulting material was characterized using solid nuclear magnetic resonance, thermogravimetric analysis, and X-ray photoelectron spectroscopy. This material demonstrated the ability to selectively and efficiently capture circulating histones from both model solutions and whole blood samples while also exhibiting satisfactory blood compatibility, good antifouling properties, and resistance to interference. Satisfactory binding affinity and efficient capture capacity toward histone were also observed for the other screened peptide P2 (QMSMDLFGSNFV)-grafted polymer, validating phage display as a reliable ligand screening strategy. These findings present an approach for the specific clearance of circulating histones and hold promise for future clinical applications in blood purification toward sepsis.

Ultrathin Gd-Oxide Nanosheet as Ultrasensitive Companion Diagnostic Tool for MR Imaging and Therapy of Submillimeter Microhepatocellular Carcinoma.

Early stage hepatocellular carcinoma (HCC) presents a formidable challenge in clinical settings due to its asymptomatic progression and the limitations of current imaging techniques in detecting micro-HCC lesions. Addressing this critical issue, we introduce a novel ultrathin gadolinium-oxide (Gd-oxide) nanosheet-based platform with heightened sensitivity for high-field MRI and as a therapeutic agent for HCC. Synthesized via a digestive ripening process, these Gd-oxide nanosheets exhibit an exceptional acid-responsive profile. The integration of the ultrathin Gd-oxide with an acid-responsive polymer creates an ultrasensitive high-field MRI probe, enabling the visualization of submillimeter-sized tumors with superior sensitivity. Our research underscores the ultrasensitive probe's efficacy in the treatment of orthotopic HCC. Notably, the ultrasensitive probe functions dually as a companion diagnostic tool, facilitating simultaneous imaging and therapy with real-time treatment monitoring capabilities. In conclusion, this study showcases an innovative companion diagnostic tool that holds promise for the early detection and effective treatment of micro-HCC.

Anti-signal recognition particle antibodies induce cardiac diastolic dysfunction via oxidative stress injury.

Objectives: Anti-signal recognition particle (SRP) antibodies, markers of immune-mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti-SRP antibodies against the myocardium through in vivo and in vitro studies. Methods: Total immunoglobulin G (IgG), purified from patients with positive anti-SRP antibodies, was passively transferred into C57BL/6 mice. Cardiac function was evaluated via echocardiography and the ventricular pressure-volume loop; cardiac histological changes were analysed using haematoxylin-eosin staining, picrosirius red staining, immunofluorescence and immunohistochemistry. Additionally, reactive oxygen species (ROS) formation was evaluated by dihydroethidium (DHE) staining; mitochondrial morphology and function were evaluated using transmission electron microscopy and seahorse mitochondrial respiration assay, respectively. The myositis cohort at our centre was subsequently reviewed in terms of cardiac assessments. Results: After the passive transfer of total IgG from patients with positive anti-SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti-SRP-specific IgG, however, recovered normal mitochondrial metabolism after treatment with N-acetylcysteine, an ROS scavenger. Moreover, patients positive for anti-SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching. Conclusion: Anti-SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti-SRP antibody-induced LVDD.

Hollow spherical nano-traps using pillararene-based polymer for efficient uranium extraction from seawater.

Herein, a hollow spherical pillar[5]arene-based polymer (P5-AO) adsorbent was synthesized. The P5-AO adsorbent was capable of effectively capturing uranium from simulated seawater (139.5 mg g-1) and real seawater (8.1 mg g-1). We also elucidated the uranium adsorption mechanism of P5-AOvia extended X-ray absorption fine structure (EXAFS). This study provides a novel direction for the development of uranium capture adsorbents.

GATIS score for predicting the prognosis of rectal neuroendocrine neoplasms: A Chinese multicenter study of 12-year experience.

BACKGROUND: There is currently a shortage of accurate, efficient, and precise predictive instruments for rectal neuroendocrine neoplasms (NENs). AIM: To develop a predictive model for individuals with rectal NENs (R-NENs) using data from a large cohort. METHODS: Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China. Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival, and two nomograms were constructed. RESULTS: A total of 1408 patients with R-NENs were included. Tumor grade, T stage, tumor size, age, and a prognostic nutritional index were important risk factors for prognosis. The GATIS score was calculated based on these five indicators. For overall survival prediction, the respective C-indexes in the training set were 0.915 (95% confidence interval: 0.866-0.964) for overall survival prediction and 0.908 (95% confidence interval: 0.872-0.944) for progression-free survival prediction. According to decision curve analysis, net benefit of the GATIS score was higher than that of a single factor. The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods. CONCLUSION: The GATIS score had a good predictive effect on the prognosis of patients with R-NENs, with efficacy superior to that of the World Health Organization grade and TNM stage.

Colorimetric and Fluorometric Determination of Fluoride in Tetrahydrofuran and Dimethyl Sulfoxide Using a 4-Hydroxypyrene Probe.

F- ions (fluoride ions) are crucial in various chemical waste and environmental safety contexts. However, excessive fluoride exposure can pose a threat to human well-being. In this study, a simple 4-substituted pyrene derivative known as 4-hydroxypyrene (4-PyOH) was designed as a colorimetric probe for detecting F- through the formation of hydrogen bonds between F- and a hydroxyl group. The probe 4-PyOH exhibited exceptional sensitivity and selectivity towards F- ions and was successfully utilized as test strips for detecting F- ions in organic solvents. The detection limit reached an impressively low level of 3.06 × 10-7 M in the organic solvent. The recognition mechanism was confirmed through 1H NMR titration.

Acute nitrite exposure causes gut microbiota dysbacteriosis and proliferation of pathogenic Photobacterium in shrimp.

Nitrite exposure has become a significant concern in the aquaculture industry, posing a severe threat to aquatic animals such as shrimp. While studies have reported the adverse effects of nitrite on shrimp growth, the part played by the gut microbiota in shrimp mortality resulting from nitrite exposure is poorly understood. Here, the effects of nitrite on shrimp gut bacterial community were investigated using 16S rRNA amplicon sequencing, bacterial isolation, genomic analysis, and infection experiments. Compared to the control_healthy group, changes in the bacterial composition of the nitrite_dead group were associated with reduced abundance of specific beneficial bacteria and increased abundance of certain pathogenic bacteria. Notably, members of the Photobacterium genus were found to be significantly enriched in the nitrite_dead group. Genomic analysis of a representative Photobacterium strain (LvS-8n3) revealed a variety of genes encoding bacterial toxins, including hemolysin, adhesin, and phospholipase. Furthermore, it was also found that LvS-8n3 exhibits strong pathogenicity, probably due to its high production of pathogenic factors and the ability to utilize nitrite for proliferation. Therefore, the proliferation of pathogenic Photobacterium species appears pivotal for driving shrimp mortality caused by nitrite exposure. These findings provide novel insights into the disease mechanism in shrimp under conditions of environmental change.

PASTICCINO2 interacting with Golgi Anti-Apoptotic Proteins resists endoplasmic reticulum stress dependent on very long-chain fatty acids.

The endoplasmic reticulum (ER) is crucial for maintaining cell homeostasis because it is the primary site for synthesizing secreted and transmembrane proteins and lipids. The unfolded protein response (UPR) is activated to restore ER homeostasis under ER stress. However, the relationship between lipids and the ER stress response in plants is not well understood. Arabidopsis Golgi anti-apoptotic proteins (GAAPs) are involved in resisting ER stress. To elucidate the function of GAAPs, PASTICCINO2 (PAS2), involved in very long-chain fatty acid (VLCFA) synthesis, was found to interact with GAAPs and IRE1. Single pas2 and gaap1/gaap2pas2 double mutants exhibited increased seedling damage and impaired UPR response under chronic ER stress. Site mutation combined with genetic analysis revealed that the role of PAS2 in resisting ER stress depended on its VLCFA synthesis domain. VLCFA contents were upregulated under ER stress, which required GAAPs. Exogenous VLCFAs partially restored the defect in UPR upregulation caused by PAS2 or GAAP mutations under chronic ER stress. These findings demonstrate that the association of PAS2 with GAAPs confers plant resistance to ER stress by regulating VLCFA synthesis and the UPR. This provides a basis for further studies on the connection between lipids and cell fate decisions under stress.

Lipid-associated macrophages for osimertinib resistance and leptomeningeal metastases in NSCLC.

Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs.

D-Limonene Inhibits Pichia kluyveri Y-11519 in Sichuan Pickles by Disrupting Metabolism.

The Pichia kluyveri, a proliferation commonly found in Sichuan pickles (SCPs), can accelerate the growth and reproduction of spoilage bacteria, causing off-odor development and decay. Although D-limonene, a common natural preservative, effectively restricts P. kluyveri, its inhibitory mechanism remains unclear. This study aimed to elucidate this molecular mechanism by investigating the impact on basic P. kluyveri metabolism. The findings revealed that D-limonene inhibited P. kluyveri growth and disrupted the transcription of the genes responsible for encoding the enzymes involved in cell wall and membrane synthesis, oxidative phosphorylation, glycolysis, and the tricarboxylic acid (TCA) cycle pathway. The results indicated that these events disrupted crucial metabolism such as cell wall and membrane integrity, adenosine triphosphate (ATP) synthesis, and reactive oxygen species (ROS) balance. These insights provided a comprehensive understanding of the inhibitory effect of D-limonene on the growth and reproduction of P. kluyveri while highlighting its potential application in the SCP industry.

High internal phase Pickering emulsions stabilized by Zein-hyaluronic acid conjugate particles and their application in active substances protection.

In recent years, active substances have been extensively applied in the fields of food, cosmetics, and pharmaceuticals. However, their preservation and transportation have posed challenges due to issues such as oxidation and photodegradation. This study proposes a method for synthesizing Zein-Hyaluronic Acid (Zein-HA) conjugate particles via the Schiff base reaction, utilizing these conjugate particles to encapsulate and protect active substances within a stable emulsion system. Compared to zein, the modified conjugate particles exhibit significantly improved dispersibility, amphiphilicity, interfacial affinity, and emulsifying properties. Consequently, these particles are capable of stabilizing high internal phase Pickering emulsions with an oil phase volume fraction of up to 80 (v/v)%, thereby enabling the carriage of a higher load of active components. Furthermore, the prepared emulsions demonstrate excellent storage stability, resistance to ionic strength (250-2000 mM NaCl), and outstanding antioxidative characteristics. Moreover, after 8 h of UV light exposure, the retention rates of the active substances (curcumin, astaxanthin, and resveratrol) exceed 60 %. Therefore, these emulsions hold substantial potential to be applied as a carrier system in the food, cosmetics, and pharmaceutical industries.

Carbon metabolism of a novel isolate from Lacticaseibacillus rhamnosus Probio-M9 derived through space mutant.

AIMS: Carbon source is a necessary nutrient for bacterial strain growth. In industrial production, the cost of using different carbon sources varies greatly. Moreover, the complex environment in space may cause metabolic a series of changes in the strain, and this method has been successfully applied in some basic research. To date, space mutagenesis is still limited number of studies, particularly in carbon metabolism of probiotics. METHODS AND RESULTS: HG-R7970-41 was isolated from bacterium suspension (Probio-M9) after space flight, which can produce capsular polysaccharide after space mutagenesis. Phenotype Microarray (PM) was used to evaluated the metabolism of HG-R7970-41 in 190 single carbon sources. RNA sequencing and total protein identification of two strains revealed their different carbon metabolism mechanisms. PM results demonstrated the metabolism of 10 carbon sources were different between Probio-M9 and HG-R7970-41. Transcriptomic and proteomic analyses revealed that this change in carbon metabolism of HG-R7970-41 mainly related to changes in phosphorylation and the glycolysis pathway. Based on the metabolic mechanism of different carbon sources and related gene cluster analysis, we found that the final metabolic activities of HG-R7970-41 and Probio-M9 were mainly regulated by PTS-specific membrane embedded permease, carbohydrate kinase and two rate-limiting enzymes (phosphofructokinase and pyruvate kinase) in the glycolysis pathway. The expanded culture test also confirmed that HG-R7970-41 had different metabolic characteristics from original strain. CONCLUSIONS: These results suggested that space environment could change carbon metabolism of Probio-M9. The new isolate (HG-R7970-41) showed a different carbon metabolism pattern from the original strain mainly by the regulation of two rate-limiting enzymes.

Digital biomarkers for precision diagnosis and monitoring in Parkinson's disease.

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder with high prevalence among the elderly, primarily manifested by progressive decline in motor function. The aging global demographic and increased life expectancy have led to a rapid surge in PD cases, imposing a significant societal burden. PD along with other neurodegenerative diseases has garnered increasing attention from the scientific community. In PD, motor symptoms are recognized when approximately 60% of dopaminergic neurons have been damaged. The irreversible feature of PD and benefits of early intervention underscore the importance of disease onset prediction and prompt diagnosis. The advent of digital health technology in recent years has elevated the role of digital biomarkers in precisely and sensitively detecting early PD clinical symptoms, evaluating treatment effectiveness, and guiding clinical medication, focusing especially on motor function, responsiveness and sleep quality assessments. This review examines prevalent digital biomarkers for PD and highlights the latest advancements.

STING is crucial for the survival of RUNX1::RUNX1T1 leukemia cells.

Even though acute myeloid leukemia (AML) patients with a RUNX1::RUNX1T1 (AE) fusion have a relatively favorable prognosis, approximately 50% relapse within 2.5 years and develop resistance to subsequent chemotherapy [1]. It is therefore imperative to identify novel therapeutic targets for AE leukemia to improve outcomes. In this study, we unveil that targeting STING effectively suppresses the growth of AE leukemia cells. Both genetic and pharmacological inhibition of STING lead to the diminish of AE leukemia cells. Importantly, in a mouse primary AE leukemia model, STING deletion significantly attenuates leukemogenesis and prolongs the animals' lifespan. Blocking the downstream inflammatory pathway of STING yields similar effects to STING inhibition in AE leukemia cells, highlighting the pivotal role of STING-dependent inflammatory responses in sustaining the survival of AE leukemia cells. Moreover, through a genome-wide CRISPR screen, we identified fatty acid desaturase 2 (FADS2) as a non-canonical factor downstream of STING inhibition that mediates cell death. Inhibition of STING releases FADS2 activity, consequently inducing the synthesis of polyunsaturated fatty acids (PUFAs) and triggering lipid peroxidation-associated cell death [2]. Taken together, these findings reveal a critical function of STING in the survival of AE-positive AML cells and suggest STING to be a potential therapeutic target for clinical intervention in these patients.

Enhancing targeted tumor treatment: A novel fuzzy logic framework for precision drug delivery strategy selection.

OBJECTIVE: This study aims to address the challenge of selecting optimal drug delivery strategies for tumor patients by introducing a novel theoretical framework. METHODS: We propose a fuzzy logic-based framework for quantitatively assessing Health States (HS) in tumor patients. This framework integrates quantified HS assessments with causality strength analyses, offering a comprehensive understanding of various drug delivery schemes' effectiveness from pharmacokinetic and pharmacodynamic perspectives. RESULTS: The efficacy of our approach is demonstrated through a series of real-world patient case studies, highlighting its potential to enhance the evaluation and selection of targeted drug delivery strategies. CONCLUSION: Our work contributes to the field by showcasing practical applications of fuzzy logic in targeted drug delivery systems (TDDs) and establishing a new benchmark for precision in drug delivery strategy selection. SIGNIFICANCE: This study has significant implications for developing personalized medical treatments, potentially revolutionizing the field with a more nuanced and scientifically rigorous method for evaluating and selecting drug delivery protocols. CONTRIBUTIONS: Development of a fuzzy logic framework for precise quantification of health states in tumor patients. Innovative integration of a causal system for comprehensively evaluating targeted drug delivery strategies.

3MT-Net: A Multi-modal Multi-task Model for Breast Cancer and Pathological Subtype Classification Based on a Multicenter Study.

Breast cancer significantly impacts women's health, with ultrasound being crucial for lesion assessment. To enhance diagnostic accuracy, computer-aided detection (CAD) systems have attracted considerable interest. This study introduces a prospective deep learning architecture called "Multi-modal Multi-task Network" (3MT-Net). 3MT-Net utilizes a combination of clinical data, B-mode, and color Doppler ultrasound. We have designed the AM-CapsNet network, specifically tailored to extract crucial tumor features from ultrasound. To combine clinical data in 3MT-Net, we have employed a cascaded cross-attention to fuse information from three distinct sources. To ensure the preservation of pertinent information during the fusion of high-dimensional and low-dimensional data, we adopt the idea of ensemble learning and design an optimization algorithm to assign weights to different modalities. Eventually, 3MT-Net performs binary classification of benign and malignant lesions as well as pathological subtype classification. In addition, we retrospectively collected data from nine medical centers. To ensure the broad applicability of the 3MT-Net, we created two separate testsets and conducted extensive experiments. Furthermore, a comparative analysis was conducted between 3MT-Net and the industrial-grade CAD product S-detect. The AUC of 3MT-Net surpasses S-Detect by 1.4% to 3.8%.

Post-transfer adaptation of HGT-acquired genes and contribution to guanine metabolic diversification in land plants.

Horizontal gene transfer (HGT) is a major driving force in the evolution of prokaryotic and eukaryotic genomes. Despite recent advances in distribution and ecological importance, the extensive pattern, especially in seed plants, and post-transfer adaptation of HGT-acquired genes in land plants remain elusive. We systematically identified 1150 foreign genes in 522 land plant genomes that were likely acquired via at least 322 distinct transfers from nonplant donors and confirmed that recent HGT events were unevenly distributed between seedless and seed plants. HGT-acquired genes evolved to be more similar to native genes in terms of average intron length due to intron gains, and HGT-acquired genes containing introns exhibited higher expression levels than those lacking introns, suggesting that intron gains may be involved in the post-transfer adaptation of HGT in land plants. Functional validation of bacteria-derived gene GuaD in mosses and gymnosperms revealed that the invasion of foreign genes introduced a novel bypass of guanine degradation and resulted in the loss of native pathway genes in some gymnosperms, eventually shaping three major types of guanine metabolism in land plants. We conclude that HGT has played a critical role in land plant evolution.

The dual role of microglia in intracerebral hemorrhage.

Intracerebral hemorrhage has the characteristics of high morbidity, disability and mortality, which has caused a heavy burden to families and society. Microglia are resident immune cells in the central nervous system, and their activation plays a dual role in tissue damage after intracerebral hemorrhage. The damage in cerebral hemorrhage is embodied in the following aspects: releasing inflammatory factors and inflammatory mediators, triggering programmed cell death, producing glutamate induced excitotoxicity, and destroying blood-brain barrier; The protective effect is reflected in the phagocytosis and clearance of harmful substances by microglia, and the secretion of anti-inflammatory and neurotrophic factors. This article summarizes the function of microglia and its dual regulatory mechanism in intracerebral hemorrhage. In the future, drugs, acupuncture and other clinical treatments can be used to intervene in the activation state of microglia, so as to reduce the harm of microglia.