Preferential adsorption of medium molecular weight proteins in extracellular polymeric substance alleviates toxicity of small-sized microplastics to Skeletonema costatum.

Extracellular polymeric substances (EPS) secreted by organisms tend to encapsulate microplastics (MPs), forming an EPS-corona that affects the fate of MPs in marine ecosystems. However, the impact of the EPS-corona on the biotoxicity of MPs to marine organisms remains poorly understood. Herein, the effect of the EPS-corona on the toxicity of polystyrene (PS) MPs of different sizes (0.1 and 1 µm) to Skeletonema costatum (S. costatum) was investigated. The preferential adsorption of medium molecule weight (∼55 kDa) proteins onto PS MPs mainly contributed to the EPS-corona formation, decreasing the surface charge negativity of small-sized PS MPs (0.1 µm) by 72.4 %. Nitrogen (N) and oxygen (O) moieties in polysaccharides and proteins were identified as the preferential adsorption sites in the EPS-PS MPs interaction. Density functional theory (DFT) calculations confirmed the nuclear magnetic resonance spectroscopy (NMR) results, revealing that the binding mode between EPS and PS MPs was mainly hydrogen bonding. In addition, EPS-corona increased the cell density of S. costatum by 35.5-36.0 % when exposed to small-sized PS MPs (0.1 µm, 25-50 mg/L). These findings provide new insights into how EPS-corona affects the environmental fate and ecological risks associated with micro- and nano-sized plastics in marine ecosystems.

Neurotoxicity of fine and ultrafine particulate matter: A comprehensive review using a toxicity pathway-oriented adverse outcome pathway framework.

Fine particulate matter (PM2.5) can cause brain damage and diseases. Of note, ultrafine particles (UFPs) with an aerodynamic diameter less than or equal to 100 nm are a growing concern. Evidence has suggested toxic effects of PM2.5 and UFPs on the brain, and links to neurological diseases. However, the underlying mechanism has not yet been fully illustrated due to the variety of the study models, and different endpoints, etc. The adverse outcome pathway (AOP) framework is a pathway-based approach which could systematize mechanistic knowledge to assist health risk assessment of pollutants. Here, we constructed AOPs by collecting molecular mechanisms in PM-induced neurotoxicity assessments. We chose particulate matter (PM) as a stressor in the Comparative Toxicogenomics Database (CTD) and identified the critical toxicity pathways based on Ingenuity Pathway Analysis (IPA). We found 65 studies investigating the potential mechanisms linking PM2.5 and UFPs to neurotoxicity, which contained 2, 675 genes in all. IPA analysis showed that neuroinflammation signaling and glucocorticoid receptor signaling were the common toxicity pathways. The upstream regulator analysis (URA) of PM2.5 and UFPs demonstrated that the neuroinflammation signaling was the most initially triggered upstream event. Therefore, neuroinflammation was recognized as the MIE. Strikingly, there is a clear sequence of activation of downstream signaling pathways with UFPs, but not with PM2.5. Moreover, we found that inflammation response and homeostasis imbalance were key cellular events in PM2.5 and emphasized lipid metabolism and mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in UFPs. Previous AOPs, which only focused on phenotypic changes in neurotoxicity upon PM exposure, we for the first time propose AOP framework in which PM2.5 and UFPs may activate pathway cascade reactions, resulting in adverse outcomes associated with neurotoxicity. Our toxicity pathway-based approach not advanced the risk assessment for PM-induced neurotoxicity but shine a spotlight on constructing AOP frameworks for new chemicals.

Exosome for mRNA delivery: strategies and therapeutic applications.

Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications.

Emergence of mcr-4.3 genes in a novel Shewanella specie isolated from the Arctic environment.

Mobile colistin resistance (mcr) genes are pivotal contributors to last-line of antimicrobial resistance in human infections. Shewanella, historically recognized as a natural environmental bacterium with metal reduction capabilities, recently has been observed in clinical settings. However, limited knowledge has been explored on genetic differences between strains from non-clinical and clinical strains. In this study, we conducted the whole genome sequencing on six Arctic strains, illustrated the phylogenetic relationships on published 393 Shewanella strains that categorized the genus into four lineages (L1 to L4). Over 86.4% of clinical strain group (CG) strains belonged to L1 and L4, carrying mcr-4 genes and a complete metal-reduction pathways gene cluster. Remarkably, a novel Arctic Shewanella strain in L3, exhibits similar genetic characteristics with CG strains that carried both mcr-4 genes and a complete metal reduction pathway gene cluster. It raised concerns about the transmission ability from environment to clinic setting causing in the potential infections, and emphasized the need for monitoring the emerging strains with human infections.

Revealing Brownish Mycena Diversity in China: New Discoveries and Taxonomic Insights.

Within the genus Mycena, species exhibiting brownish basidiomata present considerable challenges in identification due to similar coloration. This study underscores the significance of pileipellis types and cheilocystidia characteristics as critical in delimiting brownish Mycena species. To clarify the principal taxonomic characters and their utility in distinguishing between brownish Mycena species, a morphological taxonomy and phylogenetic analysis were performed. Five new species from China were introduced and characterized through a comprehensive morphological anatomy and phylogenetic substantiation: M. campanulatihemisphaerica sp. nov., M. digitifurcata sp. nov., M. kunyuensis sp. nov., M. limitis sp. nov., and M. oryzifluens sp. nov. Discussions of these taxa are supplemented with morphological illustrations. The phylogenetic relationships were inferred using Bayesian Inference and Maximum Likelihood methods based on sequences from the internal transcribed spacer and the large subunit regions of nuclear ribosomal RNA. With the addition of these five new species, the worldwide count of brownish Mycena increases to 94, and a key to the 29 known species of brownish Mycena from China is presented.

Mechanistic insights into 125I seed implantation therapy for Cholangiocarcinoma: focus on ROS-Mediated apoptosis and the role of GPX2.

OBJECTIVES: Cholangiocarcinoma (CCA) is a rare tumor with a poor prognosis and poses significant therapeutic challenges. Herein, we investigated the mechanism of efficacy of 125I seed implantation therapy in CCA, focusing on the induction of reactive oxygen species (ROS)-mediated apoptosis and the involvement of glutathione peroxidase 2 (GPX2). MATERIALS AND METHODS: Human cholangiocarcinoma cell lines QBC939 and RBE were purchased for in vitro studies. In vivo studies were performed using a rabbit VX2 CCA model. Apoptosis and proliferation were detected by TUNEL staining and clone formation, respectively. ROS generation was detected by dihydroethidium staining. Histological evaluation was performed by hematoxylin and eosin staining. Protein expression was determined by Western blotting and immunohistochemistry. RESULTS: Our results demonstrate that 125I seeds effectively inhibited tumor growth in the rabbit VX2 tumor model and promoted the apoptosis of CCA cells in vitro in a dose-dependent manner. Molecular analyses indicate a marked increase in reactive oxygen species (ROS) levels following treatment with 125I seeds, suggesting the involvement of ROS-mediated apoptosis in the therapeutic mechanism. Furthermore, the downregulation of glutathione peroxidase 2 (GPX2) was observed, indicating its potential role in modulating ROS-mediated apoptosis in CCA. CONCLUSION: 125I seed implantation therapy exerts therapeutic effects on CCA by inducing ROS-mediated apoptosis. The downregulation of GPX2 may contribute to enhanced ROS accumulation and apoptotic cell death. These findings provide mechanistic insights into the therapeutic potential of 125I seed implantation for CCA and highlight ROS-mediated apoptosis and GPX2 regulation as promising targets for further investigation and therapeutic intervention in this malignancy.

An injectable magnesium-coordinated phosphate chitosan-based hydrogel loaded with vancomycin for antibacterial and osteogenesis in the treatment of osteomyelitis.

Microbial infections of bones, particularly after joint replacement surgery, are a common occurrence in clinical settings and often lead to osteomyelitis (OM). Unfortunately, current treatment approaches for OM are not satisfactory. To address this issue, this study focuses on the development and evaluation of an injectable magnesium oxide (MgO) nanoparticle (NP)-coordinated phosphocreatine-grafted chitosan hydrogel (CMPMg-VCM) loaded with varying amounts of vancomycin (VCM) for the treatment of OM. The results demonstrate that the loading of VCM does not affect the formation of the injectable hydrogel, and the MgO-incorporated hydrogel exhibits anti-swelling properties. The release of VCM from the hydrogel effectively kills S.aureus bacteria, with CMPMg-VCM (50) showing the highest antibacterial activity even after prolonged immersion in PBS solution for 12 days. Importantly, all the hydrogels are non-toxic to MC3T3-E1 cells and promote osteogenic differentiation through the early secretion of alkaline phosphatase and calcium nodule formation. Furthermore, in vivo experiments using a rat OM model reveal that the CMPMg-VCM hydrogel effectively kills and inhibits bacterial growth, while also protecting the infected bone from osteolysis. These beneficial properties are attributed to the burst release of VCM, which disrupts bacterial biofilm, as well as the release of Mg ions and hydroxyl by the degradation of MgO NPs, which inhibits bacterial growth and prevents osteolysis. Overall, the CMPMg-VCM hydrogel exhibits promising potential for the treatment of microbial bone infections.

LDLR c.89_92dup: a novel frameshift variation in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a common inherited metabolic disease that causes premature atherosclerosis, cardiovascular disease, and even death at a young age. Approximately 95% of FH-causing genetic variants that have been identified are in the LDLR gene. However, only 10% of the FH population worldwide has been diagnosed and adequately treated, due to the existence of numerous unidentified variants, uncertainties in the pathogenicity scoring of many variants, and a substantial number of individuals lacking access to genetic testing. OBJECTIVE: The aim of this study was to identify a novel variant in the LDLR gene that causes FH in a Chinese family, thereby expanding the spectrum of FH-causing variants. METHODS: Patients were recruited from Beijing Anzhen Hospital, Capital Medical University. FH diagnosis was made according to the Dutch Lipid Clinical Network (DLCN) criteria. Whole-exome sequencing (WES) was conducted to identify the FH-causing variant in the proband, and amplicon sequencing was used to verify the variant in his family members. RESULTS: A three-generation Chinese family was recruited, and two FH patients were clinically diagnosed, both without known FH-causing variants. These two FH patients and another possible patient carried a novel variant, NC_000019.9(NM_000527.5):c.89_92dup (NP_000518.1:p.Phe32Argfs*21), in the ligand-binding domain of the low-density lipoprotein (LDL) receptor that led to a frameshift. The FH adults in the family showed severe clinical symptoms and statin therapy resistance. CONCLUSION: This study identified a novel pathogenic LDLR variant, c.89_92dup, associated with severe FH clinical manifestations and statin therapy resistance.

Palladium-Catalyzed O-Glycosylation through π-π Interactions.

A stereodivergent synthesis of ß- and α-O-glycosides using 3-O-quinaldoyl glucals was developed by palladium catalysis at 60 and 110 °C respectively. Various alcohols, monosaccharides, and amino acid were glycosylated to form ß- and α- products in good yields with high stereoselectivity. Mechanistic studies indicated no classic Pd-N (quinoline) coordination, but π-π stacking interactions promoted the anomeric stereodiversity. The practicality was demonstrated by glycosylating natural products/drugs and synthesizing a complex tetrasaccharide.

Facile synthesis of a carbon supported lithium iron phosphate nanocomposite cathode material from metal-organic framework for lithium-ion batteries.

Lithium iron phosphate (LiFePO4, LFP) has become one of the most widely used cathode materials for lithium-ion batteries. The inferior lithium-ion diffusion rate of LFP crystals always incurs poor rate capability and unsatisfactory low-temperature performances. To meet with the requirements from the ever-growing market, it is of great significance to synthesize carbon supported LFP nanocomposite (LFP/C) cathode materials using cost effective and environmentally friendly methods. In this work, an LFP/C cathode material is straightforwardly prepared from a metal-organic framework (MOF) precursor ferric gallate (Fe-GA) using its self-template effect. The Fe-GA precursor is firstly fabricated from the redox coprecipitation reaction between Fe foils and gallic acid (GA) molecules in mild aqueous phase. Then the Fe-GA is directly converted to the LFP/C sample after a following solid-state reaction. In half-cells, the LFP/C composite exhibits a reversible capacity of 109.7 mAh·g-1 after 500 cycles under the current rate of 100 mA·g-1 at 25 °C as well as good rate capabilities. In the LFP/C//graphite full-cells, the LFP/C composite can deliver a reversible capacity of 71.4 mAh·g-1 after 50 cycles in the same condition as the half-cells. The electrochemical performances of the LFP/C cathode in half-cells at lower temperature of -10 °C are also examined. Particularly, the evolution of samples has been explored and the lithium-ion storage mechanism of the LFP/C cathode has been unveiled. The sample synthesis protocol is straightforward, eco-friendly and atomic efficient, which can be considered to have good potential for scaling-up.

Inhibition of ER stress using tauroursodeoxycholic acid rescues obesity-evoked cardiac remodeling and contractile anomalies through regulation of ferroptosis.

Interrupted ER homeostasis contributes to the etiology of obesity cardiomyopathy although it remains elusive how ER stress evokes cardiac anomalies in obesity. Our study evaluated the impact of ER stress inhibition on cardiac anomalies in obesity. Lean and ob/ob obese mice received chemical ER chaperone tauroursodeoxycholic acid (TUDCA, 50 mg/kg/d, p.o.) for 35 days prior to evaluation of glucose sensitivity, echocardiographic, myocardial geometric, cardiomyocyte mechanical and subcellular Ca2+ property, mitochondrial integrity, oxidative stress, apoptosis, and ferroptosis. Intracellular Ca2+ governing domains including sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) were monitored by45Ca2+uptake and immunoblotting. Our results noted that TUDCA alleviated myocardial remodeling (fibrosis, hypertrophy, enlarged LVESD), echocardiographic anomalies (compromised fractional shortening and ejection fraction), cardiomyocyte contractile dysfunction (amplitude and velocity of cell shortening, relengthening time) and intracellular Ca2+ anomalies (compromised subcellular Ca2+ release, clearance and SERCA function), mitochondrial damage (collapsed membrane potential, downregulated mitochondrial elements and ultrastructural alteration), ER stress (GRP78, eIF2α and ATF4), oxidative stress, apoptosis and ferroptosis [downregulated SLC7A11, GPx4 and upregulated transferrin receptor (TFRC)] without affecting global glucose sensitivity and serum Fe2+ in obese mice. Obesity-evoked change in HSP90, phospholamban and Na+-Ca2+ exchanger was spared by the chemical ER chaperone. Moreover, in vitro results noted that TUDCA, PERK inhibitor GSK2606414, TFRC neutralizing antibody and ferroptosis inhibitor LIP1 mitigated palmitic acid-elicited changes in lipid peroxidation and mechanical function. Our findings favored a role for ferroptosis in obesity cardiomyopathy downstream of ER stress.

Deep learning promoted target volumes delineation of total marrow and total lymphoid irradiation for accelerated radiotherapy: A multi-institutional study.

BACKGROUND AND PURPOSE: One of the current roadblocks to the widespread use of Total Marrow Irradiation (TMI) and Total Marrow and Lymphoid Irradiation (TMLI) is the challenging difficulties in tumor target contouring workflow. This study aims to develop a hybrid neural network model that promotes accurate, automatic, and rapid segmentation of multi-class clinical target volumes. MATERIALS AND METHODS: Patients who underwent TMI and TMLI from January 2018 to May 2022 were included. Two independent oncologists manually contoured eight target volumes for patients on CT images. A novel Dual-Encoder Alignment Network (DEA-Net) was developed and trained using 46 patients from one internal institution and independently evaluated on a total of 39 internal and external patients. Performance was evaluated on accuracy metrics and delineation time. RESULTS: The DEA-Net achieved a mean dice similarity coefficient of 90.1 % ± 1.8 % for internal testing dataset (23 patients) and 91.1 % ± 2.5 % for external testing dataset (16 patients). The 95 % Hausdorff distance and average symmetric surface distance were 2.04 ± 0.62 mm and 0.57 ± 0.11 mm for internal testing dataset, and 2.17 ± 0.68 mm, and 0.57 ± 0.20 mm for external testing dataset, respectively, outperforming most of existing state-of-the-art methods. In addition, the automatic segmentation workflow reduced delineation time by 98 % compared to the conventional manual contouring process (mean 173 ± 29 s vs. 12168 ± 1690 s; P < 0.001). Ablation study validate the effectiveness of hybrid structures. CONCLUSION: The proposed deep learning framework achieved comparable or superior target volume delineation accuracy, significantly accelerating the radiotherapy planning process.

ROS-induced imbalance of the miR-34a-5p/SIRT1/p53 axis triggers chronic chondrocyte injury and inflammation.

Osteoarthritis is a chronic degenerative disease based on the degeneration and loss of articular cartilage. Inflammation and aging play an important role in the destruction of the extracellular matrix, in which microRNA (miRNA) is a key point, such as miRNA-34a-5p. Upregulation of miRNA-34a-5p was previously reported in a rat OA model, and its inhibition significantly suppressed interleukin (IL)-1ß-induced apoptosis in rat chondrocytes. However, Oxidative stress caused by reactive oxygen species (ROS) can exacerbate the progression of miRNA regulated OA by mediating inflammatory processes. Thus, oxidative stress effects induced via tert-butyl hydroperoxide (tBHP) in human chondrocytes were assessed in the current research by evaluating mitochondrial ROS production, mitochondrial cyclooxygenase (COX) activity, and cell apoptosis. We also analyzed the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). Additionally, inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-24, which contribute to OA development, were detected by enzyme-linked immunosorbent assay (ELISA). The results of this study indicated that miR-34a-5p/silent information regulator 1 (SIRT1)/p53 axis was involved in the ROS-induced injury of human chondrocytes. Moreover, dual-luciferase assay revealed that SIRT1 expression was directly regulated by miR-34a-5p, indicating the presence of a positive feedback loop in the miR-34a-5p/SIRT1/p53 axis that plays an important role in cell survival. However, ROS disrupted the miR-34a-5p/SIRT1/p53 axis, leading to the development of OA, and articular injection of SIRT1 agonist, SRT1720, in a rat model of OA effectively ameliorated OA progression in a dose-dependent manner. Our study confirms that miRNA-34a-5p could participate in oxidative stress responses caused by ROS and further regulate the inflammatory process via the SIRT1/p53 signaling axis, ultimately affecting the onset of OA, thus providing a new treatment strategy for clinical treatment of OA.

Time-Series MR Images Identifying Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Using a Deep Learning Approach.

BACKGROUND: Pathological complete response (pCR) is an essential criterion for adjusting follow-up treatment plans for patients with breast cancer (BC). The value of the visual geometry group and long short-term memory (VGG-LSTM) network using time-series dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for pCR identification in BC is unclear. PURPOSE: To identify pCR to neoadjuvant chemotherapy (NAC) using deep learning (DL) models based on the VGG-LSTM network. STUDY TYPE: Retrospective. POPULATION: Center A: 235 patients (47.7 ± 10.0 years) were divided 7:3 into training (n = 164) and validation set (n = 71). Center B: 150 patients (48.5 ± 10.4 years) were used as test set. FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted spin-echo sequence imaging, and gradient echo DCE sequence imaging. ASSESSMENT: Patients underwent MRI examinations at three sequential time points: pretreatment, after three cycles of treatment, and prior to surgery, with tumor regions of interest manually delineated. Histopathology was the gold standard. We used VGG-LSTM network to establish seven DL models using time-series DCE-MR images: pre-NAC images (t0 model), early NAC images (t1 model), post-NAC images (t2 model), pre-NAC and early NAC images (t0 + t1 model), pre-NAC and post-NAC images (t0 + t2 model), pre-NAC, early NAC and post-NAC images (t0 + t1 + t2 model), and the optimal model combined with the clinical features and imaging features (combined model). The models were trained and optimized on the training and validation set, and tested on the test set. STATISTICAL TESTS: The DeLong, Student's t-test, Mann-Whitney U, Chi-squared, Fisher's exact, Hosmer-Lemeshow tests, decision curve analysis, and receiver operating characteristics analysis were performed. P < 0.05 was considered significant. RESULTS: Compared with the other six models, the combined model achieved the best performance in the test set yielding an AUC of 0.927. DATA CONCLUSION: The combined model that used time-series DCE-MR images, clinical features and imaging features shows promise for identifying pCR in BC. TECHNICAL EFFICACY: Stage 4.

Diagnostic value of contrast-enhanced ultrasound in judging the survival of graft after heteroautoplasty for secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is one of the common complications of end-stage renal disease-uremia, and is mainly manifested as parathyroid hyperplasia and abnormal secretion of parathyroid hormone (PTH). OBJECTIVE: To investigate the value and advantages of contrast-enhanced ultrasound (CEUS) in evaluating the survival of autografts after parathyroidectomy + parathyroid autotransplantation. METHODS: In this study, 125 patients with renal failure due to polycystic kidney disease, chronic nephritis, diabetic nephropathy, lupus nephritis, and atherosclerotic nephropathy were enrolled as the participants and each of them had 4 secondary hyperactive parathyroid glands and underwent parathyroid autotransplantation. One parathyroid gland was taken from each patient and equally divided into 4 parts and placed in the subcutaneous fat of one forearm for transplantation. CEUS was performed 14 days after the transplantation to observe the micro blood supply of the graft and assess the survival and secretory function of the transplanted parathyroid. The grafts were divided into the partial survival group and the total survival group based on the enhancement characteristics. The survival of the grafts was determined by comparing the parathyroid hormone level in bilateral elbow cephalic veins 1 month after surgery. RESULTS: Among the 125 patients, 112 had linear or punctate enhancement of 2-4 parathyroid glands 14 days after surgery, and 13 patients had linear or punctate enhancement of 0-1 parathyroid gland. There were statistically significant differences in the perfusion pattern, enhancement uniformity, and parathyroid hormone levels in the cephalic veins at the elbow on both the graft and non-graft sides among all groups (P< 0.05). CONCLUSION: Compared to the detection of the difference in the parathyroid hormone level in the cephalic vein of bilateral elbows 1 month after surgery, CEUS can reflect the parathyroid survival after transplantation more quickly and accurately 2 weeks later, and provide a more rapid and agile non-invasive clinical diagnosis method.

An integrated LC-MS/MS platform for noninvasive urinary nucleus acid adductomics: A pilot study for tobacco exposure.

Tobacco smoke exposure significantly increases the level of global nucleoside damage. To evaluate all aspects of nucleic acid (NA) modifications, NA adductomics analyzes DNA, RNA and nucleobase adducts and provides comprehensive data. Liquid chromatography-tandem triple quadrupole mass spectrometry (LC-QQQ-MS/MS) and LC-Zeno-TOF-MS/MS were employed to screen for DNA, RNA and nucleobase adducts, as part of the analytical platform that was designed to combine high sensitivity and high resolution detection. We identified and distinguished urine nucleoside adducts via precursor ion and neutral loss scanning. A total of 245 potential adducts were detected, of which 28 were known adducts. The smoking group had significantly higher concentrations of nucleoside adducts in rat urine than the control group, based on MRM scanning, which was then used to perform relative quantitative analysis of these adducts. Urine nucleoside adducts were further confirmed using LC-Zeno-TOF-MS/MS. This highlights the potential of untargeted detection methods to provide comprehensive data on both known and unknown adducts. These approaches can be used to investigate the interactions among oxidative and alkylation stresses, and epigenetic modifications caused by exposure to tobacco smoke.

Aridity affects soil organic carbon concentration and chemical stability by different forest types and soil processes across Chinese natural forests.

Forest soils play a critical role in carbon (C) reservoirs and climate change mitigation globally. Exploring the driving factors of soil organic carbon (SOC) concentration and stability in forests on a large spatial scale can help us evaluate the role of forest soils in regulating C sequestration. Based on SOC quantification and solid-state 13C nuclear magnetic resonance spectroscopy, we investigated the SOC concentration and SOC chemical stability (indicated by alkyl-to-O-alkyl ratio and hydrophobic-to-hydrophilic ratio) in top 0-5 and 5-10 cm soils from 65 Chinese natural forest sites and explored their driving factors. Results showed that SOC concentration in 0-5 cm soils were highest in mixed forests but SOC chemical stability in 0-5 cm soils were highest in coniferous forests, while SOC concentration and chemical stability in 5-10 cm soil layers did not differ across forest types. SOC concentration in 0-5 cm was directly related to soil pH and soil bacterial diversity. Structural equation models showed that aridity indirectly affected SOC concentration in 0-5 cm by directly affecting soil pH. While SOC chemical stability in 0-5 cm soils was higher with increased aridity. According to the correlations, the potential mechanisms could be attributed to higher proportion of coniferous forests in more arid forest sites, lower relative abundance of O-alkyl C, higher MgO and CaO contents, and higher bacterial diversity in soils from more arid forest sites. Our study reveals the important role of aridity in mediating SOC concentration and chemical stability in top 0-5 cm soils in Chinese natural forests on a large-scale field investigation. These results will help us better understand the different mechanisms underlying SOC concentration and stability in forests and assess the feedback of forest SOC to future climate change.

Negative expression of CD117 predicted inferior OS and PFS in acute promyelocytic leukemia.

INTRODUCTION: In recent years, the correlation between CD117 antigen and the prognosis of hematological malignancies has been demonstrated. However, there is limited literature on the clinical significance of CD117 antigen in acute promyelocytic leukemia (APL). The aim of this study was to retrospectively analyze the clinical features and prognostic significance of CD117 in APL. METHODS: In this study, we retrospectively investigated the clinicopathological characteristics, outcome, and prognostic impact of negative CD117 expression (CD117-) in 169 APL patients treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) containing regimen. RESULTS: The median follow-up period was 63.0 months. CD117- was detected in 13 APL patients (7.7%). No significant differences were found in baseline characteristics between CD117+ and CD117- subgroups. However, compared to CD117+ APL, the incidence of early death (ED) was significantly higher in CD117- APL (p = 0.023). By multivariate analysis, CD117- was an independent adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) (p = 0.022 and p = 0.014, respectively). CONCLUSIONS: To sum up, CD117- is associated with greater risk of ED and has the statistical power to predict inferior OS and PFS, this marker may be considered to build prognostic scores for risk-adapted therapeutic strategies in APL management.

General In Situ Engineering of Carbon-Based Materials on Carbon Fiber for In Vivo Neurochemical Sensing.

Developing real-time, dynamic, and in situ analytical methods with high spatial and temporal resolutions is crucial for exploring biochemical processes in the brain. Although in vivo electrochemical methods based on carbon fiber (CF) microelectrodes are effective in monitoring neurochemical dynamics during physiological and pathological processes, complex post modification hinders large-scale productions and widespread neuroscience applications. Herein, we develop a general strategy for the in situ engineering of carbon-based materials to mass-produce functional CFs by introducing polydopamine to anchor zeolitic imidazolate frameworks as precursors, followed by one-step pyrolysis. This strategy demonstrates exceptional universality and design flexibility, overcoming complex post-modification procedures and avoiding the delamination of the modification layer. This simplifies the fabrication and integration of functional CF-based microelectrodes. Moreover, we design highly stable and selective H+, O2, and ascorbate microsensors and monitor the influence of CO2 exposure on the O2 content of the cerebral tissue during physiological and ischemia-reperfusion pathological processes.

Palm Kernel Cake Extracts Obtained from the Combination of Bacterial Fermentation and Enzymic Hydrolysis Promote Swine Small Intestine IPEC-J2 Cell Proliferation and Alleviate LPS-Induced Inflammation In Vitro.

Co-fermentation with bacteria and enzymes can reduce sugar content in palm kernel cake (PKC); however, the chemical changes and their effects on cell functionality are unclear. This study investigated the active components in pre-treated PKC extracts and their effects on pig small intestine IPEC-J2 cell proliferation and LPS-induced inflammation. The extracts contained 60.75% sugar, 36.80% mannose, 1.75% polyphenols and 0.59% flavone, as determined by chemical analyses, suggesting that the extracts were palm kernel cake oligosaccharides (PKCOS). Then, we found that 1000 µg/mL PKCOS counteracted the decrease in cell viability (CCK8 kit) caused by LPS induction by 5 µg/mL LPS (p < 0.05). Mechanistic studies conducted by RNA-seq and qPCR analyses suggested PKCOS promoted cell proliferation through the upregulation of TNF-α, PI3KAP1, MAP3K5 and Fos in the PI3K/MAPK signalling pathway; alleviated inflammation caused by LPS via the downregulation of the target genes Casp3 and TNF-α in association with apoptosis; and regulated the expression of the antioxidant genes SOD1, SOD2 and GPX4 to exert positive antioxidant effects (p < 0.05). Furthermore, PKCOS upregulated SLC5A1 (encoding SLGT1), HK and MPI in the glycolytic pathway (p < 0.05), suggesting cell survival. In summary, PKCOS has positive effects on promoting swine intestine cell proliferation against inflammation.