Chemical characterisation of essential oil from Sambucus williamsii Hance leaves and its hepatoprotective effects.

This study is the first to examine the effect of leaves of Sambucus williamsii Hance essential oil on acute liver injury. According to gas chromatography-mass spectrometry analysis, the major constituents of S. williamsii essential oil (SEO)were (S)-falcarinol (62.66%), 17-pentatriacontene (7.78%) and tetrapentacontane (8.64%). Mice were pre-treated with SEO for 6 days followed by inducing liver injury with CCl4. The results indicated that SEO protected the liver against CCl4-induced injuries. Elevated levels of alanine-aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP) in serum were significantly reduced on SEO pre-treatment. SEO pre-treatment significantly inhibited the oxidative stress and inflammation. Furthermore, toll-like receptor-4 (TLR4)/nuclear factor kappa-B (NF-κB) signalling pathways were significantly modulated by SEO in the liver tissue. The findings demonstrate that the essential oil of S. williamsii has enhancing the resistance to CCl4-induced liver injury.

[Effects of Pesticides Use on Pesticides Residues and Its Environmental Risk Assessment in Xingkai Lake（China）].

Xingkai Lake, located in Heilongjiang Province, is an important fishery and agricultural base and is seriously polluted by agricultural non-point sources. To clarify the residual status of many pesticides in the surface water of Xingkai Lake, 27 types of pesticides, herbicides, and their degradation products were analyzed in rice paddy, drainage, and surface water around Xingkai Lake (China) during the rice heading and maturity periods. The results showed that all 27 types of pesticides, herbicides, and their degradation products were detected during the rice heading period, and the total concentration ranged from 247.97 to 6 094.49 ng·L-1. Additionally, 25 species were detected during the rice maturity period, and the total concentration ranged from 485.36 to 796.23 ng·L-1. In comparison, more pesticides, herbicides, and derived degradation products were detected during the heading period, and their total concentration was higher as well. During the rice heading period, atrazine, simetryn, and paclobutrazol were the main detected pesticides, atrazine and isoprothiolane were the main pesticides detected during the maturity period. The distribution characteristics of pesticides and herbicides in the surface water around Xingkai Lake (China) was similar to that in drainage, so they were probably imported from the drainage and rice paddy. The average risk quotient (RQ) values of atrazine, simetryn, prometryn, butachlor, isoprothiolane, and oxadiazon were higher than 0.1 in drainage and Xingkai Lake (China), which showed a potential risk to aquatic organisms.

The ARPKD Protein DZIP1L Regulates Ciliary Protein Entry by Modulating the Architecture and Function of Ciliary Transition Fibers.

Serving as the cell's sensory antennae, primary cilia are linked to numerous human genetic diseases when they malfunction. DZIP1L, identified as one of the genetic causes of human autosomal recessive polycystic kidney disease (ARPKD), is an evolutionarily conserved ciliary basal body protein. Although it has been reported that DZIP1L is involved in the ciliary entry of PKD proteins, the underlying mechanism remains elusive. Here, an uncharacterized role of DZIP1L is reported in modulating the architecture and function of transition fibers (TFs), striking ciliary base structures essential for selective cilia gating. Using C. elegans as a model, C01G5.7 (hereafter termed DZIP-1) is identified as the sole homolog of DZIP1L, which specifically localizes to TFs. While DZIP-1 or ANKR-26 (the ortholog of ANKRD26) deficiency shows subtle impact on TFs, co-depletion of DZIP-1 and ANKR-26 disrupts TF assembly and cilia gating for soluble and membrane proteins, including the ortholog of ADPKD protein polycystin-2. Notably, the synergistic role for DZIP1L and ANKRD26 in the formation and function of TFs is highly conserved in mammalian cilia. Hence, the findings illuminate an evolutionarily conserved role of DZIP1L in TFs architecture and function, highlighting TFs as a vital part of the ciliary gate implicated in ciliopathies ARPKD.

Epigenetic regulation of H3K27me3 in laying hens with fatty liver hemorrhagic syndrome induced by high-energy and low-protein diets.

BACKGROUND: Fatty liver hemorrhagic syndrome (FLHS) in the modern poultry industry is primarily caused by nutrition. Despite encouraging progress on FLHS, the mechanism through which nutrition influences susceptibility to FLHS is still lacking in terms of epigenetics. RESULTS: In this study, we analyzed the genome-wide patterns of trimethylated lysine residue 27 of histone H3 (H3K27me3) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq), and examined its association with transcriptomes in healthy and FLHS hens. The study results indicated that H3K27me3 levels were increased in the FLHS hens on a genome-wide scale. Additionally, H3K27me3 was found to occupy the entire gene and the distant intergenic region, which may function as silencer-like regulatory elements. The analysis of transcription factor (TF) motifs in hypermethylated peaks has demonstrated that 23 TFs are involved in the regulation of liver metabolism and development. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were enriched in fatty acid metabolism, amino acid, and carbohydrate metabolism. The hub gene identified from PPI network is fatty acid synthase (FASN). Combined ChIP-seq and transcriptome analysis revealed that the increased H3K27me3 and down-regulated genes have significant enrichment in the ECM-receptor interaction, tight junction, cell adhesion molecules, adherens junction, and TGF-beta signaling pathways. CONCLUSIONS: Overall, the trimethylation modification of H3K27 has been shown to have significant regulatory function in FLHS, mediating the expression of crucial genes associated with the ECM-receptor interaction pathway. This highlights the epigenetic mechanisms of H3K27me3 and provides insights into exploring core regulatory targets and nutritional regulation strategies in FLHS.

Diagnostic utility of immunohistochemistry in detection of NPM1 mutations in acute myeloid leukemia with a patchy distribution.

Nucleophosmin 1 (NPM1) mutations occur in approximately one-third cases of adult de novo acute myeloid leukemia (AML). Identification of NPM1 mutations is important for classification, risk stratification, tailored therapy, and monitoring minimal residual disease. Mutational analysis is widely used for detecting NPM1 mutations. Immunochemistry assessing abnormal cytoplasmic localization of NPM1 protein has been used as a surrogate marker for NPM1 mutations. We present a case of AML with mutated NPM1 that was missed by sequencing analysis but detected by immunohistochemistry. This case highlights the value of immunohistochemistry in identifying NPM1 mutations in a subset of AML cases.

Neural substrates of the interaction between effort-expenditure reward decision-making and outcome anticipation.

OBJECTIVE: Reward anticipation is important for future decision-making, possibly due to re-evaluation of prior decisions. However, the exact relationship between reward anticipation and prior effort-expenditure decision-making, and its neural substrates are unknown. METHOD: Thirty-three healthy participants underwent fMRI scanning while performing the Effort-based Pleasure Experience Task (E-pet). Participants were required to make effort-expenditure decisions and anticipate the reward. RESULTS: We found that stronger anticipatory activation at the posterior cingulate cortex was correlated with slower reaction time while making decisions with a high-probability of reward. Moreover, the substantia nigra was significantly activated in the prior decision-making phase, and involved in reward-anticipation in view of its strengthened functional connectivity with the mammillary body and the putamen in trial conditions with a high probability of reward. CONCLUSIONS: These findings support the role of reward anticipation in re-evaluating decisions based on the brain-behaviour correlation. Moreover, the study revealed the neural interaction between reward anticipation and decision-making.

Regioselective super-assembly of Prussian blue analogue.

The construction of high-asymmetrical structures demonstrates significant potential in improving the functionality and distinctness of nanomaterials, but remains a considerable challenge. Herein, we develop a one-pot method to fabricate regioselective super-assembly of Prussian blue analogue (PBA) -- a PBA anisotropic structure (PBA-AS) decorated with epitaxial modules--using a step-by-step epitaxial growth on a rapidly self-assembled cubic substrate guided by thiocyanuric acid (TCA) molecules. The epitaxial growth units manifest as diverse geometric shapes, which are predominantly concentrated on the {100}, {111}, or {100}+{111} crystal plane of the cubic substrate. The crystal plane and morphology of epitaxial module can be regulated by changing the TCA concentration and reaction temperature, enabling a high level of controllability over specific assembly sites and structures. To illustrate the advantage of the asymmetrical structure, phosphated PBA-AS demonstrates improved performance in the oxygen evolution reaction compared to simple phosphated PBA nanocube. This method offers valuable insights for designing asymmetrical nanomaterials with intricate architectures and versatile functionalities.

Uncovering rearrangements in the Tibetan antelope via population-derived genome refinement and comparative analysis with homologous species.

Introduction: The Tibetan antelope (Pantholops hodgsonii) is a remarkable mammal thriving in the extreme Qinghai-Tibet Plateau conditions. Despite the availability of its genome sequence, limitations in the scaffold-level assembly have hindered a comprehensive understanding of its genomics. Moreover, comparative analyses with other Bovidae species are lacking, along with insights into genome rearrangements in the Tibetan antelope. Methods: Addressing these gaps, we present a multifaceted approach by refining the Tibetan Antelope genome through linkage disequilibrium analysis with data from 15 newly sequenced samples. Results: The scaffold N50 of the refined reference is 3.2 Mbp, surpassing the previous version by 1.15-fold. Our annotation analysis resulted in 50,750 genes, encompassing 29,324 novel genes not previously study. Comparative analyses reveal 182 unique rearrangements within the scaffolds, contributing to our understanding of evolutionary dynamics and species-specific adaptations. Furthermore, by conducting detailed genomic comparisons and reconstructing rearrangements, we have successfully pioneered the reconstruction of the X-chromosome in the Tibetan antelope. Discussion: This effort enhances our comprehension of the genomic landscape of this species.

Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation.

Cilia play critical roles in cell signal transduction and organ development. Defects in cilia function result in a variety of genetic disorders. Cep290 is an evolutionarily conserved ciliopathy protein that bridges the ciliary membrane and axoneme at the basal body (BB) and plays critical roles in the initiation of ciliogenesis and TZ assembly. How Cep290 is maintained at BB and whether axonemal and ciliary membrane localized cues converge to determine the localization of Cep290 remain unknown. Here, we report that the Cep131-Cep162 module near the axoneme and the Cby-Fam92 module close to the membrane synergistically control the BB localization of Cep290 and the subsequent initiation of ciliogenesis in Drosophila. Concurrent deletion of any protein of the Cep131-Cep162 module and of the Cby-Fam92 module leads to a complete loss of Cep290 from BB and blocks ciliogenesis at its initiation stage. Our results reveal that the first step of ciliogenesis strictly depends on cooperative and retroactive interactions between Cep131-Cep162, Cby-Fam92 and Cep290, which may contribute to the complex pathogenesis of Cep290-related ciliopathies.

Gastrointestinal Dysmotility Predisposes to Colitis through Regulation of Gut Microbial Composition and Linoleic Acid Metabolism.

Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.

From the archives of MD Anderson Cancer Center: Monomorphic epitheliotropic intestinal T-cell lymphoma: A case with an unusual immunophenotype and discussion of differential diagnosis.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and aggressive T-cell neoplasm associated with poor survival. We report a case of MEITL that presented as an ulcerated mass in the jejunum with perforation. Microscopic examination showed that the neoplasm involved the full thickness of the intestinal wall, extended into the mesentery, and was composed of monomorphic, small to medium-size cells. Immunohistochemical analysis showed that the neoplastic cells were positive for T-cell receptor (TCR) delta, CD3, CD7, CD8 (small subset), BCL-2 and TIA-1, and negative for TCR beta, CD4, CD5, CD10, CD20, CD30, CD34, CD56, CD57, CD99, ALK, cyclin D1, granzyme B, MUM1/IRF4, and TdT. The Ki-67 proliferation index was approximately 50 %. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER ISH) was negative. Next-generation sequencing (NGS) analysis showed mutations involving SETD2 and STAT5B. The patient was treated with aggressive chemotherapy and consolidative autologous stem cell transplant and had clinical remission, but relapsed after about one year. Retreatment led to another one-year interval of clinical remission, but at last follow up the patient has relapsed disease involving the ileum and colon. We also discuss the differential diagnosis of MEITL.

Evaluation of monolithic crystal detector with dual-ended readout utilizing multiplexing method.

Objective.Monolithic crystal detectors are increasingly being applied in positron emission tomography (PET) devices owing to their excellent depth-of-interaction (DOI) resolution capabilities and high detection efficiency. In this study, we constructed and evaluated a dual-ended readout monolithic crystal detector based on a multiplexing method.Approach.We employed two 12 × 12 silicon photomultiplier (SiPM) arrays for readout, and the signals from the 12 × 12 array were merged into 12 X and 12 Y channels using channel multiplexing. In 2D reconstruction, three methods based on the centre of gravity (COG) were compared, and the concept of thresholds was introduced. Furthermore, a light convolutional neural network (CNN) was employed for testing. To enhance depth localization resolution, we proposed a method by utilizing the mutual information from both ends of the SiPMs. The source width and collimation effect were simulated using GEANT4, and the intrinsic spatial resolution was separated from the measured values.Main results.At an operational voltage of 29 V for the SiPM, an energy resolution of approximately 12.5 % was achieved. By subtracting a 0.8 % threshold from the total energy in every channel, a 2D spatial resolution of approximately 0.90 mm full width at half maximum (FWHM) can be obtained. Furthermore, a higher level of resolution, approximately 0.80 mm FWHM, was achieved using a CNN, with some alleviation of edge effects. With the proposed DOI method, a significant 1.36 mm FWHM average DOI resolution can be achieved. Additionally, it was found that polishing and black coating on the crystal surface yielded smaller edge effects compared to a rough surface with a black coating.Significance.The introduction of a threshold in COG method and a dual-ended readout scheme can lead to excellent spatial resolution for monolithic crystal detectors, which can help to develop PET systems with both high sensitivity and high spatial resolution.

Research progress in parameterizing irrigation and fertilization in land surface model.

Under the context of global climate change and growing population, irrigation and fertilization have become important ways to ensure food production, with consequences on water cycling, energy flow, and materials cycling in terrestrial ecosystems. In the land surface model (LSM), coupling irrigation and fertilization schemes are of great importance for clearly understanding the land-atmosphere interactions to ensure food security. We reviewed the expression methods of three key parameters, namely, the applied method, usage, and time in the parameterization process of irrigation and fertilization (nitrogen fertilizer) in LSM. We found that the ways to irrigate and ferti-lize in LSM are different from the ways used in actual practice due to the limitation of the high resolution of spatio-temporal data, which makes it difficult to understand the actual influences of irrigation and fertilization on grain yield, environment, and local climate. Finally, we proposed future works: 1) taking the differences of crop water demand into account and making the different irrigation thresholds for different crops to properly evaluate the total and intensity of water consumption of different crops; 2) using the field records and the regional grid data of fertilization and irrigation developed in recent years to develop parameterized schemes that are more in line with actual agricultural operations, which can accurately reveal their economic, ecological, and climatic effects; 3) developing fertilization diagnosis scheme considering crop type, phenological stage, and soil basic fertility as the supplementary scheme in LSM, to improve the applicability and simulation accuracy of LSM in the areas without nitrogen fertilizer data.

Identification and validation of a pyroptosis-related prognostic model for colorectal cancer based on bulk and single-cell RNA sequencing data.

BACKGROUND: Pyroptosis impacts the development of malignant tumors, yet its role in colorectal cancer (CRC) prognosis remains uncertain. AIM: To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration. METHODS: Gene expression data were obtained from The Cancer Genome Atlas (TCGA) and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus (GEO). Pyroptosis-related gene expression in cell clusters was analyzed, and enrichment analysis was conducted. A pyroptosis-related risk model was developed using the LASSO regression algorithm, with prediction accuracy assessed through K-M and receiver operating characteristic analyses. A nomogram predicting survival was created, and the correlation between the risk model and immune infiltration was analyzed using CIBERSORTx calculations. Finally, the differential expression of the 8 prognostic genes between CRC and normal samples was verified by analyzing TCGA-COADREAD data from the UCSC database. RESULTS: An effective pyroptosis-related risk model was constructed using 8 genes-CHMP2B, SDHB, BST2, UBE2D2, GJA1, AIM2, PDCD6IP, and SEZ6L2 (P < 0.05). Seven of these genes exhibited differential expression between CRC and normal samples based on TCGA database analysis (P < 0.05). Patients with higher risk scores demonstrated increased death risk and reduced overall survival (P < 0.05). Significant differences in immune infiltration were observed between low- and high-risk groups, correlating with pyroptosis-related gene expression. CONCLUSION: We developed a pyroptosis-related prognostic model for CRC, affirming its correlation with immune infiltration. This model may prove useful for CRC prognostic evaluation.

Acute myeloid leukemia with mast cell differentiation is characterized by interstitial mast cells, complex karyotype, TP53 alterations and poor prognosis.

Not available.

Empirical analysis of lead neurotoxicity mode of action and its application in health risk assessment.

The mode of action (MOA) framework is proposed to inform a biological link between chemical exposures and adverse health effects. Despite a significant increase in knowledge and awareness, the application of MOA in human health risk assessment (RA) remains limited. This study aims to discuss the adoption of MOA for health RA within a regulatory context, taking our previously proposed but not yet validated MOA for lead neurotoxicity as an example. We first conducted a quantitative weight of evidence (qWOE) assessment, which revealed that the MOA has a moderate confidence. Then, targeted bioassays were performed within an in vitro blood-brain barrier (BBB) model to quantitatively validate the scientific validity of key events (KEs) in terms of essentiality and concordance of empirical support (dose/temporal concordance), which increases confidence in utilizing the MOA for RA. Building upon the quantitative validation data, we further conducted benchmark dose (BMD) analysis to map dose-response relationships for the critical toxicity pathways, and the lower limit of BMD at a 5% response (BMDL5) was identified as the point of departure (POD) value for adverse health effects. Notably, perturbation of the Aryl Hydrocarbon Receptor (AHR) signaling pathway exhibited the lowest POD value, measured at 0.0062 µM. Considering bioavailability, we further calculated a provisional health-based guidance value (HBGV) for children's lead intake, determining it to be 2.56 µg/day. Finally, the health risk associated with the HBGV was assessed using the hazard quotient (HQ) approach, which indicated that the HBGV established in this study is a relative safe reference value for lead intake. In summary, our study described the procedure for utilizing MOA in health RA and set an example for MOA-based human health risk regulation.

From the archives of MD Anderson Cancer Center. Mesothelial/monocytic incidental cardiac excrescence with a review of the literature.

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare benign lesion composed of monocytes and mesothelial cells that is most often encountered during cardiothoracic surgery. We describe a case in a 71-year-old man with known aortic valve stenosis who presented with gradual onset dyspnea over a few weeks, made worse with minimal exertion. A transesophageal echocardiogram revealed severe aortic stenosis and mild pericardial effusion. The patient underwent aortic valve replacement, coronary artery bypass, and amputation of the left atrial appendage. Histological examination of a 0.8 cm blood clot received along with the atrial appendage showed an aggregation of bland cells with features of monocytes associated with small strands and nodules of mesothelial cells, fat cells, fibrin and a minute fragment of bone. Immunohistochemical analysis showed that the monocytic cells were positive for CD4 and CD68 (strong) and negative for calretinin and keratin. By contrast, the mesothelial cells were positive for calretinin and keratin and negative for all other markers. In sum, the morphologic and immunohistochemical findings support the diagnosis of MICE. Based on our review of the literature, about 60 cases of MICE have been reported previously which we have tabulated. We also discuss the differential diagnosis.

Constructing CoNi-LDH/Fe MOF/NF Heterostructure Catalyst for Energy-Efficient OER and UOR at High Current Density.

The sluggish kinetics of the oxygen evolution reaction (OER) always results in a high overpotential at the anode of water electrolysis and an excessive electric energy consumption, which has been a major obstacle for hydrogen production through water electrolysis. In this study, we present a CoNi-LDH/Fe MOF/NF heterostructure catalyst with nanoneedle array morphology for the OER. In 1.0 M KOH solution, the heterostructure catalyst only required overpotentials of 275 and 305 mV to achieve high current densities of 500 and 1000 mA/cm2 for OER, respectively. The catalytic activities are much higher than those of the reference single-component CoNi-LDH/NF and Fe MOF/NF catalysts. The improved catalytic performance of the heterostructure catalyst can be ascribed to the synergistic effect of CoNi-LDH and Fe MOF. In particular, when the anodic OER is replaced with the urea oxidation reaction (UOR), which has a relatively lower thermodynamic equilibrium potential and is expected to reduce the cell voltage, the overpotentials required to achieve the same current densities can be reduced by 80 and 40 mV, respectively. The cell voltage required to drive overall urea splitting (OUS) is only 1.55 V at 100 mA/cm2 in the Pt/C/NF||CoNi-LDH/Fe MOF/NF two-electrode electrolytic cell. This value is 60 mV lower compared with that required for overall water splitting (OWS). Our results indicate that a reasonable construction of a heterostructure catalyst can significantly give rise to higher electrocatalytic performance, and using UOR to replace the anodic OER of the OWS can greatly reduce the electrolytic energy consumption.

Performance of metagenomic next-generation sequencing in cerebrospinal fluid for diagnosis of tuberculous meningitis.

Purpose. Metagenomic next-generation sequencing (mNGS) has been widely used in the diagnosis of infectious diseases, while its performance in diagnosis of tuberculous meningitis (TBM) is incompletely characterized. The aim of this study was to assess the performance of mNGS in the diagnosis of TBM, and illustrate the sensitivity and specificity of different methods.Methods. We retrospectively recruited TBM patients between January 2021 and March 2023 to evaluate the performance of mNGS on cerebrospinal fluid (CSF) samples, in comparison with conventional microbiological testing, including culturing of Mycobacterium tuberculosis (MTB), acid-fast bacillus (AFB) stain, reverse transcription PCR and Xpert MTB/RIF.Results. Of the 40 enrolled, 34 participants were diagnosed with TBM, including 15(44.12 %) definite and 19(55.88 %) clinical diagnosis based upon clinical manifestations, CSF parameters, brain imaging, pathogen evidence and treatment response. The mNGS method identified sequences of Mycobacterium tuberculosis complex (MTBC) in 11 CSF samples. In patients with definite TBM, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of mNGS were 78.57, 100, 100, 66.67 and 85 %, respectively. Compared to conventional diagnostic methods, the sensitivity of mNGS (78.57 %) was higher than AFB (0 %), culturing (0 %), RT-PCR (60 %) and Xpert MTB/RIF (14.29 %).Conclusions. Our study indicates that mNGS of CSF exhibited an overall improved sensitivity over conventional diagnostic methods for TBM and can be considered a front-line CSF test.