Moxibustion with seed-size moxa cones alleviates colonic injury in mice with ulcerative colitis by regulating TLR4/MyD88/NF-κB signaling pathway. / 麦粒灸调控TLR4/MyD88/NF-κBä¿¡å·é€šè·¯å‡è½»æºƒç–¡æ€§ç»“è‚ ç‚Žå°é¼ ç»“è‚ æŸä¼¤çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of moxibustion with seed-size moxa cones on the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear transcription factor-κB(NF-κB) signaling pathway in mice with ulcerative colitis(UC), so as to explore the therapeutic mechanism of moxibustion with seed-size moxa cones on colonic injury in UC. METHODS: Forty male C57BL/6 mice were randomly divided into blank group, model group, moxibustion group, and western medicine group, with 10 mice in each group. The UC mouse model was established by 3% DSS solution by free drinking for 7 consecutive days. Mice in the moxibustion group were treated with seed-size moxa cones at "Zhongwan"(CV12), "Tianshu"(ST25) and "Shangjuxu"(ST37), 3 moxa cones per point, with each cone applied for approximately 30 s, while mice in the western medicine group were orally administered with 300 mg/kg mesalazine solution, which were both conducted once a day for 7 consecutive days. The general condition of mice was observed every 2 days, and the disease activity index (DAI) score was calculated. HE staining was used to observe the morphology of colonic tissue in mice. ELISA was used to detect the serum interleukin(IL)-1ß, tumor necrosis factor(TNF)-α, IL-6, and IL-8 contents. Immunohistochemistry was used to detect the positive expression of TLR4 and MyD88 in colonic tissue of mice. Real-time fluorescence quantitative PCR was used to detect the expression levels of TLR4, MyD88, and NF-κB p65 mRNAs in colonic tissue. RESULTS: Compared with the blank group, varying degrees of soft or watery stools were observed, colon length and body weight were decreased(P<0.01) in mice of the model group, while DAI score, colon weight index, mucosal damage score, colonic pathological score, serum IL-1ß, TNF-α, IL-6, and IL-8 contents, positive expressions of TLR4 and MyD88, and TLR4, MyD88, and NF-κB p65 mRNA expressions in colonic tissue were increased(P<0.01). Compared with the model group, improved fecal characteristics were observed, colon length and body weight were increased(P<0.01) in mice of the moxibustion group and western medicine group, while DAI scores, colon weight indexes, mucosal damage scores, colonic pathological score, serum contents of IL-1ß, TNF-α, IL-6, and IL-8, positive expressions of TLR4 and MyD88, and TLR4, MyD88, and NF-κB p65 mRNA expressions in colonic tissue were decreased(P<0.01, P<0.05). There was no significant difference in the above indicators between the moxibustion group and the western medicine group. CONCLUSIONS: Moxibustion with seed-size moxa cones may alleviate colonic injury in UC mice by regulating the TLR4/MyD88/NF-κB signaling pathway and reducing the release of inflammatory factors.

Evolutionary innovations in conserved regulatory elements associate with developmental genes in mammals.

Transcriptional enhancers orchestrate cell type- and time point-specific gene expression programs. Genetic variation within enhancer sequences is an important contributor to phenotypic variation including evolutionary adaptations and human disease. Certain genes and pathways may be more prone to regulatory evolution than others, with different patterns across diverse organisms, but whether such patterns exist has not been investigated at a sufficient scale. To address this question, we identified signatures of accelerated sequence evolution in conserved enhancer elements throughout the mammalian phylogeny at an unprecedented scale. While different genes and pathways were enriched for regulatory evolution in different parts of the tree, we found a striking overall pattern of pleiotropic genes involved in gene regulatory and developmental processes being enriched for accelerated enhancer evolution. These genes were connected to more enhancers than other genes, which was the basis for having an increased amount of sequence acceleration over all their enhancers combined. We provide evidence that sequence acceleration is associated with turnover of regulatory function. Detailed study of one acceleration event in an enhancer of HES1 revealed that sequence evolution led to a new activity domain in the developing limb that emerged concurrently with the evolution of digit reduction in hoofed mammals. Our results provide evidence that enhancer evolution has been a frequent contributor to regulatory innovation at conserved developmental signaling genes in mammals.

A knowledge-transfer-based approach for combining ordinal regression and medical scoring system in the early prediction of sepsis with electronic health records.

OBJECTIVE: The prediction of sepsis, especially early diagnosis, has received a significant attention in biomedical research. In order to improve current medical scoring system and overcome the limitations of class imbalance and sample size of local EHR (electronic health records), we propose a novel knowledge-transfer-based approach, which combines a medical scoring system and an ordinal logistic regression model. MATERIALS AND METHODS: Medical scoring systems (i.e. NEWS, SIRS and QSOFA) are generally robust and useful for sepsis diagnosis. With local EHR, machine-learning-based methods have been widely used for building prediction models/methods, but they are often impacted by class imbalance and sample size. Knowledge distillation and knowledge transfer have recently been proposed as a combination approach for improving the prediction performance and model generalization. In this study, we developed a novel knowledge-transfer-based method for combining a medical scoring system (after a proposed score transformation) and an ordinal logistic regression model. We mathematically confirmed that it was equivalent to a specific form of the weighted regression. Furthermore, we theoretically explored its effectiveness in the scenario of class imbalance. RESULTS: For the local dataset and the MIMIC-IV dataset, the VUS (the volume under the multi-dimensional ROC surface, a generalization measure of AUC-ROC for ordinal categories) of the knowledge-transfer-based model (ORNEWS) based on the NEWS scoring system were 0.384 and 0.339, respectively, while the VUS of the traditional ordinal regression model (OR) were 0.352 and 0.322, respectively. Consistent analysis results were also observed for the knowledge-transfer-based models based on the SIRS/QSOFA scoring systems in the ordinal scenarios. Additionally, the predicted probabilities and the binary classification ROC curves of the knowledge-transfer-based models indicated that this approach enhanced the predicted probabilities for the minority classes while reducing the predicted probabilities for the majority classes, which improved AUCs/VUSs on imbalanced data. DISCUSSION: Knowledge transfer, which combines a medical scoring system and a machine-learning-based model, improves the prediction performance for early diagnosis of sepsis, especially in the scenarios of class imbalance and limited sample size.

Textureless Deformable Object Tracking with Invisible Markers.

Tracking and reconstructing deformable objects with little texture is challenging due to the lack of features. Here we introduce "invisible markers" for accurate and robust correspondence matching and tracking. Our markers are visible only under ultraviolet (UV) light. We build a novel imaging system for capturing videos of deformed objects under their original untouched appearance (which may have little texture) and, simultaneously, with our markers. We develop an algorithm that first establishes accurate correspondences using video frames with markers, and then transfers them to the untouched views as ground-truth labels. In this way, we are able to generate high-quality labeled data for training learning-based algorithms. We contribute a large real-world dataset, DOT, for tracking deformable objects with little or no texture. Our dataset has about one million video frames of various types of deformable objects. We provide ground truth tracked correspondences in both 2D and 3D. We benchmark state-of-the-art methods on optical flow and deformable object reconstruction using our dataset, which poses great challenges. By training on DOT, their performance significantly improves, not only on our dataset, but also on other unseen data.

Reconstructing human-specific regulatory functions in model systems.

Uniquely human physical traits, such as an expanded cerebral cortex and changes in limb morphology that allow us to use tools and walk upright, are in part due to human-specific genetic changes that altered when, where, and how genes are expressed during development. Over 20 000 putative regulatory elements with potential human-specific functions have been discovered. Understanding how these elements contributed to human evolution requires identifying candidates most likely to have shaped human traits, then studying them in genetically modified animal models. Here, we review the progress and challenges in generating and studying such models and propose a pathway for advancing the field. Finally, we highlight that large-scale collaborations across multiple research domains are essential to decipher what makes us human.

Expression profiling of Spodoptera exigua (Lepidoptera: Noctuidae) microRNAs and microRNA core genes by Bacillus thuringiensis GS57 infection.

MicroRNAs (miRNAs) are endogenous, non-coding RNAs, which are functional in a variety of biological processes through post-transcriptional regulation of gene expression. However, the role of miRNAs in the interaction between Bacillus thuringiensis and insects remains unclear. In this study, small RNA libraries were constructed for B. thuringiensis-infected (Bt) and uninfected (CK) Spodoptera exigua larvae (treated with double-distilled water) using Illumina sequencing. Utilising the miRDeep2 and Randfold, a total of 233 known and 726 novel miRNAs were identified, among which 16 up-regulated and 34 down-regulated differentially expressed (DE) miRNAs were identified compared to the CK. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that potential target genes of DE miRNAs were associated with ABC transporters, fatty acid metabolism and MAPK signalling pathway which are related to the development, reproduction and immunity. Moreover, two miRNA core genes, SeDicer1 and SeAgo1 were identified. The phylogenetic tree showed that lepidopteran Dicer1 clustered into one branch, with SeDicer1 in the position closest to Spodoptera litura Dicer1. A similar phylogenetic relationship was observed in the Ago1 protein. Expression of SeDicer1 increased at 72 h post infection (hpi) with B. thuringiensis; however, expression of SeDicer1 and SeAgo1 decreased at 96 hpi. The RNAi results showed that the knockdown of SeDicer1 directly caused the down-regulation of miRNAs and promoted the mortality of S. exigua infected by B. thuringiensis GS57. In conclusion, our study is crucial to understand the relationship between miRNAs and various biological processes caused by B. thuringiensis infection, and develop an integrated pest management strategy for S. exigua via miRNAs.

Inhibition of XPR1-dependent phosphate efflux induces mitochondrial dysfunction: A potential molecular target therapy for hepatocellular carcinoma?

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is the only known transporter associated with Pi efflux in mammals, and its impact on tumor progression is gradually being revealed. However, the role of XPR1 in hepatocellular carcinoma (HCC) is unknown. A bioinformatics screen for the phosphate exporter XPR1 was performed in HCC patients. The expression of XPR1 in clinical specimens was analyzed using quantitative real-time PCR, Western blot analysis, and immunohistochemical assays. Knockdown of the phosphate exporter XPR1 was performed by shRNA transfection to investigate the cellular phenotype and phosphate-related cytotoxicity of the Huh7 and HLF cell lines. In vivo tests were conducted to investigate the tumorigenicity of HCC cells xenografted into immunocompromised mice after silencing XPR1. Compared with that in paracancerous tissue, XPR1 expression in HCC tissues was markedly upregulated. High XPR1 expression significantly correlated with poor patient survival. Silencing of XPR1 leads to decreased proliferation, migration, invasion, and colony formation in HCC cells. Mechanistically, knockdown of XPR1 causes an increase in intracellular phosphate levels; mitochondrial dysfunction characterized by reduced mitochondrial membrane potential and adenosine triphosphate levels; increased reactive oxygen species levels; abnormal mitochondrial morphology; and downregulation of key mitochondrial fusion, fission, and inner membrane genes. This ultimately results in mitochondria-dependent apoptosis. These findings reveal the prognostic value of XPR1 in HCC progression and, more importantly, suggest that XPR1 might be a potential therapeutic target.

Real-time detection and resection of sentinel lymph node metastasis in breast cancer through a rare earth nanoprobe based NIR-IIb fluorescence imaging.

Sentinel lymph node (SLN) biopsy is a commonly employed procedure for the routine assessment of axillary involvement in patients with breast cancer. Nevertheless, conventional SLN mapping cannot reliably distinguish the presence and absence of metastatic disease. Additionally, the complex anatomical structures and lymphatic drainage patterns surrounding tumor sites pose challenges to the sensitivity of the near-infrared fluorescence imaging with subcutaneously injected probes. To identifying the SLN metastases, we developed a novel nanoprobe for in vivo fluorescence imaging within the second near-infrared (NIR-II) range. This nanoprobe utilizes rare-earth nanoparticles (RENPs) to emit bright fluorescence at 1525 nm and is conjugated with tumor-targeted hyaluronic acid (HA) to facilitate the detection of metastatic SLN. Upon intravenous administration, RENPs@HA effectively migrated to SLNs and selectively entered metastatic breast tumor cells through CD44-mediated endocytosis. The RENPs@HA nanoprobes exhibited rapid accumulation in metastatic inguinal lymph nodes in mouse model, displaying a 5.8-fold-stronger fluorescence intensity to that observed in normal SLNs. Consequently, these nanoprobes effectively differentiate metastatic SLNs from normal SLNs. Importantly, the probes accurately detected micrometastases. These findings underscore the potential of RENPs@HA for real-time visualization and screening of SLNs metastasis.

Cyclin F-EXO1 axis controls cell cycle-dependent execution of double-strand break repair.

Ubiquitination is a crucial posttranslational modification required for the proper repair of DNA double-strand breaks (DSBs) induced by ionizing radiation (IR). DSBs are mainly repaired through homologous recombination (HR) when template DNA is present and nonhomologous end joining (NHEJ) in its absence. In addition, microhomology-mediated end joining (MMEJ) and single-strand annealing (SSA) provide backup DSBs repair pathways. However, the mechanisms controlling their use remain poorly understood. By using a high-resolution CRISPR screen of the ubiquitin system after IR, we systematically uncover genes required for cell survival and elucidate a critical role of the E3 ubiquitin ligase SCFcyclin F in cell cycle-dependent DSB repair. We show that SCFcyclin F-mediated EXO1 degradation prevents DNA end resection in mitosis, allowing MMEJ to take place. Moreover, we identify a conserved cyclin F recognition motif, distinct from the one used by other cyclins, with broad implications in cyclin specificity for cell cycle control.

Complete genome sequence of candidate probiotic Limosilactobacillus fermentum KUFM407.

It has been reported that the administration of Limosilactobacillus fermentum alleviates diseases such as osteoporosis and colitis. In this study, we report the complete genome sequence of Limosilactobacillus fermentum KUFM407, a probiotic strain of LAB isolated from Korean traditional fermented food, Kimchi. Whole genome sequencing of L. fermentum KUFM407 was performed on the Illumina MiSeq and Oxford Nanopore MinION platform. The genome consisted of one circular chromosome (2,077,616 base pair [bp]) with a guanine cytosine (GC) content of 51.5% and one circular plasmid sequence (13,931 bp). Genome annotation identified 1,932 protein-coding genes, 15 rRNAs, and 58 tRNAs in the assembly. The function annotation of the predicted proteins revealed genes involved in the biosynthesis of bacteriocin and fatty acids. The complete genome of L. fermentum KUFM407 could provide valuable information for the development of new probiotic food and health supplements.

Hepatocyte-derived tissue extracellular vesicles safeguard liver regeneration and support regenerative therapy.

Tissue-derived extracellular vesicles (EVs) are emerging as pivotal players to maintain organ homeostasis, which show promise as a next-generation candidate for medical use with extensive source. However, the detailed function and therapeutic potential of tissue EVs remain insufficiently studied. Here, through bulk and single-cell RNA sequencing analyses combined with ultrastructural tissue examinations, we first reveal that in situ liver tissue EVs (LT-EVs) contribute to the intricate liver regenerative process after partial hepatectomy (PHx), and that hepatocytes are the primary source of tissue EVs in the regenerating liver. Nanoscale and proteomic profiling further identify that the hepatocyte-specific tissue EVs (Hep-EVs) are strengthened to release with carrying proliferative messages after PHx. Moreover, targeted inhibition of Hep-EV release via AAV-shRab27a in vivo confirms that Hep-EVs are required to orchestrate liver regeneration. Mechanistically, Hep-EVs from the regenerating liver reciprocally stimulate hepatocyte proliferation by promoting cell cycle progression through Cyclin-dependent kinase 1 (Cdk1) activity. Notably, supplementing with Hep-EVs from the regenerating liver demonstrates translational potential and ameliorates insufficient liver regeneration. This study provides a functional and mechanistic framework showing that the release of regenerative Hep-EVs governs rapid liver regeneration, thereby enriching our understanding of physiological and endogenous tissue EVs in organ regeneration and therapy.

De novo mutations promote inflammation in children with STAT3 gain-of-function syndrome by affecting IL-1ß expression.

STAT3 gain-of-function syndrome, characterized by early-onset autoimmunity and primary immune regulatory disorder, remains poorly understood in terms of its immunological mechanisms. We employed whole-genome sequencing of familial trios to elucidate the pivotal role of de novo mutations in genetic diseases. We identified 37 high-risk pathogenic loci affecting 23 genes, including a novel STAT3 c.508G>A mutation. We also observed significant down-regulation of pathogenic genes in affected individuals, potentially associated with inflammatory responses regulated by PTPN14 via miR378c. These findings enhance our understanding of the pathogenesis of STAT3 gain-of-function syndrome and suggest potential therapeutic strategies. Notably, combined JAK inhibitors and IL-6R antagonists may offer promising treatment avenues for mitigating the severity of STAT3 gain-of-function syndrome.

ß-Hydroxybutyrate alleviates brain aging through the MTA1 pathway in D-galactose injured mice.

Aging is an inevitable law of the process of life during which many physiological functions change. Brain aging is an important mechanism in the occurrence and development of degenerative diseases of the central nervous system. ß-Hydroxybutyrate (BHBA) is a water-soluble, endogenous small-molecule ketone that can cross the blood-brain barrier and induce neuroprotective effects. This study aimed to investigate the effects of BHBA on D-galactose (D-gal) induced aging in mice and its underlying mechanisms using in vitro and in vivo experiments. These results indicated that D-gal-induced senescence, oxidative stress, and inflammatory responses were inhibited by BHBA, and autophagy was promoted by BHBA. Mechanistically, we explored the role of metastasis-associated antigen-1 (MTA1) in D-gal-induced damaged in HT22 cells using small interfering RNA (siRNA). The results demonstrated that the expression of MTA1 was significantly increased by BHBA, which attenuated D-gal-induced aging, oxidative stress, and inflammatory responses, and promoted autophagy through the upregulation of MTA1. In conclusion, MTA1 may be a novel target for treating aging caused by neurological damage. BHBA improves brain aging by activating the MTA1 pathway.

Analyzing the topological properties of resting-state brain function network connectivity based on graph theoretical methods in patients with high myopia.

AIM: Recent imaging studies have found significant abnormalities in the brain's functional or structural connectivity among patients with high myopia (HM), indicating a heightened risk of cognitive impairment and other behavioral changes. However, there is a lack of research on the topological characteristics and connectivity changes of the functional networks in HM patients. In this study, we employed graph theoretical analysis to investigate the topological structure and regional connectivity of the brain function network in HM patients. METHODS: We conducted rs-fMRI scans on 82 individuals with HM and 59 healthy controls (HC), ensuring that the two groups were matched for age and education level. Through graph theoretical analysis, we studied the topological structure of whole-brain functional networks among participants, exploring the topological properties and differences between the two groups. RESULTS: In the range of 0.05 to 0.50 of sparsity, both groups demonstrated a small-world architecture of the brain network. Compared to the control group, HM patients showed significantly lower values of normalized clustering coefficient (γ) (P = 0.0101) and small-worldness (σ) (P = 0.0168). Additionally, the HM group showed lower nodal centrality in the right Amygdala (P < 0.001, Bonferroni-corrected). Notably, there is an increase in functional connectivity (FC) between the saliency network (SN) and Sensorimotor Network (SMN) in the HM group, while the strength of FC between the basal ganglia is relatively weaker (P < 0.01). CONCLUSION: HM Patients exhibit reduced small-world characteristics in their brain networks, with significant drops in γ and σ values indicating weakened global interregional information transfer ability. Not only that, the topological properties of the amygdala nodes in HM patients significantly decline, indicating dysfunction within the brain network. In addition, there are abnormalities in the FC between the SN, SMN, and basal ganglia networks in HM patients, which is related to attention regulation, motor impairment, emotions, and cognitive performance. These findings may provide a new mechanism for central pathology in HM patients.

Inflammation Can Be a High-Risk Factor for Mucosal Nonunion of MRONJ by Regulating SIRT1 Signaling When Treated with an Oncologic Dose of Zoledronate.

Purpose: Zoledronate (ZA) stands as a highly effective antiresorptive agent known to trigger medication-related osteonecrosis of the jaw (MRONJ). Its clinical dosages primarily encompass those used for oncologic and osteoporosis treatments. While inflammation is recognized as a potential disruptor of mucosal healing processes associated with ZA, prior research has overlooked the influence of varying ZA dosages on tissue adaptability. Therefore, a deeper understanding of the specific mechanisms by which inflammation exacerbates ZA-induced MRONJ, particularly when inflammation acts as a risk factor, remains crucial. Methods: Cell proliferation and migration of human oral keratinocytes (HOK) was analyzed after treatment with different doses of ZA and/or lipopolysaccharide (LPS) to assess their possible effect on mucosal healing of extraction wounds. Mouse periodontitis models were established using LPS, and histological changes in extraction wounds were observed after the administration of oncologic dose ZA. Hematoxylin and eosin (HE) staining and immunofluorescence were used to evaluate mucosal healing. Results: In vitro, LPS did not exacerbate the effects of osteoporosis therapeutic dose of ZA on the proliferation and migration of HOK cells, while aggravated these with the oncologic dose of ZA treatment by inducing mitochondrial dysfunction and oxidative stress via regulating SIRT1 expression. Furthermore, SIRT1 overexpression can alleviate this process. In vivo, local injection of LPS increased the nonunion of mucous membranes in MRONJ and decreased the expression of SIRT1, PGC-1α, and MnSOD. Conclusion: Inflammation aggravates oncologic dose of ZA-induced mitochondrial dysfunction and oxidative stress via a SIRT1-dependent pathway, enhancing the risk of impaired mucosal healing in MRONJ. Our study implies that inflammation becomes a critical risk factor for MRONJ development at higher ZA concentrations. Elucidating the mechanisms of inflammation as a risk factor for mucosal non-healing in MRONJ could inform the development of SIRT1-targeted therapies.

Experimental study on the safety of photobiologic regulation therapy in the treatment of some non-epidermal tumors.

This study investigates the impact of Photobiomodulation (PBM) at different wavelengths on non-superficial cancer cells. Utilizing three laser protocols (650 nm, 810 nm, and 915 nm), the research explores cytotoxic effects, ROS generation, and cell migration. Results reveal varied responses across cell lines, with 810 nm PBM inducing significant ROS levels and inhibiting PAN-1 cell migration. The study suggests potential therapeutic applications for PBM in non-superficial cancers, emphasizing the need for further exploration in clinical settings.

Human Accelerated Regions regulate gene networks implicated in apical-to-basal neural progenitor fate transitions.

The evolution of the human cerebral cortex involved modifications in the composition and proliferative potential of the neural stem cell (NSC) niche during brain development. Human Accelerated Regions (HARs) exhibit a significant excess of human-specific sequence changes and have been implicated in human brain evolution. Multiple studies support that HARs include neurodevelopmental enhancers with novel activities in humans, but their biological functions in NSCs have not been empirically assessed at scale. Here we conducted a direct-capture Perturb-seq screen repressing 180 neurodevelopmentally active HARs in human iPSC-derived NSCs with single-cell transcriptional readout. After profiling >188,000 NSCs, we identified a set of HAR perturbations with convergent transcriptional effects on gene networks involved in NSC apicobasal polarity, a cellular process whose precise regulation is critical to the developmental emergence of basal radial glia (bRG), a progenitor population that is expanded in humans. Across multiple HAR perturbations, we found convergent dysregulation of specific apicobasal polarity and adherens junction regulators, including PARD3, ABI2, SETD2 , and PCM1 . We found that the repression of one candidate from the screen, HAR181, as well as its target gene CADM1 , disrupted apical PARD3 localization and NSC rosette formation. Our findings reveal interconnected roles for HARs in NSC biology and cortical development and link specific HARs to processes implicated in human cortical expansion.

Structure-Based Design, Virtual Screening, and Discovery of Novel Patulin Derivatives as Biogenic Photosystem II Inhibiting Herbicides.

Computer-aided design usually gives inspirations and has become a vital strategy to develop novel pesticides through reconstructing natural lead compounds. Patulin, an unsaturated heterocyclic lactone mycotoxin, is a new natural PSII inhibitor and shows significant herbicidal activity to various weeds. However, some evidence, especially the health concern, prevents it from developing as a bioherbicide. In this work, molecular docking and toxicity risk prediction are combined to construct interaction models between the ligand and acceptor, and design and screen novel derivatives. Based on the analysis of a constructed patulin-Arabidopsis D1 protein docking model, in total, 81 derivatives are designed and ranked according to quantitative estimates of drug-likeness (QED) values and free energies. Among the newly designed derivatives, forty-five derivatives with better affinities than patulin are screened to further evaluate their toxicology. Finally, it is indicated that four patulin derivatives, D3, D6, D34, and D67, with higher binding affinity but lower toxicity than patulin have a great potential to develop as new herbicides with improved potency.

Association between higher intermuscular adipose tissue and decreased renal function in patients with systemic lupus erythematosus mediated by insulin resistance.

OBJECTIVES: To quantify the relationship between abdominal computed tomography (CT)-based body composition parameters and renal function in systemic lupus erythematosus (SLE) patients and evaluate the potential effect of insulin resistance on this relationship. METHODS: SLE patients from institutions A and B between January 2017 and August 2023 were enrolled. Areas and attenuation values of subcutaneous adipose tissue, visceral adipose tissue, intermuscular adipose tissue (IMAT), and skeletal muscle index on CT images were measured at the L3 vertebral level. Logistic regression analysis was used to identify risk factors associated with decreased renal function. Linear regression models were used to describe the relationships between body composition parameters and estimated glomerular filtration rate (eGFR). Finally, we used a single-point insulin sensitivity estimator to indirectly reflect the degree of insulin resistance and assess its mediating effect on the association between IMAT area and decreased renal function. RESULTS: Three-hundred thirty-nine SLE patients from institution A (internal dataset) and 114 SLE patients from institution B (external validation dataset) were included. Multivariate logistic regression revealed that IMAT area (odds ratio (OR)institution A: 1.05 (95% confidence intervals (95% CI): 1.01, 1.10), and ORinstitution B: 1.19 (95% CI: 1.03, 1.39)) was an independent risk factor for decreased renal function in SLE patients. In the adjusted linear regression model, high IMAT area was significantly associated with reduced eGFR (ßinstitution A = -1.15, Pinstitution A = 0.005; ßinstitution B = -0.98, Pinstitution B = 0.049). Additionally, insulin resistance contributed a mediating role of 22.8% to the association. CONCLUSION: High IMAT area was associated with decreased renal function in SLE patients and insulin resistance mediated this relationship. CRITICAL RELEVANCE STATEMENT: High intermuscular adipose tissue area is associated with decreased renal function in systemic lupus erythematosus patients mediated by insulin resistance and is correlated with chronicity index in lupus nephritis patients. KEY POINTS: High intramuscular adipose tissue (IMAT) area was associated with decreased renal function in systemic lupus erythematosus (SLE) patients. Insulin resistance mediated the association between IMAT area and eGFR. IMAT area was associated with chronicity index in lupus nephritis patients.

[Feeding ecology of Chaeturichthys stigmatias during autumn in Haizhou Bay]. / 海州湾秋季矛尾虾虎鱼的摄食生态.

Research about feeding ecology of fish is important to understand individual behavior and population development, which is also the basic to analyze trophic structure and function of aquatic ecosystems. Chaetrichthys stigmatias is one of the key species in the Haizhou Bay fisheries ecosystem, which has critical ecological niche within the food web. In this study, we collected samples through bottom trawl surveys during the fall of 2018 in the Haizhou Bay, and analyzed the feeding ecology of C. stigmatias based on both stomach content analysis and stable isotope technology. The results showed that the primary diet groups for C. stigmatias were Ophiuroidea and Shrimp, including Ophiothrix marenzelleri, Ophiopholis mirabilis, Ophiura sarsii, Penaeidae, and Alpheus japonicus. The range of δ13C values of C. stigmatias was from -19.39‰ to -15.74‰, with an average value of (-18.07±0.87)‰, which had no significant correlation with body length. The range of δ15N values was from 8.16‰ to 12.86‰, with an average value of (10.14±1.51)‰, which was positively correlated with body length. The trophic level of C. stigmatias showed a positive relationship with body length, with an average value of (3.74±0.34) and a range value of 3.32 to 4.20 among different size groups. The contribution rates of different prey groups varied significantly. Based on the structural equation modeling, we found that the feeding intensity of C. stigmatias was primally influenced by body length, sea bottom salinity, sea bottom temperature, and water depth, with a particularly signi-ficant positive correlation with body length. The combination of stable isotope technology and stomach content analysis methods could contribute to comprehensive understanding on the feeding ecology of C. stigmatias, providing essential data and foundation for research on trophic structures and resource conservation in the Haizhou Bay ecosystem.