Preparation of monoclonal antibodies recognizing pharmacologically active metabolites of metamizole based on rational hapten design and their application in the detection of animal-derived food.

Metamizole (MET) is an antipyretic and analgesic drug, the illegal use of which can result in residues of MET metabolites in edible tissues of animals. In this study, a computational chemistry-assisted hapten screening strategy was used to screen for the optimal immunogenic hapten-A and the optimal coating antigen hapten-G-OVA. A monoclonal antibody capable of recognizing two pharmacologically active metabolites of MET, 4-methylamidinoantipyrine (MAA) and 4-aminoantipyrine (AA), was prepared from the hapten-A. The antibody showed excellent specificity for MAA and AA and almost no cross-reactivity with the pharmacologically inactive metabolites 4-formamidinoantipyrine (FAA) and 4-acetamidinoantipyrine (AAA). An ic-ELISA was developed for the simultaneous detection of MAA and AA in animal-derived food, the limits of detection for MAA ranged from 0.93 to 1.18 µg/kg, while those for AA ranged from 1.74 to 4.61 µg/kg. The recovery rate fell within the range of 82 %-110 %, with a coefficient of variation less than 16.39 %.

Gold Nanoparticles in Serum and Milk and Their Effect for Label-Free Colorimetric Sensing of DNA.

Label-free gold nanoparticle (AuNP)-based colorimetric biosensors have been widely used for the detection of DNA. However, the effect of the biological sample matrix has not been fully explored. In this work, we investigated the salt-induced aggregation of AuNPs as well as DNA adsorption in serum and milk. AuNPs of 13, 30, and 50 nm were used as probes. The detection was successful only in a clean buffer but failed in serum or milk. Serum and milk exhibited excellent protective properties, even 250 mM NaCl added did not induce the aggregation of AuNPs. After centrifugation of milk, the supernatant did not protect the AuNPs, whereas the redispersed pellet showed protection. The limit concentration of serum to prevent AuNPs from aggregating was 0.04% for 13 nm AuNPs and 0.01% serum for 50 nm AuNPs. In addition, serum reduced DNA adsorption, and the DNA was adsorbed to the protein corona instead of directly to the AuNP surface. These two factors can explain the difficulty of detection in protein-containing samples. This study articulates the adsorption of proteins by AuNPs in biological samples and offers useful insights into the biosensor design.

Time-restricted feeding relieves high temperature-induced impairment on meat quality by activating the Nrf2/HO-1 pathway, modification of muscle fiber composition, and enriching the polyunsaturated fatty acids in pigs.

To assess the effects of a time-restricted feeding (TRF) regimen on meat quality of pigs exposed to high ambient temperature, a two-month feeding and heat treatment (HT) trial was conducted using a 2 × 2 factorial design. A total of 24 growing pigs (11.0 ± 1.9 kg) were randomly divided into four groups: thermal neutral group (NT, 24 ± 3 °C), HT group (exposed to a high temperature at 35 ± 2 °C from 11:00 to 15:00), TRF group and HT + TRF group (HT and TRF co-treatment group, n = 6 for each group). Pigs in TRF groups got access to feed within 5 h from 9:00 to14:00, while the others were fed at 6:00, 11:30, and 16:00. All pigs received the same diet during the trail. The results showed that HT increased the drip loss, shear force, lightness, and malondialdehyde production in Longissimus thoracis et lumborum (LTL) muscle. TRF reversely reduced the shear force and drip loss, accompanied by decreased intramuscular fat and increased moisture content. Enhanced fiber transformation from type 1 to type 2b and down-regulated expression of muscle growth-related genes were observed by HT, while TRF suppressed the fiber transformation and expression of muscle atrophy-related genes. Furthermore, TRF restored the diminished protein expressions of Nrf2 and HO-1 in LTL muscle by chronic HT. Accumulation of HSP70 in muscle of HT group was reduced by treatment of TRF. HT declined the expression of vital genes involved in fatty acids poly-desaturation and the proportion of (polyunsaturated fatty acids) PUFAs, mainly omega-6 in LTL muscle, while TRF group promoted the expression of poly-desaturation pathway and displayed the highest proportion of PUFAs. These results demonstrated that TRF relieved the chronic high temperature affected meat quality by the restored expression of Nrf2/HO-1 anti-oxidative cascade, modified muscle fiber composition, and enriched PUFAs in LTL muscle.

Analysis of spatial-temporal evolution and investment model of industrial cross-regional investment network-taking the Pearl River Delta urban agglomeration as an example.

Cross-regional investment behavior plays a pivotal role in enterprise development and regional economic growth. Nonetheless, existing investment network analyses often adopt a broad perspective, most studies tend to invest in network models and focus on a particular industry, and pay less attention to investment models in different industries. Therefore, this paper will combine the dual perspectives of space and network to observe the spatial and temporal evolution characteristics of enterprise investment and its investment model. Additionally, it delves into the unique features of investment networks within various industries at the district and county levels. The results show that enterprise investment agglomeration exhibits a development pattern characterized by points, bands, and surfaces, with a notable distance attenuation trend in investment distances. The overall structure of the industry investment network showcases characteristics of being multi-centered and multi-nodal. The investment models across different industries can be categorized into four distinct types. The research conclusion is of great significance to optimize multi-scale intercity investment, realize industrial gradient transfer and promote the coordinated development of industry.

Analysis of flower color diversity revealed the co-regulation of cyanidin and peonidin in the red petals coloration of Rosa rugosa.

Rosa rugosa is limited in landscaping applications due to its monotonous color, especially the lack of red-flowered varieties. Comprehensive assessment of petal color diversity in R. rugosa could promote to explore the mechanism of flower color formation. In this study, the variation and diversity of petal coloring of 193 R. rugosa germplasms were assessed by chromatic values (L∗, a∗, and b∗), and then divided into seven clusters belonging to three groups with pinkish-purple (185 individuals), white (6), and red (2) petals, respectively. Total anthocyanin content was the most important factor affecting flower color diversity and red hue formation of R. rugosa petals. There were significant correlations between petal color chromatic indexes and the sum content and the ratio of two major anthocyanin, namely cyanidin 3,5-O-diglucoside (Cy3G5G), peonidin 3,5-O-diglucoside (Pn3G5G). Both high levels of Cy3G5G + Pn3G5G and Cy3G5G/Pn3G5G were necessary conditions for red phenotype formation. Five cyanidin up-stream structural genes (RrF3'H1, RrDFR1, RrANS1, RrUF3GT1, RrUF35GT1) and one cyanidin down-stream structural gene (RrCCoAOMT1) were the key indicators which contributed to Cy3G5G + Pn3G5G and Cy3G5G/Pn3G5G, respectively. Functional verification showed that overexpression of RrDFR1, combined with silent expression of RrCCoAOMT1, could make R. rugosa petals redder by increasing the levels of Cy3G5G + Pn3G5G and Cy3G5G/Pn3G5G. These results provided a robust theoretical basis for further revealing the molecular mechanism of red petals coloration in R. rugosa.

Identification of Psychological Symptom Clusters and Their Influencing Factors in Women Undergoing Assisted Reproductive Technology in China: a Cross-Sectional Study.

Background: There are multiple psychological symptoms in women undergoing assisted reproductive technology, which seriously affect health-related quality of life and even cause patients to stop treatment. Aim: This study aimed to identify psychological symptom clusters and their influencing factors in women undergoing assisted reproductive technology. Methods: A cross-sectional survey was conducted from June to November 2023 at the reproductive centers of Nanjing Women and Children's Healthcare Hospital. Data on demographic and clinical characteristics and Symptom Checklist-90 were collected. Exploratory factor analysis was performed to identify psychological symptom clusters. Univariate logistic regression analysis and multivariate logistic regression analysis were performed to explore influencing factors. Results: A total of 213 patients were recruited. The study found that the included participants scored higher on all SCL scales than the general Chinese females. The three most common were trouble remembering things (81.7%), feeling easily annoyed or irritated (81.2%), and feeling low in energy or slowed down (70.9%). Six symptom clusters were identified: paranoid ideation, depression, obsessive-compulsive disorder, interpersonal sensitivity, somatization, and sleep disorders. Multivariate logistic regression analysis showed that duration of infertility treatment (>12 months) was identified as a risk factor for sleep disorder cluster (OR=2.833, 95% CI:1.355~5.922), adverse pregnancy history was identified as a risk factor for paranoid ideation cluster (OR=2.961,95% CI:1.406~6.253), depression cluster (OR=2.404,95% CI:1.240~4.660), and obsessive-compulsive cluster (OR=1.810, 95% CI:1.016~3.233), financial burden during treatment was identified as risk factors for all symptom clusters[(OR=5.869, 95% CI:1.717~20.057),(OR=6.490,95% CI:2.210~19.063),(OR=3.034,95% CI:1.560~5.898),(OR=7.078,95% CI:2.420~20.698),(OR=4.532,95% CI:1.845~10.397),(OR=2.151,95% CI:1.129~4.098)]. Conclusion: Women undergoing ART experience various psychological symptoms that are interrelated and exist in the form of symptom clusters. More attention should be paid to the psychological status of patients with longer duration of infertility treatment, adverse pregnancy history, and financial burden during treatment. This study guides the development of targeted and effective psychological interventions to facilitate symptom management in women undergoing ART.

Lessons Learned From Developing Dashboards to Support Decision-Making for Community Opioid Response by Community Stakeholders: Mixed Methods and Multisite Study.

BACKGROUND: Data dashboards are published tools that present visualizations; they are increasingly used to display data about behavioral health, social determinants of health, and chronic and infectious disease risks to inform or support public health endeavors. Dashboards can be an evidence-based approach used by communities to influence decision-making in health care for specific populations. Despite widespread use, evidence on how to best design and use dashboards in the public health realm is limited. There is also a notable dearth of studies that examine and document the complexity and heterogeneity of dashboards in community settings. OBJECTIVE: Community stakeholders engaged in the community response to the opioid overdose crisis could benefit from the use of data dashboards for decision-making. As part of the Communities That HEAL (CTH) intervention, community data dashboards were created for stakeholders to support decision-making. We assessed stakeholders' perceptions of the usability and use of the CTH dashboards for decision-making. METHODS: We conducted a mixed methods assessment between June and July 2021 on the use of CTH dashboards. We administered the System Usability Scale (SUS) and conducted semistructured group interviews with users in 33 communities across 4 states of the United States. The SUS comprises 10 five-point Likert-scale questions measuring usability, each scored from 0 to 4. The interview guides were informed by the technology adoption model (TAM) and focused on perceived usefulness, perceived ease of use, intention to use, and contextual factors. RESULTS: Overall, 62 users of the CTH dashboards completed the SUS and interviews. SUS scores (grand mean 73, SD 4.6) indicated that CTH dashboards were within the acceptable range for usability. From the qualitative interview data, we inductively created subthemes within the 4 dimensions of the TAM to contextualize stakeholders' perceptions of the dashboard's usefulness and ease of use, their intention to use, and contextual factors. These data also highlighted gaps in knowledge, design, and use, which could help focus efforts to improve the use and comprehension of dashboards by stakeholders. CONCLUSIONS: We present a set of prioritized gaps identified by our national group and list a set of lessons learned for improved data dashboard design and use for community stakeholders. Findings from our novel application of both the SUS and TAM provide insights and highlight important gaps and lessons learned to inform the design of data dashboards for use by decision-making community stakeholders. TRIAL REGISTRATION: ClinicalTrials.gov NCT04111939; https://clinicaltrials.gov/study/NCT04111939.

Functional outcome of the anterior vaginal wall in a pelvic surgery injury rat model after treatment with stem cell-derived progenitors of smooth muscle cells.

BACKGROUND: Stem-cell-derived therapy is a promising option for tissue regeneration. Human iPSC-derived progenitors of smooth muscle cells (pSMCs) exhibit limited proliferation and differentiation, which minimizes the risk of tumor formation while restoring smooth muscle cells (SMCs). Up to 29% of women suffer from recurrence of vaginal prolapse after prolapse surgery. Therefore, there is a need for therapies that can restore vaginal function. SMCs contribute to vaginal tone and contractility. We sought to examine whether human pSMCs can restore vaginal function in a rat model. METHODS: Female immunocompromised RNU rats were divided into 5 groups: intact controls (n = 12), VSHAM (surgery + saline injection, n = 35), and three cell-injection groups (surgery + cell injection using pSMCs from three patients, n = 14/cell line). The surgery to induce vaginal injury was analogous to prolapse surgery. Menopause was induced by surgical ovariectomy. The vagina, urethra, bladder were harvested 10 weeks after surgery (5 weeks after cell injection). Organ bath myography was performed to evaluate the contractile function of the vagina, and smooth muscle thickness was examined by tissue immunohistochemistry. Collagen I, collagen III, and elastin mRNA and protein expressions in tissues were assessed. RESULTS: Vaginal smooth muscle contractions induced by carbachol and KCl in the cell-injection groups were significantly greater than those in the VSHAM group. Collagen I protein expression in the vagina of the cell-injections groups was significantly higher than in the VSHAM group. Vaginal elastin protein expression was similar between the cell-injection and VSHAM groups. In the urethra, gene expression levels of collagen I, III, and elastin were all significantly greater in the cell-injection groups than in the VSHAM group. Collagen I, III, and elastin protein expression of the urethra did not show a consistent trend between cell-injection groups and the VSHAM group. CONCLUSIONS: Human iPSC-derived pSMCs transplantation appears to be associated with improved contractile function of the surgically injured vagina in a rat model. This is accompanied by changes in extracellular protein expression the vagina and urethra. These observations support further efforts in the translation of pSMCs into a treatment for regenerating the surgically injured vagina in women who suffer recurrent prolapse after surgery.

Establishing group-level brain structural connectivity incorporating anatomical knowledge under latent space modeling.

Brain structural connectivity, capturing the white matter fiber tracts among brain regions inferred by diffusion MRI (dMRI), provides a unique characterization of brain anatomical organization. One fundamental question to address with structural connectivity is how to properly summarize and perform statistical inference for a group-level connectivity architecture, for instance, under different sex groups, or disease cohorts. Existing analyses commonly summarize group-level brain connectivity by a simple entry-wise sample mean or median across individual brain connectivity matrices. However, such a heuristic approach fully ignores the associations among structural connections and the topological properties of brain networks. In this project, we propose a latent space-based generative network model to estimate group-level brain connectivity. Within our modeling framework, we incorporate the anatomical information of brain regions as the attributes of nodes to enhance the plausibility of our estimation and improve biological interpretation. We name our method the attributes-informed brain connectivity (ABC) model, which compared with existing group-level connectivity estimations, (1) offers an interpretable latent space representation of the group-level connectivity, (2) incorporates the anatomical knowledge of nodes and tests its co-varying relationship with connectivity and (3) quantifies the uncertainty and evaluates the likelihood of the estimated group-level effects against chance. We devise a novel Bayesian MCMC algorithm to estimate the model. We evaluate the performance of our model through extensive simulations. By applying the ABC model to study brain structural connectivity stratified by sex among Alzheimer's Disease (AD) subjects and healthy controls incorporating the anatomical attributes (volume, thickness and area) on nodes, our method shows superior predictive power on out-of-sample structural connectivity and identifies meaningful sex-specific network neuromarkers for AD.

On-chip multi-degree-of-freedom control of two-dimensional materials.

Two-dimensional materials (2DM) and their heterostructures offer tunable electrical and optical properties, primarily modifiable through electrostatic gating and twisting. Although electrostatic gating is a well-established method for manipulating 2DM, achieving real-time control over interfacial properties remains challenging in exploring 2DM physics and advanced quantum device technology1-6. Current methods, often reliant on scanning microscopes, are limited in their scope of application, lacking the accessibility and scalability of electrostatic gating at the device level. Here we introduce an on-chip platform for 2DM with in situ adjustable interfacial properties, using a microelectromechanical system (MEMS). This platform comprises compact and cost-effective devices with the ability of precise voltage-controlled manipulation of 2DM, including approaching, twisting and pressurizing actions. We demonstrate this technology by creating synthetic topological singularities, such as merons, in the nonlinear optical susceptibility of twisted hexagonal boron nitride (h-BN)7-10. A key application of this technology is the development of integrated light sources with real-time and wide-range tunable polarization. Furthermore, we predict a quantum analogue that can generate entangled photon pairs with adjustable entanglement properties. Our work extends the abilities of existing technologies in manipulating low-dimensional quantum materials and paves the way for new hybrid two- and three-dimensional devices, with promising implications in condensed-matter physics, quantum optics and related fields.

A Narrative Review: Immunometabolic Interactions of Host-Gut Microbiota and Botanical Active Ingredients in Gastrointestinal Cancers.

The gastrointestinal tract is where the majority of gut microbiota settles; therefore, the composition of the gut microbiota and the changes in metabolites, as well as their modulatory effects on the immune system, have a very important impact on the development of gastrointestinal diseases. The purpose of this article was to review the role of the gut microbiota in the host environment and immunometabolic system and to summarize the beneficial effects of botanical active ingredients on gastrointestinal cancer, so as to provide prospective insights for the prevention and treatment of gastrointestinal diseases. A literature search was performed on the PubMed database with the keywords "gastrointestinal cancer", "gut microbiota", "immunometabolism", "SCFAs", "bile acids", "polyamines", "tryptophan", "bacteriocins", "immune cells", "energy metabolism", "polyphenols", "polysaccharides", "alkaloids", and "triterpenes". The changes in the composition of the gut microbiota influenced gastrointestinal disorders, whereas their metabolites, such as SCFAs, bacteriocins, and botanical metabolites, could impede gastrointestinal cancers and polyamine-, tryptophan-, and bile acid-induced carcinogenic mechanisms. GPRCs, HDACs, FXRs, and AHRs were important receptor signals for the gut microbial metabolites in influencing the development of gastrointestinal cancer. Botanical active ingredients exerted positive effects on gastrointestinal cancer by influencing the composition of gut microbes and modulating immune metabolism. Gastrointestinal cancer could be ameliorated by altering the gut microbial environment, administering botanical active ingredients for treatment, and stimulating or blocking the immune metabolism signaling molecules. Despite extensive and growing research on the microbiota, it appeared to represent more of an indicator of the gut health status associated with adequate fiber intake than an autonomous causative factor in the prevention of gastrointestinal diseases. This study detailed the pathogenesis of gastrointestinal cancers and the botanical active ingredients used for their treatment in the hope of providing inspiration for research into simpler, safer, and more effective treatment pathways or therapeutic agents in the field.

Methyltransferase Like-3-Mediated N6-Methyladenosine Modification of Long Noncoding RNA Hepatocyte Nuclear Factor 1a Antisense RNA 1/Hepatocyte Nuclear Factor 4a Antisense RNA 1 Regulates Cytochrome P450 Enzyme Expression.

Interindividual variations in the expression and activity of cytochrome P450 enzymes (CYPs) led to lower therapeutic efficacy or adverse drug events. We previously demonstrated that CYPs are regulated by the long noncoding RNAs (lncRNAs) hepatocyte nuclear factor 1a antisense RNA 1 (HNF1A-AS1) and HNF4A-AS1 via transcription factors (TFs) including hepatocyte nuclear factor 1a (HNF1A), hepatocyte nuclear factor 4a (HNF4A), and pregnane X receptor (PXR). However, the upstream mechanisms regulating HNF1A-AS1 and HNF4A-AS1 are poorly understood. N6-methyladenosine (m6A) is a prevalent epitranscriptomic modification in mammalian RNA. Therefore, the aim of this study was to investigate whether m6A modification regulates the expression of HNF1A-AS1 and HNF4A-AS1 and affects CYP expression in HepG2 and Huh7 cells. The methyltransferase-like 3 (METTL3) inhibitor, STM2457, significantly suppressed the expression of HNF1A-AS1 and induced HNF4A-AS1 expression. Consistent with this, a loss-of-function assay of METTL3 in the cell lines resulted in the downregulation of HNF1A-AS1 and its downstream HNF1A, PXR, and CYPs at the RNA level, as well as the downregulation of some CYPs proteins, and upregulation of HNF4A-AS1. The results of gain-of-function experiments showed the opposite trend. Mechanistically, subsequent RNA stability experiments confirmed that METTL3 affected the stability of both lncRNAs, but in opposite ways; that is, METTL3 reduced HNF1A-AS1 stability and increased HNF4A-AS1 stability. Rescue experiments confirmed that the regulation of METTL3 on TFs and CYPs may require the involvement of these two lncRNAs. Altogether, our study demonstrates that METTL3 is involved in TFs-mediated CYP expression by affecting HNF1A-AS1/HNF4A-AS1 stability. SIGNIFICANCE STATEMENT: Although the impact of long noncoding RNAs (lncRNAs) including hepatocyte nuclear factor 1a antisense RNA 1 (HNF1A-AS1) and hepatocyte nuclear factor 4a antisense RNA 1 (HNF4A-AS1) on the downstream transcription factor (TF) and cytochrome P450 enzyme (CYP) expression is well studied, the upstream regulation of these two lncRNAs by methyltransferase-like 3 (METTL3) remains unexplored. This study reveals that METTL3 is involved in the regulation of lncRNA-TF-CYP expression by affecting the stability of HNF1A-AS1 and HNF4A-AS1 in HepG2 and Huh7 cells.

Linear polyubiquitylation of Gli protein regulates its protein stability and facilitates tumor growth in colorectal cancer.

The linear ubiquitin chain assembly complex (LUBAC) mediates the linear ubiquitination of various proteins and is involved in NF-κB signaling and immune regulation. However, the function and mechanism of linear ubiquitination in regulating oncogenic signaling and tumor growth have remained poorly understood. Herein, we identified Gli proteins, key transcription factors in the Hedgehog (Hh) signaling pathway, as novel substrates of LUBAC. Linear ubiquitination stabilizes Gli proteins, leading to the noncanonical activation of Hh signaling in CRC cells. Furthermore, LUBAC facilitates tumor growth in CRC cells. Additionally, elevated expression of LUBAC components in CRC tissues was observed, and higher expression levels of these components correlated with poor prognosis in CRC patients. Interestingly, inhibition of LUBAC using either a small molecule agonist or RNA silencing specifically suppressed cell growth in CRC cells but had no effect on normal intestinal cells. Taken together, aberrant expression of LUBAC components activates Hh signaling noncanonically by mediating linear ubiquitination, promoting tumor growth in CRC, demonstrating the novel function of linear ubiquitination in regulating the protein stability of its substrates and highlighting the potential of targeting LUBAC as a therapeutic strategy in CRC.

Characteristics of T-Cell Receptor Repertoire for Differential Response to Methotrexate Treatment for Rheumatoid Arthritis.

BACKGROUND: Methotrexate (MTX) serves as the initial treatment for rheumatoid arthritis (RA). However, a substantial proportion of RA patients, estimated between 30% and 50%, do not respond positively to MTX. While the T-cell receptor (TCR) is crucial for the immune response during RA, its role in differentiating MTX responsiveness has not been thoroughly investigated. METHODS: This study used next-generation sequencing to analyze the TCR ß-chain complementary determining region sequences in peripheral blood mononuclear cells obtained from RA patients before MTX treatment. This study aimed to compare the characteristics of the TCR repertoire between the MTX responder and non-responder groups. RESULTS: The study identified a significant difference in the TRBV6-6 gene (p = .003) concerning MTX treatment response. Additionally, a significant difference was found in the number of "3" nucleotide deletions at the 5'Jdels site (p = .023) in the VDJ rearrangement. CONCLUSION: These findings suggest distinct TCR repertoire characteristics between MTX responder and non-responder groups among RA patients. This discovery offers new insights into understanding the variable responses of RA patients to MTX therapy.

The whole genome dataset of Ichthyscopus pollicaris.

The classification of the Uranoscopidae species is controversial and the Ichthyscopus pollicaris belonging to Uranoscopidae was first reported in 2019. In the present study, the whole genome sequence of I. pollicaris were generated by PacBio and Illumina platforms for the first time. After de novo assembly and correction of the high-quality PacBio data, a 527.25 Mb I. pollicaris genome with an N50 length of 11.25 Mb was finally generated. Meanwhile, 170.41 Mb repeating sequence, 21,263 genes, 784 miRNAs, 2,225 tRNAs, 3004 rRNAs, and 1422 snRNAs were annotated in I. pollicaris genome. Furthermore, 3,168 single-copy orthologous genes were applied to reconstructed the phylogenetic relationship between I. pollicaris and other 11 species. The draft genome sequences have been deposited in NCBI database with the accession number of PRJNA1071810.

TCP1 expression alters the ferroptosis sensitivity of diffuse large B-cell lymphoma subtypes by stabilising ACSL4 and influences patient prognosis.

Diffuse large B-cell lymphoma (DLBCL), an invasive lymphoma with substantial heterogeneity, can be mainly categorised into germinal centre B-cell-like (GCB) and non-GCB subtypes. DLBCL cells are highly susceptible to ferroptosis, which offers an effective avenue for treating recurrent and refractory DLBCL. Moreover, various heat shock proteins are involved in regulating the sensitivity of tumour cells to ferroptosis. Among these proteins, tailless complex polypeptide 1 (TCP1), a subunit of chaperonin-containing T-complex protein-1 (CCT), plays a role in tumour proliferation and survival. Therefore, we explored the role of TCP1 in different DLBCL subtypes, the sensitivity of GCB and non-GCB subtypes to the ferroptosis inducer RAS-selective lethal small molecule 3 (RSL3), and the underlying molecular mechanism. In GCB cells, TCP1 promoted RSL3-induced ferroptosis. Notably, TCP1 could bind with acyl-CoA synthetase long-chain family member 4 (ACSL4), a key enzyme regulating lipid composition and facilitating ferroptosis, to reduce its ubiquitination and degradation. This interaction activated the ACSL4/LPCAT3 signalling pathway and promoted ferroptosis in the GCB subtype. However, in the non-GCB subtype, TCP1 did not act as a positive regulator but served as a predictor of an unfavourable prognosis in patients with non-GCB. In conclusion, our results suggest that in DLBCL, high TCP1 expression enhances the sensitivity of GCB tumour cells to ferroptosis and serves as a marker of poor prognosis in patients with non-GCB DLBCL.

Soil organic carbon estimation using remote sensing data-driven machine learning.

Soil organic carbon (SOC) is a crucial component of the global carbon cycle, playing a significant role in ecosystem health and carbon balance. In this study, we focused on assessing the surface SOC content in Shandong Province based on land use types, and explored its spatial distribution pattern and influencing factors. Machine learning methods including random forest (RF), extreme gradient boosting (XGBoost), and support vector machine (SVM) were employed to estimate the surface SOC content in Shandong Province using diverse data sources like sample data, remote sensing data, socio-economic data, soil texture data, topographic data, and meteorological data. The results revealed that the SOC content in Shandong Province was 8.78 g/kg, exhibiting significant variation across different regions. Comparing the model error and correlation coefficient, the XGBoost model showed the highest prediction accuracy, with a coefficient of determination (R²) of 0.7548, root mean square error (RMSE) of 7.6792, and relative percentage difference (RPD) of 1.1311. Elevation and Clay exhibited the highest explanatory power in clarifying the surface SOC content in Shandong Province, contributing 21.74% and 13.47%, respectively. The spatial distribution analysis revealed that SOC content was higher in forest-covered mountainous regions compared to cropland-covered plains and coastal areas. In conclusion, these findings offer valuable scientific insights for land use planning and SOC conservation.

UV-B Radiation Exhibited Tissue-Specific Regulation of Isoflavone Biosynthesis in Soybean Cell Suspension Cultures.

Isoflavones, a class of substances with high biological activity, are abundant in soybeans. This study investigated isoflavone biosynthesis in soybean cell suspension cultures under UV-B radiation. UV-B radiation enhanced the transcription level and activity of key enzymes involved in isoflavone synthesis in cell suspension cultures. As a result, the isoflavone contents significantly increased by 19.80% and 91.21% in hypocotyl and cotyledon suspension cultures compared with the control, respectively. Meanwhile, a significant difference was observed in the composition of isoflavones between soybean hypocotyl and cotyledon suspension cultures. Genistin was only detected in hypocotyl suspension cultures, whereas glycitin, daidzein, and genistein accumulated in cotyledon suspension cultures. Therefore, UV-B radiation exhibited tissue-specific regulation of isoflavone biosynthesis in soybean cell suspension cultures. The combination of suspension cultures and abiotic stress provides a novel technological approach to isoflavone accumulation.

LncRNA-Snhg3 regulates mouse hepatic glycogenesis under normal chow diet.

Long noncoding RNAs (lncRNAs) are strongly associated with glucose homeostasis, but their roles remain largely unknown. In this study, the potential role of lncRNA-Snhg3 in glucose metabolism was evaluated both in vitro and in vivo. Here, we found a positive relationship between Snhg3 and hepatic glycogenesis. Glucose tolerance improved in hepatocyte-specific Snhg3 knock-in (Snhg3-HKI) mice, while it worsened in hepatocyte-specific Snhg3 knockout (Snhg3-HKO) mice. Furthermore, hepatic glycogenesis had shown remarkable increase in Snhg3-HKI mice and reduction in Snhg3-HKO mice, respectively. Mechanistically, Snhg3 increased mRNA and protein expression levels of PPP1R3B through inducing chromatin remodeling and promoting the phosphorylation of protein kinase B. Collectively, these results suggested that lncRNA-Snhg3 plays a critical role in hepatic glycogenesis.

Fanlian Huazhuo Formula alleviates high-fat diet-induced non-alcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway.

BACKGROUND: Fanlian Huazhuo Formula (FLHZF) has the functions of invigorating spleen and resolving phlegm, clearing heat and purging turbidity. It has been identified to have therapeutic effects on type 2 diabetes mellitus (T2DM) in clinical application. Non-alcoholic fatty liver disease (NAFLD) is frequently diagnosed in patients with T2DM. However, the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation. AIM: To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro. METHODS: HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model. Subsequently, experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours. C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD, and then treated with the different concentrations of FLHZF for 10 weeks. RESULTS: FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro. Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress, regulating the AMPKα/SREBP-1C signaling pathway, activating autophagy, and inhibiting hepatocyte apoptosis. CONCLUSION: FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species, autophagy, apoptosis, and lipid synthesis signaling pathways, indicating its potential for clinical application in NAFLD.