Transcriptome analysis of anaerobic glycolysis effects on Jurkat T cell proliferation.

Introduction: To explore the effects of anaerobic glycolysis on Jurkat T cell proliferation and clarify the possible mechanism via transcriptomic analysis. Material and methods: The monocarboxylate transporter 1 inhibitor AZD3965 was used to target and block the transmembrane transport of lactate, thereby inhibiting anaerobic glycolysis in Jurkat T cells. Then, genes with differential expression between treated and untreated cells were detected by transcriptomic analysis, and constructs were generated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses as well as protein-protein interaction (PPI) network analysis were performed to explore the potential mechanism. Results: Inhibition of anaerobic glycolysis reduced Jurkat T-cell proliferation. RNA sequencing identified 1723 transcripts that were differentially expressed, including 1460 upregulated genes and 263 downregulated genes. GO functional enrichment analysis showed that the differentially expressed genes were mainly involved in the biological processes of response to unfolded protein, response to topologically incorrect protein, and protein folding. KEGG pathway analysis of differentially expressed genes or hub genes from the PPI network analysis revealed enrichment in the estrogen signaling and PI3K-Akt pathways. Conclusions: Anaerobic glycolysis contributes to the regulation of Jurkat T-cell proliferation. The underlying mechanism may involve the estrogen signaling pathway or PI3K-Akt signaling pathway as well as protein metabolism.

Pear twig biochar combined with nitrogen fertilizer regulates morpho-physiological growth, copper uptake and tuber quality of potato (Solanum tuberosum L.) grown in polluted soil.

Application of pear twig derived biochar and nitrogen fertilizer is strategic for addressing the challenges posed by copper pollution in soils. Their combined use aims to improve plant health and promote sustainable agricultural practices, which leads to better potato growth and quality. Therefore, this study was carried out to investigate the effects of different levels of pear twig biochar (B0:0, B1:3, B2:5, B3:7% w/w) combined with nitrogen fertilizer (N0:0, N1:150, N2:200, N3:250, N4:300 mg kg-1) on morpho-physiological growth and copper uptake of potato cultivated in Cu polluted soil. Results showed that combined approach of pear twig biochar and nitrogen significantly influenced morpho-physiology, antioxidant enzyme activity, mineral content and tuber quality of potato. B2N3 significantly increased the plant height and chlorophyll in plants as compared to B0N0 (control). Malondialdehyde and proline contents were highest in control; however, maximum reductions in MDA and proline contents were recorded at B2N4 (70.32% and 92.12% at budding stage, respectively) and at B2N3 (82.44% and 91.93% at flowering stage, respectively). Likewise, B2N3 showed maximum reduction in activities of peroxidase (7343.47 and 11077.27 U g-1), catalase (1184.98 and 165.64 U g-1) and superoxide dismutase (14.84 and 19.94 U g-1) at budding and flowering stages, respectively. However, lowest contents of soil available Cu (2.03 ± 0.5 µg g-1) and tuber flesh Cu (4.44 ± 0.3 µg g-1) were recorded at B2N3 as compared to control. Interestingly, 7% biochar at all levels of nitrogen exhibited a significant decrease in soil available Cu and tuber flesh Cu. Tuber quality traits were also significantly improved at B2N3 as compared to control. However, future research and field trials can help refine the best practices for integrating these elements in different agricultural systems.

The pathological significance and potential mechanism of ACLY in cholangiocarcinoma.

Background and aim: Cholangiocarcinoma (CCA) is a rare cancer, yet its incidence and mortality rates have been steadily increasing globally over the past few decades. Currently, there are no effective targeted treatment strategies available for patients. ACLY (ATP Citrate Lyase), a key enzyme in de novo lipogenesis, is aberrantly expressed in several tumors and is associated with malignant progression. However, its role and mechanisms in CCA have not yet been elucidated. Methods: The expression of ACLY in CCA was assessed using transcriptomic profiles and tissue microarrays. Kaplan-Meier curves were employed to evaluate the prognostic significance of ACLY in CCA. Functional enrichment analysis was used to explore the potential mechanisms of ACLY in CCA. A series of assays were conducted to examine the effects of ACLY on the proliferation and migration of CCA cells. Ferroptosis inducers and inhibitors, along with lipid peroxide probes and MDA assay kits, were utilized to explore the role of ACLY in ferroptosis within CCA. Additionally, lipid-depleted fetal bovine serum and several fatty acids were used to evaluate the impact of fatty acids on ferroptosis induced by ACLY inhibition. Correlation analyses were performed to elucidate the relationship between ACLY and tumor stemness as well as tumor microenvironment. Results: The expression of ACLY was found to be higher in CCA tissues compared to adjacent normal tissues. Patients with elevated ACLY expression demonstrated poorer overall survival outcomes. ACLY were closed associated with fatty acid metabolism and tumor-initiating cells. Knockdown of ACLY did not significantly impact the proliferation and migration of CCA cells. However, ACLY inhibition led to increased accumulation of lipid peroxides and enhanced sensitivity of CCA cells to ferroptosis inducers. Polyunsaturated fatty acids were observed to inhibit the proliferation of ACLY-knockdown cells; nonetheless, this inhibitory effect was diminished when the cells were cultured in medium supplemented with lipid-depleted fetal bovine serum. Additionally, ACLY expression was negatively correlated with immune cell infiltration and immune scores in CCA. Conclusion: ACLY promotes ferroptosis by disrupting the balance of saturated and unsaturated fatty acids. ACLY may therefore serve as a potential diagnostic and therapeutic target for CCA.

Cumulative rabbit anti-human thymocyte globulin dose to recipient weight during the peri-operative period is an independent risk factor for early postoperative urinary tract infection after kidney transplantation.

Anti-human thymocyte globulin-Fresenius (ATG-F) is frequently utilized to achieve successful induction for kidney transplantation recipients. This study aimed to examine the association between the ATG-F dose-to-recipient-weight ratio (ADR) and the risk of developing urinary tract infections (UTIs) following kidney transplantation. Data of kidney transplant recipients who underwent ATG-F-induction peri-operatively in a medical center were retrospectively collected, and the incidence of UTIs during the first postoperative year was also recorded. The risk of UTI associated with ADR was analyzed, and receiver operating characteristic curves were drawn to determine the optimal ADR, followed by Cox regression models. In total, 131 recipients were included, with an UTI incidence of 19.08% and a mean interval of 3.08 months. The optimal ADR was 6.34, involving 41 and 90 patients in the low ADR and high ADR groups, respectively. The UTI-free rate in the low ADR group was significantly higher than that in the high ADR group (p = 0.007). Cox regression analysis indicated that a high ADR independently increased the risk of UTI following kidney transplantation (hazard ratio: 5.306, 95% confidence interval: 1.243-22.660, p = 0.024). There was no significant difference in rejection rate between the high ADR and low ADR groups. In conclusion, a high ADR increased the incidence of early postoperative UTI among kidney transplant recipients.

Risk assessment of dietary perchlorate exposure in typical areas of fireworks manufacturing in China using a perchlorate intake model.

Perchlorate can disrupt the production of thyroid hormones, impact metabolism, and even affect the cognitive development of infants and toddlers. Typical areas of fireworks manufacturing might face severe perchlorate pollution due to perchlorate is an important raw material. But related study has not been reported. We assess the risk caused by perchlorate and identify the critical exposure pathways for different age/gender groups in typical area of fireworks manufacturing. Liuyang city, a major fireworks manufacturing center in China, was selected as study region. Perchlorate concentrations were measured in 230 local food samples from Liuyang using LC/MS/MS. Risks for different age/gender groups were estimated using a perchlorate intake model. The detection rate of perchlorate in samples from all eight food groups, including vegetables, fruits, meat, seafood, egg, cereal, beans, and drinking water was 100%, and the perchlorate concentrations were higher than those reported in the United States, Canada, South Korea, Kuwait, and other regions of China. Liuyang residents are currently facing an extremely high perchlorate dietary exposure risk, with the mean Estimated Daily Intakes (EDIs) approximately 6-49 times higher than US EPA's recommended reference dose (RfD, 0.7 µg/kg bw/day), and 14-115 times higher than the tolerable daily intake (TDI, 0.3 µg/kg bw/day) established by EFSA. Breast milk and drinking water are identified as the primary exposure pathways for infants and toddlers under the age of two, contributing 44-86% and 13-41% to their total exposure, respectively. For individuals > two years, vegetable consumption (constituting 54-66% of exposures) and ingestion of drinking water (constituting 23-32% of exposures) represent the chief exposure routes. The Hazard Quotient (HQ) values for Liuyang City residents all exceed 2, indicating an extremely high non-carcinogenic risk associated with perchlorate. Scientific and systematic perchlorate pollution control measures should be taken by local government.

Comparison of proximal gastrectomy and total gastrectomy in proximal gastric cancer: a meta-analysis of postoperative health condition using the PGSAS-45.

PURPOSE: Proximal gastrectomy (PG) offers advantages over total gastrectomy (TG) in enhancing the postoperative nutritional status of patients with proximal gastric cancer (PGC), yet its effect on long-term quality of life is still debated. This study aims to thoroughly compare postoperative health condition outcomes between PG and TG. METHODS: We conducted a systematic search of English-language articles from the PubMed, Web of Science, and Cochrane Library databases, covering studies published up to February 2023. Key evaluation endpoints included surgical outcomes and postoperative health condition, assessed using the Post-Gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). RESULTS: Six retrospective cohort studies were included in the analysis. The PG group demonstrated no significant negative impact on surgical outcomes compared to the TG group. Notably, patients who underwent PG experienced a superior postoperative health condition, characterized by fewer gastroesophageal reflux symptoms (WMD = -0.106, 95% CI -0.183 to -0.029, P < 0.01), less weight loss (WMD = 4.440, 95% CI 3.900 to 4.979, P < 0.01), and reduced dietary dissatisfaction (WMD = -0.205, 95% CI -0.385 to -0.025, P = 0.03). CONCLUSION: This study provides compelling evidence that PG is superior to TG in enhancing postoperative health condition for patients with proximal gastric cancer, without compromising surgical outcomes. However, further rigorous randomized controlled trials are necessary to inform surgical decision-making more effectively.

Flavor characterization of pork cuts in Chalu black pigs using multi-omics analysis.

The study investigated the flavor variations in four different fresh pork cuts (longissimus thoracis, LT; trapezius muscle, TM; hamstring muscle, HM; Pork Belly, PB) from Chalu black pigs (ten castrated boars) using multi-omics techniques. The research also explored the influence of muscle fiber type on the flavor profiles of these cuts. Results from quantitative real-time PCR (qRT-PCR) indicated significant differences in muscle fiber type across the four pork cuts in various anatomical locations. Each cut exhibited distinctive volatile organic compounds (VOCs) profiles, with HM displaying a sweet and fruity green flavor, LT showcasing a fatty and nutty taste, PB presenting a fresh, citrusy, and green flavor, and TM offering a floral and bitter note. Variations in fatty acid carbon number and saturation were observed among the cuts, with HM, LT, and PB being rich in fatty acids with C16-18, C19-21, and 3 double bonds, respectively. The metabolites specific to each cut were found to play key roles in different metabolic pathways, such as protein-related pathways for HM, arginine biosynthesis for LT, lysine biosynthesis for PB, and D-arginine and D-ornithine metabolism for TM. Differentially expressed genes (DEGs) were associated with amino acid metabolism for HM, glycolysis/gluconeogenesis for LT, and cellular aromatic compound organization for PB. Notably, HM and PB displayed unique flavor characteristics, while TM exhibited relatively neutral features. The study also identified correlations among VOCs, muscle fiber type, lipids, metabolites, and gene patterns specific to each cut, highlighting the complex interplay of factors influencing pork flavor.

Comparative transcriptome analysis and meta-QTLs mapping reveal the regulatory mechanism of cold tolerance in rice at the budding stage.

Rice (Oryza sativa L.) is one of the most extensively farmed food crops, but its development and productivity are significantly impacted by cold stress during the budding period. In this study, transcriptome sequencing was conducted on two types of rice: the cold-sensitive indica rice A117 and the substantially cold-tolerant japonica rice B106 under control and cold treatments. Differentially expressed genes between the two materials under cold conditions were analyzed using GO and KEGG enrichment analyses. The results revealed that processes such as the TCA cycle, glycolysis/glycogenesis, oxidative phosphorylation, and glutathione metabolism contribute to B106's cold tolerance. Additionally, an enrichment analysis of cold-induced genes in each material and shared genes identified significant enrichment in pathways such as glutathione metabolism, phenylpropanoid biosynthesis, and photosynthesis-antenna proteins. Initial cold tolerance QTLs at the rice bud stage were collected from published literature, and meta-QTL mapping identified 9 MQTLs. Gene expression profiling led to the identification of 75 potential DEGs within the 9 MQTLs region, from which four candidate genes (Os02g0194100, Os03g0802500, Os05g0129000, and Os07g0462000) were selected using qRT-PCR and gene annotation. These findings provide genetic resources for further research on the molecular mechanisms underlying rice's response to cold stress during the bud stage.

Clinical characteristics of sudden hearing loss during pregnancy.

Objective: The objective of this study was to explore the clinical characteristics and management of sudden hearing loss (HL) during pregnancy, thus better guiding the clinical practice. Methods: The clinical and follow-up data of 17 patients (17 ears) with sudden HL during pregnancy were analyzed retrospectively (the observe group). Twelve nonpregnant female patients (12 ears) with sudden HL of similar clinical characteristics were selected as the control group. The prognosis of the two groups was compared. All the patients were followed up after delivery, and two of them were readmitted to the hospital 1-2 months after delivery. Results: The observe group had better improvement in hearing and a higher response rate compared to the control group. The pure tone hearing and speech recognition rate of patients could still be improved after the readmitted treatment, and the hearing could partially recover spontaneously during follow-up. The laboratory indicators that affect the inflammatory response and coagulation pathway were significantly different between the two groups. Conclusions: The hearing condition of sudden HL during pregnancy is severe, and the prognosis of these patients is better than nonpregnant patients of similar clinical characteristics. Postpartum treatment is still effective, and some patients showed self-healing with time during follow-up. The inflammatory response and coagulation function may affect the hearing of patients through a metabolic pathway.

Temperature seasonality and soil phosphorus availability shape ginseng quality via regulating ginsenoside contents.

The accumulation of secondary metabolites in Panax ginseng Meyer (P. ginseng) exhibits significant geographical variation, normally due to environmental factors. The current study aimed at elucidating the key environmental factors modulating the accumulation of secondary metabolites in P. ginseng. Plant and the associated soil samples were collected from ten geographical locations within the latitudinalrange of 27.09°N - 42.39°N and longitudinal range of 99.28°E - 128.19°E. 12 secondary metabolites in P. ginseng toots were measured. And the correlation between secondary metabolites with a series of soil properties and 7 climatic factors were investigated through Pearson's correlation, mantel test, random forest and pathway analysis. The results revealed that climatic factors were stronger drivers of ginseng secondary metabolite profile than soil nutrients. Specifically, temperature seasonality (TS) and soil available phosphorus (AP) were the most effective environments to have significantly and positively influence on the secondary metabolites of ginseng. This findings contribute to identifying optimal cultivation areas for P. ginseng, and hopefully establishing methods for interfering/shaping microclimate for cultivating high-quality P. ginseng.

Impact of Alaska atmospheric blocking on the carbon flux in the Northeast Pacific Ocean.

The Northeast Pacific Ocean (NEP) is one of the important carbon sinks in the global ocean. The causes of carbon flux changes in this region have been widely studied, but the physical processes associated with large scale climate variability remain controversial primarily due to scarcity of spatially and temporally continuous observations. In this study, we constructed a high-resolution sea surface partial pressure of CO2 (pCO2) from satellite observations for the NEP from 2003 to 2020 using the machine learning based XGBoost model. By analyzing the interannual large-scale high-latitude atmospheric dynamics and ocean physical conditions over the NEP, we find that the CO2 flux density (FCO2) anomalies have a strong correlation with the Alaskan atmospheric blocking events. In the region north of 48°N, anomalous cyclones triggered by atmospheric blocking increased sea surface height (SSH), which reduced the replenishment of dissolved inorganic carbon (DIC) from deep seawater, leading to enhanced carbon uptake. By contrast, in the region south of 48°N, the increase in sea surface temperature (SST) triggered by atmospheric blocking reduced the solubility of CO2 in seawater, resulting in a decrease in regional carbon flux. These results provide new perspectives for better understanding and predicting the effects of high-latitude atmospheric dynamics on regional ocean carbon fluxes.

Sediment contamination alters the submersed macrophyte Vallisneria natans and root-associated microbiome profiles during phytoremediation.

The submerged plant Vallisneria natans plays an important role in the remediation of polycyclic aromatic hydrocarbon (PAH)-contaminated sediments. In this study, V. natans and sediments were collected from different V. natans natural vegetation zones, and sediment mesocosms were set up for phytoremediation tests. In addition, commercial-grade V. natans were obtained from the Fish-Bird-Flower market for comparison with phytoremediation. Phytoremediation using V. natans from natural growth significantly increased the degradation of PAHs in Dashui Harbor (0.0148±0.0015 d-1) and Taihu Lake bay sediments (0.0082±0.0010 d-1) but not in commercial-grade V. natans. Transplanted V. natans from natural growth had a significant (p=0.002) effect on PAH degradation, especially in highly PAH-contaminated sedimentary environments. The distinct bacterial communities were strongly affected by sediment type and V. natans type, which contributed to different phytoremediation patterns. Less complex but more stable microbial co-occurrence networks play key roles in improving PAH phytoremediation potential. In addition, V. natans from natural growth in highly PAH-contaminated sediment could adapt to PAH stress by exuding tryptophan metabolites to assemble health-promoting microbiomes. This study provides novel evidence that initial microbial and physicochemical characteristics of sediment and submerged plant types should be considered in the use of bioremediation management strategies for organic pollutant-contaminated sediments.

Covalent-Organic Framework Nanomaterials: Energy Band Engineering Generating Ultrathin Lubrication Films for Excellent Lubrication.

It is, in fact, inevitable for steel to be covered with a layer of iron oxides and/or peroxides on its surface. However, knowledge of its existence and functionality for tribological behaviors is usually ignored. Herein, covalent-organic framework nanomaterials (CONs) composed of three well-screened acceptors and a donor through the imide linkage were fabricated to explore their lubrication performances. The results indicate that the energy-level matching between CONs and iron oxides or peroxides leads to the formation of a Z-scheme heterojunction structure at the rubbing interface. Also, the friction produces an internal electric field in the heterojunction, which drives the negative atomic/ionic species from the sliding interface to immigrate into the pore of CONs and resettle inside to engender the pinning effects, producing a fixed lubrication layer. Synchronously, it also attracts the free CONs in the base oil to form an easy-shear lubrication layer assembling onto the fixed one, producing a lubrication film with two layered configurations. Finally, the unique lubrication film, despite its thickness of a dozen nanometers, still exhibits impressive friction reduction and antiwear. This finding will inspire the technology to utilize the intrinsic surface nature of steel materials to exploit lubricant additives or modulate tribological behaviors.

Apoptotic vesicles (apoVs) derived from fibroblast-converted hepatocyte-like cells effectively ameliorate liver fibrosis.

Liver fibrosis is a serious global health issue for which effective treatment remains elusive. Chemical-induced hepatocyte-like cells (ciHeps) have emerged as an appealing source for cell transplantation therapy, although they present several challenges such as the risk of lung thromboembolism or hemorrhage. Apoptotic vesicles (apoVs), small membrane vesicles generated during the apoptosis process, have gained attention for their role in regulating various physiological and pathological processes. In this study, we generated ciHep-derived apoVs (ciHep-apoVs) and investigated their therapeutic potential in alleviating liver fibrosis. Our findings revealed that ciHep-apoVs induced the transformation of macrophages into an anti-inflammatory phenotype, effectively suppressed the activity of activated hepatic stellate cells (aHSCs), and enhanced the survival of hepatocytes. When intravenously administered to mice with liver fibrosis, ciHep-apoVs were primarily engulfed by macrophages and myofibroblasts, leading to a reduction in liver inflammation and fibrosis. Proteomic and miRNA analyses showed that ciHep-apoVs were enriched in various functional molecules that modulate crucial cellular processes, including metabolism, signaling transduction, and ECM-receptor interactions. ciHep-apoVs effectively suppressed aHSCs activity through the synergistic inhibition of glycolysis, the PI3K/AKT/mTOR pathway, and epithelial-to-mesenchymal transition (EMT) cascades. These findings highlight the potential of ciHep-apoVs as multifunctional nanotherapeutics for liver fibrosis and provide insights into the treatment of other liver diseases and fibrosis in other organs.

Nuclear translocation of plasma membrane protein ADCY7 potentiates T cell-mediated antitumour immunity in HCC.

BACKGROUND: The potency of T cell-mediated responses is a determinant of immunotherapy effectiveness in treating malignancies; however, the clinical efficacy of T-cell therapies has been limited in hepatocellular carcinoma (HCC) owing to the extensive immunosuppressive microenvironment. OBJECTIVE: Here, we aimed to investigate the key genes contributing to immune escape in HCC and raise a new therapeutic strategy for remoulding the HCC microenvironment. DESIGN: The genome-wide in vivo clustered regularly interspaced short palindromic repeats (CRISPR) screen library was conducted to identify the key genes associated with immune tolerance. Single-cell RNA-seq (scRNA-seq), flow cytometry, HCC mouse models, chromatin immunoprecipitation and coimmunoprecipitation were used to explore the function and mechanism of adenylate cyclase 7 (ADCY7) in HCC immune surveillance. RESULTS: Here, a genome-wide in vivo CRISPR screen identified a novel immune modulator-ADCY7. The transmembrane protein ADCY7 undergoes subcellular translocation via caveolae-mediated endocytosis and then translocates to the nucleus with the help of leucine-rich repeat-containing protein 59 (LRRC59) and karyopherin subunit beta 1 (KPNB1). In the nucleus, it functions as a transcription cofactor of CCAAT/enhancer binding protein alpha (CEBPA) to induce CCL5 transcription, thereby increasing CD8+ T cell infiltration to restrain HCC progression. Furthermore, ADCY7 can be secreted as exosomes and enter neighbouring tumour cells to promote CCL5 induction. Exosomes with high ADCY7 levels promote intratumoural infiltration of CD8+ T cells and suppress HCC tumour growth. CONCLUSION: We delineate the unconventional function and subcellular location of ADCY7, highlighting its pivotal role in T cell-mediated immunity in HCC and its potential as a promising treatment target.

Spatial single-cell protein landscape reveals vimentinhigh macrophages as immune-suppressive in the microenvironment of hepatocellular carcinoma.

Tumor microenvironment heterogeneity in hepatocellular carcinoma (HCC) on a spatial single-cell resolution is unclear. Here, we conducted co-detection by indexing to profile the spatial heterogeneity of 401 HCC samples with 36 biomarkers. By parsing the spatial tumor ecosystem of liver cancer, we identified spatial patterns with distinct prognosis and genomic and molecular features, and unveiled the progressive role of vimentin (VIM)high macrophages. Integration analysis with eight independent cohorts demonstrated that the spatial co-occurrence of VIMhigh macrophages and regulatory T cells promotes tumor progression and favors immunotherapy. Functional studies further demonstrated that VIMhigh macrophages enhance the immune-suppressive activity of regulatory T cells by mechanistically increasing the secretion of interleukin-1ß. Our data provide deep insights into the heterogeneity of tumor microenvironment architecture and unveil the critical role of VIMhigh macrophages during HCC progression, which holds potential for personalized cancer prevention and drug discovery and reinforces the need to resolve spatial-informed features for cancer treatment.

Evaluating the behavior and environmental risks of carbamazepine and its metabolites in soil aquifer treatment: Insights from deconjugation dynamics and toxicity assessment.

The presence of pharmaceuticals in the environment has been a growing concern. Recent studies highlight the ecological risks of pharmaceuticals, but most risk assessments focus on the parent drug, neglecting metabolites. This study examines the behavior and environmental risks of carbamazepine (CBZ) and its metabolites in soil aquifer treatment (SAT) for wastewater reclamation. Findings indicate that CBZ metabolites' total concentration exceeds that of CBZ. Notably, carbamazepine-N-glucuronide (CBZ-N-Glu) concentration decreased from 48.12 ng/L to undetectable levels during SAT, while CBZ concentration increased from 64.87 to 95 ng/L, suggesting possible deconjugation of CBZ-N-Glu. Batch and column experiments confirmed the hypothesis, showing a gradual disappearance of CBZ-Glu and a corresponding rise in CBZ concentration when CBZ-N-Glu was spiked into a recirculated SAT system. Quantitative structure-activity relationships (QSAR) analysis revealed that CBZ exhibits higher acute and chronic toxicity, with metabolites showing varying levels of developmental toxicity. The study also evaluates the persistence, mobility, and toxicity (PMT) characteristics of CBZ and its metabolites, highlighting CBZ-N-Glu's particularly adverse PMT characteristics compared to CBZ. In summary, the residual pharmaceuticals in the reclaimed water process should be evaluated systematically, considering both the parent compounds and their metabolites.

Comprehensive analysis of single-nucleotide variants and alternative polyadenylation between inbred and outbred pigs.

Inbreeding can lead to the accumulation of homozygous single nucleotide polymorphisms (SNPs) in the genome, which can significantly affect gene expression and phenotype. In this study, we examined the impact of homozygous SNPs resulting from inbreeding on alternative polyadenylation (APA) site selection and the underlying genetic mechanisms using inbred Luchuan pigs. Genome resequencing revealed that inbreeding results in a high accumulation of homozygous SNPs within the pig genome. 3' mRNA-seq on leg muscle, submandibular lymph node, and liver tissues was performed to identify differences in APA events between inbred and outbred Luchuan pigs. We revealed different tissue-specific APA usage caused by inbreeding, which were associated with different biological processes. Furthermore, we explored the role of polyadenylation signal (PAS) SNPs in APA regulation under inbreeding and identified key genes such as PUM1, SCARF1, RIPOR2, C1D, and LRRK2 that are involved in biological processes regulation. This study provides resources and sheds light on the impact of genomic homozygosity on APA regulation, offering insights into genetic characteristics and biological processes associated with inbreeding.

Genome resequencing reveals the genetic basis of population evolution, local adaptation, and rewiring of the rhizome metabolome in Atractylodes lancea.

The formation of high-quality Chinese medicinal materials is a micro-evolutionary process of multiple genes involving quantitative inheritance under environmental stress. Atractylodes lancea is a traditionally used medicinal plant in China that is broadly distributed and possesses a considerable amount of essential oils. However, to date, limited research has been conducted to characterize the genetics and metabolites of A. lancea shaped by natural variation. Hence, we assembled a high-quality genome of A. lancea, featuring a contig N50 of 1.18 Mb. We further integrated population resequencing of A. lancea and conducted analyses to characterize its genetic diversity, population evolution, and rewiring of volatile metabolites. The natural variation effect exerted significant pressure on A. lancea from different geographic locations, resulting in genetic differentiation among three groups. Correlation analysis of metabolites in A. lancea revealed significant natural variations of terpenoids, heterocyclic compounds, ketones, and esters. We also found that 427 metabolites displayed noteworthy divergence due to directional selection. Additionally, our genome-wide association studies on the metabolome for medicinal quality traits identified several candidate genes, such as AlZFP706 and AlAAHY1, exhibiting significant correlations with atractylodin and hinesol levels, respectively. Overall, this study provides an intricate genomic resource for A. lancea, thereby expanding our understanding of the effect of natural variation on metabolites and facilitating the genetic improvement of its medicinal properties.

Spatial multiomics reveals a subpopulation of fibroblasts associated with cancer stemness in human hepatocellular carcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. METHODS: We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. RESULTS: We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. CONCLUSIONS: We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.