ATP-binding Cassette Research Articles

Genomic signal selection analysis reveals genes related to the lambing trait of Hotan sheep.

Lambing in ewes is a complex and crucial aspect of sheep production that directly influences economic viability and production efficiency. In the present study, we analyzed the genomes of single lamb (SLE) and twin lamb (TLE) Hotan sheep to elucidate the genetic mechanisms underlying lamb production in Hotan sheep. In this study, we used genome-wide resequencing to analyze the genomes of Hotan sheep exhibiting SLE and TLE traits. To identify the population genetic structure and linkage disequilibrium associated with SLE and TLE traits, we employed two complementary genome selection signals: the interpopulation genetic differentiation index (FST) and nucleotide diversity (Pi). Subsequently, we performed gene annotation and enrichment analyses of the selected regions of the obtained genome. Our analysis generated 801 Gb of sequence data, from which 31,864,651 high-quality single nucleotide polymorphic loci were identified. We identified 290 selected regions and 332 genes across the Hotan sheep genome by using two widely adopted selective scanning detection methods (FST statistics and Piratio). Functional annotation and enrichment analysis of these genes identified 13 genes associated with the lambing rate, which were enriched in pathways such as the transforming growth factor-β (TGF-β) signaling pathway (BMPR2, ID2, SMAD7, THBS1, and RBX1), renal cell carcinoma (PAK1, ELOC), inositol phosphate metabolism (PLCZ), non-homologous terminal junction (RAD50), ABC transporters (ABCC4), and the NET pathway (H2B, H4, and H2A). This study employed selective elimination analysis to identify candidate genes involved in the regulation of lambing trait in Hotan sheep. By investigating the molecular mechanisms underlying lambing rate in Hotan sheep, we developed molecular markers for twin lambing to enhance reproductive performance and promote the conservation and development of outstanding genetic resources in local Xinjiang sheep.

Role of ABCC5 in cancer drug resistance and its potential as a therapeutic target

Over 90% of treatment failures in cancer therapy can be attributed to multidrug resistance (MDR), which can develop intracellularly or through various routes. Numerous pathways contribute to treatment resistance in cancer, but one of the most significant pathways is intracellular drug efflux and reduced drug concentrations within cells, which are controlled by overexpressed drug efflux pumps. As a member of the family of ABC transporter proteins, ABCC5 (ATP Binding Cassette Subfamily C Member 5) reduces the intracellular concentration of a drug and its subsequent effectiveness using an ATP-dependent method to pump the drug out of the cell. Numerous studies have demonstrated that ABCC5 is strongly linked to both poor prognosis and poor treatment response. In addition, elevated ABCC5 expression is noted in a wide variety of malignancies. Given that ABCC5 is regulated by several pathways in a broad range of cancer types, it is a prospective target for cancer treatment. This review examined the expression, structure, function, and role of ABCC5 in various cancer types.

DNA Sensor ABCF1 Phase Separates With cccDNA to Inhibit Hepatitis B Virus Replication.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) contributes to viral persistence and recurrence, however, how the host innate immune system responds to cccDNA is still less known. Here, based on cccDNA-hepatic proteins interaction profiling, DNA sensor ATP-binding cassette subfamily F member 1 (ABCF1) is identified as a novel cccDNA-binding protein and host restriction factor for HBV replication. Mechanistically, ABCF1 recognizes cccDNA by KKx4 motif and forms phase-separated condensates by the poly-glutamine (PolyQ) region of the N-terminal intrinsically disordered low-complexity domain (LCD). Subsequently, ABCF1-cccDNA phase separation not only activates the type I/III interferon (IFN-I/III) pathway but also prevents Pol II accumulation on cccDNA to inhibit HBV transcription. In turn, to sustain viral replication, HBV reduces ABCF1 expression by HBx-mediated ubiquitination and degradation of SRY-box transcription factor 4（SOX4）, leading to defects in SOX4-mediated upregulation of ABCF1 transcription. Taken together, the study shows that ABCF1 interacts with cccDNA to form phase separation that dually drives innate immune signaling and HBV transcriptional inhibition. These findings shed new light on the understanding of host defense against cccDNA and provide a novel promising therapeutic strategy for HBV infection.

Chitosan oligosaccharides: A potential therapeutic agent for inhibiting foam cell formation in atherosclerosis

Foam cell formation is a key hallmark in atherosclerosis and associated cardiovascular diseases (CVDs). The potential anti-atherosclerotic potential of chitosan oligosaccharides (COS) was investigated using oxLDL-treated RAW264.7 murine cells. COS treatment led to a significant inhibition of lipid accumulation, as demonstrated by Oil Red O staining, and reduced levels of total cholesterol, free cholesterol, cholesterol esters, and triglycerides in.oxLDL-treated RAW264.7 cells. COS blocked cholesterol influx through down-regulating class A1 scavenger receptors (SR-A1) and cluster of differentiation 36 (CD36) expression and stimulated cholesterol efflux through up-regulating ABC transporters ABCA-1 and ABCG-1 expressions. Additionally, COS treatment stimulated nuclear signaling pathways involving peroxisome proliferator-activated receptor-γ (PPAR-γ) and liver X receptor α (LXR-α), and also led to the phosphorylation of AMP-activated protein kinase (AMPK). COS further demonstrated anti-inflammatory effects by inhibiting the production of pro-inflammatory cytokines and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in oxLDL-treated RAW264.7 cells, through suppression of NF-κB signaling. Furthermore, COS alleviated oxidative stress induced by oxLDL by activating Nrf2 signaling and enhancing the expression of antioxidant genes, including heme oxygenase-1 (HO-1), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and catalase (CAT). In conclusion, COS can be beneficial in preventing atherosclerosis and related diseases.

Mechanistic insight of fungal–microalgal pellets in photobioreactor for heavy-metal wastewater bioremediation

The high cost of harvesting microalgae limits their industrial application. Fungal–microalgal pellets can efficiently harvest microalgae and enhance heavy-metal adsorption. However, the molecular response mechanism of fungal–microalgal pellets under heavy-metal stress remains unclear. Fungal–microalgal pellets in a photobioreactor were used as a research object, and a 98 % harvesting efficiency could be achieved with adding exogenous carbon and nitrogen at pH 5.0–6.0 for 12 h of co-culture. Humic acid- and tryptophan-rich proteins in extracellular polymeric substances (EPS) participate in Cd(II) complexation. The Cd(II) response in fungal-microalgal pellets involves amino acids, glucose, lipids, energy metabolism, and antioxidant systems. The turning point was at 48 h. Proline, histidine, and glutamine synthesis and the adenosine-triphosphate (ATP) binding cassette (ABC) transport pathway play important roles in resistance to Cd(II) biotoxicity. This study provides a reference for the large-scale cultivation of fungal-microalgal symbiotic pellets and the practical application for industrial heavy-metal wastewater.

Structural insights into brassinosteroid export mediated by the Arabidopsis ABC transporter ABCB1

Brassinosteroids (BRs) are steroidal phytohormones indispensable for plant growth, development, and responses to environmental stresses. The export of bioactive BRs to the apoplast is essential for BR signalling initiation, which requires binding of BR molecule to the extracellular domains of the plasma membrane-localized receptor complex. We have previously shown that the Arabidopsis thaliana ATP-binding cassette (ABC) transporter, ABCB19, functions as a BR exporter, and together with its close homologue, ABCB1, positively regulate BR signalling. Here, we demonstrate that ABCB1 is another BR transporter. The ATP hydrolysis activity of ABCB1 was stimulated by bioactive BRs, and its transport activity was confirmed in proteoliposomes and protoplasts. Structures of ABCB1 in substrate-unbound (apo), brassinolide (BL)-bound, and ATP plus BL-bound states were determined. In the BL-bound structure, BL was bound to the hydrophobic cavity formed by the transmembrane domain, and triggered local conformational changes. Together, our data provide additional insights into the ABC transporter-mediated BR export.

Blood-brain barrier permeability increases with the differentiation of glioblastoma cells in vitro

BackgroundGlioblastoma multiforme (GBM) is an aggressive tumor, difficult to treat pharmacologically because of the blood-brain barrier (BBB), which is rich in ATP-binding cassette (ABC) transporters and tight junction (TJ) proteins. The BBB is disrupted within GBM bulk, but it is competent in brain-adjacent-to-tumor areas, where eventual GBM foci can trigger tumor relapse. How GBM cells influence the permeability of BBB is poorly investigated.MethodsTo clarify this point, we co-cultured human BBB models with 3 patient-derived GBM cells, after separating from each tumor the stem cell/neurosphere (SC/NS) and the differentiated/adherent cell (AC) components. Also, we set up cultures of BBB cells with the conditioned medium of NS or AC, enriched or depleted of IL-6. Extracellular cytokines were measured by protein arrays and ELISA. The intracellular signaling in BBB cells was measured by immunoblotting, in the presence of STAT3 pharmacological inhibitor or specific PROTAC. The competence of BBB was evaluated by permeability assays and TEER measurement.ResultsThe presence of GBM cells or their conditioned medium increased the permeability to doxorubicin, mitoxantrone and dextran-70, decreased TEER, down-regulated ABC transporters and TJ proteins at the transcriptional level. These effects were higher with AC or their medium than with NS. The secretome analysis identified IL-6 as significantly more produced by AC than by NS. Notably, AC-conditioned medium treated with an IL-6 neutralizing antibody reduced the BBB permeability to NS levels, while NS-conditioned medium enriched with IL-6 increased BBB permeability to AC levels. Mechanistically, IL-6 released by AC GBM cells activated STAT3 in BBB cells. In turn, STAT3 down-regulated ABC transporter and TJ expression, increased permeability and decreased TEER. The same effects were obtained in BBB cells treated with STA-21, a pharmacological inhibitor of STAT3, or with a PROTAC targeting STAT3.ConclusionsOur work demonstrates for the first time that the degree of GBM differentiation influences BBB permeability. The crosstalk between GBM cells that release IL-6 and BBB cells that respond by activating STAT3, controls the expression of ABC transporters and TJ proteins on BBB. These results may pave the way for novel therapeutic tools to tune BBB permeability and improve drug delivery to GBM.

Homocysteine S-Methyltransferase 3 Positively Regulates Cadmium Tolerance in Maize.

The increasing contamination of agricultural soils with cadmium (Cd) poses a significant threat to human health and global food security. Plants initiate a series of mechanisms to reduce Cd toxicity. However, the response of maize to Cd toxicity remains poorly understood. In this study, we identified that ZmHMT3, which encodes a homocysteine S-methyltransferases family protein, acted as a regulator of Cd tolerance in maize. Subcellular localization and in situ PCR exhibited that ZmHMT3 was localized in the cytoplasm and predominantly expressed in the phloem. Overexpression of ZmHMT3 enhanced Cd tolerance and reduced Cd concentration in both shoots and roots. In contrast, ZmHMT3 mutants attenuated Cd tolerance but did not change shoot Cd concentration. Heterologous overexpression of ZmHMT3 in rice enhanced Cd tolerance and reduced grain Cd concentration. Transcriptome analysis revealed that ZmHMT3 upregulated the expression of stress-responsive genes, especially glutathione S-transferases (GSTs) and transcription factors, including MYBs, NACs and WRKYs, and modulates the expression of different ATP-binding cassette (ABC) transporters, thereby enhancing Cd tolerance. Collectively, these findings highlight the pivotal role of ZmHMT3 in Cd tolerance and as a candidate gene for improving Cd tolerance in elite maize varieties.

Combined transcriptome and metabolome analysis reveals the mechanism of high nitrite tolerance in freshwater mussel Anodonta woodiana

Nitrite contamination and stress on aquatic organisms are increasingly emphasized in freshwater ecosystems. Freshwater bivalves exhibit high tolerance to nitrite; however, the underlying mechanism is unknown. Accordingly, this study investigated the tolerance mechanism of the globally occurring freshwater bivalve Anodonta woodiana. A. woodiana were exposed to nominal concentrations of 0, 250, 500, 1000, 2000, and 4000 mg/L nitrite for 96 h to calculate the 96-h median lethal concentration (96-h LC50). A combined transcriptome and metabolome analysis of the hemolymph (the most vital component of the bivalve immune system) was performed after exposing A. woodiana to 300 mg/L nitrite (approximately half the 96-h LC50) for 96 h. The 96-h LC50 of nitrite in A. woodiana was 618.7 mg/L. Transcriptome analysis identified 5600 differentially expressed genes (DEGs) primarily related to ribosomes, lysosomes, DNA replication, and nucleotide excision repair. Metabolome analysis identified 216 differentially expressed metabolites (DEMs) primarily involved in biosynthesis of amino acids, 2-oxocarboxylic acid metabolism, protein digestion and absorption, aminoacyl-tRNA biosynthesis, nucleotide metabolism, ABC transporters, and valine, leucine and isoleucine degradation. Combined transcriptome and metabolome analysis revealed that DEGs and DEMs were primarily associated with nucleotide (purine and pyrimidine) and amino acid metabolism (including aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, arginine and proline metabolism, and valine, leucine and isoleucine degradation) as well as the immune system (necroptosis and glutathione metabolism). This study is the first to describe the high tolerance of A. woodiana to nitrite and elucidate the molecular mechanisms underlying high nitrite tolerance in mussels.

Study on the physiological responses and tolerance mechanisms to subchronic carbonate alkalinity exposure in the gills of Paramisgurnus dabryanus

Given the reduction of freshwater resources, saline-alkaline aquaculture has emerged as an effective approach to expand the fishery's accessible space. High carbonate alkalinity (CA) is a major stressor for aquatic organisms in saline-alkaline environments. Paramisgurnus dabryanus is a potential species for culture in saline-alkaline water, making it an ideal model for investigating the physiological responses and tolerance mechanisms to CA exposure in freshwater fishes. In the current study, P. dabryanus were exposed to 15 and 30mmol/L NaHCO3, combining blood biochemical, gill histological, transcriptomic, and metabolomic methods for conjoint analysis of response mechanisms. After 28-d exposure, the gill ventilation frequency of P. dabryanus decreased significantly, gill lamellae twisted and atrophied, and gill filament epithelial cells proliferated, potentially limiting gas exchange, whereas the accessory air-breathing frequency increased significantly, possibly for greater oxygen uptake. Serum osmolality and blood pH remained relatively steady, while serum ammonia levels rose significantly. A total of 3718 differentially expressed genes (DEGs) and 205 differential metabolites (DMs) were identified between the control group and 30mmol/L NaHCO3 group, involved in ion transport (Na+/K+-ATPase, V-type ATPase, carbonic anhydrase, and ABC transporters), ammonia transport (Rh glycoproteins and Aquaporins), amino acid metabolism, carbohydrate metabolism, and fatty acid metabolism. Furthermore, DEGs were significantly associated with cell-cell/ extracellular matrix interaction and protein synthesis. An integrated multi-omics analysis revealed the activation of carbon metabolism and TCA cycle. These results indicate that in response to CA exposure, P. dabryanus may facilitate carrier-mediated ion and ammonia transport to maintain the internal osmotic equilibrium and lessen the deleterious effects of blocked ammonia excretion. Meanwhile, amino acid metabolism and protein synthesis are disturbed, P. dabryanus can modulate carbohydrate catabolism to maintain energy homeostasis. The above findings provide novel insights into saline-alkaline adaptation in freshwater fishes, paving the way for future research and development of saline-alkaline-tolerant Cobitidae strains.

Identification of Anti-Inflammatory and Anti-Cancer Compounds Targeting the NF-κB-NLRP3 Inflammasome Pathway from a Phytochemical Library of the Sideritis Genus

Ethnobotanical relevanceFor centuries, the aerial parts of Sideritis species have been known for their medicinal properties as herbal teas. Although the antioxidant and anti-inflammatory properties of the genus have been widely documented, the underlying mechanisms are yet to be sufficiently clarified. Aim of the studyWe investigated the anti-inflammatory and anticancer activities of phytochemicals of the Sideritis genus. Material and methodsThrough literature mining, a chemical library containing 657 components of the Sideritis genus was formed. We studied these compounds for binding to NLRP3 and NF-κB proteins in silico by virtual drug screening and molecular docking, and in vitro by microscale thermophoresis (MST). Liquid chromatography-high-resolution mass spectrometry analysis (LC-HRMS) was performed in the Sideritis extracts. One of the identified compounds, verbascoside, was investigated for its cytotoxic activity by mining a panel of 49 tumor cell lines in the data repository of the National Cancer Institute (NCI, USA). ResultsVirtual screening and molecular docking results highlighted two compounds targeting both proteins of interest, i.e., verbascoside (acteoside) and apigenin 7,4′-bis(trans-p-coumarate), as both had lowest binding energies of less than -10 kcal/mol. Using MST, we then verified that both compounds bound to the target proteins. Verbascoside bound to NLRP3 and NF-κB with Kd values of 0.67 ± 0.18 μM and 0.01 ± 0.08 μM, while apigenin 7,4′-bis(trans-p-coumarate) had Kd values of 4.60 ± 1.66 μM and 0.27 ± 0.75 μM, respectively. Verbascoside was abundant in the Sideritis extracts, according to LC-HRMS analysis. Since inflammation is strongly related to carcinogenesis, we investigated the anticancer activity of verbascoside in the second part of this study. We investigated the activity of verbascoside in 49 tumor cell lines of the NCI. Comparing its activity with 81 standard anticancer drugs revealed numerous interactions with DNA-damaging agents (alkylators, topoisomerase I/II inhibitors, antimetabolites), indicating that verbascoside may also affect the DNA of tumor cells. We further investigated the involvement of verbascoside in several main drug resistance mechanisms, i.e., ABC transporters, oncogenes, tumor suppressors, cellular proliferation rates, and other parameters. Except for the correlation to the mutational status of NRAS, no other significant relationships were found, indicating that verbascoside is not involved in most of the common drug resistance mechanisms. Two-dimensional cluster analysis-based heatmap generation of a proteomic profile from 40 out of 3171 proteins revealed a significant correlation between the expression of these proteins in 49 tumor cell lines, and the cellular response to verbascoside. This indicates that the presence of these proteins is a determinant for sensitivity or resistance to this natural product. ConclusionThe database established here represents a valuable resource for the screening of bioactivites of the Sideritis genus. The experimental validation of the anti-inflammatory and cytotoxic activities of selected compounds proved that virtual drug screening and molecular docking are suitable tools for the identification of putative drug candidates. Verbascoside was among the top 10 compounds binding to two key anti-inflammatory proteins, NLRP3 and NF-kB. Additionally, data from the NCI indicate that verbascoside is not linked to main drug resistance mechanisms.

BPA-free? Exploring the reproductive toxicity of BPA substitutes BPS and BPF on endometrial decidualization

Bisphenol A (BPA) exposure is linked to multiple adverse health outcomes, prompting the rise of "BPA-free" products. However, substitutes like Bisphenol S (BPS) and Bisphenol F (BPF) are equally prevalent, with detection frequencies and concentrations rivaling BPA. Our research previously identified BPA as an endocrine disruptor affecting reproductive and developmental systems. This study explores the impact of BPA, BPS, and BPF on endometrial decidualization and receptivity. We detected these bisphenols in serum samples from infertile women undergoing assisted reproductive technology (ART) treatment whose average age was 31.58 years. Human endometrial stromal cells were exposed to varying concentrations (0, 1 nM, 10 nM, 100 nM, and 1 µM) of BPA, BPS, and BPF, following hormonal induction of decidualization (10 nM E2 (Estradiol) + 0.5 mM cAMP (Cyclic adenosine monophosphate) + 1 µM MPA (Medroxyprogesterone acetate) for 6 days). Methods including CCK-8, RT-qPCR, untargeted metabolomics, and transcriptome sequencing assessed cell proliferation, molecular markers, gene expression, and metabolites. BPS levels in the serum of infertile patients were significantly higher than BPA (14.52 vs. 2.58 ng/mL) and even more pronounced in the recurrent implantation failure (RIF) group compared to the Control group (23.46 vs. 5.57 ng/mL). Findings revealed that BPA and its substitutes inhibited endometrial stromal cell proliferation and reduced decidualization markers. Differential metabolites (25, 66, 104) and gene expressions (3260, 9686, 10357) were observed with BPA, BPF, and BPS exposure, respectively. Enriched pathways included glutathione metabolism, arginine biosynthesis, ABC transporters, cAMP signaling, and glucagon signaling. Metabolomics and transcriptome analyses unveiled the reproductive toxic effects of BPA and its substitutes, suggesting significant impacts on endometrial decidualization through diverse signaling pathways.

Cryo-EM reveals a phosphorylated R-domain envelops the NBD1 catalytic domain in an ABC transporter.

Many ATP-binding cassette transporters are regulated by phosphorylation on long and disordered loops which presents a challenge to visualize with structural methods. We have trapped an activated state of the regulatory domain (R-domain) of yeast cadmium factor 1 (Ycf1) by enzymatically enriching the phosphorylated state. A 3.23 Å cryo-EM structure reveals an R-domain structure with four phosphorylated residues and the position for the entire R-domain. The structure reveals key R-domain interactions including a bridging interaction between NBD1 and NBD2 and an interaction with the R-insertion, another regulatory region. We scanned these interactions by systematically replacing segments along the entire R-domain with scrambled combinations of alanine, glycine, and glutamine and probing function under cellular conditions that require the Ycf1 function. We find a close match with these interactions and interacting regions on our R-domain structure that points to the importance of most well-structured segments for function. We propose a model where the R-domain stabilizes a transport-competent state upon phosphorylation by enveloping NBD1 entirely.

The Loss-of-Function ATP Binding Cassette Subfamily G Member 2 Polymorphism ABCG2 c.421C>A Reduces Lamotrigine Trough Concentrations in Adults with Epilepsy.

The commonly used antiseizure medication lamotrigine is a substrate to ATP binding cassette subfamily G member 2 (ABCG2) transporter. The objective of this study was to evaluate the effect of the common loss-of-function polymorphism ABCG2 c.421C>A (rs2231142) on the lamotrigine trough concentrations at steady state in adults with epilepsy. In two consecutive studies (Study 1, Study 2) in patients on lamotrigine monotherapy, carriers of the variant ABCG2 c.421C>A allele (CA/AA) were considered exposed, and wild-type homozygotes (CC) were considered controls. They were mutually balanced on covariates (age, sex, body weight, several polymorphisms in genes encoding other transporter proteins and lamotrigine-metabolizing enzymes that have been suggested to affect exposure to lamotrigine) to estimate the exposure effect (geometric means ratios, GMRs) in each study separately and overall (individual patient data meta-analysis). The overall estimate was evaluated for sensitivity to residual confounding. In both studies (exposed n = 28 vs. controls n = 103; exposed n = 44 vs. controls n = 153, in Study 1 and Study 2, respectively) and overall (exposed n = 72 vs. controls n = 256), dose-corrected lamotrigine trough concentrations were moderately lower in the exposed patients: frequentist GMR [95% CI] = 0.82 [0.63-1.08]; GMR = 0.69 [0.60-0.81] and GMR = 0.72 [0.63-0.83] in Study 1, Study 2 and overall, respectively; Bayes GMR [95% CrI] = 0.83 [0.68-1.00]; GMR = 0.69 [0.58-0.83] and GMR = 0.75 [0.65-0.86] in Study 1, Study 2 and overall, respectively. Estimates appeared resistant to unmeasured confounding-the E-values for the pooled point estimates were high, and estimates corrected for a strong hypothetical bias were GMR = 0.78 [0.68-0.90] frequentist and GMR = 0.81 [0.70-0.93] Bayes. Polymorphism ABCG2 c.421C>A moderately reduces lamotrigine concentrations in adults with epilepsy.

Identification and characterization of ATP-binding cassette transporters involved in chlorantraniliprole tolerance of model insect Drosophila melanogaster and agricultural pest Spodoptera frugiperda

Identification and characterization of ATP-binding cassette transporters involved in chlorantraniliprole tolerance of model insect Drosophila melanogaster and agricultural pest Spodoptera frugiperda

Association Between ABCC2 -24C>T and Nab-Paclitaxel-induced Peripheral Neuropathy in Japanese Patients With Pancreatic Cancer.

Nab-paclitaxel is used to treat patients with pancreatic cancer. However, it frequently induces peripheral neuropathy. Notably, pharmacokinetic factors may be associated with neuropathic symptoms as the onset depends on the cumulative dose. Therefore, we prospectively examined the association between the cumulative dose of nab-paclitaxel at the onset of peripheral neuropathy and polymorphisms of hepatic transporter genes. Patients with pancreatic cancer receiving nab-paclitaxel (125 mg/m2) and gemcitabine (1,000 mg/m2) were enrolled. Peripheral neuropathy was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), Patient-Reported Outcomes CTCAE (PRO-CTCAE), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), every 2-12 weeks, and every 4 weeks thereafter. solute carrier organic anion transporter family member 1B1 (SLCO1B1) 521T>C, 388A>G; SLCO1B3 rs11045585; ATP-binding cassette transporters, subfamily B, member 1 (ABCB1) 1236C>T, 2677G>T/A, 3435C>T; ABCC1 rs2644983; ABCC2 24C>T; and ABCG2 421C>A were analyzed by direct sequencing. Correlations between transporter genotypes and cumulative dose at symptom onset were assessed using Kaplan-Meier and log-rank tests. In total, 25 patients were enrolled. The lowest median cumulative dose for nab-paclitaxel at peripheral neuropathy onset using PRO-CTCAE was 593 mg. By CTCAE it was 800 mg, and by FACT/GOG-Ntx it was 1,090 mg (p<0.0001). At symptom onset, patients with ABCC2 -24C/T genotype had received a significantly lower median cumulative dose by PRO-CTCAE (540 mg) than those with C/C (720 mg) (p=0.0188). However, the other polymorphisms studied were not associated with symptoms. Herein, we found for the first time that ABCC2 -24C/T genotype was significantly associated with the onset of nab-paclitaxel-induced peripheral neuropathy detected with PRO-CTCAE.

Beta-cypermethrin-induced stress response and ABC transporter-mediated detoxification in Tetrahymena thermophila

β-Cypermethrin (β-CYP), a synthetic pyrethroid pesticide, is widely used for insect management. However, it also affects non-target organisms and pollutes aquatic ecosystems. Tetrahymena thermophila, a unicellular ciliated protist found in fresh water, is in direct contact with aquatic environments and sensitive to environmental changes. The proliferation of T. thermophila was inhibited and the cellular morphology changed under β-CYP stress. The intracellular ROS level significantly increased, and SOD activity gradually rose with increasing β-CYP concentrations. Under 25 mg/L β-CYP stress, 687 genes were up-regulated, primarily enriched in the organic cyclic compound binding and heterocyclic compound binding pathways. These include 8 ATP-binding cassette transporters (ABC) family genes, 2 cytochrome P450 monooxygenase genes, and 2 glutathione peroxidase related genes. Among of them, ABCG14 knockdown affected cellular proliferation under β-CYP stress. In contrast, overexpression of ABCG14 enhanced cellular tolerance to β-CYP. The results demonstrated that Tetrahymena tolerates high β-CYP concentration stress through various detoxification mechanisms, with ABCG14 playing a crucial role in detoxification of β-CYP.

Comparative transcriptome analysis of Aspergillus niger revealed its biocontrol mechanisms in response to the guava wilt pathogen Fusarium oxysporum f. sp. psidii.

Wilt is one of the major destructive diseases in guava cultivation worldwide. Biocontrol agent Aspergillus niger has been recognized for its efficacy against various plant pathogens including guava wilt disease. This biocontrol fungus has been widely studied for its mycoparasitic and antibiosis mechanisms. Still, a notable gap exists in the literature regarding the molecular mechanisms and biosynthetic pathways underlying biocontrol activity when challenged with guava wilt pathogen. In this investigation, we conducted comprehensive global RNA sequencing, which generated a total of 35.16 GB data, comprising 18–22 million reads having 52-54% GC content. Over 55,464 transcripts displayed differential expression profiles during the interaction of biocontrol and the pathogen, out of that 5,285 transcripts were expressed at FC2 and Pval 0.05. They were mainly associated with catalytic activity (48.45%), protein or DNA binding activity (44.9%), transporter activity (8.2%), and transcription regulator activity (5.5%). In the biological process category, 36.5% and 34.7% of transcripts were linked to "metabolic" and "cellular processes," respectively. The upregulated DEGs were predominantly linked to hydrolytic activity and secondary metabolite production, encompassing AB hydrolases, cyanate hydratase, Isochorismatase hydrolase, galacturan 1,4-alpha-galacturonidase B, Esterase/Lipase, MFS monosaccharide transporter, ATP-binding cassette transporter, polyamine transporter 3, endoglucanase A, and non-ribosomal siderophore peptide synthase (SidC). Our investigation highlighted that the biocontrol mechanism primarily involves the active participation of hydrolytic enzymes, transporters, transcription factors, and secondary metabolites. Additionally, the data were validated using RT-qPCR, affirming the consistency of RNA-seq findings. This study represents the inaugural effort to elucidate the biocontrol mechanism of A. niger against F. oxysporum f. sp. psidii using the RNA-seq approach. The findings shed light on the antagonistic mechanisms of A. niger at the molecular level, enhancing our comprehension of A. niger as a biocontrol agent and deepening our exploration of biocontrol and pathogen interactions.

Differential gene expression of immune response in COVID-19 and its relationship with progression of COVID-19

Human immune response evolved in virus clearance and gene expression levels of immune response may be associated with progression of Coronavirus disease 2019 (COVID-19). Our current study aims to investigate the relationship between differential gene expression of immune response and progression of COVID-19. A total of 50 participants of COVID-19 group were studied, compared with 39 participants of healthy control group. There were different gene expression profiles in pathways of activation of neutrophil, defense response and adaptive immune response for COVID-19 group before treatment compared to the healthy control group. Distinct gene expression profiles showed that pathways of chemotaxis, immune response and antibacterial humoral response involved in rehabilitation of severe COVID-19 group while pathways of immune system process, defense response to virus and negative regulation of viral genome replication involved in rehabilitation of moderate COVID-19 group. Both protein expression of ATP-binding cassette transporter A1 levels and protein expression of low affinity Fc-receptor FcγRIIIb levels were significantly and positively correlated with COVID-19-IgM levels and might be suitable as biomarkers for monitoring of COVID-19. This study showed that differential gene expression of immune response predicted onset and rehabilitation of COVID-19.

Genomic evolution and patterns of horizontal gene transfer in Papilio

The Papilio genus, known for its ecological and phenotypic diversity, is a valuable model for evolutionary studies. This study conducted a comparative genomic analysis of 11 Papilio species, revealing species-specific gene family expansions, including the UDP-glucosyltransferase 2 gene associated with insect detoxification, particularly expanding in Papilio polyxenes. Our analysis also revealed 199 horizontal gene transfer (HGT) acquired genes from 76 microbial species, with Pseudomonadota and Bacillota as common HGT donors across these genomes. Furthermore, we examined the evolutionary patterns of nine ABC transporter subfamilies, uncovering potential links between gene family evolution and environmental adaptation. This study provides new insights into evolutionary relationships and genomic adaptations within the Papilio genus, contributing to broader butterfly evolutionary research.