Scaphopoda is the sister taxon to Bivalvia: Evidence of ancient incomplete lineage sorting.

The almost simultaneous emergence of major animal phyla during the early Cambrian shaped modern animal biodiversity. Reconstructing evolutionary relationships among such closely spaced branches in the animal tree of life has proven to be a major challenge, hindering understanding of early animal evolution and the fossil record. This is particularly true in the species-rich and highly varied Mollusca where dramatic inconsistency among paleontological, morphological, and molecular evidence has led to a long-standing debate about the group's phylogeny and the nature of dozens of enigmatic fossil taxa. A critical step needed to overcome this issue is to supplement available genomic data, which is plentiful for well-studied lineages, with genomes from rare but key lineages, such as Scaphopoda. Here, by presenting chromosome-level genomes from both extant scaphopod orders and leveraging complete genomes spanning Mollusca, we provide strong support for Scaphopoda as the sister taxon of Bivalvia, revitalizing the morphology-based Diasoma hypothesis originally proposed 50 years ago. Our molecular clock analysis confidently dates the split between Bivalvia and Scaphopoda at ~520 Ma, prompting a reinterpretation of controversial laterally compressed Early Cambrian fossils, including Anabarella, Watsonella, and Mellopegma, as stem diasomes. Moreover, we show that incongruence in the phylogenetic placement of Scaphopoda in previous phylogenomic studies was due to ancient incomplete lineage sorting (ILS) that occurred during the rapid radiation of Conchifera. Our findings highlight the need to consider ILS as a potential source of error in deep phylogeny reconstruction, especially in the context of the unique nature of the Cambrian Explosion.

Psoralen and Isopsoralen, Two Estrogen-Like Natural Products from Psoraleae Fructus, Induced Cholestasis via Activation of ERK1/2.

With the increasing use of oral contraceptives and estrogen replacement therapy, the incidence of estrogen-induced cholestasis (EC) has tended to rise. Psoralen (P) and isopsoralen (IP) are the major bioactive components in Psoraleae Fructus, and their estrogen-like activities have already been recognized. Recent studies have also reported that ERK1/2 plays a critical role in EC in mice. This study aimed to investigate whether P and IP induce EC and reveal specific mechanisms. It was found that P and IP increased the expression of esr1, cyp19a1b and the levels of E2 and VTG at 80 µM in zebrafish larvae. Exemestane (Exe), an aromatase antagonist, blocked estrogen-like activities of P and IP. At the same time, P and IP induced cholestatic hepatotoxicity in zebrafish larvae with increasing liver fluorescence areas and bile flow inhibition rates. Further mechanistic analysis revealed that P and IP significantly decreased the expression of bile acids (BAs) synthesis genes cyp7a1 and cyp8b1, BAs transport genes abcb11b and slc10a1, and BAs receptor genes nr1h4 and nr0b2a. In addition, P and IP caused EC by increasing the level of phosphorylation of ERK1/2. The ERK1/2 antagonists GDC0994 and Exe both showed significant rescue effects in terms of cholestatic liver injury. In conclusion, we comprehensively studied the specific mechanisms of P- and IP-induced EC and speculated that ERK1/2 may represent an important therapeutic target for EC induced by phytoestrogens.

Neuroglobin inhibits pancreatic cancer proliferation and metastasis by targeting the GNAI1/EGFR/AKT/ERK signaling axis.

Pancreatic cancer is an extremely aggressive malignancy with a very disappointing prognosis. Neuroglobin (NGB), a member of the globin family, has been demonstrated to have a significant role in a variety of tumor forms. The possible role of NGB as a tumor suppressor gene in pancreatic cancer was investigated in this work. Information from the public dataset TCGA combined with GTEx was used to analyze the finding that NGB was commonly downregulated in pancreatic cancer cell lines and tissues, correlating with patient age and prognosis. The expression of NGB in pancreatic cancer was investigated via RT-PCR, qRT-PCR, and Western blot experiments. In-vitro and in-vivo assays, NGB elicited cell cycle arrest in the S phase and apoptosis, hindered migration and invasion, reversed the EMT process, and suppressed cell proliferation and development. The mechanism of action of NGB was predicted via bioinformatics analysis and validated using Western blot and co-IP experiments revealed that NGB inhibited the EGFR/AKT/ERK pathway by binding to and reducing expression of GNAI1 and p-EGFR. In addition, pancreatic cancer cells overexpressing NGB showed increased drug sensitivity to gefitinib (EGFR-TKI). In conclusion, NGB inhibits pancreatic cancer progression by specifically targeting the GNAI1/EGFR/AKT/ERK signaling axis.

Evidence for exposure biomarkers in dictamnine-induced liver injury resulting from metabolic activation in vitro and in mice.

Dictamnine (DTN), a furoquinoline alkaloid isolated from Dictamni Cortex, is responsible for the liver injury caused by Dictamni Cortex and the preparations. Discovering new biomarkers with high specificity and sensitivity for diagnosis and tracing the source of DTN-induced liver injury is urgently needed. Considering that metabolic activation of DTN has been suggested as a primary trigger initiating hepatotoxicity, the present study aimed to investigate the bio-activation process of DTN in vitro and in mice and to explore whether the adducts could be developed as exposure biomarkers. When trapping with N-acetyl-cysteine (NAC) and glutathione (GSH) in mouse liver microsomes and CYP3A4 overexpressed L02 cells, two isomers of DTN-NAC adducts were detected in both systems and one DTN-GSH adduct was found in mouse liver microsomes. As expected, one DTN-NAC adduct was also found in plasma and bile of mice with liver injury after DTN exposure. Moreover, mouse liver microsomes were used to simulate the conjugation of serum albumin with metabolically activated DTN. The sole modified peptide 25 DAHKSEVAHR34 was found, and the oxidative metabolites of DTN might bind to the side chain amino of albumin at Arg34. The above findings not only provided confirmative evidence that DTN was metabolically activated to induce liver injury but also suggested that the adducts had the potential to be developed as exposure biomarkers of DTN-induced liver injury.

Toxic effects of nano-TiO2 in bivalves-A synthesis of meta-analysis and bibliometric analysis.

Since the beginning of the 21st century, the increasing production and application of nano-TiO2 in consumer products have inevitably led to its release into aquatic systems and therefore caused the exposure of aquatic organisms, resulting in growing environmental concerns. However, the safety of nano-TiO2 in aquatic environments has not been systematically assessed, especially in coastal and estuary waters where a large number of filter-feeding animals live. Bivalves are considered around the world to be a unique target group for nanoparticle toxicity, and numerous studies have been conducted to test the toxic effects of nano-TiO2 on bivalves. The aim of this review was to systematically summarize and analyze published data concerning the toxicological effects of nano-TiO2 in bivalves. In particular, the toxicity of nano-TiO2 to the antioxidant system and cell physiology was subjected to meta-analysis to reveal the mechanism of the toxicological effects of nano-TiO2 and the factors affecting its toxicological effects. To reveal the cooperation, hot keywords and co-citations in this field, bibliometric analysis was conducted, and the results showed that the toxicological molecular mechanisms of nano-TiO2 and the combined effects of nano-TiO2 and other environmental factors are two major hot spots. Finally, some perspectives and insights were provided in this review for future research on nano-TiO2 toxicology in bivalves.

Rethinking Nano-TiO2 Safety: Overview of Toxic Effects in Humans and Aquatic Animals.

Titanium dioxide nanoparticles (nano-TiO2 ) are widely used in consumer products, raising environmental and health concerns. An overview of the toxic effects of nano-TiO2 on human and environmental health is provided. A meta-analysis is conducted to analyze the toxicity of nano-TiO2 to the liver, circulatory system, and DNA in humans. To assess the environmental impacts of nano-TiO2 , aquatic environments that receive high nano-TiO2 inputs are focused on, and the toxicity of nano-TiO2 to aquatic organisms is discussed with regard to the present and predicted environmental concentrations. Genotoxicity, damage to membranes, inflammation and oxidative stress emerge as the main mechanisms of nano-TiO2 toxicity. Furthermore, nano-TiO2 can bind with free radicals and signal molecules, and interfere with the biochemical reactions on plasmalemma. At the higher organizational level, nano-TiO2 toxicity is manifested as the negative effects on fitness-related organismal traits including feeding, reproduction and immunity in aquatic organisms. Bibliometric analysis reveals two major research hot spots including the molecular mechanisms of toxicity of nano-TiO2 and the combined effects of nano-TiO2 and other environmental factors such as light and pH. The possible measures to reduce the harmful effects of nano-TiO2 on humans and non-target organisms has emerged as an underexplored topic requiring further investigation.

Integrated Metabolomics and Proteomics Approach To Identify Metabolic Abnormalities in Rats with Dioscorea bulbifera Rhizome-Induced Hepatotoxicity.

Previous studies have shown that Dioscorea bulbifera rhizome (DBR) can induce hepatotoxicity in clinical practice. However, its underlying mechanisms remain largely unexplored. In the present study, we investigated the global effect of DBR exposure on the proteomic and metabolomic profiles in rats over a 12-week administration using an integrated proteomics and metabolomics approach. The abundance of 1366 proteins and 58 metabolites in the liver of rats after subchronic exposure to DBR was dose-dependently altered. The results indicated that DBR mainly damaged hepatic cells through the aberrant regulation of multiple systems mainly including purine metabolism, pyrimidine metabolism, taurine and hypotaurine metabolism, and bile acid metabolism. Notably, the deregulated proteins including Pnp, Dpyd, Upp1, and Tymp and the differential metabolites including uridine, uracil, cytidine, thymine, adenine, adenosine, adenosine 3'-monophosphate, and deoxycytidine were well correlated to purine and pyrimidine metabolism, which might be novel pathways involved in metabolic abnormalities in rats with DBR-induced liver damage. Collectively, these findings not only contributed to understanding the mechanisms underlying the hepatotoxicity of DBR, but also illustrated the power of integrated proteomics and metabolomics approaches to improve the identification of metabolic pathways and biomarkers indicative of herb-induced liver injury.

Investigation of Dioscorea bulbifera Rhizome-Induced Hepatotoxicity in Rats by a Multisample Integrated Metabolomics Approach.

The use of herbal medicines continues to expand globally, meanwhile, herb-associated hepatotoxicity is becoming a safety issue. As a conventional Chinese medicinal herb, Dioscorea bulbifera rhizome (DBR) has been documented to cause hepatic toxicity. However, the exact underlying mechanism remains largely unexplored. In the present study, we aimed to profile entire endogenous metabolites in a biological system using a multisample integrated metabolomics strategy. Our findings offered additional insights into the molecular mechanism of the DBR-induced hepatotoxicity. We identified different metabolites from rat plasma, urine, and feces by employing gas chromatography-mass spectrometry in combination with multivariate analysis. In total, 55 metabolites distributed in 33 metabolic pathways were identified as being significantly altered in DBR-treated rats. Correlation network analysis revealed that the hub metabolites of hepatotoxicity were mainly associated with amino acid, bile acid, purine, pyrimidine, lipid, and energy metabolism. As such, DBR affected the physiological and biological functions of liver via the regulation of multiple metabolic pathways to an abnormal state. Notably, our findings also demonstrated that the multisample integrated metabolomics strategy has a great potential to identify more biomarkers and pathways in order to elucidate the mechanistic complexity of toxicity of traditional Chinese medicine.

[Absorption mechanism of neobavaisoflavone in Caco-2 cell monolayer mode].

Neobavaisoflavone is one of flavonoids of traditional Chinese medicine Psoralea corylifolial. It has numerous biological properties such as antibacterial, anti-inflammatory, anti-cancer, and anti-osteoporosis effects. This paper aimed to investigate the absorption mechanism of neobavaisoflavone in Caco-2 cell monolayer model. The analyte and osalmide were separated on Thermo Syncronis C18 column with methanol-0.1% formic acid solution (90∶10) as the mobile phase, at a flow rate of 0.2 mL•min⁻¹. The concentration of neobavaisoflavone was determined in eletrospray ionization(ESI) positive ion mode with osalmide as an the internal standard. The effects of time, concentration, P-gp inhibitor verapamil, MRP-2 inhibitor MK-571 and BCRP inhibitor Ko143 on the absorption of neobavaisoflavone were investigated. According to the results, neobavaisoflavone showed a good linearity within the concentration of 10-2 000 µg•L⁻¹, and the results of its specificity, matrix effect, extraction recovery, precision, accuracy and stability all met the requirements. In the Caco-2 cell monolayer model, the transport volume of neobavaisoflavone was correlated positively with the time and concentration. The ER values of 15, 30, 50 µmol•L⁻¹ neobavaisoflavone were 1.64, 1.94,0.99, respectively. As compared with the control group, all of verapamil hyduochloride, MK-571 and Ko143 could promote the transportation of neobavaisoflavone, and the effect was more obvious in verapamil hyduochloride and Ko143. The absorption of neobavaisoflavone may be mainly of active transport in Caco-2 cell monolayer model, and also involve passive transport. Excretion mechanism of intestinal transport protein may be also involved.

Effects of elevated temperature and different crystal structures of TiO2 nanoparticles on the gut microbiota of mussel Mytilus coruscus.

Coastal habitats are exposed to increasing pressure of nanopollutants commonly combined with warming due to the seasonal temperature cycles and global climate change. To investigate the toxicological effects of TiO2 nanoparticles (TiO2 NPs) and elevated temperature on the intestinal health of the mussels (Mytilus coruscus), the mussels were exposed to 0.1 mg/L TiO2 NPs with different crystal structures for 14 days at 20 °C and 28 °C, respectively. Compared to 20 °C, the agglomeration of TiO2 NPs was more serious at 28 °C. Exposure to TiO2 NPs led to elevated mortality of M. coruscus and modified the intestinal microbial community as shown by 16S rRNA sequence analysis. Exposure to TiO2 NPs changed the relative abundance of Bacteroidetes, Proteobacteria and Firmicutes. The relative abundances of putative mutualistic symbionts Tenericutes and Fusobacteria increased in the gut of M. coruscus exposed to anatase, which have contributed to the lower mortality in this group. LEfSe showed the combined stress of warming and TiO2 NPs increased the risk of M. coruscus being infected with potential pathogenic bacteria. This study emphasizes the toxicity differences between crystal structures of TiO2 NPs, and will provides an important reference for analyzing the physiological and ecological effects of nanomaterial pollution on bivalves under the background of global climate change.

Self-Assembly of Ionic Superdiscs in Nanopores.

Discotic ionic liquid crystals (DILCs) consist of self-assembled superdiscs of cations and anions that spontaneously stack in linear columns with high one-dimensional ionic and electronic charge mobility, making them prominent model systems for functional soft matter. Compared to classical nonionic discotic liquid crystals, many liquid crystalline structures with a combination of electronic and ionic conductivity have been reported, which are of interest for separation membranes, artificial ion/proton conducting membranes, and optoelectronics. Unfortunately, a homogeneous alignment of the DILCs on the macroscale is often not achievable, which significantly limits the applicability of DILCs. Infiltration into nanoporous solid scaffolds can, in principle, overcome this drawback. However, due to the experimental challenges to scrutinize liquid crystalline order in extreme spatial confinement, little is known about the structures of DILCs in nanopores. Here, we present temperature-dependent high-resolution optical birefringence measurement and 3D reciprocal space mapping based on synchrotron X-ray scattering to investigate the thermotropic phase behavior of dopamine-based ionic liquid crystals confined in cylindrical channels of 180 nm diameter in macroscopic anodic aluminum oxide membranes. As a function of the membranes' hydrophilicity and thus the molecular anchoring to the pore walls (edge-on or face-on) and the variation of the hydrophilic-hydrophobic balance between the aromatic cores and the alkyl side chain motifs of the superdiscs by tailored chemical synthesis, we find a particularly rich phase behavior, which is not present in the bulk state. It is governed by a complex interplay of liquid crystalline elastic energies (bending and splay deformations), polar interactions, and pure geometric confinement and includes textural transitions between radial and axial alignment of the columns with respect to the long nanochannel axis. Furthermore, confinement-induced continuous order formation is observed in contrast to discontinuous first-order phase transitions, which can be quantitatively described by Landau-de Gennes free energy models for liquid crystalline order transitions in confinement. Our observations suggest that the infiltration of DILCs into nanoporous solids allows tailoring their nanoscale texture and ion channel formation and thus their electrical and optical functionalities over an even wider range than in the bulk state in a homogeneous manner on the centimeter scale as controlled by the monolithic nanoporous scaffolds.

Chromosome-level genome assembly of the caenogastropod snail Rapana venosa.

The carnivorous gastropod Rapana venosa (Valenciennes, 1846) is one of the most notorious ecological invaders worldwide. Here, we present the first high-quality chromosome-scale reference R. venosa genome obtained via PacBio sequencing, Illumina paired-end sequencing, and high-throughput chromosome conformation capture scaffolding. The assembled genome has a size of 2.30 Gb, with a scaffold N50 length of 64.63 Mb, and is anchored to 35 chromosomes. It contains 29,649 protein-coding genes, 77.22% of which were functionally annotated. Given its high heterozygosity (1.41%) and large proportion of repeat sequences (57.72%), it is one of the most complex genome assemblies. This chromosome-level genome assembly of R. venosa is an important resource for understanding molluscan evolutionary adaption and provides a genetic basis for its biological invasion control.

Methylated tumor suppressor gene SCARA5 inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma.

Background: SCARA5 may play an important role in nasopharyngeal carcinoma. Materials & methods: PCR and immunohistochemistry were used to detect the expression and promoter methylation of SCARA5. Cell proliferation assays, spheroid culture, flow cytometry analysis, Transwell assays and xenotransplantation tests were utilized to determine the functional effects of SCARA5. RNA-sequencing, western blotting, immunofluorescence and dual-luciferase reporter assays were used to assess SCARA5-mediated outcomes. Results: SCARA5 was downregulated by promoter methylation. Overexpression of SCARA5 inhibited cell migration, invasion and proliferation. SCARA5 enhanced nasopharyngeal carcinoma cell sensitivity to chemotherapy with cisplatin and 5-fluorouracil. SCARA5 drives tumor apoptosis by downregulating HSPA2. Conclusion: SCARA5 may be a useful clinical marker in nasopharyngeal carcinoma.

Transmission mechanisms of antibiotic resistance genes in arsenic-contaminated soil under sulfamethoxazole stress.

Numerous studies have revealed the spread mechanism of antibiotic resistance genes (ARGs) in single antibiotic-contaminated soils. However, the comprehensive impacts of heavy metals and antibiotics on ARGs and the underlying mechanisms are still unknown. Here, high-throughput quantitative PCR and high-throughput sequencing were used to investigate changes in ARGs and bacterial communities under various sulfamethoxazole (SMX) regimes (0, 1, 10, 50 mg kg-1) in arsenic (As) contaminated soils. The study found that the abundances of ARGs, mobile genetic elements (MGEs), and heavy metal resistance genes (HMRGs) significantly increased in the soil fortified at 10 and 50 mg kg-1 SMX concentrations. The ARGs abundance increased with the increase in the MGEs abundance. Many significant positive correlations between various ARGs subtypes and HMRGs subtypes were found. These results indicate that the HMRGs and MGEs positively contributed to the enrichment of ARGs in As-contaminated soils under SMX stress. Meanwhile, the abundance of copiotrophic (Actinobacteriota) reduced and oligotrophic (Gemmatimonadota) increased, indicating that the life history strategy of the community changed. In addition, Gemmatimonadota was positively correlated to ARGs, HMRGs, and MGEs, suggesting that Gemmatimonadota, which can cope with As and SMX stress, was the host for resistance genes in the soil. Finally, the study found that MGEs play a determinant role in ARGs proliferation due to the direct utilization of HGT, and the indirect effect for ARGs spread under a co-selection mechanism of ARGs and HMRGs, while the bacterial community showed indirect influences by altering environmental factors to act on MGEs. Collectively, this study revealed new insights into the mechanisms of resistance gene transmission under combined SMX and As contamination in soil ecosystems.

Is microplastic an oxidative stressor? Evidence from a meta-analysis on bivalves.

Microplastic pollution is a major threat to the marine environment attracting attention from scientific and public communities. Although we have sufficient evidence that microplastic is ubiquitous in all ecosystems, the question of the harmfulness of microplastic exposure is still under debate. Filter feeders like bivalves are commonly exposed to microplastics in water and sediments and thus can serve as excellent biological indicators for microplastic pollution. A relatively rich toxicological literature has been focusing on microplastic effects on bivalves but we have yet to reach an agreement on the toxic effects and mechanisms of microplastics. Here, we conducted a meta-analysis and bibliometrics analysis of the microplastic studies in bivalves. The bibliometric analysis (used to evaluate the general research trends) showed that the investigation of microplastic distribution in the marine environment and the molecular mechanisms of microplastic toxicity are the two major hot spots of research. Based on analyses of ecologically and environmentally relevant microplastics concentrations, particle sizes and polymer types, we discuss the physiological effects of microplastics on bivalves, and the severity and direction of the effects at the cellular, tissue, organ and organismal levels. The meta-analysis results show that microplastics can induce time-dependent oxidative stress in bivalves. Generally, the activities of antioxidant enzymes, such as glutathione peroxidase (GPx), glutathione-S-transferase (GST) and superoxide dismutase (SOD) increased during short-term exposure but declined after long-term exposure to microplastics. Non-linear response of GPx, GST and SOD enzymes to MP exposure over time indicate that these enzymes are not good biomarkers of MPs effects in marine bivalves. The tissue glutathione levels and catalase (CAT activity) showed an increase during both short- and long term MP exposures and thus can be used as oxidative stress biomarkers of sublethal MPs effects in marine bivalves.

Physiological effects of plastic particles on mussels are mediated by food presence.

Plastic particles cause toxic effects on marine organisms but whether food particles can affect the toxic effects of plastic particles on filter feeding animals remains unknown. To evaluate the intake and physiological effects of different size particles and their exposure ways, the thick shell mussels Mytilus coruscus were exposed to polystyrene (PS) nanoplastics (NPs, 70 nm) and microplastics (MPs, 10 µm) respectively for two weeks by mixing NPs/MPs with microalgae or exposed to MNPs individually after feeding. Intake of particles and their physiological effects including energy budget, digestive enzymes and oxidative responses were assessed after exposure. Results indicated food presence mediate the effects while MPs decrease the energy budget and increase the catalase activity and malondialdehyde levels. Moreover, exposure way significantly affected energy budget and size of particle had a significant impact on enzyme activities. Our results showed MPs induce more significant effects than NPs on mussels, emphasized the importance of particle exposure way and suggested that mixture exposure with microalgae alleviate the influences on mussels caused by plastic particles alone. This study emphasized that we need to take the food particles into account for evaluating the toxic effects of plastic particles on filter feeding animals in the natural environment.

Poly(hydrophobic amino acid)-Based Self-Adjuvanting Nanoparticles for Group A Streptococcus Vaccine Delivery.

Peptide antigens have been widely used in the development of vaccines, especially for those against autoimmunity-inducing pathogens and cancers. However, peptide-based vaccines require adjuvant and/or a delivery system to stimulate desired immune responses. Here, we explored the potential of self-adjuvanting poly(hydrophobic amino acids) (pHAAs) to deliver peptide-based vaccine against Group A Streptococcus (GAS). We designed and synthesized self-assembled nanoparticles with a variety of conjugates bearing a peptide antigen (J8-PADRE) and polymerized hydrophobic amino acids to evaluate the effects of structural arrangement and pHAAs properties on a system's ability to induce humoral immune responses. Immunogenicity of the developed conjugates was also compared to commercially available human adjuvants. We found that a linear conjugate bearing J8-PADRE and 15 copies of leucine induced equally effective, or greater, immune responses than commercial adjuvants. Our fully defined, adjuvant-free, single molecule-based vaccine induced the production of antibodies capable of killing GAS bacteria.

[Effect and Mechanism of Foliar Application Nano-MnO2 on Cadmium Enrichment of Rice].

Cadmium (Cd) is easily enriched in rice, resulting in an excessive Cd content in the grain, which seriously threatens human health. Manganese (Mn) is an essential element of plants. In a field experiment on Cd-contaminated acid soils, we investigated the effectiveness and mechanism of Mn in minimizing Cd accumulation in rice via foliar spraying using 0.1%, 0.3%, and 0.5% nano-MnO2 solutions at an early stage of heading. Compared with a control treatment, foliar spraying effectively reduced the Cd content of rice leaves, husks, and brown rice; increased the Mn content of all rice organs; but had no effect on rice yield. Foliar application of nano-MnO2 alleviated the plant stress induced by Cd by improving leaf photosynthesis, inhibiting lipid peroxidation, and increasing the content of the oxidative stress protein kinase. In addition, foliar application of nano-MnO2 limited the absorption of Cd by roots by increasing the content of iron-manganese plaque on the surfaces of rice roots and strengthening its adsorption/co-precipitation of Cd. Therefore, foliar application of nano-MnO2 during the early stages of rice heading is an effective measure to increase the Mn content and reduce the Cd content of brown rice.

Roles of 5,10-Methylenetetrahydrofolate Reductase C677T Polymorphisms in First-Episode, Drug-Naive Adult Patients With Depression.

5,10-Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is considered as a predisposition and promising genetic candidate to major depressive disorder (MDD), as it is associated with impaired one-carbon cycles, which may be involved in the pathogenesis of depression. Cortical thickness (CT) and subcortical structure volumes have been extensively studied in MDD and have been proposed as one of the phenotypes for MDD. We intend to discuss the association between CT, subcortical structure volume, and MTHFR C677T polymorphism in first-episode, treatment-naive patients with MDD. In this study, 127 adult patients with MDD and 101 age- and gender-matched healthy controls (HCs) were included. All subjects underwent T1-weighted MRI, MTHFR C677T genotyping, and FreeSurfer software-based morphological analysis. MDD patients have been detected to have significantly decreased volumes in the left nucleus accumbens (P < 0.001). The MTHFR 677 T allele carriers manifested with thinner CT in the left caudal anterior cingulate cortex (cACC, P = 0.009) compared with CC genotype. There were significant genotype-by-diagnosis interactions for the CT in the left cACC (P = 0.009), isthmus cingulate (P = 0.002), medial orbitofrontal lobe (P = 0.012), posterior cingulate (P = 0.030), and the right lateral orbitofrontal lobe (P = 0.012). We also found a trend in the interaction effect on the volume of the left putamen (P = 0.050). Our results revealed that MTHFR C677T polymorphism may be involved in the dysfunction of limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuits mediating emotion processing, which may contribute to pathogenesis of MDD.

The crucial role of metabolic regulation in differential hepatotoxicity induced by furanoids in Dioscorea bulbifera.

Diterpenoid lactones (DLs), a group of furan-containing compounds found in Dioscorea bulbifera L. (DB), have been reported to be associated with hepatotoxicity. Different hepatotoxicities of these DLs have been observed in vitro, but reasonable explanations for the differential hepatotoxicity have not been provided. Herein, the present study aimed to confirm the potential factors that contribute to varied hepatotoxicity of four representative DLs (diosbulbins A, B, C, F). In vitro toxic effects were evaluated in various cell models and the interactions between DLs and CYP3A4 at the atomic level were simulated by molecular docking. Results showed that DLs exhibited varied cytotoxicities, and that CYP3A4 played a modulatory role in this process. Moreover, structural variation may cause different affinities between DLs and CYP3A4, which was positively correlated with the observation of cytotoxicity. In addition, analysis of the glutathione (GSH) conjugates indicated that reactive intermediates were formed by metabolic oxidation that occurred on the furan moiety of DLs, whereas, GSH consumption analysis reflected the consistency between the reactive metabolites and the hepatotoxicity. Collectively, our findings illustrated that the metabolic regulation played a crucial role in generating the varied hepatotoxicity of DLs.