CO2-Promoted and Copper-Catalyzed Dehydroxylative Coupling of Benzylic Alcohols by the NaBH4/I2 System.

An efficient and CO2-promoted dehydroxylative coupling of benzylic alcohols catalyzed by ligand-free cuprous chloride has been achieved. The discovered catalytic reductive coupling reaction is a newly C-C bond-forming transformation of alcohols. Mechanistic insight is gained through control reactions.

Oleate Promotes Triple-Negative Breast Cancer Cell Migration by Enhancing Filopodia Formation through a PLD/Cdc42-Dependent Pathway.

Breast cancer, particularly triple-negative breast cancer (TNBC), poses a global health challenge. Emerging evidence has established a positive association between elevated levels of stearoyl-CoA desaturase 1 (SCD1) and its product oleate (OA) with cancer development and metastasis. SCD1/OA leads to alterations in migration speed, direction, and cell morphology in TNBC cells, yet the underlying molecular mechanisms remain elusive. To address this gap, we aim to investigate the impact of OA on remodeling the actin structure in TNBC cell lines, and the underlying signaling. Using TNBC cell lines and bioinformatics tools, we show that OA stimulation induces rapid cell membrane ruffling and enhances filopodia formation. OA treatment triggers the subcellular translocation of Arp2/3 complex and Cdc42. Inhibiting Cdc42, not the Arp2/3 complex, effectively abolishes OA-induced filopodia formation and cell migration. Additionally, our findings suggest that phospholipase D is involved in Cdc42-dependent filopodia formation and cell migration. Lastly, the elevated expression of Cdc42 in breast tumor tissues is associated with a lower survival rate in TNBC patients. Our study outlines a new signaling pathway in the OA-induced migration of TNBC cells, via the promotion of Cdc42-dependent filopodia formation, providing a novel insight for therapeutic strategies in TNBC treatment.

Spatio-temporal dynamics of phytoplankton community structure in the coastal waters of the Southern Beibu Gulf.

This study was conducted during October 2021 (autumn) and April 2022 (spring) to explore the phytoplankton community structure, their distribution characteristics, and the influence of environmental factors in the coastal waters of the Southern Beibu Gulf. The 15 sampling sites were grouped based on the difference in offshore distance to analyze the temporal and spatial differences in community structure and environmental driving in the investigated sea area of the coastal waters of the Southern Beibu Gulf. Permutational multivariate analysis of variance was conducted on the sample data in time and space, revealing that there is no significant difference in space (p > 0.05), but there is significant difference in time (p < 0.05). Notably, water pressure, pH, chemical oxygen demand, nitrite, and labile phosphate were higher in autumn, while total ammonia nitrogen, dissolved oxygen, and suspended solids were significantly higher in spring. Additionally, the study identified 87 phytoplankton species belonging to 6 phyla, dominating by Bacillariophyta, followed by Dinophyta and Cyanophyta. The phytoplankton density, Shannon Weiner's diversity index (H'), Pielou's evenness index (J), and Margalef's richness index (D) ranged from 84.88 to 4675.33 cells L-1, 0.56 to 2.58, 0.26 to 0.89, and 1.21 to 3.64, respectively. Permutational multivariate analysis of variance showed non-significant spatial differences in phytoplankton composition (p > 0.05) but seasonal differences (p < 0.05). Furthermore, canonical correspondence analysis (CCA) identified pH, dissolved oxygen, suspended solids, chemical oxygen demand, nitrite, and labile phosphate as key environmental factors influencing the phytoplankton community structure (p < 0.05). In this study, the dynamic changes of phytoplankton community structure and environmental factors in the southern coastal waters of Beibu Gulf were analyzed in detail from two aspects of time and space. The key environmental factors to protect the ecological environment in the southern coastal area of Beibu Gulf were found out. It provides a reference method and theoretical basis for the management and protection of Beibu Gulf and other tropical marine environment.

Right, but not left, posterior superior temporal gyrus is causally involved in vocal feedback control.

The posterior superior temporal gyrus (pSTG) has been implicated in the integration of auditory feedback and motor system for controlling vocal production. However, the question as to whether and how the pSTG is causally involved in vocal feedback control is currently unclear. To this end, the present study selectively stimulated the left or right pSTG with continuous theta burst stimulation (c-TBS) in healthy participants, then used event-related potentials to investigate neurobehavioral changes in response to altered auditory feedback during vocal pitch regulation. The results showed that, compared to control (vertex) stimulation, c-TBS over the right pSTG led to smaller vocal compensations for pitch perturbations accompanied by smaller cortical N1 and larger P2 responses. Enhanced P2 responses received contributions from the right-lateralized temporal and parietal regions as well as the insula, and were significantly correlated with suppressed vocal compensations. Surprisingly, these effects were not found when comparing c-TBS over the left pSTG with control stimulation. Our findings provide evidence, for the first time, that supports a causal relationship between right, but not left, pSTG and auditory-motor integration for vocal pitch regulation. This lends support to a right-lateralized contribution of the pSTG in not only the bottom-up detection of vocal feedback errors but also the involvement of driving motor commands for error correction in a top-down manner.

Cuproptosis-related LncRNA signatures as a prognostic model for head and neck squamous cell carcinoma.

Cuproptosis is a novel, distinct form of regulated cell death. However, little is known about the role of cuproptosis-related lncRNAs (CRlncRNAs) in head and neck squamous cell carcinoma (HNSCC). This study aimed to identify a CRlncRNAs signature, explore its prognostic value in HNSCC. RNA-seq data and relevant clinical data were downloaded from The Cancer Genome Atlas (TCGA) database, and cuproptosis-related genes were identified from a search of the relevant candidate-gene literature. Analysis of differentially expressed lncRNAs (DElncRNAs) was performed using the R package "edgeR". The intersection of the lncRNAs between DElncRNAs and CRlncRNAs was obtained using the R package "Venn Diagram". Univariate Cox regression was used to identify cuproptosis-related prognostic lncRNAs. LASSO-Cox method was used to narrow these cuproptosis-related prognostic lncRNAs and construct a prognostic model. Multiple statistical methods were used to evaluate the predictive ability of the model. Moreover, the relationships between the model and immune cell subpopulations, related functions and pathways and drug sensitivity were explored. Then, two risk groups were established according to the risk score calculated by the CRlncRNAs signature included three lncRNAs. In HNSCC patients, the risk score was a better predictor of survival than traditional clinicopathological features. In addition, significant differences in immune cells such as B cells, T cells and macrophages were observed between the two groups. Finally, the high-risk group had a lower IC50 for certain chemotherapeutic agents, such as cisplatin and cetuximab. This 3 CRlncRNAs signature is a powerful prognostic biomarker for predicting clinical outcomes and therapeutic responses in HNSCC patients.

Stemness-related lncRNAs signature as a biologic prognostic model for head and neck squamous cell carcinoma.

Cancer stem cells (CSCs) and long non-coding RNAs (lncRNAs) are particularly important for tumor cell growth and migration, and recurrence and drug resistance, including head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to explore stemness-related lncRNAs (SRlncRNAs) that could be used for prognosis of patients with HNSCC. HNSCC RNA sequencing data and matched clinical data were obtained from TCGA database, and stem cell characteristic genes related to HNSCC mRNAsi were obtained from the online database by WGCNA analysis, respectively. Further, SRlncRNAs were obtained. Then, the prognostic model was constructed to forecast patient survival through univariate Cox regression and LASSO-Cox method based on SRlncRNAs. Kaplan-Meier, ROC and AUC were used to evaluate the predictive ability of the model. Moreover, we probed the underlying biological functions, signalling pathways and immune status hidden within differences in prognosis of patients. We explored whether the model could guide personalized treatments included immunotherapy and chemotherapy for HNSCC patients. At last, RT-qPCR was performed to analyze the expressions levels of SRlncRNAs in HNSCC cell lines. A SRlncRNAs signature was identified based on 5 SRlncRNAs (AC004943.2, AL022328.1, MIR9-3HG, AC015878.1 and FOXD2-AS1) in HNSCC. Also, risk scores were correlated with the abundance of tumor-infiltrating immune cells, whereas HNSCC-nominated chemotherapy drugs were considerably different from one another. The final finding was that these SRlncRNAs were abnormally expressed in HNSCCCS according to the results of RT-qPCR. These 5 SRlncRNAs signature, as a potential prognostic biomarker, can be utilized for personalized medicine in HNSCC patients.

The role of heavy metals in the development of colorectal cancer.

OBJECTIVE: To investigate the relationship among 18 heavy metals, microsatellite instability (MSI) status, ERCC1, XRCC1 (rs25487), BRAF V600E and 5 tumor markers and their role in the development of colorectal cancer (CRC). METHODS: A total of 101 CRC patients and 60 healthy controls were recruited in the present study. The levels of 18 heavy metals were measured by ICP-MS. MSI status and the genetic polymorphism were determined by PCR (FP205-02, Tiangen Biochemical Technology Co., Ltd., Beijing, China) and Sanger sequencing. Spearman's rank correlation was used to analyze the relationship among various factors. RESULTS: The level of selenium (Se) was lower in the CRC group compared with the control group (p < 0.01), while vanadium (V), arsenic (As), tin (Sn), barium (Ba) and lead (Pb) were higher (p < 0.05), chromium (Cr) and copper (Cu) were significantly higher (p < 0.0001) in the CRC group than those in the control group. Multivariate logistic regression analysis indicated that Cr, Cu, As and Ba were the risk factors for CRC. In addition, CRC was positively correlated with V, Cr, Cu, As, Sn, Ba and Pb, but negatively correlated with Se. MSI was positively correlated with BRAF V600E, but negatively correlated with ERCC1. BRAF V600E was positively correlated with antimony (Sb), thallium (Tl), CA19-9, NSE, AFP and CK19. XRCC1 (rs25487) was found to be positively correlated with Se but negatively correlated with Co. The levels of Sb and Tl were significantly higher in the BRAF V600E positive group compared to the negative group. The mRNA expression level of ERCC1 was significantly higher (P = 0.035) in MSS compared to MSI. And there was a significant correlation between XRCC1 (rs25487) polymorphism and MSI status (P<0.05). CONCLUSION: The results showed that low level of Se and high levels of V, As, Sn, Ba, Pb, Cr, and Cu increased the risk of CRC. Sb and Tl may cause BRAF V600E mutations, leading to MSI. XRCC1 (rs25487) was positively correlated with Se but negatively correlated with Co. The expression of ERCC1 may be related to MSS, while the XRCC1 (rs25487) polymorphism is related to MSI.

A spectral learning path for simultaneous multi-parameter detection of water quality.

Water quality parameters (WQP) are the most intuitive indicators of the environmental quality of water body. Due to the complexity and variability of the chemical environment of water body, simple and rapid detection of multiple parameters of water quality becomes a difficult task. In this paper, spectral images (named SPIs) and deep learning (DL) techniques were combined to construct an intelligent method for WQP detection. A novel spectroscopic instrument was used to obtain SPIs, which were converted into feature images of water chemistry and then combined with deep convolutional neural networks (CNNs) to train models and predict WQP. The results showed that the method of combining SPIs and DL has high accuracy and stability, and good prediction results with average relative error of each parameter (anions and cations, TOC, TP, TN, NO3--N, NH3-N) at 1.3%, coefficient of determination (R2) of 0.996, root mean square error (RMSE) of 0.1, residual prediction deviation (RPD) of 16.2, and mean absolute error (MAE) of 0.067. The method can achieve rapid and accurate detection of high-dimensional water quality multi-parameters, and has the advantages of simple pre-processing and low cost. It can be applied not only to the intelligent detection of environmental waters, but also has the potential to be applied in chemical, biological and medical fields.

Recombinant human thrombopoietin (rhTPO) of different dosing regimens for refractory/relapsed primary immune thrombocytopenia: a multicenter, randomized controlled trial and pharmacokinetics study.

Recombinant human TPO (rhTPO) is effective for refractory/relapsed primary immune thrombocytopenia (ITP), but optimal dosing regimen remains elusive. In this multicenter, randomized, controlled trial, a total of 282 adult ITP patients (mean age 47.3 years; 82 men) with a platelet count ≤30 × 109/L or >30 × 109/L with active bleeding randomly received a once daily (QD) subcutaneous injection of 7500 U (n = 64) or 15000 U rhTPO for 14 injections, or 15000 U or 30000 U rhTPO once every other day (QOD) for 7 injections. The primary outcomes included change from baseline in platelet count and total response rate (TRR) on day 14. On day 14, the median increase of platelet count from baseline was the highest in the 15000-U QD group (167.5 × 109/L, interquartile range [IQR] 23.0-295.0 × 109/L), followed by the 30000-U QOD group (57.5 × 109/L, IQR 9.0-190.0 × 109/L) (ANCOVA P < .001; P = .266 with baseline count as a covariate). The TRR on day 14 was also the highest in the 15000-U QD group (63.2%), followed by the 30000-U QOD group (59.7%). The rate of grade 3 and above adverse events did not differ among the four groups. There were no new safety concerns. All 4 regimens are safe and well-tolerated. The 30000-U QOD regimen is practically indistinguishable in efficacy to the 15000-U QD regimen.

What is the context? Relative thrombopoietin deficiency is implicated in primary immune thrombocytopenia (ITP), which is characterized by increased platelet destruction and impaired megakaryopoiesis.Patients who are innately unresponsive to or have relapsed after glucocorticoid treatment have limited treatment options.Recombinant human thrombopoietin (rhTPO) improves treatment response of primary ITP patients when added to high-dose dexamethasone.What is new? This trial sought to identify an optimal dosing regimen of rhTPO for patients who had failed or relapsed after glucocorticoid therapy.Of the 4 regimens, once daily 15000 U rhTPO for 14 injections yielded the greatest median increase in platelet count (167.5 × 10⁹/L) from baseline and attained the highest total response rate on day 14 (63.2%).30000 U rhTPO once every other day for 7 injections was effective in rapidly increasing platelet counts in the first 7 days.All 4 regimens were safe and well-tolerated.What is the impact? The 30000 U rhTPO once every other day regimen may offer an effective and safe regimen with less frequent injections, but future trials with longer follow-up are needed.

Species-specific arsenic species and health risk assessment in seaweeds from tropic coasts of South China Sea.

Arsenic (As) is a notorious toxic contamination in marine environments, while the toxicity and health risk of As is highly dependent on As species in seafoods. In this study, we hypothesized that the species-specific As bioaccumulation and species resulted in species-specific healthy risk of As in seaweeds. To test the hypothesis, we collected 10 common edible seaweeds from the coast of Hainan Island in South China Sea. Then we comparatively quantified concentration of total As and 5 major As species [AsB, DMA, MMA, As(III), and As(V)] in seaweeds. The results revealed that the concentrations of total As varied significantly among 10 seaweed species. Specially, the highest total As concentration were found in brown seaweeds, followed by red seaweeds, and green seaweeds. Furthermore, the percentage of 5 As species to total As differed significantly among 10 seaweeds. The percentage of AsB was highest in Caulerpa lentillifera (53%) and lowest in Sargassum oligocystum (13%), while that of As(V) was lowest in Caulerpa lentillifera (21%) and highest in Sargassum oligocystum (81%). The iAs [As(III) + As(V)] exhibited highest value in brown seaweeds and least value in green seaweeds. The potential human health risk assessment indicated that the consumption of brown seaweeds of Sargassum oligocystum and Sargassum polycystum could cause a considerable carcinogenic risk and non-carcinogenic risk to residents. Overall, our findings here largely validated our hypothesis that the species-specific As bioaccumulation and As species had great significance to healthy risk of As in seaweeds.

A spatially-controlled DNA triangular prism nanomachine for AND-gated intracellular imaging of ATP in acidic microenvironment.

A DNA triangular prism nanomachine (TPN)-based logic device for intracellular AND-gated imaging of adenosine triphosphate (ATP) has been constructed. By using i-motif sequences and ATP-binding aptamers as logic control units, the TPN logic device is qualified to respond to the acidic environment and ATP in cancer cell lysosomes. Once internalized into the lysosome, the specific acidic microenvironment in lysosome causes the i-motif sequence to fold into a tetramer, resulting in compression of DNA tri-prism. Subsequently, the split ATP aptamer located at the tip of the collapsed triangular prism binds stably to ATP, which results in the fluorescent dyes (Cy3 and Cy5) modified at the ends of the split aptamer being in close proximity to each other, allowing Förster Resonance Energy Transfer (FRET) to occur. The FRET signals are excited at a wavelength of 543 nm and can be collected within the emission range of 646-730 nm. This enables the precise imaging of ATP within a cell. We also dynamically operate AND logic gates in living cells by modulating intracellular pH and ATP levels with the help of external drugs. Owing to the AND logic unit on TPN it can simultaneously recognize two targets and give corresponding intelligent logic judgment via imaging signal output. The accuracy of molecular diagnosis of cancer can be improved thus eliminating the false positive signal of single target-based detection. Hence, this space-controlled TPN-based logical sensing platform greatly avoids sensitivity to extracellular targets during the cell entry process, providing a useful tool for high-precision imaging of the cancer cell's endogenous target ATP.

Unveiling the MUFA-Cancer Connection: Insights from Endogenous and Exogenous Perspectives.

Monounsaturated fatty acids (MUFAs) have been the subject of extensive research in the field of cancer due to their potential role in its prevention and treatment. MUFAs can be consumed through the diet or endogenously biosynthesized. Stearoyl-CoA desaturases (SCDs) are key enzymes involved in the endogenous synthesis of MUFAs, and their expression and activity have been found to be increased in various types of cancer. In addition, diets rich in MUFAs have been associated with cancer risk in epidemiological studies for certain types of carcinomas. This review provides an overview of the state-of-the-art literature on the associations between MUFA metabolism and cancer development and progression from human, animal, and cellular studies. We discuss the impact of MUFAs on cancer development, including their effects on cancer cell growth, migration, survival, and cell signaling pathways, to provide new insights on the role of MUFAs in cancer biology.

Spatio-temporal variation in water quality and phytoplankton community structure in Changwang, Meishe, and Wuyuan Rivers in Hainan Island, China.

For the first time, this study explored spatio-temporal variation in water quality and phytoplankton community structure in Changwang, Meishe, and Wuyuan Rivers in tropical Hainan Island, China. Phytoplankton samples and water were collected between March and December 2019 and analyzed using standard methods. Two-way ANOVA revealed significant spatial and seasonal variation in physico-chemical parameters (p < 0.05). Wuyuan had high TP (0.06 ± 0.04 mg L-1), TN (1.14 ± 0.71 mg L-1), NH4+-N (0.07 ± 0.09 mg L-1), Secchi depth (2.28 ± 3.79 m), salinity (3.60±5.50 ppt), and EC (332.50 ± 219.10 µS cm-1). At the same time, Meishe had high TP (0.07 ± 0.03 mg L-1), TN (1.04 ± 0.74 mg L-1), NH4+-N (0.07 ± 0.10 mg L-1), EC (327.61 ± 63.22 µS cm-1), and turbidity (40.25 ± 21.16 NTU). In terms of seasons, spring recorded high average TP, TN, NH4+-N, COD, and DO, while summer had a high temperature, Chl-a, salinity, and EC. Generally, the physico-chemical parameters met the China water quality standard limits (GB 3838-2002). Overall, 197 phytoplankton species belonging to Cyanophyta, Chlorophyta, Cryptophyta, Bacillariophyta, Pyrrophyta, Euglenophyta, Xanthophyta, and Chrysophyta were identified, with Cyanophyta being dominant. Phytoplankton density showed spatial changes varying from 18 × 106 cell L-1 to 84 × 106 cell L-1. The phytoplankton diversity ranged from 1.86 to 2.41, indicating a mesotrophic state. One-way ANOSIM showed no significant spatial dissimilarity in phytoplankton composition (R = 0.042, p = 0.771) but indicated a significant seasonal difference (R = 0.265, p = 0.001). Therefore, SIMPER analysis revealed that Lyngbya attenuata, Merismopedia tenuissima, Cyclotella sp., Merismopedia glauca, Merismopedia elegans, and Phormidium tenue contributed to the seasonal differences. Furthermore, CCA demonstrated that TP, TN, NH4+-N, COD, Chl-a, and Secchi depth greatly influenced the phytoplankton community. This study shows the spatio-temporal variation in water quality and phytoplankton communities, useful for managing riverine quality.

A causal link between left supplementary motor area and auditory-motor control of vocal production: Evidence by continuous theta burst stimulation.

The supplementary motor area (SMA) has been implicated in the feedforward control of speech production. Whether this region is involved in speech motor control through auditory feedback, however, remains uncertain. The present event-related potential (ERP) study examined the role of the left SMA in vocal pitch regulation in a causal manner by combining auditory feedback manipulations and neuronavigated continuous theta bust stimulation (c-TBS). After receiving c-TBS over the left SMA or the control site (vertex), twenty young adults vocalized the vowel sound /u/ while hearing their voice unexpectedly pitch-shifted -50 or -200 cents. Compared to the control stimulation, c-TBS over the left SMA led to decreased vocal compensations for pitch perturbations of -50 and -200 cents. A significant decrease of N1 and P2 responses to -200 cents perturbations was also found when comparing active and control stimulation. Major neural generators of decreased P2 responses included the right-lateralized superior and middle temporal gyrus and angular gyrus. Notably, a significant correlation was found between active-control differences in the vocal compensation and P2 responses for the -200 cents perturbations. These findings provide neurobehavioral evidence for a causal link between the left SMA and auditory-motor integration for vocal pitch regulation, suggesting that the left SMA receives auditory feedback information and mediates vocal compensations for feedback errors in a bottom-up manner.

Regulator of G Protein Signaling Contributes to the Development and Aflatoxin Biosynthesis in Aspergillus flavus through the Regulation of Gα Activity.

Heterotrimeric G-proteins play crucial roles in growth, asexual development, and pathogenicity of fungi. The regulator of G-protein signaling (RGS) proteins function as negative regulators of the G proteins to control the activities of GTPase in Gα subunits. In this study, we functionally characterized the six RGS proteins (i.e., RgsA, RgsB, RgsC, RgsD, RgsE, and FlbA) in the pathogenic fungus Aspergillus flavus. All the aforementioned RGS proteins were also found to be functionally different in conidiation, aflatoxin (AF) biosynthesis, and pathogenicity in A. flavus. Apart from FlbA, all other RGS proteins play a negative role in regulating both the synthesis of cyclic AMP (cAMP) and the activation of protein kinase A (PKA). Additionally, we also found that although RgsA and RgsE play a negative role in regulating the FadA-cAMP/PKA pathway, they function distinctly in aflatoxin biosynthesis. Similarly, RgsC is important for aflatoxin biosynthesis by negatively regulating the GanA-cAMP/PKA pathway. PkaA, which is the cAMP-dependent protein kinase catalytic subunit, also showed crucial influences on A. flavus phenotypes. Overall, our results demonstrated that RGS proteins play multiple roles in the development, pathogenicity, and AF biosynthesis in A. flavus through the regulation of Gα subunits and cAMP-PKA signals. IMPORTANCE RGS proteins, as crucial regulators of the G protein signaling pathway, are widely distributed in fungi, while little is known about their roles in Aspergillus flavus development and aflatoxin. In this study, we identified six RGS proteins in A. flavus and revealed that these proteins have important functions in the regulation of conidia, sclerotia, and aflatoxin formation. Our findings provide evidence that the RGS proteins function upstream of cAMP-PKA signaling by interacting with the Gα subunits (GanA and FadA). This study provides valuable information for controlling the contamination of A. flavus and mycotoxins produced by this fungus in pre- and postharvest of agricultural crops.

Bioaccumulation of dietary CrPic, Cr(III) and Cr(VI) in juvenile coral trout (Plectropomus leopardus).

The form of chromium (Cr) is an important factor that influences its bioavailability and potential toxicity, while the difference of Cr bioaccumulation between organic and inorganic Cr has been rarely investigated. The present study compared the bioaccumulation of organic Cr (e.g., chromium picolinate (CrPic)) and inorganic Cr (e.g., trivalent (Cr(III)) and hexavalent (Cr(VI))) in juvenile coral trout (Plectropomus leopardus). The fish were exposed to a gradient level of different forms of dietary Cr for 66 days. Then the Cr bioaccumulation in fish were comparatively quantified between CrPic, Cr(VI) and Cr(III) groups. The results showed that the Cr bioaccumulation was form- and tissue-specific, dose- and time-dependent. Specifically, the newly bioaccumulated Cr in fish generally increased with the increasing dietary Cr level and exposure time, while the CrPic groups accumulated the highest Cr in most cases, followed by Cr(VI) and Cr(III) groups. The highest Cr content was observed in gut for CrPic groups, while it was highest in heart for Cr(VI) and Cr(III) groups, followed by kidney, skin, fin, liver, gill, bone, eyes and muscle in order. Overall, the results here firstly demonstrated that the dietary organic Cr(III) had significantly higher bioaccumulation than inorganic Cr (Cr(III) and Cr(VI)). Our findings suggested the complexity and variability of form-specific Cr bioavailability and toxicity should be cautiously evaluated in aquatic environments, which has been largely overlooked previously.

Waterborne Cr3+ and Cr 6+ exposure disturbed the intestinal microbiota homeostasis in juvenile leopard coral grouper Plectropomus leopardus.

BACKGROUND: Chromium (Cr) mainly has two stable forms: Cr3+ and Cr6+. Cr and its compound are widely used in the printing, dyeing, leather making, and metallurgy industry. They are evitably released into the environment and pose a significant threat to creatures, for instance, the excessive chromium (Cr) burden in the marine ecosystem is often harmful to fish. Intestinal microbiota greatly affects fish performance, but how waterborne Cr affects fish intestinal microbiota is unclear. To test the hypothesis that the waterborne Cr exposure could significantly affect fish' intestinal microbiota homeostasis, and the effect was highly dependent on Cr concentration and speciation, the juvenile leopard coral grouper Plectropomus leopardus were exposed to waterborne Cr3+ and Cr6+ (0.1, 0.5 ppm) for 7 days, and the intestinal microbiota was determined by Amplicon sequencing of the 16S rRNA. RESULTS: In all Cr treatment groups, the alpha diversity of intestinal microbiota communities of P. leopardus was decreased. The phyla Proteobacteria, Firmicutes, Actinobacteria, Chloroflexi and Bacteroidetes were the dominant intestinal microbiota. The Chao index diversity significantly declined in Cr treatment group, indicating the intestinal microbiota community structure was changed. Among the dominant intestinal microbiota, Proteobacteria was most sensitive to Cr exposure, and it increased after xposure. The PICRUSt predicted that 0.5 ppm Cr3+ expousure caused metabolism disordered in the intestinal of P. leopardus. CONCLUSIONS: Waterborne Cr3+ and Cr6+ significantly disturbed intestinal microbiota homeostasis in P. leopardus, including their diversity, composition, and community structure. The metabolism level of intestinal microbiota in P. leopardus was decreased by Cr3+ exposure. High concentrations of Cr3+ may pose potential risks to the intestinal homeostasis of P. leopardus.

Speciation-specific Cr bioaccumulation, morphologic and transcriptomic response in liver of Plectropomus leopardus exposed to dietary Cr(III) and Cr(VI).

Trivalent chromium (Cr(III)) and hexavalent chromium (Cr(VI)) are the two mainly stable oxidation states of Cr in aquatic environments, while the difference of their bioavailability and toxicity by dietary exposure has been rarely known in aquatic organisms. Using juvenile coral trout (Plectropomus leopardus), Cr(III) and Cr(VI) as model system, this study tested the hypothesis that the dietary Cr bioaccumulation and toxicity in fish were highly dependent on Cr speciation. The fish were chronically exposed to 200 mg kg-1 of dietary Cr(III) and Cr(VI) for 8 weeks, and then the Cr bioaccumulation, morphologic change, and RNA-Seq in fish liver were determined. The results showed that dietary Cr(III) and Cr(VI) exposure significantly induced fish weight gain, while 1.17 folds and 1.26 folds increased in relation to Control group, respectively. Cr contents in liver was increased significantly in dietary Cr(VI) but not in Cr(III) groups. Both Cr treatment induced lipid deposition in liver tissue structure, moreover, pancreatic part was increased in dietary Cr(III) but its reduced in Cr(VI) exposure. RNA-Seq in fish liver were significantly different as well. Specifically, there were 138 differentially expressed genes (DEGs) in dietary Cr(III) group, including 76 up-regulated and 62 down-regulated, and these DEGs were mainly involved in lipid metabolism, while there were 175 DEGs in dietary Cr(VI) group, including 85 up-regulated and 90 down-regulated, and these DEGs were mainly involved in immune system. The qRT-PCR confirmed the RNA-seq data were reliable. Overall, these results supported our hypothesis that the chronic dietary Cr(III) and Cr(VI) exposure resulted in apparently different Cr bioaccumulation and toxicity in fish. Our findings here help us to fill in a big gap in our knowledge of speciation-specific Cr bioavailability and toxicity in aquatic organisms, which has been largely unclear previously. CAPSULE: Dietary Cr(III) increased lipid metabolism and dietary Cr(VI) activated immune system in liver of coral trout at transcription levels.

Maternal oxidized soybean oil exposure in rats during lactation damages offspring kidneys via Nrf2/HO-1 and NF-κB signaling pathway.

BACKGROUND: Cooking oil is an indispensable component of the human diet. However, oils usually undergo thermal oxidation. Oxidized soybean oil (OSO) has been shown to have detrimental effects on humans and has emerged as a root cause of many chronic diseases. The objective of this work was to evaluate the effects of puerpera exposure to OSO on kidney damage in the mother and offspring using lactating rats as an experimental model. RESULTS: Pathological sections and ultrastructure showed that OSO exposure resulted in various levels of damage to lactating rats and their offspring. OSO induced oxidative stress in the kidneys of lactating rats, as evidenced by increased levels of hydrogen peroxide, interleukin (IL)-1ß, and IL-8. OSO increased the activities of glutathione peroxidase and superoxide dismutase. OSO upregulated the expression of apoptosis-related genes, nuclear factor-erythroid 2-related factor 2 (Nrf2), and nuclear factor κB-related inflammatory factor genes. In the offspring of the OSO-exposed mothers, hydrogen peroxide, malondialdehyde, IL-6, and tumor necrosis factor-alpha contents were increased. Furthermore, OSO enhanced the levels of Nrf2, NAD(P)H quinone oxidoreductase 1, heme oxygenase 1, and p65 and decreased B-cell lymphoma 2. CONCLUSION: These findings indicated that the kidneys of two generations of rats were compromised by oxidative damage when fed OSO during lactation. This study provides evidence for increasing the genes expression of the Nrf2/heme oxygenase 1 pathway to alleviate the kidney damage caused by OSO in the mother and offspring. © 2021 Society of Chemical Industry.

Activation of Bombyx mori neuropeptide G protein-coupled receptor A19 by neuropeptide RYamides couples to Gq protein-dependent signaling pathways.

RYamides constitute a novel family of neuropeptides newly identified in insects, and play important roles in regulating a variety of physiological processes. However, the signaling characteristics and physiological actions of RYamide signaling system remain largely unknown. In the present study, we cloned the full-length complementary DNA of the RYamide receptor BNGR-A19 from Bombyx mori larvae. After expression in mammalian HEK293T and insect Sf9 cells, functional assays revealed that BNGR-A19 was activated by synthetic RYamide peptides, triggering a significant increase in cAMP-response element controlled luciferase activity and Ca2+ mobilization in a Gq inhibitor-sensitive manner. Upon activation by RYamide peptides, BNGR-A19 elicited ERK1/2 phosphorylation via a Gq -PLC-PKC pathway, and also underwent a rapid internalization from the cell surface to the cytoplasm. Further cross-activity analysis indicated that BNGR-A19 exhibited very weak response upon stimulation by high concentration (1 µM) of Bombyx sulfakinin-1, neuropeptide F-1, and short neuropeptide F-1, and vice versa, Bombyx RYamides also showed slight potency for activating Bombyx NPF receptor (BNGR-A4) and sNPF receptor (BNGR-A11). In addition, the quantitative reverse-transcription polymerase chain reaction results showed that the high-level expression of BNGR-A19 was detected in the hindgut and testis, suggesting that the RYamide signaling is likely involved in the regulation of feeding, water homeostasis and testis development. This study provides the first in-depth information on the insect RYamide signaling system, facilitating the further clarification of its endocrinological roles in insect physiology.