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Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid (CSF) flow by beating their motile cilia coordinately. The ependymal denudation or ciliary dysfunction causes hydrocephalus. Here, we report that the deficiency of regulator of G-protein signaling 22 (RGS22) results in severe congenital hydrocephalus in both mice and rats. Interestingly, RGS22 is specifically expressed in ependymal cells within the brain. Using conditional knock-out mice, we further demonstrate that the deletion of Rgs22 exclusively in nervous system is sufficient to induce hydrocephalus. Mechanistically, we show that Rgs22 deficiency leads to the ependymal denudation and impaired ciliogenesis. This phenomenon can be attributed to the excessive activation of lysophosphatidic acid receptor (LPAR) signaling under Rgs22 -/- condition, as the LPAR blockade effectively alleviates hydrocephalus in Rgs22 -/- rats. Therefore, our findings unveil a previously unrecognized role of RGS22 in the central nervous system, and present RGS22 as a potential diagnostic and therapeutic target for hydrocephalus., (© 2024. Science China Press.)

Medullary Thyroid Carcinoma (MTC), a neuroendocrine malignancy that arises from the calcitonin-secreting parafollicular C-cells of the thyroid, constitutes a minor yet impactful fraction of thyroid malignancies. Distinguished by its propensity for aggressive growth and a pronounced tendency for metastasis, MTC poses formidable obstacles to the early diagnosis and therapeutic intervention. The molecular genetics of MTC, particularly the role of the RET gene and the RAS gene family, have been extensively studied, offering insights into the pathogenesis of the disease and revealing potential therapeutic targets. This comprehensive review synthesizes the latest advancements in the molecular genetics of MTC, the evolution of precision therapies, and the identification of novel biomarkers. We also discuss the implications of these findings for clinical practice and the future direction of MTC research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huai, Wang, Zhang, Lou, Wang, Huang, Sun and Zhou.)

The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity., (© The Author(s) (2024). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

The objective of this research was to investigate how dietary antimicrobial peptides (AMP), namely, Isalo scorpion cytotoxic peptide (IsCT), affect the gill physical barrier function and immune function of grass carp challenged with Flavobacterium columnare ( F. columnare ). Five hundred forty grass carp were randomly allocated to six groups and fed to varying levels of IsCT in the diet (0, 0.6, 1.2, 1.8, 2.4, and 3.0 mg/kg diet) for a duration of 60 days. Afterward, the grass carps faced a challenge from F. columnare . The results revealed that the use of optimal IsCT dramatically mitigated gill damage in grass carp that were infected with F. columnare . Additionally, IsCT exhibited a notable enhancement in gill antioxidant capabilities, as evidenced by a significant reduction in ROS, MDA, and PC levels, an elevation in antioxidant enzyme activities, and an upregulation of antioxidant-related genes and Nrf2 mRNA levels. Conversely, the expression of Keap1a and Keap1b mRNA was decreased. Besides, IsCT exhibited its capability to inhibit apoptosis via downregulating the mRNA levels of caspase-2 , caspase-3 , caspase-7 , caspase-8 , caspase-9 , Apaf1 , Fasl , Bax , and JNK while concurrently increasing the mRNA levels of Bcl-2 , Mcl-1 , and IAP in fish gills. Additionally, IsCT promoted the integrity of tight junction barrier by increasing the gene expression of claudin-b , claudin-c , claudin-3c , ZO-1 , ZO-2b , occludin , and JAM while suppressing MLCK signaling. Additionally, optimal dietary IsCT improved antibacterial ability, as evidenced by heightened LZ, ACP activities, and elevated levels of C3, C4, and IgM. Additionally, there was an upregulation in β-defensin-1 , LEAP-2A , LEAP-2B , hepcidin , and mucin-2 mRNA expression in the gills. Simultaneously, the inclusion of optimal dietary IsCT in the diet resulted in improved gill immunity barriers through the reduction of proinflammatory cytokine mRNA levels and the increase in the expression of anti-inflammatory cytokine mRNA levels. This was partly facilitated by the I κ Ba/NF- κ B p65 signaling pathway and TOR/S6K1 signaling pathways in the gills of grass carp. Therefore, supplementing the diet with IsCT has potential advantages in enhancing gill health by improved physical barriers and immunity in grass carp. Based on LZ activity and against lipid peroxidation, optimum IsCT concentrations in on-growing grass carp (136.88 ± 0.72 g) were found to be 1.68 and 1.54 mg/kg diet, respectively., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Qiu-Yan Chen et al.)

Competing Interests: Declaration of competing interest The authors declare no conflict of interest.

Background: Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research., Methods: The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD., Results: Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels., Conclusions: Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD., Trial Registration: Registered number in PROSPERO: CRD42023405052., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiang, Cao, Sun, Li, Qi, Zhang, Zhang, Yan and Zhou.)

Ochratoxin A (OTA) is one of the most common pollutants in aquatic feed. As a first line of defense, intestinal barriers could be utilized against OTA in order to prevent disorders. Natural product supplementation is one of the most popular strategies to alleviate toxicity induced by mycotoxins, but there is a lack of knowledge about how it functions in the teleost intestine. In this study, 720 juvenile grass carp of about 11 g were selected and four treatment groups (control group, OTA group, curcumin [Cur] group, and OTA + Cur group) were set up to conduct a 60-day growth test. After the test, the growth performance and intestinal health related indexes of grass carp were investigated. The addition of dietary Cur could have the following main results: (1) inhibit absorption and promote efflux transporters mRNA expression, reducing the residuals of OTA, (2) decrease oxidative stress by reducing oxidative damage and enhancing the expression of antioxidant enzymes, (3) promote mitochondrial fusion proteins to inhibit the expression of mitotic proteins and mitochondrial autophagy proteins and enhance mitochondrial function, (4) reduce necroptosis-related gene expression through inhibiting the tumor necrotic factor receptor-interacting protein kinase/mixed lineage kinase domain-like pathway, (5) reduce the expression of pro-inflammatory factors by inhibiting the Toll-like receptor 4/nuclear factor-κB signaling pathway to alleviate the intestinal inflammatory response. In summary, the results suggested that Cur could alleviate OTA-induced intestinal damage by enhancing antioxidant capacity and mitochondrial function as well as reducing necroptosis and inflammation in the grass carp intestine. This study provided a theoretical basis and production implications for dietary Cur that could improve growth performance and alleviate the intestinal damage induced by OTA in fish., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2024 The Authors.)

According to the International Agency for Research on Cancer (IARC), aflatoxin B1 (AFB1) has been recognized as a major contaminant in food and animal feed and which is a common mycotoxin with high toxicity. Previous research has found that AFB1 inhibited zebrafish muscle development. However, the potential mechanism of AFB1 on fish muscle development is unknown, so it is necessary to conduct further investigation. In the present research, the primary myoblast of grass carp was used as a model, we treated myoblasts with AFB1 for 24 h. Our results found that 5 μM AFB1 significantly inhibited cell proliferation and migration (P < 0.05), and 10 μM AFB1 promoted lactate dehydrogenase (LDH) release (P < 0.05). Reactive oxygen species (ROS), protein carbonyl (PC) and malondialdehyde (MDA) levels were increased in 15, 5 and 10 μM AFB1 (P < 0.05), respectively. Catalase (CAT), glutathione peroxidase (GPx) and total superoxide dismutase (T-SOD) activities were decreased in 10, 10 and 15 μM AFB1 (P < 0.05), respectively. Furthermore, 15 μM AFB1 induced oxidative damage by Nrf2 pathway, also induced apoptosis in primary myoblast of grass carp. Meanwhile, 15 μM AFB1 decreased MyoD gene and protein expression (P < 0.05). Importantly, 15 μM AFB1 decreased the protein expression of collagen Ⅰ and fibronectin (P < 0.05), and increased the protein levels of urokinase plasminogen activator (uPA), matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 2 (MMP-2), and p38 mitogen-activated protein kinase (p38MAPK) (P < 0.05). As a result, our findings suggested that AFB1 damaged the cell morphology, induced oxidative damage and apoptosis, degraded ECM components, in turn inhibiting myoblast development by activating the p38MAPK/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase (MMPs)/extracellular matrix (ECM) signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Muscle is the main edible part of bony fish. The purpose of this study was to investigate the influences of phenylalanine (Phe) on muscle quality, amino acid composition, fatty acid composition, glucose metabolism, and protein deposition in adult grass carp. The diets at 2.30, 4.63, 7.51, 10.97, 13.53, and 17.07 g/kg Phe levels were fed for 9 weeks. The results manifested that Phe (10.97-13.53 g/kg) increased the pH of the fillets and decreased muscle cooking loss and lactic acid content; Phe (7.51-17.07 g/kg) improved the composition of the fillets in terms of flavor (free) amino acids, bound amino acids (especially EAA), and fatty acids (especially EPA and DHA); Phe (7.51-13.53 g/kg) increased muscle glycogen content (possibly related to the AMPK signaling pathway) and muscle protein deposition (possibly related to IGF-1/4EBP1/TOR and AKT/FOXOs signaling pathways). In conclusion, a diet with appropriate Phe levels could improve fillet quality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This research evaluated the effects of copper (Cu) on intestinal antioxidant capacity and apical junctional complex (AJC) in juvenile grass carp. A total of 1080 healthy juvenile grass carp (11.16 ± 0.01 g) were fed six diets including different dosages of Cu, namely 0, 2, 4, 6, 8 mg/kg (Cu citrate [CuCit] as Cu source) and 3 mg/kg (CuSO 4 ·5H 2 O as Cu source). The trial lasted for 9 weeks. The findings revealed that dietary optimal Cu supplementation (2.2 to 4.1 mg/kg) promoted intestinal growth, including intestinal length, intestinal length index, intestinal weight, and intestinal somatic index ( P  < 0.05). Furthermore, optimal Cu boosted the intestinal mucosal barrier in juvenile grass carp. On the one hand, optimal Cu reduced diamine oxidase and D-lactate levels in serum ( P  < 0.05), reduced levels of the oxidative damage indicators malondialdehyde, reactive oxygen species (ROS), protein carbonyl, superoxide dismutase ( P  < 0.05), and catalase mRNA levels were elevated ( P  < 0.05), thus boosting intestinal antioxidant capacity, the binding protein Keap1a/1b/Nrf2 signaling pathway might be involved. Optimal Cu had no impact on glutathione peroxidase 1b ( GPx1b ) gene expression ( P  > 0.05). On the other hand, optimal Cu increased intestinal tight junction (TJ) proteins (except for claudin 15b) and adherens junction (AJ) proteins (E-cadherin, α-catenin, β-catenin, nectin and afadin) mRNA levels ( P  < 0.05), which could be connected to the signaling pathway formed by the Ras homolog gene family, member A (RhoA), Rho-associated kinase (ROCK), and myosin light chain kinase (MLCK). Finally, based on serum indicator D-lactate and intestinal oxidative damage index (ROS), Cu requirement (CuCit as Cu source) for juvenile grass carp from initial weight to final weight (from 11 to 173 g) was determined to be 4.14 and 4.12 mg/kg diet, respectively. This work may provide a theoretical foundation for identifying putative Cu regulation pathways on fish intestinal health., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2024 The Authors.)

In nature, aflatoxins, especially aflatoxin B1 (AFB1), are the common mycotoxins, which cause serious health problems for humans and animals. This paper aimed to study the effects of AFB1 on flesh flavor and muscle development of grass carp ( Ctenopharyngodon idella ) and its mechanism. There were 1440 individual fish in total, with 6 treatments and each treatment replicated 3 times. The 6 treatments were fed a control diet with different doses of AFB1 (0.04, 29.48, 58.66, 85.94, 110.43 and 146.92 μg/kg diet) for 60 d. AFB1 increased myofiber diameter, as well as decreased myofiber density of grass carp muscle ( P  < 0.05). The contents of free amino acid decreased gradually ( P  < 0.05) as dietary AFB1 increased in the muscle of grass carp. The levels of reactive oxygen species, malonaldehyde and protein carbonyl (PC) were increased ( P  < 0.05) with the dietary AFB1 increased. The levels of antioxidant enzyme (glutathione peroxidase, glutathione, glutathione reductase, total antioxidant capacity, anti-superoxide anion, and anti-hydroxyl radical) were decreased ( P  < 0.05) with the dietary AFB1 increased. In addition, dietary AFB1 decreased the content of collagen, and downregulated the mRNA and protein levels of transforming growth factor-β (TGF-β)/Smads signaling pathway in grass carp muscle ( P  < 0.05). The mRNA and protein levels of myogenic regulatory factors were downregulated in grass carp muscle ( P  < 0.05). Furthermore, the activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were increased ( P  < 0.05), and the protein levels of phosphorylate-38 mitogen-activated protein kinase (p-p38MAPK), phosphorylate-c-Jun N-terminal kinase, urokinase-type plasminogen activator (uPA), MMP-2 and MMP-9 were upregulated ( P  < 0.05), but collagen Ⅰ, laminin β1 and fibronectin were downregulated ( P  < 0.05) with the dietary AFB1 increased in the muscle of grass carp. Based on the results of this study, we can draw the following conclusion: dietary AFB1 might damage flesh flavor and inhibit the muscle development through MAPK/uPA/MMP/extracellular matrix (ECM) signaling pathway in grass carp. Moreover, the recommended safe limit of AFB1 in feed is no more than 26.77 μg/kg diet according to the PC levels in grass carp muscle., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2024 The Authors.)

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality. Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages, but it is often ineffective and suffers from problems such as multidrug resistance, rapid drug clearance, nonspecific targeting, high side effects, and low drug accumulation in tumor cells. In response to these limitations, recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC. This review focuses on recent advances in nanoparticle-based targeted drug delivery systems, with special attention to various receptors overexpressed on HCC cells. These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC. We comprehensively summarize the current understanding of these receptors, their role in nanoparticle targeting, and the impact of such targeted therapies on HCC. By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies, more effective and precise treatment of HCC can be achieved., Competing Interests: Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Aims: Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by progressive biliary inflammation and bile duct injury. Berberine (BBR) is a bioactive isoquinoline alkaloid found in various herbs and has multiple beneficial effects on metabolic and inflammatory diseases, including liver diseases. This study aimed to examine the therapeutic effect of BBR on cholestatic liver injury in a PSC mouse model (Mdr2 -/- mice) and elucidate the underlying mechanisms., Methods: Mdr2 -/- mice (12-14 weeks old, both sexes) received either BBR (50 mg/kg) or control solution daily for eight weeks via oral gavage. Histological and serum biochemical analyses were used to assess fibrotic liver injury severity. Total RNAseq and pathway analyses were used to identify the potential signaling pathways modulated by BBR in the liver. The expression levels of key genes involved in regulating hepatic fibrosis, bile duct proliferation, inflammation, and bile acid metabolism were validated by qRT-PCR or Western blot analysis. The bile acid composition and levels in the serum, liver, small intestine, and feces and tissue distribution of BBR were measured by LC-MS/MS. Intestinal inflammation and injury were assessed by gene expression profiling and histological analysis. The impact on the gut microbiome was assessed using 16S rRNA gene sequencing., Results: BBR treatment significantly ameliorated cholestatic liver injury, evidenced by decreased serum levels of AST, ALT, and ALP, and reduced bile duct proliferation and hepatic fibrosis, as shown by H&E, Picro-Sirius Red, and CK19 IHC staining. RNAseq and qRT-PCR analyses indicated a substantial inhibition of fibrotic and inflammatory gene expression. BBR also mitigated ER stress by downregulating Chop, Atf4 and Xbp-1 expression. In addition, BBR modulated bile acid metabolism by altering key gene expressions in the liver and small intestine, resulting in restored bile acid homeostasis characterized by reduced total bile acids in serum, liver, and small intestine and increased fecal excretion. Furthermore, BBR significantly improved intestinal barrier function and reduced bacterial translocation by modulating the gut microbiota., Conclusion: BBR effectively attenuates cholestatic liver injury, suggesting its potential as a therapeutic agent for PSC and other cholestatic liver diseases., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Bacterial pathogens destroy the structural integrity of functional organs in fish, leading to severe challenges in the aquaculture industry. Vitamin D 3 (VD 3 ) prevents bacterial infections and strengthens immune system function via vitamin D receptor (VDR). However, the correlation between VD 3 /VDR and the structural integrity of functional organs remains unclarified. This study aimed to investigate the influence of VD 3 supplementation on histological characteristics, apoptosis, and tight junction characteristics in fish intestine during pathogen infection. A total of 540 healthy grass carp (257.24 ± 0.63 g) were fed different levels of VD 3 (15.2, 364.3, 782.5, 1,167.9, 1,573.8, and 1,980.1 IU/kg) for 70 d. Subsequently, fish were challenged with Aeromonas hydrophila , a pathogen that causes intestinal inflammation. Our present study demonstrated that optimal supplementation with VD 3 (1) alleviated intestinal structural damage, and inhibited oxidative damage by reducing levels of oxidative stress biomarkers; (2) attenuated excessive apoptosis-related death receptor and mitochondrial pathway processes in relation to p38 mitogen-activated protein kinase signaling ( P  < 0.05); (3) enhanced tight junction protein expression by inhibiting myosin light chain kinase signaling ( P  < 0.05); and (4) elevated VDR isoform expression in fish intestine ( P  < 0.05). Overall, the results demonstrated that VD 3 alleviates oxidative injury, apoptosis, and the destruction of tight junction protein under pathogenic infection, thereby strengthening pathogen defenses in the intestine. This finding supports the rationale for VD 3 intervention as an essential practice in sustainable aquaculture., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2024 The Authors.)

Vitamin E (VE) is an essential lipid-soluble vitamin that improves the fish flesh quality. However, the underlying molecular mechanisms remain unclear. This study aimed to investigate the effects of VE on growth performance and flesh quality in sub-adult grass carp ( Ctenopharyngodon idella ). A total of 450 fish (713.53 ± 1.50 g) were randomly divided into six treatment groups (three replicates per treatment) and fed for nine weeks with different experimental diets (dietary lipid 47.8 g/kg) that contained different levels of VE (5.44, 52.07, 96.85, 141.71, 185.66, and 230.12 mg/kg diet, supplemented as dl-α-tocopherol acetate). Notably, the treatment groups that were fed with dietary VE ranging from 52.07 to 230.12 mg/kg diet showed improvement in the percent weight gain, special growth rate, and feed efficiency of grass carp. Moreover, the treatment groups supplemented with dietary VE level of 141.71, 185.66, and 230.12 mg/kg diet showed enhancement in crude protein, lipid, and α-tocopherol contents in the muscle, and the dietary levels of VE ranging from 52.07 to 141.71 mg/kg diet improved muscle pH 24h and shear force but reduced muscle cooking loss in grass carp. Furthermore, appropriate levels of VE (52.07 to 96.85 mg/kg diet) increased the muscle polyunsaturated fatty acid content in grass carp. Dietary VE also increased the mRNA levels of fatty acid synthesis-related genes, including fas , scd-1 , fad , elovl , srebp1 , pparγ , and lxrα , and up-regulated the expression of SREBP-1 protein. However, dietary VE decreased the expression of fatty acid decomposition-related genes, including hsl , cpt1 , acox1 , and pparα , and endoplasmic reticulum stress-related genes, including perk , ire1 , atf6 , eif2α , atf4 , xbp1 , chop , and grp78 , and down-regulated the expression of p-PERK, p-IRE1, ATF6, and GRP78 proteins. In conclusion, dietary VE increased muscle fatty acid synthesis, which may be partly associated with the alleviation of endoplasmic reticulum stress, and ultimately improves fish flesh quality. Moreover, the VE requirements for sub-adult grass carp (713.53 to 1590.40 g) were estimated to be 124.9 and 122.73 mg/kg diet based on percentage weight gain and muscle shear force, respectively., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2024 The Authors.)

The neurotoxic methylmercury (MeHg) in paddy soils can accumulate in rice grains. Microbial demethylation is an important pathway of MeHg degradation in soil, but the effect of soil type on microbial degradation of MeHg remains unclear. Therefore, we investigated MeHg degradation in eight typical paddy soils and analyzed the associations between soil physiochemical properties and microbial degradation efficiencies of MeHg. Results showed that MeHg was significantly degraded in unsterilized paddy soils, and the microbial degradation efficiency ranged from 10.8% to 64.6% after a 30-day incubation. The high microbial degradation efficiency of MeHg was observed in the soils with high levels of clay content, whereas relatively low degradation efficiency was found in the red paddy soils. We identified that Paenibacillaceae was the most important microbial predictor of MeHg degradation and was positively correlated with the degradation efficiency in the soils. The abundances of these microbial taxa associated with MeHg degradation were positively correlated with clay content. In addition, Eh, pH, and SOC could influence microbial degradation of MeHg by regulating certain microbial communities. Our results indicate that soil type is crucial in driving MeHg degradation, which has important implications for the mitigation of MeHg pollution in various croplands., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Low-glutelin-content rice, a type of functional rice with glutelin levels below 4%, is an essential dietary supplement for chronic kidney disease (CKD) patients. Developing low-glutelin-content rice varieties is crucial to catering to the growing CKD population. In this study, we aimed to create a new low-glutelin indica rice variety with excellent agronomic traits. To achieve this, we employed a combination of molecular-marker-assisted selection and traditional breeding techniques. The cultivars W3660, Wushansimiao (WSSM), and Nantaixiangzhan (NTXZ) were crossbred, incorporating the Lgc-1 , Pi-2 , Xa23 , and fgr alleles into a single line. The result of this breeding effort was "Yishenxiangsimiao", a new indica rice variety that inherits the desirable characteristics of its parent lines. Yishenxiangsimiao (YSXSM) possesses not only a low glutelin content but also dual resistance to blast and bacterial blight (BB). It exhibits high-quality grains with a fragrant aroma. This new low-glutelin indica cultivar not only ensures a stable food supply for CKD patients but also serves as a healthy dietary option for the general public. We also performed RNA-seq of these rice varieties to investigate their internal gene expression differences. The YSXSM exhibited a higher biotic-resistance gene expression in comparison to NTXZ. In summary, we successfully developed a novel low-glutelin indica rice variety, "Yishenxiangsimiao", with superior agronomic traits. This rice variety addresses the dietary needs of CKD patients and offers a nutritious choice for all consumers.

Background: Sex and reproductive status differences exist in both non-alcoholic fatty liver disease (NAFLD) and body composition. Our purpose was to investigate the relationship between body composition and the severity of liver steatosis and fibrosis in NAFLD in different sex and reproductive status populations., Methods: This cross-sectional study included 880 patients (355 men, 417 pre-menopausal women, 108 post-menopausal women). Liver steatosis and fibrosis and body composition data were measured using FibroScan and a bioelectrical impedance body composition analyzer (BIA), respectively, and the following parameters were obtained: liver stiffness measurement (LSM), controlled attenuation parameter (CAP), waist circumference (WC), body mass index (BMI), percent body fat (PBF), visceral fat area (VFA), appendicular skeletal muscle mass (ASM), appendicular skeletal muscle mass index (ASMI), fat mass (FM), fat free mass (FFM), and FFM to FM ratio (FFM/FM). Multiple ordinal logistic regression (MOLR) was used to analyze the independent correlation between body composition indicators and liver steatosis grade and fibrosis stage in different sex and menopausal status populations., Results: Men had higher WC, ASM, ASMI, FFM, and FFM/FM than pre- or post-menopausal women, while pre-menopausal women had higher PBF, VFA, and FM than the other two groups (p < 0.001). Besides, men had greater CAP and LSM values (p < 0.001). For MOLR, after adjusting for confounding factors, WC (OR, 1.07; 95% CI, 1.02-1.12; P = 0.011) and FFM/FM (OR, 0.52; 95% CI, 0.31-0.89; P = 0.017) in men and visceral obesity (OR, 4.16; 95% CI, 1.09-15.90; P = 0.037) in post-menopausal women were independently associated with liver steatosis grade. WC and visceral obesity were independently associated with liver fibrosis stage in men (OR, 1.05; 95% CI, 1.01-1.09, P = 0.013; OR, 3.92; 95% CI, 1.97-7.81; P < 0.001, respectively)., Conclusions: Increased WC and low FFM/FM in men and visceral obesity in post-menopausal women were independent correlates of more severe liver steatosis. In addition, increased WC and visceral obesity were independent correlates of worse liver fibrosis in men. These data support the sex- and reproductive status-specific management of NAFLD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Ovules are female reproductive organs of angiosperms, consisting of sporophytic integuments surrounding female gametophytes, that is, embryo sacs. Synchronization between integument growth and embryo sac development requires intracellular communication. However, signaling routes through which cells of the two generations communicate are unclear. We report that symplastic signals through plasmodesmata (PDs) of integuments are critical for the development of female gametophytes. Genetic interferences of PD biogenesis either by functional loss of CHOLINE TRANSPORTER-LIKE1 (CTL1) or by integument-specific expression of a mutated CALLOSE SYNTHASE 3 (cals3m) compromised PD formation in integuments and reduced fertility. Close examination of pINO:cals3m or ctl1 ovules indicated that female gametophytic development was either arrested at various stages after the formation of functional megaspores. In both cases, defective ovules could not attract pollen tubes, leading to the failure of fertilization. Results presented here demonstrate a key role of the symplastic route in sporophytic control of female gametophytic development., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

Ochratoxin A (OTA) is a common fungal toxin that pollutes raw materials of aquatic feeds (such as corn, soybean meal, and wheat). This study explored the effects of OTA through diet on muscle toxicity in juvenile grass carp (Ctenopharyngodon idella). The following results were obtained for the muscle. (1) With an increase in dietary OTA, the residue of OTA in muscle increased, muscle fiber diameter and density decreased, and even muscle fiber breakage. (2) OTA caused oxidative stress by downregulating GPx1 (a, b) and Trx via inhibited the PGC1-α/Nrf2 signaling pathway. (3) OTA exacerbated endoplasmic reticulum stress in the muscle by causing endoplasmic reticulum expansion (results of transmission electron microscopy) and upregulating the expression of GRP78, eIF2α, ATF6, PERK, and CHOP. (4) OTA reduced muscle fiber diameter by inhibiting protein synthesis (AKT, TOR, and S6K1) and promoting the mRNA expression of protein degradation-related genes (MURF1, MAFBX, and FoxO3a), as well as by reducing AKT and promoting the immunofluorescence expression of FoxO3. (5) OTA inhibits collagen deposition by downregulating TGF-β1, TGF-βR1, Smad2, Smad3, Smad4, CTGF, TIMP, PHD, and LOX mRNA expressions as well as the CTGF immunofluorescence expression. Moreover, based on the GSH and collagen content contents, the upper safe dose for OTA-induced toxicity was 963.6 and 1129.6 μg/kg diet, respectively. Using the example of OTA, our research has provided new insights that raise concerns about the quality of aquatic products by exploring muscle toxicity caused by mycotoxins., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Khat is a common plant that grows primarily in Eastern Africa and the Arabian Peninsula. Cathinone, norpseudoephedrine, and norephedrine are the main psychoactive components of khat. Experimental studies have shown that red and green khat have similar cathinone contents, but green khat contains more norpseudoephedrine and norephedrine than red khat. Research indicates that Ethiopians believe that red khat has stronger psychoactive effects than green khat. Therefore, we speculated that other substances in red khat may enhance its psychoactive effects. Using the sampling method, we identified two other psychoactive components in khat: methcathinone and ethcathinone. At present, only a few studies on the extraction and detection of alkaloids from khat have been published in China, and no reports on the extraction and detection of methcathinone and ethcathinone from khat are available. In this study, we established an extraction and detection method for five alkaloids in dried khat using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF MS). To establish the extraction method, we optimized the extraction solvent and process. The amounts of dichloromethane and sodium hydroxide added during the purification step were also optimized. To establish the detection method, we optimized the chromatographic and MS conditions. The final extraction and detection method was as follows: Dried khat powder (0.1 g) was loaded into a polypropylene centrifuge tube, added with 1 mL of 0.05 mol/L hydrochloride aqueous solution, and vortex-oscillated for 3 min for extraction. The sample was centrifuged at 10000 r/min for 3 min. Next, 600 μL of the supernatant was placed in a centrifuge tube, added with 1 mL of dichloromethane, shaken for 1 min, and centrifuged at 10000 r/min for 3 min. Subsequently, 300 μL of the supernatant was placed in a centrifuge tube, added with 80 μL of 1 mol/L sodium hydroxide aqueous solution, shaken for 1 min, and added with 1 mL of acetonitrile. Vortex oscillation was performed for 2 min to extract the sample, after which solid sodium chloride (0.4 g) was added to the mixture, followed by shaking for 1 min to separate the acetonitrile and aqueous phases. The mixture was then centrifuged at 10000 r/min for 3 min. Finally, the supernatant was collected and diluted for further testing. The five target analytes were separated on a ZORBAX Eclipse Plus Phenyl-Hexyl column (100 mm×3.0 mm, 1.8 μm) via gradient elution using 0.1% acetic acid aqueous solution and acetonitrile as mobile phases with a flow rate of 0.3 mL/min and column temperature of 30 ℃. The analytes were identified using the targeted MS/MS method under positive electrospray ionization mode and quantified using the external standard method. The five alkaloids showed good correlations (all correlation coefficients ( r 2 )≥0.9976) with their respective linear ranges. The limits of detection were between 0.08 and 0.75 μg/L, and the limits of quantification were between 0.25 and 2.50 μg/L. The average recoveries of the five alkaloids from two plants with different alkaloid contents were between 90.7% and 105.2%. The intra-sample precision ranged from 0.5% to 2.3%, the intra-day precision was between 1.0% and 2.5%, and the inter-day precision was between 1.3% and 3.3%. Using the developed method, we extracted and analyzed 15 khat samples, and detected five alkaloids. This method enables rapid sample pretreatment and has high sensitivity, good stability, and suitable accuracy. Based on the above results, we conclude that the proposed method meets the inspection and identification requirements for khat. Thus, it can provide a valuable reference for the physical and chemical identification of khat and support for further studies on its psychoactive components.

Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.

The habenula has been implicated in the pathogenesis of pain and analgesia, while evidence concerning its function in chronic low back pain (cLBP) is sparse. This study aims to investigate the resting-state functional connectivity (rsFC) and effective connectivity of the habenula in 52 patients with cLBP and 52 healthy controls (HCs) and assess the feasibility of distinguishing cLBP from HCs based on connectivity by machine learning methods. Our results indicated significantly enhanced rsFC of the habenula-left superior frontal cortex (SFC), habenula-right thalamus, and habenula-bilateral insular pathways as well as decreased rsFC of the habenula-pons pathway in cLBP patients compared to HCs. Dynamic causal modelling revealed significantly enhanced effective connectivity from the right thalamus to right habenula in cLBP patients compared with HCs. RsFC of the habenula-SFC was positively correlated with pain intensities and Hamilton Depression scores in the cLBP group. RsFC of the habenula-right insula was negatively correlated with pain duration in the cLBP group. Additionally, the combination of the rsFC of the habenula-SFC, habenula-thalamus, and habenula-pons pathways could reliably distinguish cLBP patients from HCs with an accuracy of 75.9% by support vector machine, which was validated in an independent cohort (N = 68, accuracy = 68.8%, p = .001). Linear regression and random forest could also distinguish cLBP and HCs in the independent cohort (accuracy = 73.9 and 55.9%, respectively). Overall, these findings provide evidence that cLBP may be associated with abnormal rsFC and effective connectivity of the habenula, and highlight the promise of machine learning in chronic pain discrimination., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The vertebrate mucosal barrier comprises physical and immune elements, as well as bioactive molecules, that protect organisms from pathogens. Vitamin D is a vital nutrient for animals and is involved in immune responses against invading pathogens. However, the effect of vitamin D on the mucosal barrier system of fish, particularly in the skin, remains unclear. Here, we elucidated the effect of vitamin D supplementation (15.2, 364.3, 782.5, 1167.9, 1573.8, and 1980.1 IU/kg) on the mucosal barrier system in the skin of grass carp ( Ctenopharyngodon idella ) challenged with Aeromonas hydrophila . Dietary vitamin D supplementation (1) alleviated A. hydrophila -induced skin lesions and inhibited oxidative damage by reducing levels of reactive oxygen species, malondialdehyde, and protein carbonyl; (2) improved the activities and transcription levels of antioxidant-related parameters and nuclear factor erythroid 2-related factor 2 signaling; (3) attenuated cell apoptosis by decreasing the mRNA and protein levels of apoptosis factors involved death receptor and mitochondrial pathway processes related to p38 mitogen-activated protein kinase and c-Jun N-terminal kinase signaling; (4) improved tight junction protein expression by inhibiting myosin light-chain kinase signaling; and (5) enhanced immune barrier function by promoting antibacterial compound and immunoglobulin production, downregulating pro-inflammatory cytokine expression, and upregulating anti-inflammatory cytokines expression, which was correlated with nuclear factor kappa B and the target of rapamycin signaling pathways. Vitamin D intervention for mucosal barrier via multiple signaling correlated with vitamin D receptor a. Overall, these results indicate that vitamin D supplementation enhanced the skin mucosal barrier system against pathogen infection, improving the physical and immune barriers in fish. This finding highlights the viability of vitamin D in supporting sustainable aquaculture.

Copper (Cu) is a trace element, essential for fish growth. In the current study, in addition to growth performance, we first explored the effects of Cu on collagen synthesis and myofiber growth and development in juvenile grass carp ( Ctenopharyngodon idella) . A total of 1080 fish (11.16 ± 0.01 g) were randomly divided into 6 treatments (3 replicates per treatment) to receive five doses of organic Cu, which were Cu citrate (CuCit) at 0.99 (basal diet), 2.19, 4.06, 6.15, and 8.07 mg/kg, and one dose of inorganic Cu (CuSO 4 ·5H 2 O at 3.15 mg/kg), for 9 weeks. The results showed appropriate Cu level (4.06 mg/kg) enhanced growth performance, improved nutritional Cu status, and downregulated Cu-transporting ATPase 1 mRNA levels in the hepatopancreas, intestine, and muscle of juvenile grass carp. Meanwhile, collagen content in fish muscle was increased after Cu intake, which was probably due to the following pathways: (1) activating CTGF/TGF-β1/Smads signaling pathway to regulate collagen transcription; (2) upregulating of La ribonucleoprotein domain family 6 ( LARP6) mRNA levels to regulate translation initiation; (3) increasing proline hydroxylase, lysine hydroxylase, and lysine oxidase activities to regulate posttranslational modifications. In addition, optimal Cu group increased myofiber diameters and the frequency of myofibers with diameter >50 μm, which might be associated with upregulation of cyclin B, cyclin D, cyclin E, proliferating cell nuclear antigen, myogenic determining factor (MyoD) , myogenic factor 5, myogenin ( MyoG) , myogenic regulatory factor 4 and myosin heavy chain ( MyHC) and downregulation of myostatin mRNA levels, increasing protein levels of MyoD, MyoG and MyHC in fish muscle. Finally, based on percentage weight gain (PWG), serum ceruloplasmin (Cp) activity and collagen content in fish muscle, Cu requirements were determined as 4.74, 4.37 and 4.62 mg/kg diet (CuCit as Cu source) of juvenile grass carp, respectively. Based on PWG and Cp activity, compared to CuSO 4 ·5H 2 O, the efficacy of CuCit were 131.80% and 115.38%, respectively. Our findings provide new insights into Cu supplementation to promote muscle growth in fish, and help improve the overall productivity of aquaculture., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Ochratoxin A (OTA), a notorious pollutant widely present worldwide, seriously pollutes aquafeeds. This paper aims to explore the toxicity effects of OTA by the way of diet on the skin barrier in grass carp (Ctenopharyngodon idella). Results were shown as follows in the skin: (1) OTA increased the mRNA abundances of uptake transporter proteins (e.g., OAT3) and decreased efflux transporter proteins (e.g., ABCG2), which caused the accumulation of OTA in the skin of grass carp. (2) OTA upregulated the gene expression related to ROS production by enhancing the NOX (1, 2, 4) signaling pathway and decreased the ability to ROS elimination with downregulation of GPx1 (a,b), Trx by inhibiting the PGC1-α/Nrf2 signaling pathway, which caused oxidative damage to the skin. (3) OTA exacerbated apoptosis in the skin by upregulating the expression of apoptosis-related proteins mediated by ways of endoplasmic reticulum stress and mitochondrial apoptosis. Moreover, OTA down-regulated the mRNA and protein abundances of tight junction-related proteins by inhibiting the MLCK signaling pathway, which in turn disrupted the tight junctions. (4) OTA reduced the number of mucous cup cells and decreased f LZ activities and IgM contents, and finally down-regulated the mRNA abundances of mucin (2, 3), LEAP-2 (A, B), and β-defensin (1, 2, 3), which in turn resulted in impairing skin chemical barrier. Moreover, based on the antimicrobial-related indexes (LZ activities and IgM contents), the OTA-safe upper doses were 814.827 and 813.601 μg/kg., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The n6/n3 ratios improved meat quality of terrestrial animals, but alpha-linolenic acid/linoleic acid (ALA/LNA) ratios were rarely studied in aquatic animals. In this study, sub-adult grass carp (Ctenopharyngodon idella) were fed diets fed diets containing six varying ALA/LNA ratios (0.03, 0.47, 0.92, 1.33, 1.69, and 2.15) for 9 weeks and the total value of n3 + n6 (1.98) was kept constant for all six treatments. The results indicated optimal ALA/LNA ratio improved growth performance, changed fatty acid composition in grass carp muscle, and promoted glucose metabolism. Additionally, optimal ALA/LNA ratio improved chemical attributes by increasing crude protein and lipid contents, and technological attributes by increasing pH 24h value and shear force in grass carp muscle. The signaling pathways related to fatty acid metabolism and glucose metabolism (LXRα/SREBP-1, PPARα, PPARγ, AMPK) might be responsible for these changes. Dietary optimal ALA/LNA ratio based on PWG, UFA and glucose contents was 1.03, 0.88 and 0.92, respectively., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Cochlear implantation is currently the most successful intervention for severe-to-profound sensorineural hearing loss, particularly in deaf infants and children. Nonetheless, there remains a significant degree of variability in the outcomes of CI post-implantation. The purpose of this study was to understand the cortical correlates of the variability in speech outcomes with a cochlear implant in pre-lingually deaf children using functional near-infrared spectroscopy (fNIRS), an emerging brain-imaging technique., Methods: In this experiment, cortical activities when processing visual speech and two levels of auditory speech, including auditory speech in quiet and in noise with signal-to-noise ratios of 10 dB, were examined in 38 CI recipients with pre-lingual deafness and 36 normally hearing children whose age and sex matched CI users. The HOPE corpus (a corpus of Mandarin sentences) was used to generate speech stimuli. The regions of interest (ROIs) for the fNIRS measurements were fronto-temporal-parietal networks involved in language processing, including bilateral superior temporal gyrus, left inferior frontal gyrus, and bilateral inferior parietal lobes., Results: The fNIRS results confirmed and extended findings previously reported in the neuroimaging literature. Firstly, cortical responses of superior temporal gyrus to both auditory and visual speech in CI users were directly correlated to auditory speech perception scores, with the strongest positive association between the levels of cross-modal reorganization and CI outcome. Secondly, compared to NH controls, CI users, particularly those with good speech perception, showed larger cortical activation in the left inferior frontal gyrus in response to all speech stimuli used in the experiment., Discussion: In conclusion, cross-modal activation to visual speech in the auditory cortex of pre-lingually deaf CI children may be at least one of the neural bases of highly variable CI performance due to its beneficial effects for speech understanding, thus supporting the prediction and assessment of CI outcomes in clinic. Additionally, cortical activation of the left inferior frontal gyrus may be a cortical marker for effortful listening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Zhang, Xi, Leng, Liu, Liu, Zhang and Yuan.)

The hard-shelled mussel ( Mytilus coruscus ) has been used as a traditional Chinese medicine and health food in China for centuries. Polysaccharides from mussel has been reported to have multiple biological functions, however, it remains unclear whether mussel polysaccharide (MP) exerts protective effects in intestinal functions, and the underlying mechanisms of action remain unclear. The aim of this study was to investigate the protective effects and mechanism of MP on intestinal oxidative injury in mice. In this study, 40 male BALB/C mice were used, with 30 utilized to produce an animal model of intestinal oxidative injury with intraperitoneal injection of cyclophosphamide (Cy) for four consecutive days. The protective effects of two different doses of MP (300 and 600 mg/kg) were assessed by investigating the change in body weight, visceral index, and observing colon histomorphology. Moreover, the underlying molecular mechanisms were investigated by measuring the antioxidant enzymes and related signaling molecules through ELISA, real-time PCR, and western blot methods. The results showed that MP pretreatment effectively protected the intestinal from Cy-induced injury: improved the colon tissue morphology and villus structure, increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and reduced malondialdehyde (MDA) content in serum and colon tissues. Meanwhile, MP also significantly increased the expression levels of SOD, GSH-Px, heme oxygenase-1 (HO-1), and nuclear factor E2-related factor 2 (Nrf2) mRNA in colon tissues. Further, western blot results showed that the expression of Nrf2 protein was significantly upregulated while kelch-like ECH-associated protein 1 (Keap1) was significantly downregulated by MP in the colonic tissues. This study indicates that MP can ameliorate Cy-induced oxidative stress injury in mice, and Nrf2-Keap1 signaling pathway may mediate these protective effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Aquafeeds are susceptible to contamination caused by aflatoxin B1 (AFB1). The gill of fish is an important respiratory organ. However, few studies have investigated the effects of dietary AFB1 exposure on gill. This study aimed to discuss the effects of AFB1 on the structural and immune barrier of grass carp gill. Dietary AFB1 increased reactive oxygen species (ROS) levels, protein carbonyl (PC) and malondialdehyde (MDA) contents, which consequently caused oxidative damage. In contrast, dietary AFB1 decreased antioxidant enzymes activities, relative genes expression (except MnSOD) and the contents of glutathione (GSH) (P < 0.05), which are partly regulated by NF-E2-related factor 2 (Nrf2/Keap1a). Moreover, dietary AFB1 caused DNA fragmentation. The relative genes of apoptosis (except Bcl-2, McL-1 and IAP) were significantly upregulated (P < 0.05), and apoptosis was likely upregulated through p38 mitogen-activated protein kinase (p38MAPK). The relative expressions of genes associated with tight junction complexes (TJs) (except ZO-1 and claudin-12) were significantly decreased (P < 0.05), and TJs were likely regulated by myosin light chain kinase (MLCK). Overall, dietary AFB1 disrupted the structural barrier of gill. Furthermore, AFB1 increased gill sensitivity to F. columnare, increased Columnaris disease and decreased the production of antimicrobial substances (P < 0.05) in grass carp gill, and upregulated the expression of genes involved with pro-inflammatory factors (except TNF-α and IL-8) and the pro-inflammatory response partly attributed to the regulation by nuclear factor κB (NF-κB). Meanwhile, the anti-inflammatory factors were downregulated (P < 0.05) in grass carp gill after challenge with F. columnare, which was partly attributed to the target of rapamycin (TOR). These results suggested that AFB1 aggravated the disruption of the immune barrier of grass carp gill after being challenge with F. columnare. Finally, the upper limit of safety of AFB1 for grass carp, based on Columnaris disease, was 31.10 μg/kg diet., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Soil contamination is one of the main threats to ecosystem health and sustainability. Yet little is known about the extent to which soil contaminants differ between urban greenspaces and natural ecosystems. Here we show that urban greenspaces and adjacent natural areas (i.e., natural/semi-natural ecosystems) shared similar levels of multiple soil contaminants (metal(loid)s, pesticides, microplastics, and antibiotic resistance genes) across the globe. We reveal that human influence explained many forms of soil contamination worldwide. Socio-economic factors were integral to explaining the occurrence of soil contaminants worldwide. We further show that increased levels of multiple soil contaminants were linked with changes in microbial traits including genes associated with environmental stress resistance, nutrient cycling, and pathogenesis. Taken together, our work demonstrates that human-driven soil contamination in nearby natural areas mirrors that in urban greenspaces globally, and highlights that soil contaminants have the potential to cause dire consequences for ecosystem sustainability and human wellbeing., (© 2023. The Author(s).)

Methylmercury (MeHg) is a potent neurotoxin that bioaccumulates along food chains. The conversion of MeHg from mercury (Hg) is mediated by a variety of anaerobic microorganisms carrying hgcAB genes. Mangrove sediments are potential hotspots of microbial Hg methylation; however, the microorganisms responsible for Hg methylation are poorly understood. Here, we conducted metagenomic and metatranscriptomic analyses to investigate the diversity and distribution of putative microbial Hg-methylators in mangrove ecosystems. The highest hgcA abundance and expression occurred in surface sediments in Shenzhen, where the highest MeHg concentration was also observed. We reconstructed 157 metagenome-assembled genomes (MAGs) carrying hgcA and identified several putative novel Hg-methylators, including one Asgard archaea (Lokiarchaeota). Further analysis of MAGs revealed that Deltaproteobacteria, Euryarchaeota, Bacteroidetes, Chloroflexi, and Lokiarchaeota were the most abundant and active Hg-methylating groups, implying their crucial role in MeHg production. By screening publicly available MAGs, 104 additional Asgard MAGs carrying hgcA genes were identified from a wide range of coast, marine, permafrost, and lake sediments. Protein homology modelling predicts that Lokiarchaeota HgcAB proteins contained the highly conserved amino acid sequences and folding structures required for Hg methylation. Phylogenetic tree revealed that hgcA genes from Asgard clustered with fused hgcAB genes, indicating a transitional stage of Asgard hgcA genes. Our findings thus suggest that Asgard archaea are potential novel Hg-methylating microorganisms and play an important role in hgcA evolution., (© 2023. The Author(s), under exclusive licence to International Society for Microbial Ecology.)

The Holliday Junction-Recognition Protein (HJURP) was upregulated in several tumors, which was associated with poor outcome. This study investigated the effects of the HJURP-mediated c-Jun N-terminal kinase (JNK)/ signal transducer and activator of transcription 3 (STAT3) pathway on bladder urothelial carcinoma (BLUC). Online databases were used to analyze HJURP expression in BLUC and the correlation of HJURP to JNK1 [mitogen-activated protein kinase 8 (MAPK8)], JNK2 (MAPK9), STAT3, marker of proliferation Ki-67 (MKI67), proliferating cell nuclear antigen (PCNA), cyclin dependent kinase 2 (CDK2), CDK4 and CDK6. HJURP expression was detected in BLUC cells and human normal primary bladder epithelial cells (BdECs). BLUC cells were treated with HJURP lentivirus activation /shRNA lentivirus particles or JNK inhibitor SP600125. HJURP was upregulated in BLUC tissues and correlated with poor prognosis of patients (all P < 0.05). HJURP in tumor positively correlated with MAPK8 (R = 0.30), MAPK9 (R = 0.30), STAT3 (R = 0.15), MKI67 (R = 0.60), PCNA (R = 0.46), CDK2 (R = 0.39), CDK4 (R = 0.24) and CDK6 (R = 0.21). The JNK inhibitor SP600125 decreased p-JNK/JNK and p-STAT3/STAT3 in BLUC cells, which was reversed by HJURP overexpression (P < 0.05). The HJURP-mediated JNK/STAT3 pathway promoted BLUC cell proliferation and inhibited cell apoptosis (P < 0.05). HJURP reversed the arrested G0/G1 phase of BLUC cells by SP600125. HJURP acted as an oncogene to regulate BLUC cell proliferation, apoptosis and the cell cycle by mediating the JNK/STAT3 pathway. Therefore, HJURP targeting might be an attractive novel therapeutic target for early diagnosis and treatment in BLUC.

The Youganwo Formation oil shale located in the Maoming Basin represents a large commercially valuable lacustrine oil shale resource and a potential bio-shale gas reservoir in South China. With the aim of deepening the understanding of factors that influence organic matter enrichment, this research conducted a geochemical investigation to reconstruct the depositional paleoenvironment of bioproductivity, preservation and dilution. Youganwo Formation oil shale is mainly deposited in semi-deep to deep-lake environments with relatively warm and humid paleoclimate in the subtropical-temperate zone. The total organic carbon (TOC) content (1.46-11.85%), S 2 values (4.79-115.80 mg HC/mg rock) and HI (328-1040 mg HC/mg TOC) indicate that the oil shale has a good oil source rock potential. TOC content, (S 1  + S 2 ) values and vitrinite reflectance values show that its marginally mature organic matter (OM) belongs to kerogen type I-III with good oil-generating potential. A 3rd order sequence was identified in the Yougnwo formation. Subsequently, the multiple factors including bioproductivity, preservation and dilution that control the OM enrichment of oil shale within system tracts were discussed. Moderate-quality oil shales (O y-1 ) were developed in the transgressive systems tract (TST) in an oxidizing condition with abundant detrital input. High-quality oil shales (O y-2 ) were deposited during the high-stand systems tract (HST) with increased accommodation space, improved preservation conditions, warm and humid climate, higher water bioproductivity and minimum detrital matter input. During the regressive systems tract (RST, O y-3 ), higher detrital matter input and fresher water led to lower TOC values. Among these multiple factors, dilution condition was the major one that influences OM abundance and variation on the basis of sufficient organic matter input. Thus, OM enrichment models of O y-1 , O y-2 and O y-3 sub-members were established. The OM enrichment and quality in oil shale were controlled by the combined effect of bioproductivity, preservation, and dilution., Competing Interests: The authors declare no conflict of interest., (© 2023 Published by Elsevier Ltd.)

Metal-organic frameworks (MOFs) are widely used in the adsorption separation of various gases. A fundamental understanding of the effective separation of xylene isomers helps improve aromatic products' separation efficiency and reduce industrial separation costs. Grand Canonical Monte Carlo (GCMC) simulations combined with Molecular Science is widely used to predict gas adsorption and diffusion in single crystals with metal-organic frameworks. We performed a GCMC + MD combined approach to study xylene isomers' adsorption and separation in Cu-HKUST-1 to predict the permeability and selectivity of the ternary gas mixture in the MOF with the adsorption and diffusion usage data. Most current studies take into account the computational cost and difficulty. Most recent research models are limited to the adsorption of a single or specific molecule, such as hydrogen, methane, carbon dioxide, etc. For this reason, we report an attempt to study the adsorption separation of aromatic gases ( p -xylene/ o -xylene/ m -xylene) based on Cu-HKUST-1 single-crystal materials based on some previous research methods with an appropriate increase in computational cost. To predict the adsorption selectivity and permeability of the ternary mixture of xylene isomers on the MOF surface, the model simulation calculates key parameters of gas adsorption, including gas adsorption volume ( N ), the heat of adsorption ( Q st ), Henry coefficient ( K ), and diffusion coefficient ( D )., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Aflatoxin B1 (AFB1) is kind of a common mycotoxin in food and feedstuff. Aquafeeds are susceptible to contamination of AFB1. In teleost fish, the spleen and head kidney are key immune organ. Moreover, the fish skin is a critical mucosal barrier system. However, there was little study on the effects of dietary AFB1 on the immune response of these immune organs in fish. This study aimed to explore the impacts of oral AFB1 on the immune competence and its mechanisms in the skin, spleen, and head kidney of grass carp. Our work indicated that dietary AFB1 reduced antibacterial compounds and immunoglobulins contents, and decreased the transcription levels of antimicrobial peptides in grass carp immune organs. In addition, dietary AFB1 increased the transcription levels of pro-inflammatory cytokines and reduced the transcription levels of anti-inflammatory cytokines in the grass carp immune organs, which might be regulated by NF-κB and TOR signaling, respectively. Meanwhile, we evaluated the content of AFB1 in the grass carp diet should not exceed 29.48 μg/kg diet according to the levels of acid phosphatase and lysozyme. In summary, dietary AFB1 impaired immune response in grass carp skin, spleen, and head kidney., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Zeng, Wu, Jiang, Liu, Jiang, Kuang, Tang, Feng and Zhou.)

Soils are the foundation of all terrestrial ecosystems 1 . However, unlike for plants and animals, a global assessment of hotspots for soil nature conservation is still lacking 2 . This hampers our ability to establish nature conservation priorities for the multiple dimensions that support the soil system: from soil biodiversity to ecosystem services. Here, to identify global hotspots for soil nature conservation, we performed a global field survey that includes observations of biodiversity (archaea, bacteria, fungi, protists and invertebrates) and functions (critical for six ecosystem services) in 615 composite samples of topsoil from a standardized survey in all continents. We found that each of the different ecological dimensions of soils-that is, species richness (alpha diversity, measured as amplicon sequence variants), community dissimilarity and ecosystem services-peaked in contrasting regions of the planet, and were associated with different environmental factors. Temperate ecosystems showed the highest species richness, whereas community dissimilarity peaked in the tropics, and colder high-latitudinal ecosystems were identified as hotspots of ecosystem services. These findings highlight the complexities that are involved in simultaneously protecting multiple ecological dimensions of soil. We further show that most of these hotspots are not adequately covered by protected areas (more than 70%), and are vulnerable in the context of several scenarios of global change. Our global estimation of priorities for soil nature conservation highlights the importance of accounting for the multidimensionality of soil biodiversity and ecosystem services to conserve soils for future generations., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Nitrite poses a serious threat to intensive aquaculture. Protein, as a major nutrient in animals, is vital for protecting animal tissues from damage. In this study, we investigated the protective effect of dietary protein on gill tissue structure and the underlying mechanisms in sub-adult grass carp (Ctenopharyngodon idella) exposed to nitrite stress. Six iso-energetic semi-purified diets containing different protein levels (16-31 %) were formulated, and fed to fish for 60 d. The fish were then exposed to a nitrite solution for 4 d. Histopathological observation and determination of related indices (serum glucose, serum cortisol, nitric oxide, peroxynitrite, reactive oxygen species, malondialdehyde, and protein carbonyl) showed that 22-25 % dietary protein significantly alleviated the nitrite-induced stress response, gill tissue damage and oxidative damage. Further research found that a suitable dietary protein suppressed the nitrite-induced endoplasmic reticulum stress (ERS) 78 kDa glucose-regulated protein (GRP78) related signaling pathway which possibly activated autophagy and apoptosis. Interestingly, we discovered that proper dietary protein reduced autophagy, probably through unc-51-like kinase 1 (Ulk1), BCL-2-interacting myosin-like coiled-coil protein (Beclin1), autophagy-related gene 5 (Atg5), Atg12, microtubule-associated protein1 light chain 3 (LC3), BCL-2 interacting protein 3 (BNIP3) and autophagy receptor P62 (p62). We also found that an appropriate dietary protein inhibited nitrite-induced apoptosis via mitochondrial and death receptor pathways. In summary, our findings are the first to demonstrate that 22-25 % of dietary protein levels can play a protective role against nitrite-induced gill injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent years, mannose oligosaccharide (MOS) as a functional additive is widely used in aquaculture, to enhance fish immunity. An evaluation of the effect of dietary MOS supplementation on the immune barrier function and related signaling molecules mechanism of grass carp ( Ctenopharyngodon idella ) was undertaken in the present study. Six diets with graded amounts of MOS supplementation (0, 200, 400, 600, 800, and 1000 mg/kg) were fed to 540 grass carp over 60 days. To examine the immune response and potential mechanisms of MOS supplementation on the intestine, a challenge test was conducted using injections of Aeromonas hydrophila for 14 days. Results of the study on the optimal supplementation with MOS were found as follows (1) MOS enhances immunity partly related to increasing antibacterial substances content and antimicrobial peptides expression; (2) MOS attenuates inflammatory response partly related to regulating the dynamic balance of intestinal inflammatory cytokines; (3) MOS regulates immune barrier function may partly be related to modulating TLRs/MyD88/NFκB and TOR/S6K1/4EBP signalling pathways. Finally, the current study concluded that MOS supplementation could improve fish intestinal immune barrier function under Aeromonas hydrophila infected conditions., Competing Interests: Authors S-YK, LT, S-WL, C-BZ were employed by Sichuan Animtech Feed Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lu, Feng, Jiang, Wu, Liu, Jiang, Kuang, Tang, Li, Zhong and Zhou.)

Objective: To examine the relationship between miRNA-3679 and hepatocellular carcinoma (HCC) cell lines, and to verify the downstream target genes of miRNA-3679., Methods: PCR was used to determine the expression of miRNA-3679 in liver cancer cell lines, and databases, including ENCORI, miRDB and TargetScan, were used to predict the downstream target genes of miRNA-3679. qPCR of the normal control group (or NC group), miR-3679 inhibitor group and transfection negative control group (or inhibitor NC group) was done to determine the transfection efficiency of the target gene, thereby identifying zinc-binding alcohol dehydrogenase domain containing 2 ( ZADH2 ) as the target gene. Western blot was used to determine the ZADH2 protein expression after miRNA-3679 inhibitor transfection. 5-Ethynyl-2'-deoxyuridine (EdU) staining was done to determine the effect of transfection of miRNA-3679 inhibitor and simultaneous transfection of miRNA-3679 and ZADH2 inhibitors on cell proliferation. Clone formation assay was done to determine the ability of cell clone formation. Flow cytometry was done to examine cell apoptosis., Results: The expression level of miRNA-3679 in HCC cell lines was higher than that in normal human liver cell lines ( P <0.05). Through screening conducted with the databases, six genes, including GLUD 1, B 3 GAT 1, SLC 46 A 3, MAP 2 K 3, ATF 5, and ZADH 2, were found to be down-regulated in HCC. qPCR showed that ZADH 2 expression increased significantly after transfection with miRNA-3679 inhibitor ( P <0.01) and luciferase activity increased after transfection with miR-3679 inhibitor ( P <0.01). Western blot results showed that ZADH2 protein expression of the miR-3679 inhibitor group was higher than that of the NC group ( P <0.01). EdU analysis showed that the number of positive cells in the miRNA-3679 inhibitor group was lower than that in the NC group and the Inhibitor NC group ( P <0.05). The clone count of the miR-3679 inhibitor+si- ZADH 2 group was significantly higher than that of the miR-3679 inhibitor group ( P <0.01). Flow cytometry showed that the number of apoptotic cells of the miR-3679 inhibitor+si- ZADH 2 group was significantly lower than that of the miR-3679 inhibitor group ( P <0.01)., Conclusion: miRNA-3679 is significantly highly expressed in HCC cells and miRNA-3679 can directly interact with ZADH 2 gene and affect its expression. Moreover, miRNA-3679 promotes the proliferation of HCC cells and inhibits their apoptosis by suppressing ZADH2., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

We studied the effects of conjugated linoleic acid (CLA) on the amount of nutrients, flavour substances, and healthcare fatty acids, the physicochemical properties, and the potential molecular mechanisms in the muscles of sub-adult grass carp ( Ctenopharyngodon idella ). Fish were fed graded levels of CLA (0.0, 3.1, 6.4, 9.6, 12.7, and 15.9 g/kg diets) for 60 days. Protein, glutamic acid, alanine, inosine monophosphate (IMP), eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3), and total CLA contents ( p  < 0.05) increased in CLA 3.1 ∼ 12.7, 6.4 ∼ 9.6, 6.4 ∼ 9.6, 6.4 ∼ 15.9, 3.1 ∼ 9.6, 3.1 ∼ 9.6, and 3.1 ∼ 15.9 g/kg diet, respectively ( p  < 0.05). In addition, optimal CLA significantly increased pH 24 , shear force, collagen content, and myofibre density in the muscle ( P  < 0.05); however, it decreased myofibre diameter ( p  < 0.05). We concluded that 6-9 g/kg CLA in the diet could improve the flesh quality of sub-adult grass carp., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

The present study explored the impacts of Ile on muscle fatty acid and amino acid profiles, lipid metabolism, and autophagy in hybrid catfish. Seven isonitrogenous (387.8 g/kg protein) semi-purified diets were formulated to contain 5.0 (control), 7.5, 10.0, 12.5, 15.0, 17.5, and 20.0 g Ile/kg diet respectively. The fish (initial weight of 33.11 ± 0.09 g) were randomly assigned to 7 groups for a 56-day trial. Each group has 3 replicates with 30 fish per replicate, fed at 08:00 and 18:00 each day. Results showed that muscle protein and lipid, C14:0, C18:0, C22:0, C14:1, C18:1n-9, polyunsaturated fatty acid (PUFA), Arg, Ile, Ala, Cys, Gly, Tyr, essential amino acid (EAA), and total amino acid (TAA) contents and flavor amino acid (FAA)/TAA in muscle had positive linear and/or quadratic responses to dietary Ile levels ( P  < 0.05). Fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD), acetyl-CoA carboxylase (ACC), and lipoprotein lipase (LPL) activities had positive linear and/or quadratic responses, but carnitine palmitoyl transferase 1 (CPT1) activity had a negative response with increasing dietary Ile levels ( P  < 0.05). The mRNA expressions of FAS , SCD , ACC , LPL , fatty acid binding protein 4 ( FABP4 ), FATP1 , sterol response element-binding protein 1c ( SREBP-1c ), sequestosome 1 ( SQSTM1 ), and adenosine 5'-monophosphate-activated protein kinase ( AMPK ) had positive linear and/or quadratic responses to dietary Ile levels ( P  < 0.05). The mRNA expressions of hormone-sensitive lipase ( HSL ), CPT1 , peroxisome proliferator-activated receptor α ( PPARα ), PPARγ , uncoordinated 51-like kinase 1 ( ULK1 ), beclin1 ( Becn1 ), autophagy-related protein 9α ( Atg9α ), Atg4b , Atg7 , autophagy marker light chain 3 B ( LC3B ), and SQSTM1 in muscle had negative linear and/or quadratic responses to dietary Ile levels ( P  < 0.05). The p-AMPK and ULK1 protein levels, and p-AMPK/AMPK were decreased by 12.5 g Ile/kg in the diet ( P  < 0.05). Finally, SQSTM1 protein level had the opposite effect ( P  < 0.05). The above results indicate that dietary Ile improves fish muscle fatty acid and amino acid profiles potentially via respectively regulating lipid metabolism and autophagy. The Ile requirement of hybrid catfish (33 to 72 g) were estimated to be 12.63, 13.77, 13.75, 11.45, 10.50, 12.53 and 12.21 g/kg diet based on the regression analysis of protein, lipid, SFA, PUFA, FAA, EAA, and TAA muscle contents, respectively., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)