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The nitrogen removal performance, enzymatic activity, antioxidant response and metabolic pathway of Chlorella pyrenoidosa (C. pyrenoidosa) under different salinities have been investigated during the treatment of aquaculture wastewater. The growth, chlorophyll content and photosynthetic activity of C. pyrenoidosa were negatively correlated with the salinity from 1% to 3%. The removal performance of chemical oxygen demand (COD) and nitrogen compounds for C. pyrenoidosa decreased with the increase of salinity from 1% to 3%, which was due to the decrease of their corresponding metabolism enzymatic activities. The equilibrium between the reactive oxygen species production and antioxidant defensive system in C. pyrenoidosa was destroyed under high salinity stress and then caused an irreversible damage, which decreased the nitrogen assimilation of C. pyrenoidosa. The metabolic pathway of C. pyrenoidosa under 3% salinity had some obvious variation by comparison with 1% salinity, which led to the discrepancy in the microalgae activity and nitrogen transformation performance. Additionally, high salinity could inhibit the expression of gene associated with the chlorophyll synthesis and damaged the photosystem II reaction center. This study can provide an insight into the effect of salinity on the nitrogen removal from aquaculture wastewater by microalgae., 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 Elsevier Inc. All rights reserved.)

Background: The patterns of direct oral anticoagulant (DOAC) selection and switching to a different oral anticoagulant (OAC) in patients with atrial fibrillation (AF) are unknown., Objectives: To describe temporal patterns in first DOAC prescriptions, estimate the incidence, and identify predictors of switching to a different OAC within 1 year in OAC-naive AF patients., Methods: In this retrospective cohort study, using a near-nationwide prescription registry (IQVIA, the Netherlands), we determined the number of patients per month initiated on each DOAC and identified predictors of switching within 1 year with robust Poisson regression., Results: We included 94,874 patients. From November 2015 to November 2019, the monthly use of apixaban ( n  = 366 to n  = 1066, +191%), rivaroxaban ( n  = 379 to n  = 868, +129%), and edoxaban ( n  = 2 to n  = 305, +15,150%) increased, whereas that of dabigatran decreased ( n  = 317 to n  = 179, -44%). In the 66,090 patients with ≥1 year of available calendar time, 7% switched to a different OAC within 1 year. Strong predictors of switching to a different DOAC were using dabigatran (adjusted risk ratio [aRR], 3.33; 95% CI, 3.02-3.66) or edoxaban (aRR, 1.56; 95% CI, 1.34-1.82) rather than apixaban and using a standard DOAC dose (aRR, 2.54; 95% CI, 2.23-2.88). Strong predictors of switching to a vitamin K antagonist were using rivaroxaban (aRR, 1.36; 95% CI, 1.19-1.54 vs apixaban) and using a standard DOAC dose (aRR, 1.49; 95% CI, 1.26-1.77)., Conclusion: In the Netherlands, factor Xa inhibitors are increasingly being selected for OAC-naive AF patients. Seven percent of patients switch to a different OAC within 1 year, and the initial DOAC type and dose are strong predictors of switching., (© 2024 The Author(s).)

The transient chlorophenol shock under some emergency conditions might directly affect the pollutant removal of bioreactor. Therefore, the recovery of bioreactor performance after transient chlorophenol shock is a noteworthy issue. In the present research, the performance, antioxidant response, microbial succession and functional genes of sequencing batch reactor (SBR) were evaluated under transient 2,4,6-trichlorophenol (2,4,6-TCP) shock. The chemical oxygen demand (COD) and ammonia nitrogen (NH 4 + -N) removal efficiencies decreased sharply in the first 4 days after 60 mg/L 2,4,6-TCP shock for 24 h and gradually recovered to normal in the subsequent 8 days. The nitrogen removal rates and their corresponding enzymatic activities rapidly decreased after transient 2,4,6-TCP shock and then gradually increased to normal. The increase of antioxidant enzymatic activity, Cu-Zn SOD genes and Fe-Mn SOD genes contributed to the recovery of SBR performance. The abundance of genes encoding ammonia monooxygenase and hydroxylamine dehydrogenase decreased after transient 2,4,6-TCP shock, including amoA, amoC and nxrA. Thauera, Dechloromonas and Candidatus_Competibacter played key roles in the restorative process, which provided stable abundances of narG, norB , norC and nosZ. The results will deeply understand into the effect of transient 2,4,6-TCP shock on bioreactor performance and provide theoretical basis to build promising recoveries strategy of bioreactor performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sinomenine is a pure alkaloid isolated from Sinomenium acutum. This study is aimed to investigate the critical role of the nuclear factor erythroid 2-related factor 2 (Nrf2)-kelch-like ECH-associated protein-1(Keap1)-antioxidant response element (ARE) antioxidative signaling pathway in protecting sinomenine against H 2 O 2 -induced oxidative injury. Cytotoxicity and antioxidant experiments to initially determine the protective effects of sinomenine show that sinomenine has no effect on the decreased cell viability and presents similar potency in scavenging all three free radicals. The binding affinity between sinomenine and Keap1 was determined via fluorescence polarization assay, with IC 50 of 13.52 μM. Quantum chemical calculation and theoretical simulation illustrated that sinomenine located into the Nrf2-binding site of Keap1 via hydrophobic and hydrogen interactions, showing high stability and binding affinity. On the basis of the stable binding of sinomenine with Keap1, sinomenine efficiently induced nuclear translocation of Nrf2, and increased in ARE activity in a concentration-dependent manner. Quantitative polymerase chain reaction provided further evidences that sinomenine-induced protection upregulated ARE-dependent genes, such as NAD(P)H quinone oxidoreductase 1, hemeoxygenase-1, and glutamate-cysteine ligase modifier subunit. Western blot confirmed that sinomenine increased the expressions of these antioxidative enzymes. Taken together, in vitro and in silico evaluations demonstrate that sinomenine inhibits the binding of Keap1 to Nrf2, promotes the nuclear accumulation of Nrf2 and thus leads to the upregulated expressions of Nrf2-dependent antioxidative genes. Our findings also highlight the use of sinomenine for pharmacological or therapeutic regulation of the Nrf2-Keap1-ARE system, which is a novel strategy to prevent the progression of oxidative 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 © 2024 Elsevier Inc. All rights reserved.)

The detection and attribution of biodiversity change is of great scientific interest and central to policy effects aimed at meeting biodiversity targets. Yet, how such a diverse climate scenarios influence forest biodiversity and composition dynamics remains unclear, particularly in high diversity systems of subtropical forests. Here we used data collected from the permanent sample plot spanning 26 years in an old-growth subtropical forest. Combining various climatic events (extreme drought, subsequent drought, warming, and windstorm), we analyzed long-term dynamics in multiple metrics: richness, turnover, density, abundance, reordering and stability. We did not observe consistent and directional trends in species richness under various climatic scenarios. Still, drought and windstorm events either reduced species gains or increased species loss, ultimately increased species turnover. Tree density increased significantly over time as a result of rapid increase in smaller individuals due to mortality in larger trees. Climate events caused rapid changes in dominant populations due to a handful of species undergoing strong increases or declines in abundance over time simultaneously. Species abundance composition underwent significant changes, particularly in the presence of drought and windstorm events. High variance ratio and species synchrony weaken community stability under various climate stress. Our study demonstrates that all processes underlying forest community composition changes often occur simultaneously and are equally affected by climate events, necessitating a holistic approach to quantifying community changes. By recognizing the interconnected nature of these processes, future research should accelerate comprehensive understanding and predicting of how forest vegetation responds to global climate change., Competing Interests: Declaration of competing interest The authors declare no competing interest to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Tetracycline is prevalent in wastewater treatment plants and poses a potential threat to biological nitrogen removal under long-term exposure. In the present study, the influence of different tetracycline concentrations on the nitrogen removal, bioactivity response, and the spread of antibiotic resistance genes (ARGs) was assessed in sequencing batch reactor (SBR). The nitrogen removal efficiency, nitrification rate, and denitrification rate and their corresponding enzymatic activities gradually decreased with an increase in tetracycline concentration from 0.5 to 15 mg/L. The remarkable toxicity induced by tetracycline led to a significant increase in the peroxidation and the response of antioxidant system, as evidenced by strengthened antioxidant enzymatic activity and abundant genes (SOD12, katG, PXDN, gpx, and apx). Tetracycline addition significantly inhibited the ammonia-oxidizing bacterium Nitrosomonas and functional genes (amoA, amoB, and amoC). The presence of tetracycline decreased the abundance of citrate synthase and genes (CS, IDH3, and acnA) and interfered with carbon source metabolism, leading to impaired bioactivity and treatment performance. In addition, the presence of tetracycline induces diversity and differences in ARGs. The results provide reliable basic data for a deeper understanding of the effects of tetracycline on the nitrogen removal performance of bioreactors and provide a theoretical basis to build a promising strategy for relieving antibiotic-caused process fluctuations., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest to this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Candida rugosa lipase (CRL, EC3.1.1.3) is one of the main enzymes synthesizing esters, and ZIF-8 was chosen as an immobilization carrier for lipase. Enzyme activity testing often requires expensive reagents as substrates, and the experiment processes are time-consuming and inconvenient. As a result, a novel approach based on near-infrared spectroscopy (NIRs) was developed for predicting CRL/ZIF-8 enzyme activity. The absorbance of the immobilized enzyme catalytic system was evaluated using UV-Vis spectroscopy to investigate the amount of CRL/ZIF-8 enzyme activity. The powdered samples' near-infrared spectra were obtained. The sample's enzyme activity data were linked with each sample's original NIR spectra to establish the NIR model. A partial least squares (PLS) model of immobilized enzyme activity was developed by coupling spectral preprocessing with a variable screening technique. The experiments were completed within 48 h to eliminate inaccuracies between the reduction in enzyme activity with increasing laying-aside time throughout the test and the NIRs modeling. The root-mean-square error of cross-validation (RMSECV), the correlation coefficient of validation set (R) value, and the ratio of prediction to deviation (RPD) value were employed as assessment model indicators. The near-infrared spectrum model was developed by merging the best 2nd derivative spectral preprocessing with the Competitive Adaptive Reweighted Sampling (CARS) variable screening method. This model's root-mean-square error of cross-validation (RMSECV) was 0.368 U/g, the correlation coefficient of calibration set (R_cv) value was 0.943, the root-mean-square error of prediction (RMSEP) set was 0.414 U/g, the correlation coefficient of validation set (R) value was 0.952, and the ratio of prediction to deviation (RPD) was 3.0. The model demonstrates that the fitting relationship between the predicted and the reference enzyme activity value of the NIRs is satisfactory. The findings revealed a strong relationship between NIRs and CRL/ZIF-8 enzyme activity. As a result, the established model could be implemented to quantify the enzyme activity of CRL/ZIF-8 quickly by including more variations of natural samples. The prediction method is simple, rapid, and adaptable to be the theoretical and practical basis for further studying other interdisciplinary research work in enzymology and spectroscopy., 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 B.V. All rights reserved.)

Gap junction intercellular communication (GJIC) among granulosa cells plays an important role in folliculogenesis, and it is temporal-spatially regulated during follicular development. Connexin (Cx) proteins predominantly form the basal structure of gap junctions in granulosa cells. In our study, immunohistochemical analysis revealed that Cx43 is the most widely expressed connexin in porcine follicles, especially among the large antral follicles. With application of insulin on porcine granulosa cells, we found that insulin significantly facilitated the protein level of Cx43, not mRNA level. This process is dependent on the phosphorylated activities of AKT and Erk since selective AKT and Erk inhibitors, LY294002 and U0126, respectively, hampered the potential of insulin to up-regulate Cx43 protein expression. As a consequence, the insulin-enhanced Cx43-couple GJIC activity in porcine granulosa cells was corresponding attenuated by the administration of LY294002 and U0126. Our findings provide a new insight into the molecular mechanisms by which insulin mediates cell-cell communication in porcine granulosa cells and sheds light on nutrition-reproduction interactions., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

During growth, proliferation, differentiation, atresia, ovulation, and luteinization, the morphology and function of granulosa cells (GCs) change. Estrogen and progesterone are steroid hormones secreted by GCs that regulate the ovulation cycle of sows and help maintain pregnancy. miR-10a-5p is highly expressed in GCs and can inhibit GC proliferation. However, the role of miR-10a-5p in the steroid hormone synthesis of porcine GCs is unclear. In this study, miR-10a-5p agomir or antagomir was transfected into GCs. Overexpression of miR-10a-5p in GCs inhibited steroid hormone secretion and significantly downregulated steroid hormone synthesis via 3β-hydroxy steroid dehydrogenase and cytochrome P450 family 19 subfamily A member 1. Interference with miR-10a-5p had the opposite effect. Bodipy and Oil Red O staining showed that overexpression of miR-10a-5p significantly reduced the formation of lipid droplets. Overexpression significantly inhibited the content of total cholesterol esters in GCs. The mRNA and protein levels of 3-hydroxy-3-methylglutaryl-CoA reductase and scavenger receptor class B member 1 decreased significantly, and the opposite effects were seen by interference with miR-10a-5p. Bioinformatic analysis of potential targets identified cAMP-responsive element binding protein 1 as a potential target and dual-luciferase reporter system analysis confirmed that miR-10a-5p directly targets the 3' untranslated region. These findings suggest that miR-10a-5p inhibits the expression of 3β-hydroxy steroid dehydrogenase and cytochrome P450 family 19 subfamily A member 1 to inhibit the synthesis of steroid hormones in GCs. In addition, miR-10a-5p inhibits the cholesterol metabolism pathway of GCs to modulate steroid hormone synthesis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pyrogenic carbon (PC) including black carbons and engineered carbons can mediate the extracellular electron transfer to facilitate the biogeochemical reaction with organic pollutants. Yet, the role of carbon structures and iron minerals on PC-mediated microbial degradation is still lacking of understanding. Herein, we studied the electrochemical properties of PCs produced from varied feedstock with regards to the mediated degradation of p-nitrophenol (PNP) by Shewanella putrefaciens CN32 in anoxic system. Mediated degradation by PCs was enhanced by facilitating extracellular electron transfer through oxygenated group and graphitic structure. Graphitic crystallites improved the electron-accepting capacity (as suggested by I D /I G and EAC) and diminished the electrochemical impedance (as suggested by Rct), contributing to PNP degradation under the anoxic system. Furthermore, more interfacial adsorption was conducive to the mediated reduction by the graphitic structure on PCs of high-temperature. In the presence of iron minerals, both hematite and goethite significantly facilitated PC-mediated degradation, which could be ascribed to the enhancement of the electron-donating capacity of microorganism and the accumulation of the reductive-state PCs by the interaction with generated Fe(II). This work paves a feasible way to the technical design on the remediation of phenolic contaminants by PC-mediated microbial degradation in environment., 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 B.V. All rights reserved.)

Immature oocyte (germinal vesicle stage, GV) vitrification can avoid a cycle of ovarian stimulation, which is friendly to patients with hormone-sensitive tumors. However, the in vitro maturation of vitrification-thawed GV oocyte usually results in aneuploidy, and the underlying mechanism remains unclear. Stable spindle poles are important for accurate chromosome segregation. Acentriolar microtubule-organizing centers (aMTOCs) undergo fragmentation and reaggregation to form spindle poles. Microtubule nucleation is facilitated via the perichromosome Ran after GVBD, which plays an important role in aMTOCs fragmentation. This study showed that vitrification may reduce microtubule density by decreasing perichromosomal Ran levels, which reduced the localization of pKIF11, thereby decreased the fragmentation of aMTOCs and formed a more focused spindle pole, ultimately resulted in aneuploidy. This study revealed the mechanism of abnormal spindle pole formation in vitrified oocytes and offered a theoretical support to further improve the quality of vitrified oocytes., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Oocyte vitrification has been widely application in female fertility preservation. Recent studies found that vitrification of immature (germinal vesicle stage, GV) oocytes increased the risk of aneuploidy during meiotic maturation; however, the underlying mechanisms and the strategies to prevent this defect remain unexplored. In this study, we found that vitrification of GV oocytes decreased the first polarbody extrusion rate (90.51 ± 1.04% vs. 63.89 ± 1.39%, p < 0.05) and increased the aneuploid rate (2.50% vs. 20.00%, p < 0.05), accompanied with a series of defects during meiotic maturation, including aberrant spindle morphology, chromosome misalignment, incorrect Kinetochore-Microtubule attachments (KT-MTs) and weakened spindle assembly checkpoint protein complex (SAC) function. We also found that vitrification disrupted mitochondrial function by increasing mitochondrial Ca 2+ levels. Importantly, inhibition of mitochondrial Ca 2+ entry by 1 μM Ru360 significantly restored mitochondrial function and rescued the meiotic defects, indicating that the increase of mitochondrial Ca 2+ , at least, was a cause of meiotic defects in vitrified oocytes. These results shed light on the molecular mechanisms of oocyte vitrification-induced adverse effects of meiotic maturation and provided a potential strategy to improve oocyte cryopreservation protocols further., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Circadian locomotor output cycles kaput (CLOCK) is a critical component of the mammalian circadian clock system and regulates ovarian physiology. However, the functions and mechanisms of CLOCK in porcine granulosa cells (GCs) are poorly understood. The present study focused on CLOCK's effects on estradiol synthesis. Similarity analysis showed that CLOCK is highly conserved between pigs and other species. The phylogenetic tree analysis indicated that porcine CLOCK was most closely related to that in Arabian camels. CLOCK significantly reduced E 2 synthesis in GCs. CLOCK reduced the expression of steroidogenesis-related genes at the mRNA and protein levels, including CYP19A1, CYP11A1, and StAR. CYP17A1 levels were significantly downregulated. We demonstrated that CLOCK dramatically decreased ATP content, mitochondrial copy number, and mitochondrial membrane potential (MMP) and increased reactive oxygen species levels in GCs. We observed that mitochondria were severely damaged with fuzzy and fractured cristae and swollen matrix. These findings suggest that mitochondrial function and E 2 synthesis are impaired following the alteration of CLOCK gene expression in porcine ovarian GCs., 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 Inc. All rights reserved.)

Disc degeneration is the common pathology underlying various degenerative spinal disorders and currently there is no effective cure. Here, we found nucleus pulposus (NP) cell senescence was closely associated with the severity of disc degeneration, and exosomes (Exos) derived from mesenchymal stem cells (MSCs) ameliorated NP cell senescence and promoted extracellular matrix (ECM) deposition. As chitosan-based hydrogels have been widely used as vehicles to deliver Exos due to their prominent antibacterial capacity, biocompatibility, and biodegradability, we developed an Exos-laden hydrogel based on quaternized chitosan (QCS) and oxidized starch (OST) to treat disc degeneration. The synthesized QCS-OST hydrogel is injectable, self-healing, biocompatible, and demonstrated desirable pore size, injectable properties, and sustainable release of Exos. In a rat model of disc degeneration, the QCS-OST/Exos hydrogel was able to rejuvenate NP cell senescence, promote ECM remodeling, and partially restore the structures of NP and annulus fibrosis. Our findings suggested that the novel QCS-OST/Exos hydrogel is an effective therapeutic strategy for treating disc degeneration via alleviating NP cell senescence., 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 B.V. All rights reserved.)

Phosphoric acid-assisted pyrolysis (PAAP) is a pyrolysis technique with potential for the engineered and environmental application. Nevertheless, the volatilisation, immobilisation, and dissolution of phosphorus (P) species have been neglected during PAAP of lignocellulose. Therefore, we compared the transformation of P species with direct-pyrolysis and PAAP system, using multiple techniques including gas chromatography tandem mass spectrometry (GCMS) and 31 P nuclear magnetic resonance (NMR). It was also investigated that the properties of pyrogenic and modified carbons obtained from lignocellulose pyrolysis at 200-650 °C. As the temperature increased, volatile P species evolved into gas-phase during PAAP, inhibiting the formation of the macromolecular volatile components. Compared with pyrogenic carbons, modified carbons with more aromatic structures experienced a higher degree of dehydration and cyclisation via catalytic crosslinking reaction. PAAP system facilitated more generation of persistent free radical (PFR) below 500 °C and the attenuation of PFR signals was observed at 500-650 °C, which may be associated with the sequestration and elimination of P species between carbon matrix. Notably, three configurations of C 3 PO, CPO, and COP were the major combinations of P and C elements on modified carbons. Increased gaseous P and decreased soluble P were observed with elevated temperatures in PAAP system. The species proportion of immobilised P clearly demonstrated the transformation of partial P species from inorganic to organic through pyrolysis. The immobilised P could serve as a potential sustained-release source participating in P biogeochemical cycles. These findings are fundamental for the technical design of lignocellulose pyrolysis., 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. Published by Elsevier B.V.)

Background: Cancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF)., Objectives: We aimed to describe current anticoagulant practice in patients with AF and active cancer, present incidences of thromboembolic and bleeding complications, and evaluate the association between cancer type or anticoagulant management strategy with AF-related complications., Methods: This retrospective study identified patients with AF and active cancer in 2 hospitals between January 1, 2012, and December 31, 2017. Follow-up lasted for 2 years. Data on cancer and anticoagulant treatment were collected. The outcomes of interest included ischemic stroke or transient ischemic attack (TIA) and clinically relevant nonmajor bleeding (CRNMB/MB). Incidence rates (IRs) per 100 patient-years and subdistribution hazard ratios (SHRs) with corresponding 95% Cis were estimated., Results: We identified 878 patients with AF who developed cancer (cohort 1) and 335 patients with cancer who developed AF (cohort 2). IRs for ischemic stroke/TIA and MB/CRNMB were 3.9 (2.8-5.3) and 15.7 (13.3-18.5) for cohort 1 and 4.0 (2.2-6.7) and 16.7 (12.6-21.7) for cohort 2. 14.2% (cohort 1) and 19.1% (cohort 2) of patients with a CHA 2 DS 2 -VASc score of ≥2 did not receive anticoagulant treatment. Withholding anticoagulants was associated with thromboembolic complications (SHR: 5.1 [3.20-8.0]). In nonanticoagulated patients with a CHA 2 DS 2 -VASc score of <2, IRs for stroke/TIA were 4.5 (0.75-15.0; cohort 1) and 16.0 (5.1-38.7; cohort 2)., Conclusion: Patients with AF and active cancer experience high rates of thromboembolic and bleeding complications, underlying the complexity of anticoagulant management in these patients. Our data suggest that the presence of cancer is an important factor in determining the indication for anticoagulants in patients with a low CHA 2 DS 2 -VASc score., (© 2023 The Authors.)

The structural behavior of TmVO 4 at pressures up to ∼ 55 GPa was investigated by Raman spectroscopy. The changes in Raman spectra suggest the existence of three phase transitions upon compression. The first phase transition appeared at ∼ 7.7 GPa, which was an irreversible phase transition from the ambient-pressure zircon phase to the scheelite phase, confirming previous X-ray measurements. Subsequently, the second reversible phase transition from the scheelite phase to the fergusonite phase occurred at ∼ 23 GPa. Additional changes in the Raman spectra were observed at ∼ 37 GPa, validating the third phase transition. Based on a comparison to related rare earth orthovanadates, we assumed that the post-fergusonite of TmVO 4 has an orthorhombic structure described by space group Cmca. The wavenumbers of the Raman modes and their pressure coefficients for all four phases of TmVO 4 are reported. Our study provides the vibrational difference in various polymorphs of TmVO 4 , which will refine our understanding of the structural behavior of rare-earth orthovanadates., 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 Elsevier B.V. All rights reserved.)

The intensive use of chemical fertilizer, particularly nitrogen (N) has resulted in not only markedly increased crop yields but also detrimental effects on ecosystems. Plant microbiomes represent an eco-friendly alternative for plant nutrition and productivity, and the effect of N fertilization on plant and soil microbes has been well studied. However, if and how N fertilization modulates seed endophytic microbiomes and grain quality remains largely unknown. Here, we investigated the effect of different N fertilization rates on rice seed endophytic bacterial and fungal communities as well as on grain quality. Higher bacterial and fungal community diversity and richness, but lower grain protein and amino acid contents were found in seeds of rice treated moderate N fertilization than those treated insufficient or excessive N input. There were also more complex co-occurrence networks, and an enrichment of putative beneficial bacterial taxa in seeds under moderate N application, while there was an opposite trend under the excessive N treatment. In addition, the grain amylose and amylopectin contents were positively correlated with the relative abundance of bacterial and fungal dominant genera, while the grain amino acid contents were negatively correlated with the bacterial dominant genera but positively associated with fungal dominant genera. Together, we demonstrate that moderate N fertilization can enhance bacterial and fungal community colonization in seeds and improve grain eating and cooking qualities. This study extends our knowledge regarding the significant role of rational fertilization on seed-microbe interactions in sustainable agriculture., 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. Published by Elsevier B.V.)

The proliferation and steroidogenesis of mammalian ovarian granulosa cells (GCs) are related to follicular development. Previous studies found that fibroblast growth factor 21 (FGF21) regulated female fertility through the hypothalamic-pituitary-gonad axis. However, FGF21 receptors are expressed on GCs, so we speculate that it might affect female reproduction by regulating their physiological activities. Here, we showed that FGF21, fibroblast growth factor receptor-1(FGFR1), and beta-klotho (KLB) were expressed in porcine GCs. ELISA assays showed that estradiol (E 2 ) production was increased significantly when treating GCs with recombinant FGF21 (rFGF21). In addition, rFGF21 upregulated the mRNA and protein levels of E 2 synthesis-related genes including StAR, CYP11A1, and CYP19A1 in porcine GCs. Correspondingly, FGF21 siRNA inhibited E 2 levels and its synthesis-related gene expression. After rFGF21 treatment, CCK8 showed increased cell viability, and flow cytometry showed that the number of S phase increased, and cycle-related genes also increased. However, treatment with FGF21 siRNA to porcine GCs suppressed the cell cycle, viability, and EdU positive cell number. Consequently, FGF21/FGFR1/KLB forms a complex to activate the phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway and further promote the proliferation and E 2 synthesis in porcine GCs. Collectively, these findings suggests that FGF21 regulates porcine ovarian folliculogenesis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are common persistent organic pollutants that are carcinogenic, teratogenic and mutagenic, causing a variety of harm to human health. In this study, we investigated the mechanism of how valproic acid (VPA) interferes with the carcinogenesis of PAHs protect normal tissues via the regulation of macrophages' function. Using the established model of transformed malignant breast cancer by 7,12-dimethylbenz[a]anthracene (DMBA), a representative PAH carcinogen, we discovered VPA induces the polarization of macrophages toward the M1 phenotype in the tumor tissues, facilitates the expression of pro-inflammatory cytokines such as IFN-γ, IL-12 and TNF-α, activates CD8 + T cells to secret Granzyme B thus to promote the apoptosis of tumor cells and suppresses the viability of vascular endothelial cells in tissue stroma of tumor. Surprisingly, VPA selectively induces macrophages to polarize towards the M2 phenotype in normal tissues and promotes the expression of anti-inflammatory cytokines such as IL-10 to enhance cell proliferation. Additionally, at the cellular level, VPA can directly regulate the polarization of macrophages to affect the growth of vascular endothelial cells by simulating the living conditions of tumor and normal cells. Collectively, VPA exerts an interventional effect on tumor growth and a protective effect on normal tissues by regulation of selective macrophages' polarization in their microenvironment., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

α-Glucosidase is one of the main enzymes causing elevated blood glucose, and Coreopsis tinctoria extract can be used as a natural inhibitor of α-Glucosidase. Therefore, a new method was proposed for predicting the inhibitory activity on α-Glucosidase of Coreopsis tinctoria extract based on near infrared spectroscopy. The absorbance of the inhibitory system was measured by ultraviolet spectroscopy, which was used to study the inhibitory activity on a-glucosidase of Coreopsis tinctoria extract. The near infrared spectra of the solid samples were collected. By selecting spectral preprocessing and optimizing spectral bands, a rapid prediction model of the inhibitory activity was established by partial least squares regression. The root mean square error of cross-validation (RMSECV), correlation coefficient (R) value and the ratio of prediction to deviation (RPD) value were used as indicators of the evaluation model. The near infrared spectrum model was established by combining the best spectral preprocessing of the continuous wavelet transform (CWT) and the best spectral band. The root mean square error of cross-validation (RMSECV) of this model was 0.815%, the correlation coefficient (R) value was 0.942, and the ratio of prediction to deviation (RPD) was 3.0. The root mean square error of prediction (RMSEP) of the model by prediction set was 0.819%, the correlation coefficient (R) value was 0.950, and the RPD was 3.2. The model shows that the fitting relationship between the predicted inhibition value and the reference inhibition value of the near infrared spectral model is good. The results showed that there was a good correlation between near infrared spectroscopy and the inhibitory activity of Coreopsis tinctoria extract. Thus, the established model was robust and effective and could be used for rapid quantification of α-Glucosidase inhibitory activity. The prediction method is simple and rapid, and can be extended to study the inhibition of other medicinal plants., 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 © 2021. Published by Elsevier B.V.)

The circadian system performs an important role in mammalian reproduction with significant effects on hormone secretion. Nuclear receptor subfamily 1 group D member 1 (NR1D1) functions as a transcriptional repressor in the circadian system and affects granulosa cells (GCs), but how it regulates estrogen synthesis has not been clarified. We investigated the effect of NR1D1 on estrogen synthesis and found that NR1D1 was highly expressed in GCs, mainly in cell nuclei. Additionally, the expression of NR1D1 and estrogen synthesis key genes CYP19A1, CYP11A1 and StAR showed rhythmic changes in porcine ovarian GCs. Activation of NR1D1 enhances its ability to inhibit the transcriptional activity of CYP19A1 by binding to the RORE on the CYP19A1 promoter, resulting in a decrease in estradiol content. Interference with NR1D1 can eliminate the transcriptional inhibition of CYP19A1 and promote the synthesis of estradiol. The results suggest that the hormone secretion of the ovary itself is also regulated by the biological clock, and any factors that affect the circadian rhythm can affect the endocrine and reproductive performance of sows, so the natural rhythm of sows should be maintained in production., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Phthalic acid esters (PAEs) pollution has become an increasing issue worldwide, but little is known about its effects on ammonia-oxidizers and nitrous oxide (N 2 O) in the soil environment. Here, a 50-day soil microcosm experiment was conducted using low and high doses bis (2-Ethylhexyl) phthalate (DEHP) to estimate the effect of DEHP exposure on soil N 2 O emissions and the nitrifying community in calcareous soil. The results showed that DEHP exposure at 10 and 100 mg kg -1 doses significantly reduced N 2 O by 67.5% and 73.6%, respectively, relative to the DEHP absent treatment. The microbial biomass carbon and nitrogen (MBC and MBN) were consistently and significantly decreased with DEHP exposure at 5, 22, and 50 days after incubation, especially with high-dose. The bipartite association networks showed that DEHP exposure changed the compositions of both ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) communities. Moreover, the AOA and AOB amoA gene abundances were significantly decreased by DEHP addition to the soil (P < 0.05). Random forest modeling showed that the AOB Shannon index and pH were the most important biotic and abiotic factors affecting N 2 O emissions in the soil with DEHP exposure, respectively. Partial least squares path modeling (PLS-PM) demonstrated that the reduction of N 2 O emissions due to DEHP exposure was mainly ascribed to the changes of the AOB community. The results from this study highlight the toxicity of DEHP on the ammonia oxidizers, and its mitigating effect on N 2 O emissions in the soil where ammonia-oxidation is largely driven by AOB., (Copyright © 2021. Published by Elsevier Inc.)

Background: Whereas accumulating studies on patients with coronavirus disease 2019 (COVID-19) report high incidences of thrombotic complications, large studies on clinically relevant thrombosis in patients with other respiratory tract infections are lacking. How this high risk in COVID-19 patients compares to those observed in hospitalized patients with other viral pneumonias such as influenza is unknown., Objectives: To assess the incidence of venous and arterial thrombotic complications in hospitalized patients with influenza as opposed to that observed in hospitalized patients with COVID-19., Methods: This was a retrospective cohort study; we used data from Statistics Netherlands (study period: 2018) on thrombotic complications in hospitalized patients with influenza. In parallel, we assessed the cumulative incidence of thrombotic complications-adjusted for competing risk of death-in patients with COVID-19 in three Dutch hospitals (February 24 to April 26, 2020)., Results: Of the 13 217 hospitalized patients with influenza, 437 (3.3%) were diagnosed with thrombotic complications, versus 66 (11%) of the 579 hospitalized patients with COVID-19. The 30-day cumulative incidence of any thrombotic complication in influenza was 11% (95% confidence interval [CI], 9.4-12) versus 25% (95% CI, 18-32) in COVID-19. For venous thrombotic (VTC) complications and arterial thrombotic complications alone, these numbers were, respectively, 3.6% (95% CI, 2.7-4.6) and 7.5% (95% CI, 6.3-8.8) in influenza versus 23% (95% CI, 16-29) and 4.4% (95% CI, 1.9-8.8) in COVID-19., Conclusions: The incidence of thrombotic complications in hospitalized patients with influenza was lower than in hospitalized patients with COVID-19. This difference was mainly driven by a high risk of VTC complications in the patients with COVID-19 admitted to the Intensive Care Unit. Remarkably, patients with influenza were more often diagnosed with arterial thrombotic complications., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Storm runoff is important for maintaining surface water resources, while this function is significantly affected by land use and land cover changes, e.g., afforestation and reforestation. The Chinese Loess Plateau (CLP) has undergone large-scale vegetation rehabilitation, especially afforestation over the past 20 years. We hypothesize that afforestation has profoundly changed the amounts and mechanisms of storm runoff generation in headwater catchments on the CLP. To test this hypothesis, rainfall, soil moisture, and streamflow were monitored in a grass catchment and an adjacent forest catchment for two consecutive years. The objective of this study was to elucidate the varied mechanisms of storm runoff generation in these two contrasting revegetated catchments. Results showed that (1) average runoff coefficient in the grassland catchment (0.042) was approximately ten times higher than that in the forestland catchment (0.004), confirming the impact of catchment afforestation on the suppression of storm runoff generation. (2) Peak rainfall intensity was the first-order control of the runoff coefficient in the grassland catchment, but not in the forestland catchment. (3) Threshold values for antecedent soil moisture (~18%) and the sum of antecedent soil moisture index and event precipitation (~210 mm) were identified in the grassland catchment, above which storm runoff significantly increased. (4) Two extraordinary high runoff coefficient events were observed in the grassland catchment, one due to high peak rainfall intensity and strong surface runoff and the other due to high rainfall amount and high antecedent soil moisture. We conclude that long-term afforestation has changed the mechanisms and patterns of storm runoff generation, and different conditions of rainfall intensity, rainfall amount and antecedent soil moisture determined the hydrological connectivity between the upper hillslope and downhill gully in the catchment. This study deepens our understanding of the mechanisms and thresholds of storm runoff generation in headwater catchments on the CLP., Competing Interests: Declaration of competing interest The authors stated that this paper has no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Forest age serves as an essential factor in determining the accuracy of historical and future carbon (C) uptake quantifications, which is especially critical for China since the forest C stock dynamics are sensitive to the fast-growing, young-age plantations. However, a spatially explicit forest age maps with specific focus on forest plantations is not available yet. In this study, we developed a 1-km resolution age and type maps of forest plantations, and quantified their uncertainties spatially using field-measured data, national forest inventory data, digitalized forest maps, and remote sensing-based forest height maps. Simulation results showed forest plantations were 16.5 years old at national scale in 2005, which is close to the age of 16.6 years old derived from the 7th national inventory data using medium age in each forest plantation group with weighted area. Interestingly, we found that human management played an important role in forest age map reconstruction, which has not yet been considered in former studies. We also suggest that forest age and type maps should be used consistently in C stock simulations to avoid biases from mismatch information. Large uncertainty found in this study suggests further endeavors are required for improving the forest age and type maps., 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 © 2020 Elsevier B.V. All rights reserved.)

T-cell-mediated approaches have shown promise in myeloma treatment. However, there are currently a limited number of specific myeloma antigens that can be targeted, and multiple myeloma (MM) remains an incurable disease. G-protein-coupled receptor class 5 member D (GPRC5D) is expressed in MM and smoldering MM patient plasma cells. Here, we demonstrate that GPRC5D protein is present on the surface of MM cells and describe JNJ-64407564, a GPRC5DxCD3 bispecific antibody that recruits CD3+ T cells to GPRC5D+ MM cells and induces killing of GPRC5D+ cells. In vitro, JNJ-64407564 induced specific cytotoxicity of GPRC5D+ cells with concomitant T-cell activation and also killed plasma cells in MM patient samples ex vivo. JNJ-64407564 can recruit T cells and induce tumor regression in GPRC5D+ MM murine models, which coincide with T-cell infiltration at the tumor site. This antibody is also able to induce cytotoxicity of patient primary MM cells from bone marrow, which is the natural site of this disease. GPRC5D is a promising surface antigen for MM immunotherapy, and JNJ-64407564 is currently being evaluated in a phase 1 clinical trial in patients with relapsed or refractory MM (NCT03399799)., (© 2020 by The American Society of Hematology.)

Background: Tissue engineering of the annulus fibrosus (AF) shows promise as a treatment for patients with degenerative disc disease (DDD). However, it remains challenging due to the intrinsic heterogeneity of AF tissue. Fabrication of scaffolds recapitulating the specific cellular, componential, and microstructural features of AF, therefore, is critical to successful AF tissue regeneration., Methods: Poly-L-lactic acid (PLLA) fibrous scaffolds with various fiber diameters and orientation were prepared to mimic the microstructural characteristics of AF tissue using electrospinning technique. AF-derived stem cells (AFSCs) were cultured on the PLLA fibrous scaffolds for 7 days., Results: The morphology of AFSCs significantly varied when cultured on the scaffolds with various fiber diameters and orientation. AFSCs were nearly round on scaffolds with small fibers. However, they became spindle-shaped on scaffolds with large fibers. Meanwhile, upregulated expression of collagen-I gene happened in cells cultured on scaffolds with large fibers, while enhanced expression of collagen-II and aggrecan genes was seen on scaffolds with small fibers. The production of related proteins also showed similar trends. Further, culturing AFSCs on a heterogeneous scaffold by overlaying membranes with different fiber sizes led to the formation of a hierarchical structure approximating native AF tissue., Conclusion: Findings from this study demonstrate that fibrous scaffolds with different fiber sizes effectively promoted the differentiation of AFSCs into specific cells similar to the types of cells at various AF zones. It also provides a valuable reference for regulation of cell differentiation and fabrication of engineered tissues with complex hierarchical structures using the physical cues of scaffolds., The Translational Potential of This Article: Effective AF repair is an essential need for treating degenerative disc disease. Tissue engineering is a promising approach to achieving tissue regeneration and restoring normal functions of tissues. By mimicking the key structural features of native AF tissue, including fiber size and alignment, this study deciphered the effect of scaffold materials on the cell differentiation and extracellular matrix deposition, which provides a solid basis for designing new strategies toward more effective AF repair and regeneration., Competing Interests: The authors have no conflicts of interest to disclose in relation to this article., (© 2020 The Author(s).)

Biochar has been demonstrated to reduce nitrous oxide (N 2 O) emissions from soils, but its effect is highly soil-dependent. In particular, in soils with strong nitrification potential, biochar addition may increase N 2 O emissions. Thus, in soils with strong nitrification potential, the combination of biochar with the nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) may be more effective in reducing N 2 O emissions than biochar alone. However, the combined use of biochar and DMPP on soil N 2 O emissions is relatively unexplored, and underlying microbial mechanisms of how biochar and/or DMPP amendment affect N 2 O emissions is still largely unknown. Here, a 30-day incubation experiment was established with four treatments: CK (control), BC (biochar), DMPP, and BD (biochar and DMPP), all at agronomically recommended rates, and N cycling assessed following addition of urea. Treatment of soil with BC, DMPP and BD reduced N 2 O emissions (compared with urea alone) by 59.1%, 95.5% and 74.1%, respectively. Quantification of N cycling genes (amoA, nirS, nirK, and nosZ) indicated that biochar stimulated growth of ammonia oxidizing archaea (AOA) and bacteria (AOB), while DMPP alone inhibited the activity and growth of AOB. In the BD treatment, DMPP was absorbed onto biochar reducing its efficacy in inhibiting AOB growth. The response patterns of nirS/nirK nitrite-reducing denitrifiers to biochar and/or DMPP addition varied among clades. Notably, biochar and/or DMPP increased the abundance of nosZI and nosZII-N 2 O reducers, but nosZI-clade taxa were more closely associated with reducing N 2 O emission than nosZII taxa. Overall, our findings proved that the dynamics of AOB and nosZI-N 2 O reducers resulting from the addition of biochar and/or DMPP played a key role in governing soil N 2 O emissions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Biochar, a carbon-rich material, has attracted immense attention owing to its applications in soil remediation. However, the mechanisms by which heterogeneous carbon structures of biochars immobilize organic contaminants are not yet fully understood. In this study, the noncondensed aromatic components in biochars were selectively removed through bleaching. Different techniques, such as 13 C nuclear magnetic resonance, were applied to characterize the biochar compositions, and thus the role of the different carbon structures in organic contaminant sorption was discussed. The aromatic carbon structures in biochars were gradually developed and evolved from noncondensed to condensed structure with increasing pyrolytic temperatures from 300 to 700 °C. Based on elemental analysis, the carbon removed by bleaching decreased from 43.9% to 5.92% with increasing temperatures. After the surface area normalization of the apparent sorption, bleaching increased the sorption of carbamazepine and bisphenol A on biochars produced at 500 °C, but not for those produced at 300 and 700 °C. Bleaching removed noncondensed aromatics and enriched condensed aromatics, which resulted in increased sorption. However, bleaching also resulted in the blockage of micropores in biochars with abundant condensed aromatics, causing decreased sorption. The apparent sorption was determined by the balancing of these two opposite effects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nuclear receptor-binding SET domain-containing protein 1 (Nsd1) acts as a histone lysine methyltransferase, and its role in oxidative stress-related abnormal embryonic heart development remains poorly understood. In the present study, H 2 O 2 decreased the expression of Nsd1 and NK2 transcription factor related locus 5 (Nkx2.5). We further focused on Nkx2.5 modulating the transcription of Nsd1 in response to H 2 O 2 . Luciferase activity analysis indicated that a regulatory region from - 646 to - 282 is essential for the basal transcriptional activity, in which, an a Nkx2.5-binding element (NKE) was identified at - 412/- 406 of the Nsd1 promoter by electrophoresis mobility shift assay and a chromatin immunoprecipitation assay. H 2 O 2 obviously reduced the p646-luc promoter activity, and the depletion of Nkx2.5 expression weakened H 2 O 2 inhibition on the p646-luc promoter. The overexpression of Nkx2.5 increase Nsd1 p646-luc promoter activity, but did not affected p646-luc-mut. Furthermore, overexpression and depletion of Nkx2.5 led to the increase and decrease of Nsd1 protein and mRNA levels. These data indicated that H 2 O 2 -induced Nsd1 suppression resulted from the decrease of Nkx2.5 expression through the NKE element.

Annulus fibrosus (AF) tissue engineering has attracted increasing attention as a promising therapy for degenerative disc disease (DDD). However, regeneration of AF still faces many challenges due to the tremendous complexity of this tissue and lack of in-depth understanding of the structure-function relationship at cellular level within AF is highly required. In light of the fact that AF is composed of various types of cells and has gradient mechanical, topographical and biochemical features along the radial direction. In this study, we aimed to achieve directed differentiation of AF-derived stem cells (AFSCs) by mimicking the mechanical and topographical features of native AF tissue. AFSCs were cultured on four types of electrospun poly(ether carbonate urethane)urea (PECUU) scaffolds with various stiffness and fiber size (soft, small size; stiff, small size; soft, large size and stiff, large size). The results show that with constant fiber size, the expression level of the outer AF (oAF) phenotypic marker genes in AFSCs increased with the scaffold stiffness, while that of inner AF (iAF) phenotypic marker genes showed an opposite trend. When scaffold stiffness was fixed, the expression of oAF phenotypic marker genes in AFSCs increased with fiber size. While the expression of iAF phenotypic marker genes decreased. Such substrate stiffness- and topography-dependent changes of AFSCs was in accordance with the genetic and biochemical distribution of AF tissue from the inner to outer regions. Further, we found that the Yes-associated protein (YAP) was translocated to the nucleus in AFSCs cultured with increasing stiffness and fiber size of scaffolds, yet it remained mostly phosphorylated and cytosolic in cells on soft scaffolds with small fiber size. Inhibition of YAP down-regulated the expression of tendon/ligament-related genes, whereas expression of the cartilage-related genes was upregulated. The results illustrate that matrix stiffness is a potent regulator of AFSC differentiation. Moreover, we reveal that fiber size of scaffolds induced changes in cell adhesions and determined cell shape, spreading area, and extracellular matrix expression. In all, both mechanical property and topography features of scaffolds regulate AFSC differentiation, possibly through a YAP-dependent mechanotransduction mechanism. STATEMENT OF SIGNIFICANCE: Physical cues such as mechanical properties, topographical and geometrical features were shown to profoundly impact the growth and differentiation of cultured stem cells. Previously, we have found that the differentiation of annulus fibrosus-derived stem cells (AFSCs) could be regulated by the stiffness of scaffold. In this study, we fabricated four types of poly(ether carbonate urethane)urea (PECUU) scaffolds with controlled stiffness and fiber size to explore the potential of induced differentiation of AFSCs. We found that AFSCs are able to present different gene expression patterns simply as a result of the stiffness and fiber size of scaffold material. This work has, for the first time, demonstrated that larger-sized and higher-stiffness substrates increase the amount of vinculin assembly and activate YAP signaling in pre-differentiated AFSCs. The present study affords an in-depth comprehension of materiobiology, and be helpful for explain the mechanism of YAP mechanosensing in AF in response to biophysical effects of materials., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Adipogenesis, which directly control body fat mass, plays a crucial role in lipid metabolism and obesity-related diseases. Hedgehog interacting protein (Hhip) belongs to Hedgehog (Hh) signaling pathway. The Hh signaling pathway was already linked with adipogenesis in previous reports, however, the physiological functions of Hhip on lipid deposition are still poorly understood. In this study, the level of Hhip was down-regulated during the development of porcine adipose tissues. Recombinant Hedgehog interacting protein (rHhip) could down-regulate cell cycle related genes and cell numbers in S phage to inhibit cell proliferation. Moreover, rHhip could increase adipocytes differentiation by targeting canonical Hh signaling, indicated by the increase of lipid accumulation and up-regulation of Glut4 and PPARγ expression. Collectively, these findings illustrated the essential role of Hhip in the proliferation and differentiation of adipocytes, and provided a potential novel target for preventing obesity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

An increasing body of evidence suggests an association between cancer and atrial fibrillation (AF). The exact magnitude and underlying mechanism of this association are however unclear. Cancer-related inflammation, anti-cancer treatment and other cancer-related comorbidities are proposed to affect atrial remodelling, increasing the susceptibility of cancer patients for developing AF. Moreover, cancer is assumed to modify the risk of thromboembolisms and bleeding. A thorough and adequate understanding of these risks is however lacking, as current literature is scarce and show ambiguous results in AF patients. The standardized risk-models that normally aid the clinician in the decision of initiating anticoagulant therapy do not take the presence of malignancy into account. Other factors that complicate risk assessment in AF patients with cancer include drug-drug interactions and other cancer-related comorbidities such as renal impairment. In this review, we highlight the available literature regarding epidemiological association, risk assessment and anticoagulation therapy in AF patients with cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The Zero Litter Initiative (ZLI) of bringing self-generated litter down the mountain is a new attempt to reduce tourism litter generation on climbing trails in China. The extended theory of planned behavior (TPB) was used to analyze the influencing factors of tourists' environmentally responsible behavioral intention to participate in the ZLI, including three additional explaining variables of personal norms (moral obligation to do ZLI), past behavior, and incentive measures, as well as three control variables of gender, age, and educational level. A total of 372 valid questionnaires were collected from tourists in Huangshan National Park. The results of the hierarchical regression analysis showed that: (1) the extended TPB model had stronger predictive power than the original TPB model; (2) tourists' intention to participate in the ZLI was significantly and positively influenced by their attitude toward the behavior (positive or negative opinions), subjective norms (perceived social pressures from referents), perceived behavioral control (perceived ease or difficulty), past behavior, and the strongest predictor of personal norms; (3) incentive measures mainly referred to economic incentives (e.g., lower ticket prices) and non-economic incentives (e.g., a gift and honorary title), which had no significant influences on tourists' intention, and there may be a "crowding-out effect" on intrinsic motivations for collective action in public space; (4) gender had significant influences on tourists' intention, which showed females had stronger participation intention than males. Age had significant and positive influences on tourists' intention, which indicated older tourists were more willing to participate in the ZLI than younger tourists. However, the educational level had significant and negative influences on tourists' intention. Lastly, the study presented practical suggestions for enhancing tourism litter management and achieving sustainable development in mountainous tourism areas., (Copyright © 2018 Elsevier B.V. All rights reserved.)

C1q/tumor necrosis factor-related protein 6 (CTRP6) is a newly identified adiponectin paralog with modulating effects on metabolism and inflammation. CTRP6 transcript is detected in human ovarian tissue. However, the expression pattern and function of CTRP6 on ovary have been rarely studied. In the present study, we preliminarily examined the structure feature and function of CTRP6 in porcine granulosa cells. The results indicated that the signaling peptide of CTRP6 was located at among positions 21 and 22, and the phosphorylation sites were at 15 (Ser), 4 (Thr) and 4 (Tyr), respectively. Meanwhile, CTRP6 was extremely homologous in livestock and chiropteran. The qPCR results showed that CTRP6 was moderately expressed in porcine follicle. Immunohistochemistry manifested that CTRP6 was presented in various types of ovarian cells. Immunofluorescence revealed that CTRP6 was located in cytoplasm in primary porcine granulosa cells. ELISA results showed that the concentration of CTRP6 in the follicular fluid was gradually decreased with the growth of antral follicle. In addition FSH increased CTRP6 expression levels in a time- and dose-dependent manner in primary porcine granulosa cells, while LH had no effect on CTRP6 basal gene expression, which suggesting CTRP6 is an FSH-responsive gene in porcine granulosa cells. Our findings imply that the CTRP6 may be a candidate gene to regulate folliculogenesis and reproductive performance., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Heat shock protein 90 family members (HSP90s), as molecular chaperones, have conserved roles in the physiological processes of eukaryotes regulating cytoprotection, increasing host resistance and so on. However, whether HSP90s affect regeneration in animals is unclear. Planarians are emerging models for studying regeneration in vivo. Here, the roles of three hsp90 genes from planarian Dugesia japonica are investigated by WISH and RNAi. The results show that: (1) Djhsp90s expressions are induced by heat and cold shock, tissue damage and ionic liquid; (2) Djhsp90s mRNA are mainly distributed each side of the body in intact worms as well as blastemas in regenerative worms; (3) the worms show head regression, lysis, the body curling and the regeneration arrest or even failure after Djhsp90s RNAi; (4) Djhsp90s are involved in autophagy and locomotion of the body. The research results suggest that Djhsp90s are not only conserved in cytoprotection, but also involved in homeostasis maintenance and regeneration process by regulating different pathways in planarians., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Adiponectin (AdipoQ) is an adipocyte-derived hormone with positive function on systemic glucose and lipid metabolism. Long noncoding RNA (lncRNA) is emerging as a vital regulator of adipogenesis. However, AdipoQ-related lncRNAs in lipid metabolism have not been explored. Here, AdipoQ antisense (AS) lncRNA was first identified, and we further found that it inhibited adipogenesis. The half-life of AdipoQ AS lncRNA was 10 h, whereas that of AdipoQ mRNA was 4 h. During adipogenic differentiation, AdipoQ AS lncRNA translocated from nucleus to cytoplasm. AdipoQ AS lncRNA and AdipoQ mRNA formed an RNA duplex. Moreover, AdipoQ AS lncRNA delivered via injection of adenovirus expressing AdipoQ AS lncRNA decreases white adipose tissue (WAT), brown adipose tissue (BAT) and liver triglycerides (TG) in mice consuming a high fat diet (HFD). Interestingly, the non-overlapping region of AdipoQ AS lncRNA improved serum glucose tolerance and insulin sensitivity in HFD mice, but not AdipoQ AS lncRNA. In conclusion, AdipoQ AS lncRNA transfer from nucleus to cytoplasm inhibits adipogenesis through formation of an AdipoQ AS lncRNA/AdipoQ mRNA duplex to suppress the translation of AdipoQ mRNA. Taken together, we suggest that AdipoQ AS lncRNA is a novel therapeutic target for obesity-related metabolic diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Methionine adenosyltransferase (MAT) is a critical biological enzyme and that can catalyze L-met and ATP to form S-adenosylmethionine (SAM), which is acted as a biological methyl donor in transmethylation reactions involving histone methylation. However, the regulatory effect of methionine adenosyltransferase2A (MAT2A) and its associated methyltransferase activity on adipogenesis is still unclear. In this study, we investigate the effect of MAT2A on adipogenesis and its potential mechanism on histone methylation during porcine preadipocyte differentiation. We demonstrated that overexpression of MAT2A promoted lipid accumulation and significantly up-regulated the levels of adipogenic marker genes including PPARγ, SREBP-1c, and aP2. Whereas, knockdown of MAT2A or inhibition MATII enzyme activity inhibited lipid accumulation and down-regulated the expression of the above-mentioned genes. Mechanistic studies revealed that MAT2A interacted with histone-lysine N-methyltransferase Ezh2 and was recruited to Wnt10b promoter to repress its expression by promoting H3K27 methylation. Additionally, MAT2A interacted with MafK protein and was recruited to MARE element at Wnt10b gene. The catalytic activity of MAT2A as well as its interacting factor-MAT2B, was required for Wnt10b repression and supplying SAM for methyltransferases. Moreover, MAT2A suppressed Wnt10b expression and further inhibited Wnt/β-catenin signaling to promote adipogenesis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The effects of consecutive application of chemical fertilizer with or without organic fertilizer on soil N 2 O emissions and denitrifying community structure in a drip-irrigated field were determined. The four fertilizer treatments were (i) unfertilized, (ii) chemical fertilizer, (iii) 60% chemical fertilizer plus cattle manure, and (iv) 60% chemical fertilizer plus biofertilizer. The treatments with organic amendments (i.e. cattle manure and biofertilizer) reduced cumulative N 2 O emissions by 4.9-9.9%, reduced the N 2 O emission factor by 1.3-42%, and increased denitrifying enzyme activities by 14.3-56.2%. The nirK gene copy numbers were greatest in soil which received only chemical fertilizer. In contrast, nirS- and nosZ-copy numbers were greatest in soil amended with chemical fertilizer plus biofertilizer. Chemical fertilizer application with or without organic fertilizer significantly changed the community structure of nirK-type denitrifiers relative to the unfertilized soil. In comparison, the nirS- and nosZ-type denitrifier genotypes varied in treatments receiving organic fertilizer but not chemical fertilizer alone. The changes in the denitrifier communities were closely associated with soil organic carbon (SOC), NO 3 - , NH 4 + , water holding capacity, and soil pH. Modeling indicated that N 2 O emissions in this soil were primarily associated with the abundance of nirS type denitrifying bacteria, SOC, and NO 3 - . Overall, our findings indicate that (i) the organic fertilizers increased denitrifying enzyme activity, increased denitrifying-bacteria gene copy numbers, but reduced N 2 O emissions, and (ii) nirS- and nosZ-type denitrifiers were more sensitive than nirK-type denitrifiers to the organic fertilizers., (Copyright © 2017. Published by Elsevier B.V.)

Transforming growth factor β (TGF-β), acting as the auto/para endocrine factors, has multi-function in mammalian follicle development. Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is considered as a pseudoreceptor in the TGF-β signal pathway which has the similar extracellular structure of TGF-β receptor but lack of intracellular serine/threonine kinase domains. However, the biological function of BAMBI involved in porcine granulosa cell steroidogenesis remains unknown. This study was thus carried out to explore the effect of BAMBI on the steroidogenesis process in porcine primary granulosa cells. Our results showed overexpression of BAMBI promoted aromatase and StAR, but not P450scc and 3β-HSD mRNA and protein expression levels in porcine primary granulosa cells, and increased the accumulation of estradiol and progesterone in the culture medium. Meanwhile, knockdown endogenous BAMBI decreased the mRNA expression levels of Cyp19a1 and Star and the accumulation levels of estradiol and progesterone. TGF-β1 could decrease Cyp19a1 and Star mRNA expression and estradiol and progesterone production in a dose-dependent manner. Pre-treatment with BAMBI adenovirus reversed TGFβ1-induced downregulation of Cyp19a1 and Star mRNA expression. Moreover, TGF-β1 could induce the phosphorylation of SMAD3 in porcine granulosa cells. Pre-transfected with BAMBI adenovirus also inhibited TGF-β1-induced downregulation of estradiol and progesterone production as well as TGF-β1-induced phosphorylation of SMAD3 in porcine granulosa cells. These findings provided a potential mechanism by which BAMBI could regulate porcine granulosa cell steroidogenesis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In mammals, granulosa cell proliferation, differentiation, luteinization, apoptosis, and hormone synthesis are tightly related to oocyte maturation, follicular development and ovarian function. In current study, we investigated the role of the key circadian clock gene, brain and muscle arnt-like protein-1 (Bmal1), on porcine granulosa cell hormone secretion and apoptosis. The transcription levels of circadian clock genes, including Bmal1 and period circadian clock 2 (Per2), were detected by RT-qPCR. We found that the circadian clock genes exhibited rhythmic change and were further enhanced by dexamethasone synchronization in granulosa cells. Bmal1 knockdown reduced transcriptional levels of hormone receptor genes, including follicle stimulating hormone receptor (Fshr), luteinizing hormone/choriogonadotropin receptor (Lhcgr) and estrogen receptor 2 (Esr2), and decreased the mRNA and protein levels of cytochrome P450 family 11 subfamily A member 1 (Cyp11a1), cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) and steroidogenic acute regulatory protein (Star), which are the key enzymes involved in hormone synthesis. Synthesis of progesterone and estradiol were also inhibited by Bmal1 siRNA treatment in granulosa cells. Moreover, flow cytometry analysis demonstrated suppressing Bmal1 promoted granulosa cells apoptosis. Western blot analysis showed that Bmal1 interference inactivated the PI3K/Akt/mTOR signaling pathway. In conclusion, Bmal1 plays a critical role in secretion of hormone and apoptosis of porcine granulosa cells via the PI3K/Akt/mTOR signaling pathway., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Injection of botulinum toxin type A for cosmetic purposes is common. It is believed to be safe, but adverse reactions have been reported, including dysphagia, generalized paralysis, respiratory depression, and death caused by focal injection of the toxin. Early administration of antitoxin in patients with adverse reactions is the mainstay of management, but the time window for its clinical efficacy is not well defined., Case Reports: Two female adult patients with clinical botulism after botulinum toxin type A injection are described. Both patients had received intramuscular injection of botulinum toxin type A in their calves at beauty shops for cosmetic reasons. They developed clinical botulism about 3 days postinjection. They presented late to the emergency department. Monovalent type A botulinum antitoxin was administered 7 and 9 days from symptom onset, respectively. Both patients showed clinical improvement after the antitoxin treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients may present to the emergency department with systemic effects of botulinum toxin type A after cosmetic injection. Clinical efficacy of botulinum antitoxin treatment was observed in two patients who were given the drug 7 and 9 days after the occurrence of symptoms of botulism after cosmetic injection of botulinum toxin type A. It may be worthwhile to commence antitoxin treatment even if patients present late., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Pre-processing of near-infrared (NIR) spectral data has become a necessary part of chemometrics modeling and is widely used in many practical applications. The objective of the pre-processing is to remove physical phenomena in the spectra in order to improve subsequent qualitative or quantitative analysis. Herein, a localized version of standard normal variate (SNV) is proposed, in which the correction parameters are estimated from local spectral areas. The method of determining the optimal spectral segmentation is also presented. Compared with full range methods, the local method demonstrates advantages in spectral linearity correction, model interpretation and prediction accuracy. Several benchmark NIR data sets were studied in our experiments; the proposed method achieved comparable performance against proven full range methods, with the reduction of prediction errors being statistically significant in many cases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

With the continuing increase in anthropogenic activities, acid rain remains a serious environmental threat, especially in the fast developing areas such as southern China. To detect how prolonged deposition of acid rain would influence soil organic carbon accumulation in mature subtropical forests, we conducted a field experiment with simulated acid rain (SAR) treatments in a monsoon evergreen broadleaf forest at Dinghushan National Nature Reserve in southern China. Four levels of SAR treatments were set by irrigating plants with water of different pH values: CK (the control, local lake water, pH ≈ 4.5), T1 (water pH=4.0), T2 (water pH=3.5), and T3 (water pH=3.0). Results showed reduced pH measurements in the topsoil exposed to simulated acid rains due to soil acidification. Soil respiration, soil microbial biomass and litter decomposition rates were significantly decreased by the SAR treatments. As a result, T3 treatment significantly increased the total organic carbon by 24.5% in the topsoil compared to the control. Furthermore, surface soil became more stable as more recalcitrant organic matter was generated under the SAR treatments. Our results suggest that prolonged acid rain exposure may have the potential to facilitate soil organic carbon accumulation in the subtropical forest in southern China., (Copyright © 2015 Elsevier B.V. All rights reserved.)

It has been reported that ethanol contributes to neuronal damage. However, the mechanisms mediating the actions of ethanol on neurons remain elusive. The present study was designed to test whether ethanol directly induced HMGB1 release and to explore the cellular and molecular mechanism mediating its action. It was found that ethanol increased significant HMGB1 release from SH-SY5Y cells and from cultured primary cortical neurons as detected by ELISA assay. Meanwhile, ethanol induced the expression of NOX2 subunits such as gp91 and p47(phox) and increased the activation of NLRP1 inflammasome. However, when cells were pretreated with NADPH oxidase inhibitor, apocynin, HMGB1 release was significantly decreased. Moreover, apocynin also prevented the activation of NLRP1 inflammasome as detected the levels of cleaved caspase-1. In addition, z-YVAD-fmk, an inhibitor of caspase-1, decreased the ethanol-induced HMGB1 release. It is concluded that ethanol-induced HMGB1 release is associated with NOX2/NLRP1 inflammasome signaling, which represents a novel mechanism of ethanol-associated neuron injury., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ring-opening reaction with synchronous hydrolysis was used to prepare 4-butylaniline-modified attapulgite (abbreviated as BA-ATP) for pre-concentration of bisphenol A (BPA) in trace quantity. The preparation was achieved under mild condition, and the material was characterized by Fourier transform infrared spectroscopy (FT-IR), elemental analysis, nuclear magnetic resonance (NMR) and scanning electron microscopy. BA-ATP was used in solid phase extraction (SPE), and SPE was performed in a neutral condition without regard to ionic strength. The results indicate that BA-ATP has high affinity to BPA with a maximum adsorption amount of 44mg g(-1), and the adsorption can be described by Langmuir isotherm model. The content of bisphenol A in water samples was analyzed by HPLC method with the pre-concentration using BA-ATP. The limit of detection (LOD) can be as low as 3.9ng mL(-1), and the average recoveries are in a range of 93-97% with relative standard deviation (RSD) of less than 2%., (Copyright © 2015 Elsevier B.V. All rights reserved.)