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Syphilis is a sexually transmitted disease caused by Treponema pallidum. The mechanisms enabling T. pallidum to persist despite macrophage eradication efforts in syphilis remain unclear. Pathogens can exploit senescent cells to enhance host susceptibility, and cellular senescence can be induced by pyroptosis, which known as inflammatory senescence. While recent studies have linked metabolic reprogramming to inflammatory senescence, their role in syphilis remained to be clarified. This study investigated the mechanisms of Tp47 on metabolic reprogramming and inflammatory senescence in macrophages. The results demonstrated that Tp47 triggered NLRP3 inflammasome-mediated pyroptosis by activating the phosphorylation of EIF2AK2 (a protein kinase), increasing senescence-associated pro-inflammatory cytokines secretion and leading to inflammatory senescence in macrophages. Additionally, Tp47 competitively bound to pyruvate kinase M2 (PKM2) with STUB1(a ubiquitin ligase), thereby inhibiting PKM2 ubiquitination degradation. By promoting the Y105 phosphorylation of PKM2, Tp47 modulated the intracellular function of PKM2, and facilitated PKM2-mediated metabolic reprogramming, which produced lactate that subsequently led to EIF2AK2 phosphorylation. Furthermore, inhibitors targeting EIF2AK2, lactate, glycolysis, and PKM2 effectively suppressed the inflammatory senescence induced by Tp47. In conclusion, Tp47 could mediate immune metabolic reprogramming through interaction with PKM2 to trigger macrophage inflammatory senescence. These discoveries offer a novel perspective for targeted therapies against syphilis., 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. Published by Elsevier B.V.)

To know the influence of lauric acid (LA) on wheat flour fresh noodles (WFN) quality and the latent mechanism, the effect of LA on cooking properties, digestibility and structure of WFN with/without sodium bicarbonate (SB) and the properties of wheat flour (WF) with/without SB were studied. The results indicated that LA reduced cooking loss and digestibility of WFN with SB and slightly decreased water adsorption and increased the free water binding ability and hardness of WFN without SB. Furthermore, LA increased the degree of short- and long-range order and molecular weight of starch in cooked WFN with/without SB and it had greater effect on the degree of short- and long-range order and molecular weight of starch in cooked WFN with SB than that without SB. Differential scanning calorimeter (DSC) and rapid viscosity analysis (RVA) displayed that WFN with LA and SB formed more starch-LA or/and starch-LA-protein complexes than WFN with LA. Additionally, the impact of LA on WFN quality and WF properties was influenced by SB concentration. This study will provide theoretical basis and new thoughts for the design of high-quality fresh noodles with low digestibility, low cooking loss and high hardness., 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 B.V. All rights reserved.)

Eighteen compounds including eleven previously undescribed diterpenes were isolated from the leaves of Croton mangelong. The structures were determined by HRESIMS, IR, NMR, X-ray diffraction and ECD spectroscopic analysis. All isolates were assayed for their anti-hyperglycemic activities in insulin resistance (IR) 3T3-L1 adipocytes, and compound 4 was tested for its anti-diabetic activity in vivo. Results suggested compound 4 could effectively reduce blood glucose level in diabetic SD rats in a dose of 30 mg/kg., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To study the relationship between umbilical cord blood vitamin A (VA) and neonatal lung diseases and explore the impact of umbilical cord blood VA on neonatal lung diseases., Method: Umbilical vein blood was collected at birth, and its VA content was measured. According to the VA levels in umbilical cord blood, a VA deficiency (VAD) group, a marginal deficiency group and a normal group were created and followed up until 28 days after birth., Results: The umbilical cord blood VA level in the neonatal group with lung disease was 0.13 ± 0.05 mg/L, while the result for the VA level in the non-lung disease group was 0.15 ± 0.05 mg/L. The umbilical cord blood VA levels in the neonatal lung disease group were significantly lower than those in the non-lung disease group. The incidence of neonatal pulmonary diseases was highest in the VAD group, and the incidence decreased as the level of VA in umbilical cord blood increased. Umbilical cord blood VAD and premature birth were found to be independent risk factors for neonatal respiratory disease., Conclusion: Umbilical cord blood VAD and premature birth are independent risk factors for neonatal pulmonary diseases. The lower the level of VA in umbilical cord blood, the more susceptible infants will be to neonatal respiratory infections in the neonatal period., Competing Interests: Declaration of competing interest All of the authors had no any personal, financial, commercial, or academic conflicts of interest separately., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

The S2 subunit of infectious bronchitis virus (IBV) is a heavily glycosylated protein that can impact various characteristics of the virus. It is currently known that N-glycosylation modifications are predominantly located on the S2 subunit. However, the exact role of their N-glycosylation modification remains undisclosed. To elucidate the function of these N-glycosylation sites, we identified 14 common sites distributed on the S2 subunit of the 5 genotypes of IBV in present study. Subsequently, we selected 7 sites to generate mutants and assessed their impact on viral virulence, replication ability, and antigenicity. Our finding revealed that only 2 substitutions, N545S and K717N, increased the viral replication titer and antigenicity, and ultimately the pathogenicity in chicks. To delve into the mechanisms underlying this increased pathogenicity, we discovered that K717N can change the structure of antigenic epitopes. The N545S substitution not only influenced antigenic epitope structure, but also enhanced the ability of the virus to enter CEKs during the early stages of viral replication. These results suggest that the enhanced viral pathogenicity associated with N545S and K717N substitutions is multifaceted, with acceleration of the viral membrane fusion process and alterations in epitope structure representing crucial factors in the capability of N-glycosylation modifications to boost viral virulence. These insights provide valuable guidance for the efficient development of live attenuated vaccines., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Seeds are important microbial vectors, and seed-associated pathogens can be introduced into a country through trade, resulting in yield and quality losses in agriculture. The aim of this study was to characterize the microbial communities associated with barley seeds, and based on which, to develop technical approaches to trace their geographical origins, and to inspect and identify quarantine pathogens. Our analysis defined the core microbiota of barley seed and revealed significant differences in the barley seed-associated microbial communities among different continents, suggesting a strong geographic specificity of the barley seed microbiota. By implementing a machine learning model, we achieved over 95% accuracy in tracing the origin of barley seeds. Furthermore, the analysis of co-occurrence and exclusion patterns provided important insights into the identification of candidate biocontrol agents or microbial inoculants that could be useful in improving barley yield and quality. A core pathogen database was developed, and a procedure for inspecting potential quarantine species associated with barley seed was established. These approaches proved effective in detecting four fungal and three bacterial quarantine species for the first time in the port of China. This study not only characterized the core microbiota of barley seeds but also provided practical approaches for tracing the regional origin of barley and identifying potential quarantine pathogens., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, 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 position presented in, or the review of, the manuscript entitled, “Characterization of core microbiota of barley seeds from different continents for origin tracing and quarantine pathogen assessment”., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study was the first to evaluate the effect of CYP3A4 gene polymorphisms on the plasma concentration and effectiveness of perampanel (PER) in Chinese pediatric patients with epilepsy., Methods: We enrolled 102 patients for this investigation. The steady-state concentration was determined after patients maintained a consistent PER dosing regimen for at least 21 days. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final check-up., Results: The CYP3A4×10 GC phenotype exhibited the highest average plasma concentration of PER at 491.1 ± 328.1 ng/mL, in contrast to the CC phenotype at 334.0 ± 161.1 ng/mL. The incidence of adverse events was most prominent in the CYP3A4×1 G TT and CYP3A4×10 GC groups, with rates of 77.8 % (7 of 9 patients) and 50.0 % (46 of 92 patients), respectively. Moreover, the percentage of patients for whom PER was deemed ineffective was least in the CYP3A4×1 G TT and CYP3A4×10 CC groups, recorded at 11.1 % (1 of 9 patients) and 10.0 % (1 of 10 patients), respectively. There was a significant correlation between PER plasma concentration and either exposure or toxicity (both with p < 0.05). We suggest a plasma concentration range of 625-900 ng/mL as a suitable reference for PER in Chinese patients with epilepsy., Conclusion: The CYP3A4×10 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A4 genetic phenotype should be factored in when prescribing PER to patients with epilepsy., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to disclose. The authors confirm that they have read the Journal's policy on issues involved in ethical publication, and affirm that this study is consistent with those guidelines., (Copyright © 2024. Published by Elsevier Ltd.)

Nanotechnology has emerged as a transformative force in modern agriculture, offering innovative solutions to address challenges related to fungal plant diseases and overall agricultural productivity. Specifically, the antifungal activities of metal, metal oxide, bio-nanoparticles, and polymer nanoparticles were examined, highlighting their unique mechanisms of action against fungal pathogens. Nanoparticles can be used as carriers for fungicides, offering advantages in controlled release, targeted delivery, and reduced environmental toxicity. Nano-pesticides and nano-fertilizers can enhance nutrient uptake, plant health, and disease resistance were explored. The development of nanosensors, especially those utilizing quantum dots and plasmonic nanoparticles, promises early and accurate detection of fungal pathogens, a crucial step in timely disease management. However, concerns about their potential toxic effects on non-target organisms, environmental impacts, and regulatory hurdles underscore the importance of rigorous research and impact assessments. The review concludes by emphasizing the significant prospects of nanotechnology in reshaping the future of agriculture but advocates for a balanced approach that prioritizes safety, sustainability, and environmental stewardship., 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 B.V. All rights reserved.)

Proteins must be sorted to specific subcellular compartments to perform their functions. Abnormal protein subcellular localizations are related to many diseases. Although many efforts have been made in predicting protein subcellular localization from various static information, including sequences, structures and interactions, such static information cannot predict protein mis-localization events in diseases. On the contrary, the IHC (immunohistochemistry) images, which have been widely applied in clinical diagnosis, contains information that can be used to find protein mis-localization events in disease states. In this study, we create the Vislocas method, which is capable of finding mis-localized proteins from IHC images as markers of cancer subtypes. By combining CNNs and vision transformer encoders, Vislocas can automatically extract image features at both global and local level. Vislocas can be trained with full-sized IHC images from scratch. It is the first attempt to create an end-to-end IHC image-based protein subcellular location predictor. Vislocas achieved comparable or better performances than state-of-the-art methods. We applied Vislocas to find significant protein mis-localization events in different subtypes of glioma, melanoma and skin cancer. The mis-localized proteins, which were found purely from IHC images by Vislocas, are in consistency with clinical or experimental results in literatures. All codes of Vislocas have been deposited in a Github repository (https://github.com/JingwenWen99/Vislocas). All datasets of Vislocas have been deposited in Zenodo (https://zenodo.org/records/10632698)., 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 Ltd. All rights reserved.)

Background: Role ambiguity is recognized as a significant psychological risk stressor in nursing practice, which undermines the psychological well-being of nurses. Since the well-being of nurses plays a crucial role in ensuring positive patient outcomes, it becomes imperative to identify strategies for improving nurses' psychological well-being., Objectives: This study aimed to explore the effects of role ambiguity on anxiety in intensive care unit nurses and the mechanisms mediating emotional intelligence., Methods: In April-June 2023, a convenience sampling method was used to collect data from 360 intensive care unit nurses in a total of 7 hospitals in Shaanxi Province, Hunan Province, Beijing, and Jiangsu Province, China. A linear regression model was used to verify the mediating effect., Results: Role ambiguity was significantly and positively associated with anxiety in ICU nurses (p < 0.01). A mediating mechanism between role ambiguity and anxiety was established for emotional intelligence (p < 0.01)., Conclusions: Role ambiguity has a significant impact on the mental health of intensive care nurses, and emotional intelligence plays a mediating role in reducing role ambiguity and anxiety in nurses., Implications for Clinical Practice: This study highlights that role ambiguity in the intensive care unit setting increases nurses' anxiety, while emotional intelligence alleviates the anxiety associated with role ambiguity. Creating support systems and improving the environment is a top priority for nursing administrators. This includes, but is not limited to, clarifying the roles of nurses, conducting social-emotional training, and developing emotional intelligence to prevent and regulate nurses' anxiety and maintain mental health., 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 Ltd.)

In scenarios involving sudden releases of unidentified gases or concealed pollution emergencies, source control emerges as a critical procedure to safeguard residential air quality. Appropriate inverse source tracking methodology depending on diverse measurement data could be utilized to promptly identify pollutant source parameters. In this study, source term estimation (STE) method, i.e., jointly combining probability adjoint method with the Bayesian inference method, has been proposed. General form of the pollutant inverse transport equation was firstly established. Subsequently, the pollution source information, assumed from single continuous point releases during Fusion Field Trials 2007 under an unsteady wind field, was identified using the Bayesian inference probability adjoint inverse method. Metropolis-Hastings Markov Chain Monte Carlo (MH-MCMC) and Differential Evolution Markov Chain Monte Carlo (DE-MCMC) were then compared as sampling methods for Bayesian inference. Results indicated that the DE-MCMC algorithm has superior convergence and could present higher accuracy of pollutant source information than that of MH-MCMC algorithm, particularly for highly nonlinear and multi-modal distribution systems. Furthermore, the integration of Union standard Adjoint Location Probability (UALP) as prior information into the Bayesian inference probability adjoint inverse method effectively narrowed the sampling range, enhancing both the accuracy and robustness of the proposed approach. Finally, the impact of the covariance matrix on the inverse identification accuracy was explored. Overall, this research has provided insights into the future applicability of this Bayesian inference inversion technique for point source identification., 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 B.V. All rights reserved.)

In situ mitochondrial oxidative stress amplification is an effective strategy to improve efficacy of cancer treatment. In this work, a tumor and mitochondria dual-targeted multifunctional nanoplatform CMS@AIPH@PDA@COTPP@FA (CAPCTF) was prepared, in which a thermally decomposable radical initiator AIPH was loaded inside the mesoporores of Cu x Mo y S z (CMS) nanoparticles with polydopamine (PDA) covered films that were further covalently functionalized by a mitochondria-targeted CO donor (COTPP) and a directing group of folic acid (FA). The prepared CAPCTF nanoplatform selectively accumulated in cancer cells and further targeted the mitochondrial organelle where carbon monoxide (CO) and O 2 -independent free radicals (•OH/•R) were in situ generated upon 1064 nm laser irradiation. Furthermore, the CMS nanocarrier was capable of depleting the GSH overexpressed in the tumor microenvironment (TME), thus preventing free radical scavenging. As a result, the CAPCTF nanoplatform exhibited outstanding in vitro and in vivo antitumor efficacy under hypoxic conditions. This provides an innovative strategy that combines O 2 -independent free radicals (•OH/•R) generation, CO delivery and GSH consumption to amplify intracellular oxidative stresses and induce mitochondrial dysfunction, thus leading to cancer cells eradication, which may have significant implications for personalized hypoxic tumor treatment., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Retinoid X receptor (RXR), particularly RXRα, has been implicated in cardiovascular diseases. However, the functional role of RXR activation in myocardial infarction (MI) remains unclear. This study aimed to determine the effects of RXR agonists on MI and to dissect the underlying mechanisms. Sprague-Dawley (SD) rats were subjected to MI and then treated (once daily for 4 weeks) with either RXR agonist bexarotene (10 or 30 mg/kg body weight) or vehicle. Heart function was determined using echocardiography and cardiac hemodynamic measurements. Four weeks post MI, myocardial tissues were collected to evaluate cardiac remodeling. Primary cardiac fibroblasts (CFs) were treated with or without RXR ligand 9-cis-RA followed by stimulation with TGF-β1. Immunoblot, immunofluorescence, and co-immunoprecipitation were performed to elucidate the regulatory role of RXR agonists in TGF-β1/Smad signaling. In vivo treatment with Bexarotene moderately affects systemic inflammation and apoptosis and ameliorated left ventricular dysfunction after MI in rat model. In contrast, bexarotene significantly inhibited post-MI myocardial fibrosis. Immunoblot analysis of heart tissue homogenates from MI rats revealed that bexarotene regulated the activation of the TGF-β1/Smad signaling pathway. In vitro, 9-cis-RA inhibited the TGF-β1-induced proliferation and collagen production of CFs. Importantly, upon activation by 9-cis-RA, RXRα interacted with p-Smad2 in cytoplasm, inhibiting the TGF-β1-induced nuclear translocation of p-Smad2, thereby negatively regulating TGF-β1/Smad signaling and attenuating the fibrotic response of CFs. These findings suggest that RXR agonists ameliorate post-infarction myocardial fibrosis, maladaptive remodeling, and heart dysfunction via attenuation of fibrotic response in CFs through inhibition of the TGF-β1/Smad pathway activation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The aberrant protein sorting has been observed in many conditions, including complex diseases, drug treatments, and environmental stresses. It is important to systematically identify protein mis-localization events in a given condition. Experimental methods for finding mis-localized proteins are always costly and time consuming. Predicting protein subcellular localizations has been studied for many years. However, only a handful of existing works considered protein subcellular location alterations. We proposed a computational method for identifying alterations of protein subcellular locations under drug treatments. We took three drugs, including TSA (trichostain A), bortezomib and tacrolimus, as instances for this study. By introducing dynamic protein-protein interaction networks, graph neural network algorithms were applied to aggregate topological information under different conditions. We systematically reported potential protein mis-localization events under drug treatments. As far as we know, this is the first attempt to find protein mis-localization events computationally in drug treatment conditions. Literatures validated that a number of proteins, which are highly related to pharmacological mechanisms of these drugs, may undergo protein localization alterations. We name our method as PLA-GNN (Protein Localization Alteration by Graph Neural Networks). It can be extended to other drugs and other conditions. All datasets and codes of this study has been deposited in a GitHub repository (https://github.com/quinlanW/PLA-GNN)., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Soluble epoxide hydrolase (sEH) serves as a potential target in inflammation-related diseases. Based on the bioactivity-guided separation, a new sesquiterpenoid inulajaponoid A (1) was isolated from Inula japonica with a sEH inhibitory effect, together with five known compounds, such as 1-O-acetyl-6-O-isobutyrylbritannilactone (2), 6β-hydroxytomentosin (3), 1β,8β-dihydroxyeudesma-4(15),11(13)-dien-12,6α-olide (4), (4S,6S,7S,8R)-1-O-acetyl-6-O-(3-methylvaleryloxy)-britannilactone (5), and 1-acetoxy-6α-(2-methylbutyryl)eriolanolide (6). Among them, compounds 1 and 6 were assigned as mixed and uncompetitive inhibitors, respectively. The result of immunoprecipitation (IP)-MS demonstrated the specific binding of compound 6 to sEH in the complex system, which was further confirmed by the fluorescence-based binding assay showing its equilibrium dissociation constant (K d  = 2.43 μM). The detail molecular stimulation revealed the mechanism of action of compound 6 with sEH through the hydrogen bond of amino acid residue Gln384. Furthermore, this natural sEH inhibitor (6) could suppress the MAPK/NF-κB activation to regulate inflammatory mediators, such as NO, TNF-α, and IL-6, which confirmed the anti-inflammatory effect of inhibition of sEH by 6. These findings provided a useful insight to develop sEH inhibitors upon the sesquiterpenoids., 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.)

Background: Muscle-derived stem cells (MDSCs) contribute to the repair of injured muscles. However, the myogenicity of MDSCs generated from patients with Duchenne muscular dystrophy (DMD) relative to healthy individuals remains unclear., Methods: A human DMD model was established using the stem cells prepared from muscle derived from patients with DMD (DMD-hMDSCs). The expression of myogenic lineage-specific markers in MDSCs was examined with immunofluorescence, real-time polymerase chain reaction, and western blotting., Results: It was demonstrated that, compared with cells from healthy subjects, DMD-hMDSCs are primed to self-differentiate in growth-inducing medium (GM) and robustly differentiate into myotubes in differentiation-inducing medium(DM). This feature was termed "myogenesis activation," and it was speculated that it contributes to the depletion of myogenic progenitors. Furthermore, MDSCs consistently express pax7, but the time-course of this expression does not correlate with the expression of the myogenic lineage-specific markers., Conclusions: The myogenesis activation in DMD-hMDSCs demonstrated in this study may provide novel mechanistic insights into DMD pathogenesis and potential therapies., Competing Interests: Declaration of Competing Interest The authors declared that there was no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A hollow mesoporous manganese dioxide-based (H-MnO 2 ) multifunctional nanoplatform, H-MnO 2 @AFIPB@PDA@Ru-NO@FA (MAPRF NPs), was prepared for synergistic cancer treatment, in which a histone deacetylase inhibitor AFIPB was loaded in its hollow cavity and a ruthenium nitrosyl donor (Ru-NO) and a folic acid (FA) targeting group were covalently decorated on its covered polydopamine (PDA) layer. The MAPRF NPs showed tumor microenvironment (TME)-responsive properties of depletion of glutathione (GSH) to disrupt the antioxidant defense system and on-demand drug delivery. And the released Mn 2+ further catalyzed the decomposition of endogenous H 2 O 2 to produce highly toxic hydroxyl radicals (·OH) for enhanced chemodynamic therapy (CDT). Furthermore, upon 808 nm light irradiation MAPRF NPs exhibited controlled nitric oxide (NO) delivery and simultaneously produced significant photothermal effect. Consequently, MAPRF NPs showed high mortality toward cancer cells in the presence of 808 nm light irradiation. This work provides a paradigm of multimodal synergistic therapy that combines NO-based gas therapy with TME modulation for efficient antitumor therapy., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Conservation agriculture (CA) has been adopted worldwide on about 200 Mha to enhance soil organic carbon (SOC) for mitigating climate change. However, as a crucial mechanism to sequester SOC, how the protection of aggregates responds to the interaction between no-till and crop rotations (two principles of CA) remains unknown. Thus, a field experiment with six treatments [e.g., no-till or rotary tillage under the maize-wheat-soybean-wheat system (NT-MWSW, RT-MWSW), no-till or rotary tillage under the maize-wheat system (NT-MW, RT-MW), and no-till or rotary tillage under the soybean-wheat system (NT-SW, RT-SW)] was conducted from June 2018 to June 2021 in the North China Plain (NCP) to assess their effects on aggregation and SOC. Results indicated that macroaggregates (> 0.25 mm) were the main contributors to the soil carbon (C) pool, comprised 64.7-87.3 % of aggregates, and encompassed 64.9-73.1 % of the SOC stock. NT increased not only the proportion of macroaggregates but also aggregate stability (i.e., mean weight diameter and geometric mean diameter). Significant positive effects from legumes were observed under NT. SW increased by 13.6 % macroaggregate-associated SOC under NT in 0-20 cm compared to that under MW. Additionally, the conversion rate of straw C input under NT-SW was higher than that in other treatments, augmenting it by 9.4-21.9 %. This may be attributed to the higher macroaggregate total nitrogen (increased by 1.7-15.9 %) in 0-10 cm under legume-based crop rotations compared to that under MW, resulting in lower C: N ratios, which promoted the decomposition of straw. Furthermore, the total potential mineralization of macroaggregates under NT legume-based crop rotations was 3.0-16.0 % higher than that of MW. Thus, a legume-based NT system can significantly improve soil macro-aggregation, increase the conversion rate of straw C input, and reduce C loss, which can be a viable practice to enhance SOC sequestration capacity under CA in the NCP., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

CDK2 forms a complex with cyclin A and cyclin E to promote the progress of cell cycle, but when cyclin A and cyclin E are dissociated from the complex and degraded by the ubiquitin proteasome pathway, the fate of the inactive CDK2 is unclear. In this study, we found that the inactive CDK2 protein was degraded by autophagy-lysosome pathway. In the classic model of G0/G1 phase arrest induced by serum starvation, we found that the mRNA level in CDK2 did not change but the protein level decreased. Subsequently, using PI3K and AKT inhibitors and gene knockout methods, it was found that CDK2 degradation was mediated by the inhibition of PI3Kα/AKT T308 . In addition, P62/SQSTM1 was found to bind to the inactivated CDK2 protein to help it enter autophagy-lysosome degradation in a CTSB-dependent manner. Taken together, these results confirm that the PI3Kα/AKT T308 inhibition leads to degradation of CDK2 protein in the autophagy-lysosome pathway. These data reveal a new molecular mechanism of CDK2 protein degradation and provide a new strategy and method for regulating CDK2 protein., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Conservation agriculture (CA) can be an important strategy for improving soil organic carbon (SOC) and total nitrogen (TN). Numerous studies have examined SOC and TN dynamics in different cropping systems. However, there is some uncertainty regarding the relative impacts of some CA practices, and it is not always clear how other agricultural management, particularly nitrogen addition, interacts with these practices to influence SOC and TN sequestration. Thus, we conducted a global meta-analysis of 752 comparisons from 97 papers to analyze the impacts of nitrogen fertilizers and CA practices (namely crop diversification, minimal soil disturbance (no-tillage) and permanent soil cover), on SOC and TN content worldwide. Overall, our study showed the most significant increase of SOC [21.39 % (CI = 15.16 to 28.64)] and TN [54.34 % (CI = 26.19 to 96.69)] stock with CA practices compared to conventional practices in the 0-15 cm soil depth. It also showed a significant increase in SOC and TN stock with all the individual components of CA compared to conventional practices in the 0-15 cm soil depth. However, the impact of CA on SOC and TN is reduced in 0-60 cm depths compared to surface soil depths due to the limited input of crop residue deeper in the soil profile. Manure and manure mixed with mineral-N led to greater SOC sequestration [20.67 % (CI = 15.23 to 27.10) and 41.67 % (CI = 31.03 to 52.79), respectively] than mineral-N alone [9.08 % (CI = 6.44 to 11.83)]. Cropping systems that included legume residue decreased the C/N ratio. This highlights that adequate mineral-N fertilizer addition may also be required in conjunction with residue retention practices to improve SOC and TN content. Overall, these results show that CA systems that include legume residue and manure mixed with mineral-N have great potential to increase SOC and TN, particularly at 0-15 cm and 0-30 cm soil depth., 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.)

With increasing attention being placed on mitigating global warming and achieving agricultural sustainable intensification, conservation agriculture practices have gradually been implemented in the North China Plain (NCP). However, there are still knowledge gaps on the effects of conservation practices on greenhouse gas (GHG) emissions in this area. In this study, a four-year field experiment was conducted from 2014 to 2018 to assess the effects of tillage and crop residue management practices on the emissions of nitrous oxide (N 2 O) and methane (CH 4 ). Subsequently, crop yields, area-scaled and yield-scaled total non-carbon dioxide (CO 2 ) GHG emissions were assessed. Our research found that no-till (NT) decreased N 2 O emissions by 22.6% compared with conventional tillage (CT) in winter wheat (Triticum aestivum L.) seasons, but there was no difference between tillage practices in summer maize (Zea mays L.) seasons. Crop residue retention practice (+R) increased N 2 O emissions by 28.1% and 26.7% compared with residue removal practice (-R) in winter wheat and summer maize seasons, respectively. The NT soils took up more CH 4 compared with the CT soils in summer maize seasons. Area-scaled total non-CO 2 GHG emissions showed trends similar to those of N 2 O emission. Since crop residue retention improved the maize yield compared with the residue removal treatments, yield-scaled total non-CO 2 GHGs emission did not differ between residue management practices in summer maize seasons. Our four-year field measurements indicated that no-till practice could be more useful as an option to mitigate non-CO 2 GHG emissions in the wheat - maize cropping system., 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 sensitivity of soil organic carbon (SOC) mineralization to temperature could affect the future atmospheric CO 2 levels under global warming. Sieved soils are widely used to assess SOC mineralization and its temperature sensitivity (Q 10 ) via laboratory incubation. However, sieved soils cause a temporary increase in mineralization due to the destruction of soil structure, which can affect estimates of SOC mineralization, especially in soils managed with no-till (NT). To identify the effects of soil sieving on SOC mineralization and Q 10 , soil was collected from an 11-year field experiment under a wheat-maize cropping system managed with a combination of tillage [NT and plow tillage (PT)] and residue [residue returning (RR) and residue removal (R0)]. Soil was either sieved or left in an undisturbed state and incubated at 15 °C and 25 °C. SOC mineralization in sieved soils at 25 °C was 47.28 g C kg -1 SOC, 160.1% higher than SOC mineralization in undisturbed soils (P < 0.05). Interestingly, Q 10 values in sieved soils were 1.29, 77.6% lower than Q 10 in undisturbed soils (P < 0.05). Highly significant correlations (P < 0.01) were observed between sieved and undisturbed soils for SOC mineralization (r = 0.85-0.98) and Q 10 (r = 0.78-0.87). Soil macro-aggregates had lower SOC mineralization by 6.1-21.9%, but higher Q 10 values by 4.7-6.5% compared with micro-aggregates, contributing to lower mineralization and higher Q 10 under NT and RR. Furthermore, structure equation and random forest modelling showed that increased SOC contents in NT and RR could not only reduce SOC mineralization, but also constrained the improvement of Q 10 in NT and RR. Overall, these results indicated that although sieved soils overestimated SOC mineralization and underestimated Q 10 due to the destruction of macro-aggregates, the patterns between treatments were similar and sieving soil for incubation is considered as a suitable approach to evaluate the relative impacts of NT and RR on SOC mineralization and Q 10 ., 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 Elsevier B.V. All rights reserved.)

A multifunctional nanoplatform APIPB-MnCO@TPP@N,P-GQDs (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl) benzamide, TPP = triphenylphosphine, Mn = manganese, CO = carbon monoxide, and GQDs = graphene quantum dots), nanoplatform (1), was synthesized, which consists of a fluorescent N, P-doped GQDs carrier with its surface covalently functionalized by an CO donor APIPB-MnCO with histone deacetylases (HDAC) inhibitory property and a TPP derivative directing group. Nanoplatform (1) selectively localized in the mitochondria of HeLa cells to inhibit HDAC activity, and released CO upon 808 nm near-infrared light irradiation, destroying the mitochondria and thus inducing cancer cells apoptosis. The targeted subcellular mitochondrial CO delivery combined with inhibitory HDAC activity maximized the cytotoxicity of the nanoplatform which may provide new insights for CO-mediated multimodal therapies for cancer treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Intestinal commensal fungi are vital to human health, and their metabolites play a key role in the reciprocal relationship. In the present work, eighteen alkaloids and seven monoterpenoids were isolated from the fermentation of the human intestinal fungus Penicillium oxalicum SL2, including seven undescribed alkaloids (penicilloxalines A-G), three undescribed monoterpenoids (penicilloxalines H-J), and fifteen reported compounds. The structures of the isolated compounds were identified by HRESIMS, 1D and 2D NMR, electronic circular dichroism spectra and quantum chemical calculations. Some metabolites displayed moderate agonistic effects against the pregnane X receptor (PXR), whereas (6R)3,7-dimethyl-6,7-dihydroxy-2(Z)-octenoic acid displayed a significant agonistic effect against the farnesoid X receptor (FXR) with an EC 50 value of 0.43 μM, which was verified by investigating FXR downstream target genes and proteins, such as small heterodimer partner 1 (SHP1), fibroblast growth factor (FGF), and bile salt export pump (BSEP)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Proper regulation of p53 signaling is critical for the maintenance of hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). The hematopoietic cell-specific mechanisms regulating p53 activity remain largely unknown. Here, we demonstrate that conditional deletion of acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) in hematopoietic cells impairs repopulation capacity and postinjury regeneration of HSCs. Mechanistically, ANP32B forms a repressive complex with p53 and thus inhibits the transcriptional activity of p53 in hematopoietic cells, and p53 deletion rescues the functional defect in Anp32b-deficient HSCs. Of great interest, ANP32B is highly expressed in leukemic cells from patients with chronic myelogenous leukemia (CML). Anp32b deletion enhances p53 transcriptional activity to impair LSC function in a murine CML model and exhibits synergistic therapeutic effects with tyrosine kinase inhibitors in inhibiting CML propagation. In summary, our findings provide a novel strategy to enhance p53 activity in LSCs by inhibiting ANP32B and identify ANP32B as a potential therapeutic target in treating CML., (© 2021 by The American Society of Hematology.)

Continuous single tillage has the potential to increase greenhouse gas (GHG) emissions and decrease the accumulation of soil organic carbon (SOC), thus increasing carbon footprints (CFs). However, in a wheat-maize cropping system, limited information was available about the effects of strategic tillage on CFs. Thus, a four-year field experiment was conducted, including continuous rotary tillage (RT), continuous no-till (NT), RT + subsoiling (RS), and NT + subsoiling (NS), to investigate the effects of NS (strategic tillage) on the unit area and unit yield. The results showed that CO 2 emission was the highest contributor to CFs (73.92%) in a winter wheat-summer maize cropping system, following the order of NS < NT < RS < RT. The direct N 2 O emissions from fertilizers and residues were 4.43-4.51 t CO 2 -eq ha -1 yr -1 during the wheat and maize seasons, and indirect N 2 O emissions from irrigation and fertilizer inputs had a proportion of >80% from total agricultural inputs. The differences in SOC storage significantly affected the CFs. Although the NS treatment increased the amount of GHG emissions from the residues returned and consumption of diesel, the enhancement of SOC storage by deeper SOC increased. Thus, lower area-scaled CFs were observed in the NS treatment. Furthermore, a higher grain yield and an annual change of SOC storage compared with other treatments were observed under the NS system, which helped to reduce the CFs. The yield-scaled CFs followed the order of RT > RS > NT > NS when considering the changes in SOC storage. Therefore, the NS treatment resulted in a higher grain yield and SOC sequestration with lower CFs, and thus, it could be recommended as the best tillage method to achieve sustainable production and environmental balance in a wheat-maize cropping system., 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 Elsevier B.V. All rights reserved.)

Sudan I is one of the industry dyes and widely used in cosmetics, wax agent, solvent and textile. Sudan I has multiple toxicity such as carcinogenicity, mutagenicity, genotoxicity and oxidative damage. However, Sudan I has been illegally used as colorant in food products, triggering worldwide attention about food safety. Nevertheless, the toxicity of Sudan I on reproduction, particularly on oocyte maturation is still unclear. In the present study, using mouse in vivo models, we report the toxicity effects of Sudan I on mouse oocyte. The results reflect that Sudan I exposure disrupts spindle organization and chromosomes alignment as well as cortical actin distribution, thus leading to the failure of polar body extrusion. Based on the transcriptome results, it is found that the exposure of Sudan I leads to the change in expression of 764 genes. Moreover, it's further reflected that the damaging effects of Sudan I are mediated by the destruction of mitochondrial functions, which induces the accumulated ROS to stimulate oxidative stress-induced apoptosis. As an endogenous hormone, melatonin within the ovarian follicle plays function on improving oocyte quality and female reproduction by efficiently suppressing oxidative stress. Moreover, melatonin supplementation also improves oocyte quality and increases fertilization rate during in vitro culture. Consistent with these, we find that in vivo supplementation of melatonin efficaciously suppresses mitochondrial dysfunction and the accompanying apoptosis, thus reverses oocyte meiotic deteriorations. Collectively, our results prove the reproduction toxicity of Sudan I for the exposure of Sudan I reduces the oocyte quality, and demonstrate the protective effects of melatonin against Sudan I-induced meiotic deteriorations., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Di (2-ethylhexyl) phthalate (DEHP) is widely used as a plastic additive and it could induce reproduction defects and fertility in mammals as environmental endocrine disruptor. However, the effects and potential mechanism of DEHP exposure during lactation stage on follicular development of offspring are still unclear. In this study, we found that the total primordial follicle number and antral follicles in the suckling of mice exposed to DEHP during lactation was significantly reduced. RNA-seq analysis results showed that the transcription levels of genes related to steroid production, ovarian hormone secretion and oxidative stress were significantly changed, which led to a decrease in 17β-estradiol and an increase in oxidative stress. The proportion of DNA damage marker γH2AX in the ovary of female suckling exposed to DEHP was significantly increased. We also found an increase in the level of ovarian apoptosis, and the proliferation of ovarian granulosa cells was inhibited. These alterations also lead to abnormal spindle and chromosome misalignment during oocyte maturation. Overall, our data indicate that lactation exposure to DEHP can affect the secretion of hormones and the development of antral follicles in suckling mice by affecting the secretion pathways of ovarian hormone enzymes and oxidative stress pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The electrostatic interactions between chiral solutes and polysaccharide (PS)-based chiral selectors are the key to achieving chiral recognition; however, PS-based sorbents, derivatized of phenyl moieties, can exhibit considerably non-polar characteristics, and they are also useful for the separation of enantiomers in the reversed-phase mode. In this study, an immobilized amylose 3,5-dimethylphenylcarbamate-based sorbent was used to investigate the balance between electrostatic interactions and solvophobic interactions, with complementary effects on solute retention behavior when the isopropanol (IPA) concentration was altered. It was proposed that in both normal- and reversed-phase modes, information on the retention mechanisms could be obtained by observing the curvature of the logarithm of the retention factor versus the logarithm of the IPA concentration, and the slope values of the curves were related to the number of displaced IPA molecules upon solute adsorption. Using the proposed model and the two-site adsorption model, the retention behaviors of pantolactone (PL) enantiomers in both normal- and reversed-phase modes were investigated. The PL-sorbent interactions were classified into four types: electrostatic/enantioselective, electrostatic/nonselective, solvophobic/enantioselective, and solvophobic/nonselective. At IPA concentrations below 50 vol.% in n-hexane, the retention behaviors of PL were dominated by electrostatic/enantioselective sites, whereas at IPA concentrations beyond 50 vol.%, the solvophobic interactions of PL-sorbent were strengthened and mostly nonselective. By contrast, in the reversed-phase mode, a reverse in the enantiomeric elution order of PL was observed at 10 vol.% IPA, and considerably different enantioselectivity behaviors were found below and above 20 vol.%, indicating an abrupt change in the sorbent molecular environment. At IPA concentrations beyond 40 vol.%, the presence of PL-sorbent electrostatic interactions enhanced chiral recognition., 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.)

Background: This study evaluated the survival benefit of asparaginase (ASP)-based versus non-ASP-based chemotherapy combined with radiotherapy in a real-world cohort of patients with early-stage extranodal nasal-type natural killer/T-cell lymphoma (ENKTCL)., Patients and Methods: We identified 376 patients who received combined radiotherapy with either ASP-based (ASP, platinum, and gemcitabine; n = 286) or non-ASP-based (platinum and gemcitabine; n = 90) regimens. The patients were stratified into low-, intermediate-, and high-risk groups using the early stage-adjusted nomogram-revised risk index. Overall survival (OS) and distant metastasis (DM)-free survival (DMFS) between the chemotherapy regimens were compared using inverse probability of treatment weighting (IPTW) and multivariable analyses., Results: ASP-based (versus non-ASP-based) regimens significantly improved 5-year OS (84.5% versus 73.2%, P = 0.021) and DMFS (84.4% versus 74.5%, P = 0.014) for intermediate- and high-risk patients, but not for low-risk patients in the setting of radiotherapy. Moreover, ASP-based regimens decreased DM, with a 5-year cumulative DM rate of 14.9% for ASP-based regimens compared with 25.1% (P = 0.014) for non-ASP-based regimens. The survival benefit of ASP-based chemotherapy and radiotherapy remained consistent after adjusting the confounding variables using IPTW and multivariate analyses; additional sensitivity analyses confirmed these results., Conclusions: The findings provided support for ASP-based chemotherapy and radiotherapy as a first-line treatment strategy for intermediate- and high-risk early-stage ENKTCL., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Inhibition of soluble epoxide hydrolase (sEH) is considered to be an effective treatment for inflammation-related diseases, and small molecules origin from natural products show promising activity against sEH. Two undescribed protostanes, 3β-hydroxy-25-anhydro-alisol F (1) and 3β-hydroxy-alisol G (2) were isolated from Alisma orientale and identified as new sEH inhibitors with IC 50 values of 10.06 and 30.45 μM, respectively. Potential lead compound 1 was determined as an uncompetitive inhibitor against sEH, which had a K i value of 5.13 μM. In-depth molecular docking and molecular dynamics simulations revealed that amino acid residue Ser374 plays an important role in the inhibition of 1, which also provides an idea for the development of sEH inhibitors based on protostane-type triterpenoids., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Carbon (C) sequestration in agricultural systems is recommended as a beneficial measure for climate change mitigation and food security. Despite much research, the relationship between soil organic carbon (SOC) storage and sustainable crop productivity has not been identified for various agricultural ecosystems, especially in the paddy ecosystem where conservation tillage has been adopted. Thus, a long-term experiment was conducted to evaluate the effects of tillage practices on SOC storage, yield, and their relationship in a double-cropped rice (Oryza sativa L.) paddy in Southern China from 2005 to 2018. Four tillage systems were investigated: no-till with residue retained on the soil surface (NTS), rotary tillage with residue retention (RTS), plow tillage with residue retention (CTS), and plow tillage with residue removed (CT). The SOC accumulation in the 0-20 cm layer in tillage systems included two stages: the rapid accumulation stage (2005-2007) and the slow fluctuation stage (2007-2018), with a tendency for C saturation. After reaching C saturation, the increase in SOC storage was not obvious, even with continued C input, and the SOC storage under different tillage systems was inconsistent. In general, SOC storage under NTS was the greatest. Interannual changes were not significant, while cumulative yield (2005-2018) was highest under CTS (162.13 t ha -1 ), followed by RTS (158.46 t ha -1 ), NTS (153.99 t ha -1 ), and CT (149.70 t ha -1 ). Tillage practices had no effect on the yield stability of late rice, but a significant difference in early rice was noticed between CTS and RTS. A non-linear relationship between rice yield and SOC storage was significant (P < 0.0001). With increasing SOC, yields tended to increase first and then decrease. Thus, innovative tillage strategies (such as NTS) could increase SOC storage before it reaches C saturation, but maintaining SOC storage within a reasonable range and optimizing SOC distribution might be more beneficial for crop productivity than a higher SOC storage, especially in C-rich paddy fields., Competing Interests: Declaration of competing interest We declare that we 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.)

Amphotericin B (AmB), an effective polyene drug with broad spectrum antifungal activity, is used for serious fungal infections. Liposomal amphotericin B (LAmB) is a lipid dosage form, which has a significantly improved toxicity profile compared with conventional amphotericin B deoxycholate (DAmB). This study focused on verifying the gender differences in the acute toxicity of LAmB and further exploring its causes. Acute toxicity study of LAmB and DAmB were performed in rats, and toxicity responses and mortality of different sexes were observed and recorded. Concentrations of AmB in rat plasma and tissues were determined by a fully validated UPLC-MS/MS assay. The results demonstrated that LAmB showed significant gender differences in acute toxicity, with more severe toxic symptoms and higher mortality for female rats at different doses, but the same differences were not observed for DAmB under the same condition. To explore the cause of differences, toxicokinetic and tissue distribution studies were performed and the results showed that female animals had higher drug exposure, longer half-life and lower plasma clearance compared to male rats, and the drug was mostly distributed in the liver and kidneys, in which female rats displayed a significant higher concentration than that of male rats., 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.)

Multifunctional drugs with synergistic effects have been widely developed to enhance the treatment efficiency of various diseases, such as malignant tumors. Herein, a novel bifunctional manganese(I)-based prodrug [MnBr(CO) 3 (APIPB)] (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl)benzamide) with inhibitory histone deacetylase (HDAC) activity and light-controlled carbon monoxide (CO) delivery was successfully designed and synthesized. [MnBr(CO) 3 (APIPB)] readily released CO under visible light irradiation (λ > 400 nm) through which the amount of released CO could be controlled by manipulating light power density and illumination time. In the absence of light irradiation, the cytotoxic effect of [MnBr(CO) 3 (APIPB)] on cancer cells was greater than that of the commercially available HDAC inhibitor MS-275. Consequently, with a combination of CO delivery and HDAC inhibitory activity, [MnBr(CO) 3 (APIPB)] showed a remarkably enhanced antitumor effect on HeLa cells (IC 50  = 3.2 μM) under visible light irradiation. Therefore, this approach shows potential for the development of medicinal metal complexes for combined antitumor therapies., (Copyright © 2021. Published by Elsevier Inc.)

Florfenicol, apramycin, and danofloxacin are antibiotics approved only for veterinary use and that have good therapeutic effects on chicken respiratory infections caused by Escherichia coli. We established epidemiological cutoff values (ECV) for these antibiotics using 363 E. coli isolates from tracheal samples of chickens in 5 veterinary clinics in Guangdong Province, China. The minimum inhibitory concentrations (MIC) were determined using the agar dilution method as per Clinical and Laboratory Standards Institution guidelines. The ECV were then calculated using the statistical method and verified by normalized resistance interpretation and ECOFFinder software programs. The ECV of florfenicol, apramycin, and danofloxacin against E. coli were 16, 16, and 0.125 μg/mL, respectively. Susceptibility tests indicated that these isolates were resistant to florfenicol (66.7%), apramycin (22.3%), and danofloxacin (92.3%). Strains carrying floR were distributed in the range of MIC ≥32 μg/mL for florfenicol. Apramycin resistance was found in 77 strains (77/363, 21.1%), and isolates that carried aac(3)-IV were all in the range of MIC ≥512 μg/mL. Danofloxacin resistance was found in the range of MIC ≤0.125 μg/mL, but there were no mutations in the quinolone resistance-determining regions and plasmid-mediated quinolone resistance genes qnrA, qnrB, qnrC, qnrD, aac-(6')-Ib-cr, qep, and oqxB. The presence of the qnrS gene was verified in a few of the strains with an MIC of 0.06 μg/mL. The establishment of ECV was significant for monitoring of resistance development and therapy guidance., (Copyright © 2020. Published by Elsevier Inc.)

Background: The aim of the study was to assess the analytical performance of the HISCL NT-proBNP assay, a newly developed chemiluminescence immunoassay, for the detection of NT-proBNP., Methods: The within-run and total imprecision of the NT-proBNP assay were determined with HISCL cardiac marker controls. The linear ranges of the NT-proBNP assays were evaluated based on the CLSI EP6-A document using selected serum samples. Two hundred serum samples were evaluated to compare the HISCL NT-proBNP and Elecsys NT-proBNP assays. Five additional high NT-proBNP concentrations serum samples were evaluated to assess if there was high-dose hook effect in the HISCL NT-proBNP assay., Results: The total and within-run imprecision values of the HISCL NT-proBNP assay were 5.85%, 0.81%, 2.56% and 0.54% and 6.07%, 0.73%, 2.61% and 0.59% at 6.1, 129.83, 3732.84and39737.33 pg/ml, respectively. The assay was verified to be linear for NT-proBNP levels ranging between 6.1 and 39737.33 pg/ml. The assay comparison showed that HISCL NT-proBNP = 0.9803 × Elecsys NT-proBNP -4.383. The sensitivity of HISCL NT-proBNP was 87.23%, and the specificity was 85.61%. The AUC of HISCL NT-proBNP (0.90 (95% CI, 0.86-0.93)) did not differ from that of Elecsys NT-proBNP(0.89 (95% CI, 0.85-0.93)) (P = 0.638). The results of five high NT-proBNP concentrations samples (44448, 54206, 55634, 55728 and 109406 pg/ml, measured with the Elecsys NT-proBNP assay) tested with HISCL NT-proBNP assay were all displayed with ">40000 pg/ml"., Conclusions: The HISCL NT-proBNP chemiluminescence immunoassay showed good analytical and diagnostic performance for the detection of NT-proBNP and could be used in routine clinical practice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Two new atranones T and U (1 and 2), and three known analogues atranone B (3), atranone Q (4), and stachatranone C (5) were isolated from the toxigenic fungus Stachybotrys chartarum. Their structures and absolute configurations were elucidated by spectroscopic data and calculated ECD analyses. The cytotoxicities of all the atranones (1-5) were evaluated against MG-63 human osteosarcoma cell lines. Compound 4 exhibited significant cytotoxic effect against MG-63 with IC 50 value of 8.6 μM, being more active than the positive control, 5-FU (IC 50 10.4 μM). Morphological features of apoptosis activities were evaluated in 4-treated MG-63 cells. Compound 4 effectively induced apoptosis of MG-63, which was associated with G 0 /G 1 -phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 4 significantly induced MG-63 cell apoptosis in a dose-dependent manner., Competing Interests: Declaration of Competing Interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed. We deeply appreciate your consideration of our manuscript, and we look forward to receiving comments from the reviewers. If you have any queries, please don't hesitate to contact me at the address below., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Japanese encephalitis virus (JEV), a major cause of Japanese encephalitisis, is an arbovirus that belongs to the genus Flavivirus of the family Flaviviridae. Currently, there is no effective drugs available for the treatment of JEV infection. Therefore, it is important to establish efficient antiviral screening system for the development of antiviral drugs. In this study, we constructed a full-length infectious clone of eGFP-JEV reporter virus by inserting the eGFP gene into the capsid-coding region of the viral genome. The reporter virus RNA transfected-BHK-21 cells generated robust eGFP fluorescence signals that were correlated well with viral replication. The reporter virus displayed growth kinetics similar to wild type (WT) virus although replicated a little slower. Using a known JEV inhibitor, NITD008, we demonstrated that the reporter virus could be used to identify inhibitors against JEV. Furthermore, an eGFP-JEV-based high throughput screening (HTS) assay was established in a 96-well format and used for screening of 1443 FDA-approved drugs. Sixteen hit drugs were identified to be active against JEV. Among them, five compounds which are lonafarnib, cetylpyridinium chlorid, cetrimonium bromide, nitroxoline and hexachlorophene, are newly discovered inhibitors of JEV, providing potential new therapies for treatment of JEV infection., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with a poor prognosis. Although many factors have been identified that possibly trigger or aggravate IPF, such as viral infection, the exact cause of IPF remains unclear. Until now, there has been no systematic review to assess the role of viral infection in IPF quantitatively., Objective: This meta-analysis aims to present a collective view on the relationship between viral infection and IPF., Methods: We searched studies reporting the effect of viral infection on IPF in the PubMed, Embase, Cochrane Library, Web of Science, and Wiley Online Library databases. We calculated ORs with 95% CIs to assess the risk of virus in IPF. We also estimated statistical heterogeneity by using I 2 and Cochran Q tests and publication bias by using the funnel plot, Begg test, Egger test, and trim-and-fill methods. Regression, sensitivity, and subgroup analyses were performed to assess the effects of confounding factors, such as sex and age., Results: We analyzed 20 case-control studies from 10 countries with 1,287 participants. The pooled OR of all viruses indicated that viral infection could increase the risk of IPF significantly (OR, 3.48; 95% CI, 1.61-7.52; P = .001), but not that of exacerbation of IPF (OR, 0.99; 95% CI, 0.47-2.12; P = .988). All analyzed viruses, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 7 (HHV-7), and human herpesvirus 8 (HHV-8), were associated with a significant elevation in the risk of IPF, except human herpesvirus 6 (HHV-6)., Conclusions: The presence of persistent or chronic, but not acute, viral infections, including EBV, CMV, HHV-7, and HHV-8, significantly increases the risk of developing IPF, but not exacerbation of IPF. These findings imply that viral infection could be a potential risk factor for IPF., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Aniline detection is of great importance in many industries, but most of the aniline sensors suffers from tedious and time consuming process. Herein, we present an efficient aniline sensor based on Pd decorated ZnO nanomaterials. Ultrathin ZnO nanosheets were synthesized by a facile one-step hydrothermal method. The nanosheets were corrugated into a unique agaric morphology, endorsing the nanomaterials with high surface area that is ideal for gas sensing applications. The obtained ZnO nanosheets were then uniformly decorated with uniform Pd nanoparticles (Pd NPs) around 5 nm in diameter. Gas sensing experiment on the ZnO decorate with different amount of Pd nanoparticles were systematically evaluated. The sample decorated with 0.3 % Pd NPs (Pd-ZnO-0.3) exhibited the highest sensitivity to aniline, which is about two orders higher than that of the pure ZnO nanosheet. The gas sensor based on Pd-ZnO-0.3 has a detection limit to aniline down to 0.5 ppm, with very short response and recovery times of 29 s and 23 s, respectively to 100 ppm aniline. First-principles DFT study was employed to provide the sensing mechanism. The improved sensing performance could be attributed to the increasing adsorbed oxygen and tunable band alignment for Pd-ZnO materials. This work provides new insights to the design strategy of Pd-decorated ZnO nanomaterials for high performance gas sensors., Competing Interests: Declaration of Competing Interest The authors declare no conflict interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Four new sesquiterpenoids, conyterpenols A - D (1-4), along with nineteen known analogues (5-23) were isolated from the aerial parts of Conyza japonica. The structures of 1-4 were determined through spectroscopic analysis, while their absolute configurations were determined by comparison of calculated and experimental electronic circular dichroism (ECD) spectra. Conyterpenol D (4) was a new type of sesquiterpenoid with a seven-membered lactone ring. Compounds 1-23 were evaluated for their inhibitory activity against LPS-induced nitric oxide production in RAW264.7 macrophages and cytotoxicity against human hepatoma cell line (HepG2) and human breast adenocarcinoma cell line (MCF-7). Compounds 3, 4, and 12 displayed moderate inhibition against NO production with IC 50 values in the range of 26.4-33.6 μM. And all compounds showed no obvious cytotoxicity against these two cancer cell lines at 100 μM., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Nodal skip metastasis (NSM) is a prognostic factor in certain malignant tumors, but the clinical and prognostic implications of NSM in esophageal squamous cell carcinoma (ESCC) are still unclear. The study aimed to assess its risk factors and prognostic value in thoracic ESCC., Methods: A retrospective study was conducted in patients with thoracic ESCC who underwent esophagectomy from March 2009 to March 2012 in the Department of Thoracic Surgery, West China Hospital, Sichuan University. The prognostic implications and risk factors of NSM were assessed in our study., Results: The incidence of NSM in the entire cohort was 37.9%. Tumor location (P = .016), pT stage (P = .029), and pN stage (P < .001) were identified to be independent risk factors for NSM. The overall survival (OS) was similar between patients with and without NSM. The OS had no significant difference between pN1 patients with and without NSM, whereas the OS was significantly worse in pN2 patients with NSM than those without NSM (P = .001). The OS was similar between patients with NSM level 1 and NSM level 2, but the OS was significantly better in patients with NSM level 1 than NSM level 2 among patients with lower thoracic ESCC (P = .013)., Conclusions: The effect of NSM on prognosis of thoracic ESCC may be mainly reflected in patients with pN2 stage. The prognostic value of NSM level for thoracic ESCC may be mainly reflected in patients with lower thoracic tumor., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)