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Li Dong,1 Yu-Min Zheng,2 Xiao-Guang Luo,3 Zhi-Yi He2 1Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of South University of Science and Technology, The Second Clinical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Xiao-Guang LuoDepartment of Neurology, The First Affiliated Hospital of South University of Science and Technology, The Second Clinical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, People’s Republic of ChinaEmail guanche537@126.comZhi-Yi HeDepartment of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaEmail yizizhan40559@163.comBackground: Parkinson’s disease is a common neurodegenerative disease in the elderly. The incidence of various cancers in Parkinson’s disease patients is significantly lower than in healthy people. Parkinson’s disease patients are individuals with a high tendency for inflammation, whose peripheral immune system is represented in an activated state. We hypothesized that the hyperinflammatory predisposition of Parkinson’s disease patients is pathogenic.Methods: DBA/1 mice were used to simulate “highly inflammatory individuals”, and the carcinogen DEN was used to induce malignancy. Hematoxylin & eosin (H&E) staining was used to observe the formation of lung tumors. Apoptosis of neurons was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Immunohistochemistry and flow cytometry were used to observe CD4, CD28, major histocompatibility complex II (MHCII), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and programmed death 1 (PD-1). The ionized calcium binding adaptor molecule-1 (IBA-1) + inducible nitric oxide synthase (iNOS) was used to label M1 microglia, and IBA-1 + arginase 1 (Arg1) was used to label M2 microglia by immunofluorescence. The expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and anti-inflammatory cytokines IL-10 and IL-4 was detected by ELISA.Results: DBA/1 mice with high inflammatory tendency showed a continuous increase of peripheral inflammation, promoting intracranial inflammation, decreasing the tumor incidence and increasing the neurodegeneration under induction of malignant change. CD28 and CTLA-4/PD-1 reduced the T-cell-dominated inflammatory response, reduced the intracerebral inflammatory response, protected from neurodegeneration, and increased the incidence of tumor. Combination of CTLA-4 and PD-1 blocker can overactivate T cells, worsen peripheral and intracranial inflammation, reduce the incidence of tumor, cause damage to dopamine neurons, and promote the occurrence of neurodegeneration.Conclusion: High inflammatory tendency induced by malignant stimulation through the imbalance of CD28 and CTLA-4/PD-1 leads to dopamine neuron injury.Keywords: high inflammatory tendency, malignant stimulation, CD28, CTLA-4/PD-1, dopamine neuron injury

Jianbin Shen,1,* Xiagang Luo,2,* Xiao Zhou,3 Chengwu Tang,1 Huanyu Ju,2 Yongqiang Xu,1 Lianjin Qin1 1Department of General Surgery, First People’s Hospital Affiliated to Huzhou Normal College, Huzhou, Zhejiang, 2Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 3Department of Orthopedics, People’s Hospital of Zhangqiu, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study was to investigate the effect of Xiaozhi decoction (XZD) on posthemorrhoidectomy pain and analgesic medication consumption.Methods: From May 2013 to March 2015, 315 patients who underwent open hemorrhoidectomy in our hospital were enrolled in this study, of whom, 160 patients were randomly assigned to accept sitz bath with warm water after hemorrhoidectomy (control group) and 155 patients were randomly assigned to accept sitz bath with XZD (XZD group) after hemorrhoidectomy. Postoperative pain at 12 hours after surgery and on postoperative days (PODs) 1, 2, 7, 14 and 28 was evaluated by Visual Analog Scale (VAS). Pain on defecation on PODs 1, 2, 7, 14 and 28 was also recorded using the VAS. The consumption of analgesics was also analyzed.Results: No significant difference was found in baseline characteristics between the two groups. Postoperative pain score of the XZD group was significantly lower on POD 2 (6.04±1.11 vs 6.33±1.14, P=0.0229), POD 7 (3.35±0.75 vs 4.22±0.87, P=0.0000) and POD 14 (2.87±0.64 vs 3.64±0.77, P=0.0000) than that of the control group. Similarly, patients in the XZD group experienced significantly less pain on defecation on POD 2 (5.02±1.34 vs 5.43±1.56, P=0.0130), POD 7 (3.08±1.17 vs 3.52±1.29, P=0.0017) and POD 14 (2.31±0.85 vs 2.68±0.99, P=0.0004). Patients in the XZD group consumed significantly less analgesic medication on POD 2 (P=0.0136), POD 7 (P=0.0074) and POD 14 (P=0.0046) than the control group. Conclusion: XZD could effectively relieve postoperative pain and reduce analgesic medication consumption after hemorrhoidectomy. Keywords: hemorrhoids, hemorrhoidectomy, traditional Chinese medicine, posthemorrhoidectomy pain

Jialing Yuan,1 Ruiqi Duan,1 Huan Yang,2 Xiangang Luo,2 Mingrong Xi11Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, 2State Key Laboratory of Optical Technologies for Microfabrication, Institute of Optics and Electronics, Chinese Academy of Science, Chengdu, ChinaBackground: Detection of the human epididymis secretory protein 4 (HE4) biomarker plays an important role in the early diagnosis of ovarian cancer. This study aimed to develop a novel localized surface plasmon resonance (LSPR) biosensor for detecting HE4 in blood samples from patients with ovarian cancer.Methods: Silver nanoparticles were fabricated using a nanosphere lithography method. The anti-HE4 antibody as a probe, which can distinctly recognize HE4, was assembled onto the nanochip surface using an amine coupling method. Detection was based on the shift in the extinction maximum of the LSPR spectrum before and after the HE4-anti-HE4 antibody reaction. These nanobiosensors were applied to detect HE4 in human serum samples and compare them using an enzyme-linked immunosorbent assay.Results: Tests relating to the detection of HE4 demonstrated that the LSPR-based biosensor featured a fast detection speed, good specificity, effective reproducibility, and long-term stability. The linear range for LSPR was between 10 pM and 10,000 pM, with a detection limit of 4 pM. An excellent correlation between LSPR and enzyme-linked immunosorbent assay results was observed in human serum.Conclusion: This study is the first clinical diagnostic application of the LSPR biosensor in ovarian cancer. The LSPR biosensor, a rapid, low-cost, label-free and portable screening tool, can serve as a very effective alternative for the clinical serological diagnosis of ovarian cancer.Keywords: localized surface plasmon resonance system, nanobiosensor, ovarian cancer biomarker, serum HE4 protein

To elucidate the effects of long-term (20 years) afforestation with different woody plant species on the soil microenvironment in coal gangue polymetallic contaminated areas. This study analyzed the soil physicochemical properties, soil enzyme activities, soil ionophore, bacterial community structure, soil metabolite, and their interaction relationships at different vertical depths. Urease, sucrase, and acid phosphatase activities in the shallow soil layers increased by 4.70-7.45, 3.83-7.64, and 3.27-4.85 times, respectively, after the restoration by the four arboreal plant species compared to the plant-free control soil. Additionally, it reduced the content of available elements in the soil and alleviated the toxicity stress for Cd, Ni, Co, Cr, As, Fe, Cu, U, and Pb. After the long-term restoration of arboreal plants, the richness and Shannon indices of soil bacteria significantly increased by 4.77-23.81% and 2.93-7.93%, respectively, broadening the bacterial ecological niche. The bacterial community structure shaped by different arboreal plants exhibited high similarity, but the community similarity decreased with increasing vertical depth. Soils Zn, U, Sr, S, P, Mg, K, Fe, Cu, Ca, Ba, and pH were identified as important influencing factors for the community structure of Sphingomonas, Pseudarthrobacter, Nocardioides, and Thiobacillus. The metabolites such as sucrose, raffinose, L-valine, D-fructose 2, 6-bisphosphate, and oxoglutaric acid were found to have the greatest effect on the bacterial community in the rhizosphere soils for arboreal plants. The results of the study demonstrated that long-term planting for woody plants in gangue dumps could regulate microbial abundance and symbiotic patterns through the accumulation of rhizosphere metabolites in the soil, increase soil enzyme activity, reduce heavy metal levels, and improve the soil environment in coal gangue dumps., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Plant enrichment and tolerance to heavy metals are crucial for the phytoremediation of coal gangue mountain. However, understanding of how plants mobilize and tolerate heavy metals in coal gangue is limited. This study conducted potted experiments using Setaria viridis as a pioneer remediation plant to evaluate its tolerance to coal gangue, its mobilization and enrichment of metals, and its impact on the soil environment. Results showed that the addition of 40% gangue enhanced plant metal and oxidative stress resistance, thereby promoting plant growth. However, over 80% of the gangue inhibited the chlorophyll content, photoelectron conduction rate, and biomass of S. viridis, leading to cellular peroxidative stress. An analysis of metal resistance showed that endogenous S in coal gangue promoted the accumulation of glutathione, plant metal chelators, and non-protein thiols, thereby enhancing its resistance to metal stress. Setaria viridis cultivation affected soil properties by decreasing nitrogen, phosphorus, conductivity, and urease and increasing sucrase and acid phosphatase in the rhizosphere soil. In addition, S. viridis planting increased V, Cr, Ni, As, and Zn in the exchangeable and carbonate-bound states within the gangue, effectively enriching Cd, Cr, Fe, S, U, Cu, and V. The increased mobility of Cd and Pb was correlated with a higher abundance of Proteobacteria and Acidobacteria. Heavy metals, such as As, Fe, V, Mn, Ni, and Cu, along with environmental factors, including total nitrogen, total phosphorus, urease, and acid phosphatase, were the primary regulatory factors for Sphingomonas, Gemmatimonas, and Bryobacter. In summary, S. viridis adapted to gangue stress by modulating antioxidant and elemental enrichment systems and regulating the release and uptake of heavy metals through enhanced bacterial abundance and the recruitment of gangue-tolerant bacteria. These findings highlight the potential of S. viridis for plant enrichment in coal gangue areas and will aid the restoration and remediation of these environments., 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 Ltd.)

The ecological risk of tritiated wastewater into the environment has attracted much attention. Assessing the ecological risk of tritium-containing pollution is crucial by studying low-activity tritium exposure's environmental and biological effects on freshwater micro-environment and the enrichment potential of organically bound tritium (OBT) in microalgae and aquatic plants. The impact of tritium-contaminated wastewater on the microenvironment of freshwater systems was analyzed using microcosm experiments to simulate tritium pollution in freshwater systems. Low activity tritium pollution (10 5  Bq/L) induced differences in microbial abundance, with Proteobacteria, Bacteroidota, and Desulfobacterota occupying important ecological niches in the water system. Low activity tritium (10 5 -10 7  Bq/L) did not affect the growth of microalgae and aquatic plants, but OBT was significantly enriched in microalgae and two aquatic plants (Pistia stratiotes, Spirodela polyrrhiza), with the enrichment coefficients of 2.08-3.39 and 1.71-2.13, respectively. At the transcriptional level, low-activity tritium (10 5  Bq/L) has the risk of interfering with gene expression in aquatic plants. Four dominant cyanobacterial strains (Leptolyngbya sp., Synechococcus elongatus, Nostoc sp., and Anabaena sp.) were isolated and demonstrated good environmental adaptability to tritium pollution. Environmental factors can modify the tritium accumulation potential in cyanobacteria and microalgae, theoretically enhancing food chain transfer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The soil microbial diversity in the gangue accumulation area is severely stressed by a variety of heavy metals, while the influence of long-term recovery of herbaceous plants on the ecological structure of gangue-contaminated soil is to be explored. Therefore, we analysed the differences in physicochemical properties, elemental changes, microbial community structure, metabolites and expression of related pathways in soils in the 10- and 20-year herbaceous remediation areas of coal gangue. Our results showed that phosphatase, soil urease, and sucrase activities of gangue soils significantly increased in the shallow layer after herbaceous remediation. However, in zone T 1 (10-year remediation zone), the contents of harmful elements, such as Thorium (Th; 1.08-fold), Arsenic (As; 0.78-fold), lead (Pb; 0.99-fold), and uranium (U; 0.77-fold), increased significantly, whereas the soil microbial abundance and diversity also showed a significant decreasing trend. Conversely, in zone T 2 (20-year restoration zone), the soil pH significantly increased by 1.03- to 1.06-fold and soil acidity significantly improved. Moreover, the abundance and diversity of soil microorganisms increased significantly, the expression of carbohydrates in soil was significantly downregulated, and sucrose content was significantly negatively correlated with the abundance of microorganisms, such as Streptomyces. A significant decrease in heavy metals was observed in the soil, such as U (1.01- to 1.09-fold) and Pb (1.13- to 1.25-fold). Additionally, the thiamin synthesis pathway was inhibited in the soil of the T 1 zone; the expression level of sulfur (S)-containing histidine derivatives (Ergothioneine) was significantly up-regulated by 0.56-fold in the shallow soil of the T 2 zone; and the S content in the soil significantly reduced. Aromatic compounds were significantly up-regulated in the soil after 20 years of herbaceous plant remediation in coal gangue soil, and microorganisms (Sphingomonas) with significant positive correlations with benzene ring-containing metabolites, such as Sulfaphenazole, were identified., 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.)

Purpose: To establish a parameter-based grading system for evaluating bladder trabeculation (BT)., Materials and Methods: A retrospective analysis was conducted on children diagnosed with posterior urethral valve (PUV) or neurogenic bladder (NB) who underwent voiding cystourethrogram (VCUG), urodynamic testing, and urological ultrasonography between January 2016 and October 2022. Cases involving urologic surgery, secondary bladder pathology, and an interval of more than 12 months between examinations were excluded. A parameter named Bladder Dispersion (BD) was calculated through fluoroscopic images, and the grading system was developed as follows: BD < 40 (Grade 0), 40 ≤ BD < 60 (Grade 1), 60 ≤ BD < 90 (Grade 2), BD ≥ 90 (Grade 3). Grades 0-1 were classified as low-risk group, while grades 2-3 were classified as high-risk group. Analysis of variance, Kruskal-Wallis test, and Chi-square test were performed to compare urodynamic results and complications across different grades and groups., Results: A total of 74 patients were eligible to participate, which included 46 boys (62.2%) and 28 girls (37.8%), the mean age was 75.18 ± 48.39 months. Among them, 11 (14.9%) were PUV, 50 (67.6%) were NB, and 13 (17.5%) were PUV and NB. Significant differences were observed in maximum detrusor pressure, post-void residual urine ratio, and compliance among grades 0-3. Severe hydronephrosis and histories of urinary tract infection were more prevalent in the high-risk group., Conclusion: A reliable grading system with objective standards was proposed which could aid in the assessment of BT severity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The capacity of Spanish moss (Tillandsia usneoides), an aerial plant, to adsorb radon (Rn) and absorb CO 2 was assessed to analyze its capacity to remove pollutants from indoor air and to determine its radon (Rn) tolerance mechanism. Transcriptomics and metabolomics techniques were used to analyze the response of the plant to Rn exposure. Spanish moss absorbed indoor CO 2 at night using the type of photosynthesis termed crassulacean acid metabolism. The CO 2 absorption efficiency of the plant was mainly affected by the light duration and diurnal temperature differences. The highest purification efficiency was 48.25%, and the scales on the Spanish moss leaf surface were the key sites for Rn adsorption. Metabolome analysis showed that Rn exposure induced differential metabolites significantly enriched in the metabolism of lipids, amino acids, nucleotides, and carbohydrates. Transcriptome analysis showed significantly upregulated expression levels of functional genes in Rn-exposed leaves. Rn had significant effects on respiratory metabolism, as indicated by upregulated expression of metabolites and functional genes related to the glycolysis pathway, pyruvate oxidation, tricarboxylic acid cycle, and oxidative phosphorylation pathway. These responses indicated that the internal mechanism by which Spanish moss alleviates Rn stress involves an enhancement of cellular energy supplies and regulation of respiratory metabolic pathways to allow adaptation to Rn pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cancer progression is an evolutionary process shaped by both deterministic and stochastic forces. Multi-region and single-cell sequencing of tumors enable high-resolution reconstruction of the mutational history of each tumor and highlight the extensive diversity across tumors and patients. Resolving the interactions among mutations and recovering recurrent evolutionary processes may offer greater opportunities for successful therapeutic strategies. To this end, we present a novel probabilistic framework, called TreeMHN, for the joint inference of exclusivity patterns and recurrent trajectories from a cohort of intra-tumor phylogenetic trees. Through simulations, we show that TreeMHN outperforms existing alternatives that can only focus on one aspect of the task. By analyzing datasets of blood, lung, and breast cancers, we find the most likely evolutionary trajectories and mutational patterns, consistent with and enriching our current understanding of tumorigenesis. Moreover, TreeMHN facilitates the prediction of tumor evolution and provides probabilistic measures on the next mutational events given a tumor tree, a prerequisite for evolution-guided treatment strategies., (© 2023. The Author(s).)

The ecological risk posed by tritium (T) and carbon-14 (C-14) discharge from nuclear accidents has gained attention. This study evaluated the toxic impact of T and C-14 (at a concentration of 37 kBq/L for 15 days) on the cyanobacteria (Synechococcus elongatus). The results showed that the assimilation efficiency of cyanobacteria was significantly higher for C-14 than T, and the intracellular C-14 activity reached 30.62-40.58 kBq/kg. T and C-14 exposure had no significant effect on cell proliferation but impacted photosynthesis and respiration. T exposure increased the content of Ca, Mg, Na, P, K, and Mn, while C-14 exposure primarily affected trace element absorption in cyanobacteria. 31, 27, and 58 different metabolites (DEMs) were identified under T, C-14, and combined exposure conditions. These DEMs were enriched in the amino acid biosynthesis pathway, and nitrogen assimilation was one of the crucial pathways affected by T and C-14 exposure. The absorption of mineral elements by cyanobacteria was influenced by the variation in metabolites in the ABC transporter pathway caused by T and C-14 exposure. Our findings provide insights into the metabolic response of cyanobacteria to T and C-14 exposure and will help to guide the ecological risk evaluation of nuclear accidents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The potential ecological risks caused by entering radioactive wastewater containing tritium and carbon-14 into the sea require careful evaluation. This study simulated seawater's tritium and carbon-14 pollution and analyzed the effects on the seawater and sediment microenvironments. Tritium and carbon-14 pollution primarily altered nitrogen and phosphorus metabolism in the seawater environment. Analysis by 16S rRNA sequencing showed changes in the relative abundance of microorganisms involved in carbon, nitrogen, and phosphorus metabolism and organic matter degradation in response to tritium and carbon-14 exposure. Metabonomics and metagenomic analysis showed that tritium and carbon-14 exposure interfered with gene expression involving nucleotide and amino acid metabolites, in agreement with the results seen for microbial community structure. Tritium and carbon-14 exposure also modulated the abundance of functional genes involved in carbohydrate, phosphorus, sulfur, and nitrogen metabolic pathways in sediments. Tritium and carbon-14 pollution in seawater adversely affected microbial diversity, metabolic processes, and the abundance of nutrient-cycling genes. These results provide valuable information for further evaluating the risks of tritium and carbon-14 in marine environments.

It is always big challenges for hyaluronic acid (HA) in transmembrane absorbing and efficient delivering to the skin. Pep-1, as one of the cell-penetrating peptides, has been documented to permeate various substances across cellular membranes without covalent binding. Here, a novel hyaluronic acid binding peptide (named HaBP) is designed, and then combined with Pep-1 to enhance the cell-penetrating efficiency of HA. The results of ELISA and immunofluorescence assay show that HaBP could bind with HA very well, and a combination of Pep-1 and HaBP could efficiently improve the transmembrane ability of HA. Furthermore, HA gradually enters the dermis from the surface of the skin in mice when it is administrated with both HaBP and Pep-1, while there are no obvious allergies or other adverse reactions during this process. This study finds a new method to promote the efficient transmembrane and transdermal absorption of HA, and throws some light on further research on the development of hyaluronic acid and its related cosmetics or drugs., (© 2023 Wiley-VCH GmbH.)

Background: The bi-tensor free water imaging may provide more specific information in detecting microstructural brain tissue alterations than conventional single tensor diffusion tensor imaging. The study aimed to investigate microstructural changes in deep gray matter (DGM) nuclei of Wilson's disease (WD) using a bi-tensor free water imaging and whether the findings correlate with the neurological impairment in WD patients., Methods: The study included 29 WD patients and 25 controls. Free water and free water corrected fractional anisotropy (FA T ) in DGM nuclei of WD patients were calculated. The correlations of free water and FA T with the Unified WD Rating Scale (UWDRS) neurological subscale of WD patients were performed., Results: Free water and FA T values were significantly increased in multiple DGM nuclei of neurological WD patients compared to controls. WD patients with normal appearing on conventional MRI also had significantly higher free water and FA T values in multiple DGM nuclei than controls. Positive correlations were noted between the UWDRS neurological subscores and free water values of the putamen and pontine tegmentum as well as FA T values of the dentate nucleus, red nucleus, and globus pallidus. In addition, the measured free water and FA T values of specific structures also showed a positive correlation with specific clinical symptoms in neurological WD patients, such as dysarthria, parkinsonian signs, tremor, dystonia, and ataxia., Conclusions: Free water imaging detects microstructural changes in both normal and abnormal appearing DGM nuclei of WD patients. Free water imaging indices were correlated with the severity of neurological impairment in WD patients., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Human industrial activities have caused environmental uranium (U) pollution, resulting in uranium(VI) had radiotoxicity and chemical toxicity. Here, a cellulase-producing Penicillium fungus was screened and characterized by X-ray fluorescence (XRF), and Fourier transform infrared reflection (FT-IR), as well as by GC/MS metabolomics analysis, to study the response to uranium(VI) stress. The biomass of Penicillium decreased after exposure to 100 mg/L U. Uranium combined with carboxyl groups, amino groups, and phosphate groups to form uranium mineralized deposits on the surface of this fungal strain. The α-activity concentration of uranium in the strain was 2.57×10 6 Bq/kg, and the β-activity concentration was 2.27×10 5 Bq/kg. Metabolomics analysis identified 118 different metabolites, as well as metabolic disruption of organic acids and derivatives. Further analysis showed that uranium significantly affected the metabolism of 9 amino acids in Penicillium. These amino acids were related to the TCA cycle and ABC transporter. At the same time, uranium exhibited nucleotide metabolism toxicity to Penicillium. This study provides an in-depth understanding of the uranium tolerance mechanism of Penicillium and provides a theoretical basis for Penicillium to degrade hyper-enriched plants., (Copyright © 2022. Published by Elsevier B.V.)

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder prevalent in school-age children. At present, however, its etiologies and risk factors are unknown. Transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor regulatory protein γ-8 (TARP γ-8, also known as calcium voltage-gated channel auxiliary subunit gamma 8 (CACNG8)) is an auxiliary AMPA receptor (AMPAR) subunit. Here, we report an association between TARP γ-8 and ADHD, whereby adolescent TARP γ-8 knockout (KO) mice exhibited ADHD-like behaviors, including hyperactivity, impulsivity, anxiety, impaired cognition, and memory deficits. Human single-nucleotide polymorphism (SNP) analysis also revealed strong associations between intronic alleles in CACNG8 genes and ADHD susceptibility. In addition, synaptosomal proteomic analysis revealed dysfunction of the AMPA glutamate receptor complex in the hippocampi of TARP γ-8 KO mice. Proteomic analysis also revealed dysregulation of dopaminergic and glutamatergic transmissions in the prefrontal cortices of TARP γ-8 KO mice. Methylphenidate (MPH), which is commonly used to treat ADHD, significantly rescued the major behavioral deficits and abnormal synaptosomal proteins in TARP γ-8 KO mice. Notably, MPH significantly reversed the up-regulation of Grik2 and Slc6a3 in the prefrontal cortex. MPH also significantly improved synaptic AMPAR complex function by up-regulating other AMPAR auxiliary proteins in hippocampal synaptosomes. Taken together, our results suggest that TARP γ-8 is involved in the development of ADHD in humans. This study provides a useful alternative animal model with ADHD-like phenotypes related to TARP γ-8 deficiency, which has great potential for the development of new therapies.

This research provides a complete degradation scheme for acrylic copolymer/cellulose acetate butyrate peelable decontamination films. This study analyzed the removal efficiency of uranium by peelable decontamination film. More importantly, the degradability of the films was evaluated by a combined treatment with UV radiation and microbial biodegradation. The results showed that UV radiation would rupture the surface of the decontamination films, which leaded the weight-average molecular weight decreased by 55.3% and number-average molecular weight decreased by 75.83%. Additionally, the microbial flora induced light-degradable decontamination film weight-average molecular weight and number-average molecular weight decreased by 9.3% and 30.73%, respectively. 16S rRNA microbial diversity analysis indicated that Pantoea, Xylella, Cronobacter, and Olivibacter were the major degrading bacteria genera. Among them, 4 key strains that can be stripped of decontamination films have been isolated and identified from the dominant degrading bacteria group. The results show that UV radiation combined with microbial flora can achieve rapid degradation of the decontamination films., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Key Message: Alfalfa has the ability to degrade TNT. TNT exposure caused root disruption of mineral nutrient metabolism. The exposure of TNT imbalanced basal cell energy metabolism. The mechanism of 2,4,6-trinitrotoluene (TNT) toxicity effects was analyzed in alfalfa (Medicago sativa L.) seedlings by examining the mineral nutrition and secondary metabolism of the plant roots. Exposure to 25-100 mg·L -1 TNT in a hydroponic solution for 72 h resulted in a TNT absorption rate of 26.8-63.0%. The contents of S, K, and B in root mineral nutrition metabolism increased significantly by 1.70-5.46 times, 1.38-4.01 times, and 1.40-4.03 times, respectively, after TNT exposure. Non-targeted metabolomics analysis of the roots identified 189 significantly upregulated metabolites and 420 significantly downregulated metabolites. The altered metabolites were primarily lipids and lipid-like molecules, and the most significant enrichment pathways were alanine, aspartate, and glutamate metabolism and glycerophospholipid metabolism. TNT itself was transformed in the root system into several intermediate products, including 4-hydroxylamino-2,6-dinitrotoluene, 4-amino-2,6-dinitrotoluene, 2-hydroxylamino-4,6-dinitrotoluene, 2,4',6,6'-tetranitro-2',4-azoxytoluene, 4,4',6,6'-tetranitro-2,2'-azoxytoluene, and 2,4-dinitrotoluene. Overall, TNT exposure disturbed the mineral metabolism balance, and significantly interfered with basic plant metabolism., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Explosive pollutants remaining in global soils are serious threats to human health and ecological safety. Soils contaminated by trinitrotoluene (TNT) and cyclotrimethylene trinitramine (RDX) are simulated in this study and remediated using vetiver grass and effective microorganism (EM) flora to determine the efficacy of combined remediation in reshaping the microenvironment and bacterial community of soils contaminated by explosives. The degradation rates of TNT and RDX after 60 days of combined remediation were 95.66% and 84.37%, respectively. Soil microbial activity and enzyme activities related to the nitrogen cycle were upregulated. The content of soil elements in the remediation group changed significantly. Vetiver remediation increased the diversity and significantly changed the structure of the microbial community. Notably, bacteria, such as Sphingomonadaceae and Actinobacteriota, which can degrade explosives, occupied the soil niche, and the Proteobacteria and Bacteroidota, which are involved in sugar metabolism, showed particularly increased abundance. The metabolism of soil carbohydrates, fatty acids, and amino acids was upregulated in the vetiver, EM flora, and combined vetiver+EM flora remediation groups, and the most significantly upregulated pathway was galactose metabolism. The combined vetiver and EM flora treatment of soil contaminated by explosives greatly improved the ecology of the soil microenvironment., 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 soil ecological health risks and toxic effects of coal gangue accumulation were examined after 10 years of elm/poplar phytoremediation. The changes in soil enzyme activities, ionome metabolism, and microbial community structure were analyzed at shallow (5-15 cm), intermediate (25-35 cm), and deep (45-55 cm) soil depths. Soil acid phosphatase activity in the restoration area increased significantly by 4.36-7.18 fold (p < 0.05). Soil concentrations of the metal ions Cu, Pb, Ni, Co, Bi, U, and Th were significantly reduced, as were concentrations of the non-metallic element S. The repair effect was shallow > middle > deep. The soil community structure, determined by 16S diversity results, was changed significantly in the restoration area, and the abundance of microorganisms increased at shallow soil depths. Altererythrobacter and Sphingomonas species were at the center of the microbial weight network in the restoration area. Redundancy analysis (RDA) showed that S and Na are important driving forces for the microbial community distributions at shallow soil depths. The KEGG function prediction indicated enhancement of the microbial function of the middle depth soil layers in the restoration area. Overall, phytoremediation enhanced the biotransformation of soil phosphorus in the coal gangue restoration area, reduced the soil content of several harmful metal elements, significantly changed the structure and function of the microbial community, and improved the overall soil ecological environment., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Elucidation of the phytotoxic mechanisms of thorium (Th) is important for controlling Th accumulation in crops and improving the efficiency of phytoremediation. Here, we analyzed the subcellular distribution of Th in Vicia faba seedlings and the toxic reaction of seedlings to Th (5-40 μmol·L -1 ) at the subcellular and cellular levels. Increasing the phosphate level in the culture medium from 0.01 to 0.1 mmol·L -1 decreased the Th accumulation by the roots by 47-57%. Th was mainly distributed in the root cell walls (94-96%) and existed mainly in the form of residue (92-94%). Th accumulation in the root was similar to the changes observed for P, Ni, Cu, and Fe. High concentrations of Th (40 μmol·L -1 ) induced abnormal root growth and leaf photosynthetic metabolism. At the cellular level, Th (40 μmol·L -1 ) induced root edge cell death and inhibited root respiration and cell mitosis. SOD, POD and CAT activities were involved in the regulation of reactive oxygen species accumulation in the roots. Untargeted metabolomics identified 580 and 262 differentially expressed metabolites in roots and leaves. At the metabolic level, its toxicological mechanism involved a severe inhibition of the expression of nucleotides in roots and leaves., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Polyethylene film is the most widely used plastic film in agricultural production activities, and its depolymerization products are mainly polyethylene-particles (PE-particles) of different molecular weights. However, the impact of the molecular weights of the PE-particles on soil-crop microenvironment has not been elucidated. In this study, a potted microcosmic simulation system was used to evaluate the impact of low, medium and high molecular weight PE-particles on soil metabolism, microbial community structure, and crop growth. There were obvious differences in the shape and surface microstructure of PE-particles with different molecular weights. Soil sucrase and peroxidase had significant responses to PE-particles of different molecular weights. In the rhizosphere, the number of microorganisms and the microbial alpha diversity index increased with increasing PE-particles molecular weight. Rhizobacter, Nitrospira, and Sphingomonas were the dominant microorganisms induced by PE-particles to regulate the metabolism of elements. Carbohydrate and amino acid contents in rhizosphere soils were the key factors affecting the species abundance of Lysobacter, Polyclovorans, Rhizobacter, and Sphingomonas. In plants, PE-particles treatment reduced the plant biomass and photosynthetic rate and disrupted normal mineral nutrient metabolism. Different molecular weight PE-particles may therefore have adverse effects on the soil-plant system., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The effects of polystyrene nanoplastics (PSNPs) on the physiological and molecular metabolism of corn seedlings were examined by treating corn (Zea mays L.) seedlings with 100, 300, and 500 nm diameter PSNPs and examining plant photosynthetic characteristics, antioxidant enzyme systems, and molecular metabolism. After 15 days of exposure to PSNPs with different particle sizes (50 mg·L -1 ), the photosynthetic characteristics of the plant remained stable, and the maximum photochemical quantum yield (Fv/Fm) and non-photochemical quenching coefficient (NPQ) had no significant effects. The root microstructure was damaged and the antioxidant enzyme system was activated, and the content of malondialdehyde (MDA) was significantly increased by 2.25-4.50-fold. In addition, 100 nm and 300 nm PSNPs exposure caused root superoxide dismutase (SOD) activity to increase 1.28-fold and 1.53-fold, and glutathione-peroxidase (GSH-PX) activity increased 1.30-fold and 1.58-fold. Non-targeted metabolomics analysis identified a total of 304 metabolites. Exposure to 100, 300, and 500 nm PSNPs led to the production of 85 (upregulated: 85, downregulated: 0), 73 (upregulated: 73, downregulated: 0), and 86 (upregulated: 84, downregulated: 2) differentially expressed metabolites, respectively, in the plant roots. Co-expressed differential metabolites accounted for 38.2% of the metabolites and indicated a metabolic imbalance primarily in organic acids and derivatives in the root system. The most significant enrichment pathways were those of alanine, aspartate, and glutamate metabolism. Overall, exposure to PSNPs of different particle sizes activated the root antioxidant enzyme system and interfered with plant basic metabolism. The alanine, aspartate, and glutamate metabolic pathways appear to be closely related to plant mechanisms for tolerance/detoxification of PSNPs., 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.)

Objective: Alkaline phosphatase (ALP) is a ubiquitous enzyme in humans that can be used for diagnosing childhood diseases. Infants have the highest rapid growth rate and are susceptible to metabolic bone diseases. In infants, ALP activities exhibit significant month-wise variations, and authoritative standards are lacking. The present study aimed to provide a reference for the diagnosis of diseases related to abnormal ALP activities in infants., Methods: This study included 24,618 samples collected from infants aged 0-12 months from three medical centers in Chongqing, China. Samples of infants diagnosed with diseases that may affect ALP activity have been exclude. ALP activity was analyzed using an automatic biochemical analyzer. A percentile curve for ALP activity in male and female infants was constructed using MATLAB, and the skewness-median-coefficient of variation method was employed for curve fitting., Results: ALP activity in male and female infants peaked at 0-4 months; the peak appeared at 1-2 months and declined gradually thereafter. After 4-5 months of age, the ALP activities declined further, with the lowest values observed at 11-12 months of age. A comparison between the data from this study and a those from a published German study indicates that Chinese infants exhibited peak ALP activity later and subsequent decline greater than German infants., Conclusions: A percentile curve was constructed for month-wise ALP activity in male and female infants, which could provide a reference for diagnosing diseases related to abnormal ALP activity in infants., (Copyright © 2021. Published by Elsevier Inc.)

The cellulase produced by Trichoderma sp. was characterized by investigating the adsorption and enrichment of U and the physiological response to U exposure. The effects of U exposure (0 and 400 μM) on the growth, morphological characteristics, cellulase production, U adsorption, and U enrichment capacity of the Trichoderma strain were assessed. The effects of U exposure on the basic metabolism of this fungus were also analyzed by non-targeted metabolomics. Exposure to U (400 μM) for 24 h resulted in OD 600 turbidity of 0.278, and activities of carboxymethyl cellulase (CMC), filter paper enzyme (FPA), and β-glucosidase of 12834 U·mL -1 , 9285 U·mL -1 , and 12574 U·mL -1 , respectively. The measurement of the background α and β radioactivity showed an α activity concentration of 3.35 × 10 6 Bq·kg -1 in the fungus, a β activity concentration of 6.28 × 10 5 Bq·kg -1 , and a U enrichment rate of 70.4 ± 4.5%. GC-MS metabolomics analysis identified a total of 319 metabolites (34 up-regulated and 30 down-regulated), which mainly caused the metabolic imbalance of organic acids and derivatives. The alanine, aspartate, and glutamate metabolic pathways were the most significantly enriched. Trichoderma sp. therefore has a strong ability to tolerate/accumulate U and continues to produce cellulase under U (400 μM) exposure. However, U interferes with the basic metabolism of this fungus., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The aim of this study was to reveal the mechanism underlying the toxicity of TNT (trinitrotoluene), RDX (cyclotrimethylene trinitroamine), and HMX (cyclotetramethylene tetranitramine) explosives pollution in plants. Here, the effects of exposure to these three explosives were examined on chlorophyll fluorescence, antioxidant enzyme activity, and the metabolite spectrum in alfalfa (Medicago sativa) plants. The degradation rates for TNT, RDX, and HMX by alfalfa were 26.8%, 20.4%, and 18.4%, respectively, under hydroponic conditions. TNT caused damage to the microstructure of the plant roots and inhibited photosynthesis, whereas RDX and HMX induced only minor changes. Exposure to any of the three explosives caused disturbances in the oxidase system. Non-targeted metabolomics identified a total of 6185 metabolites. TNT exposure induced the appearance of 609 differentially expressed metabolites (189 upregulated, 420 downregulated), RDX exposure induced 197 differentially expressed metabolites (155 upregulated and 42 downregulated), and HMX induced 234 differentially expressed metabolites (132 upregulated and 102 downregulated). Of these differentially expressed metabolites, lipids and lipid-like molecules were the main metabolites induced by explosives poisoning. TNT mainly caused significant changes in the alanine, aspartate, and glutamate metabolism metabolic pathways, RDX mainly caused disorders in the arginine biosynthesis metabolic pathway, and HMX disrupted the oxidative phosphorylation metabolic pathway. Taken together, the results show that exposure to TNT, RDX, and HMX leads to imbalances in plant photosynthetic characteristics and antioxidant enzyme systems, changes the basic metabolism of plants, and has significant ecotoxicity effects., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Hypericum attenuatum Choisy is a traditional Chinese herbal plant with multiple therapeutic effects. In this study, bioactivity-guided fractionation of Hypericum attenuatum Choisy extracts afforded three major flavonoids (including astragalin, guaijaverin and quercetin), which possessed α-Glucosidase inhibitory activity with IC 50 values of 33.90±0.68 μM, 17.23±0.75 μM and 31.90±0.34 μM, respectively. Circular dichroism analysis revealed that all the three compounds could interact with α-glucosidase by inducing conformational changes of the enzyme. Molecular docking results indicated that they could bind to the active site in α-glucosidase, and the binding force was driven mainly by hydrogen bond. Additionally, isobolographic analysis of the interactions between two compounds showed that all the combinations presented a synergistic α-glucosidase inhibitory effect at lower concentrations, and the combination between quercetin and guaijaverin or astragalin exhibited the best synergistic effect. This research might provide a theoretical basis for the application of Hypericum attenuatum Choisy in treating hyperglycemia., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

This experiment was conducted to evaluate the ecotoxicity of typical explosives and their mechanisms in the soil microenvironment. Here, TNT (trinitrotoluene), RDX (cyclotrimethylene trinitramine), and HMX (cyclotetramethylene tetranitramine) were used to simulate the soil pollution of single explosives and their combination. The changes in soil enzyme activity and microbial community structure and function were analyzed in soil, and the effects of explosives exposure on the soil metabolic spectrum were revealed by non-targeted metabonomics. TNT, RDX, and HMX exposure significantly inhibited soil microbial respiration and urease and dehydrogenase activities. Explosives treatment reduced the diversity and richness of the soil microbial community structure, and the microorganisms able to degrade explosives began to occupy the soil niche, with the Sphingomonadaceae, Actinobacteria, and Gammaproteobacteria showing significantly increased relative abundances. Non-targeted metabonomics analysis showed that the main soil differential metabolites under explosives stress were lipids and lipid-like molecules, organic acids and derivatives, with the phosphotransferase system (PTS) pathway the most enriched pathway. The metabolic pathways for carbohydrates, lipids, and amino acids in soil were specifically inhibited. Therefore, residues of TNT, RDX, and HMX in the soil could inhibit soil metabolic processes and change the structure of the soil microbial community., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A newly identified tardigrade species from China, Pilatobius nuominensis sp. nov., belongs to the group of species with cuticle of the dorsal and lateral caudal region with evident irregular polygonal sculpture. Nucleotide sequences of two nuclear (18S rRNA, 28S rRNA) and one mitochondrial (COI) DNA fragments of the new species are provided, which allows an independent verification of the taxonomic status of the new species. This is the first record of the genus Pilatobius in the Great Hinggan Mountains.

This study aims to reveal the biodegradation and interaction mechanism of cyclotetramethylenete-tranitramine (HMX) by a newly isolated bacteria. In this study, a bacterial strain (Bacillus aryabhattai) with high efficiency for HMX degradation was used as the test organism to analyze the changes in growth status, cell function, and mineral metabolism following exposure to different stress concentrations (0 and 5 mg L -1 ) of HMX. Non-targeted metabonomics was used to reveal the metabolic response of this strain to HMX stress. The results showed that when the HMX concentration was 5 mg L -1 , the removal rate of HMX within 24 h of inoculation with Bacillus aryabhatta was as high as 90.5%, the OD 600 turbidity was 1.024, and the BOD 5 was 225 mg L -1 . Scanning electron microscope (SEM) images showed that the morphology of bacteria was not obvious Variety, Fourier transform infrared spectroscopy (FTIR) showed that the cell surface -OH functional groups drifted, and ICP-MS showed that the cell mineral element metabolism was disturbed. Non-targeted metabonomics showed that HMX induced the differential expression of 254 metabolites (133 upregulated and 221 downregulated). The main differentially expressed metabolites during HMX stress were lipids and lipid-like molecules, and the most significantly affected metabolic pathway was purine metabolism. At the same time, the primary metabolic network of bacteria was disordered. These results confirmed that Bacillus aryabhattai has a high tolerance to HMX and can efficiently degrade HMX. The degradation mechanism involves the extracellular decomposition of HMX and transformation of the degradation products into intracellular purines, amino sugars, and nucleoside sugars that then participate in cell metabolism., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A fluorescence turn-on probe, 2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl 2,4-dinitrobenzenesulfonate (NT-SH), has been constructed for sensing of hydrogen sulfide (H 2 S). NT-SH exhibited excellent detection performance including favorable water solubility, low fluorescence background, high enhancement (45-fold), large linear response range (0-50 μM) and low detection limit (80.01 nM) for H 2 S in aqueous. In addition, the response mechanism of NT-SH for H 2 S was confirmed by the theoretical calculation and mass spectral analysis. More importantly, the imaging experiments of H 2 S in vitro and in vivo confirmed that NT-SH had low cytotoxicity, and favorable biocompatibility. In addition, it illustrated that NT-SH was able to detected exogenous H 2 S in living cells and zebrafish. These results suggested that NT-SH can be act as a potential molecular tool for detecting of H 2 S in aqueous solution, in vitro and in vivo., 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.)

Liraglutide is an analog of human glucagon-like peptide-1 which play essential roles in regulation of glycolipid metabolism. To investigate role of lactic acid bacteria (LAB) in lipid-lowering effect of liraglutide, 40 mice were divided into normal food diet (NFD), high-fat food (HFD), 10.0 mg/kg/d simvastatin-treated HFD (SIM + HFD), 200 and 400 µg/kg/d liraglutide-treated HFD (LL + HFD and HL + HFD) groups for 5 weeks. We found that liraglutide could upregulate cholesterol 7α-hydroxylase (CYP7A1) and LDL-receptor (LDLR), whereas downregulate 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Besides, liraglutide enhance abundance of lactobacillaceae in gut of hyperlipidemic mice and increase bile tolerance ability of LAB by upregulating bile salt hydrolases, and the lysate of liraglutide-sensitive LAB could also directly downregulate HMGCR, the key enzyme in cholesterol synthesis, and inhibit hepatocyte steatosis. These findings might provide new theoretical guidance for clinical application of liraglutide and research and development of antiobesity, hypolipidemic, and cholesterol-lowering drugs or functional foods., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

The purpose of this study was to reveal the accumulation and phytotoxicity mechanism of sweet potato (Ipomoea batatas L.) roots following exposure to toxic levels of uranium (U) and cadmium (Cd). We selected two accumulation-type sweet potato cultivars as experimental material. The varietal differences in U and Cd accumulation and physiological metabolism were analyzed by a hydroponic experiment. High concentrations of U and Cd inhibited the growth and development of sweet potato and damaged the microstructure of root. The roots were the main accumulating organs of U and Cd in both sweet potato. Root cell walls and vacuoles (soluble components) were the main distribution sites of U and Cd. The chemical forms of U in the two sweet potato varieties were insoluble and oxalate compounds, while Cd mainly combined with pectin and protein. U and Cd changed the normal mineral nutrition metabolism in the roots, and also significantly inhibited the photosynthetic metabolism of sweet potatoes. RNA-seq showed that the cell wall and plant hormone signal transduction pathways responded to either U or Cd toxicity in both varieties. The inorganic ion transporter and organic compound transporter in roots of both sweet potato varieties are sensitive to U and Cd toxicity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The aim of this study was to reveal the biodegradation characteristics and physiological response mechanism of a newly isolated bacterium to 2,4,6-trinitrotoluene (TNT) contamination. A Klebsiella variicola strain with high efficiency of TNT degradation was used as the test strain to analyze the changes in cell growth, morphology, and functional groups under different TNT concentrations (0, 100 mg⋅L -1 ) and the effects of TNT stress on the metabolic profile as revealed by non-targeted metabonomics. A TNT concentration of 100 mg L -1 caused a significant increase in the 5-day biochemical oxygen demand (BOD 5 ) to 950 mg L -1 , while the degradation rate of TNT reached 100% within 30 h after inoculation with Klebsiella variicola. Fourier transform infrared spectroscopy (FTIR) analysis showed changes in the characteristic peak of triamide by TNT treatment. Non-targeted metabonomics identified a total of 544 differentially produced metabolites under TNT treatment (252 upregulated and 292 downregulated), mainly lipids and lipid-like molecules. The metabolic pathways associated with amino acid biosynthesis and metabolism were the most significantly enriched pathways, and simultaneous detection showed that TNT was degraded to 4-amino-2,6-dinitrotoluene (DNT), 2-hydroxylamino-4,6-DNT, 2-amino-4,6-DNT, 2-amino-4-nitrotoluene, and 2,4-DNT. These results confirmed that Klebsiella variicola has a high tolerance to TNT and efficiently degrades it. The degradation mechanism involves TNT-induced accelerated amino acid biosynthesis, production of a protease to catalyze the TNT transformation, and the participation of the transformed TNT products in cell metabolism., 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 Ltd. All rights reserved.)

Context: Oridonin exhibits various pharmacological and physiological activities, including antioxidant, antibacterial, anti-inflammatory, pro-apoptotic, anticancer and neurological effects. However, its role in rheumatoid arthritis (RA) is yet to be revealed. Objective: We evaluated the effects of oridonin on the survival and autophagy of RA-fibroblast-like synoviocytes (FLSs). Materials and methods: RA-FLSs were treated with oridonin at serial concentrations of 0, 2, 4, 6, 8 and 10 µg/mL for 24, 48 and 72 h. Then, cell proliferation and apoptosis were measured. A GFP-LC3 plasmid was transfected into the cells to determine autophagy. Results: Oridonin suppressed RA-FLS proliferation in a dose-dependent manner. The half maximal inhibitory concentrations (IC 50 ) of oridonin at 24, 48 and 72 h were 8.28, 7.88 and 8.35 µg/mL, respectively. Treatment with oridonin for 24 h increased apoptosis by 4.1%, and increased the protein levels of Bax and cleaved caspase-3 but significantly decreased the levels of IL-1β in the culture supernatant ( p  < 0.05). In addition, 6 h of oridonin treatment significantly decreased the number of GFP-LC3 punctate dots and inhibited the protein levels of ATG5 and Beclin1 by 80.01% and 42.12%, respectively. Chloroquine (CQ) significantly reinforced the effects of oridonin on inhibition of autophagy, suppression of proliferation, and induction of apoptosis in RA-FLSs ( p  < 0.05). Conclusions: Our results indicate that treatment with oridonin in combination with CQ inhibits autophagy and cell proliferation and induces apoptosis in RA-FLSs more effectively than treatment oridonin alone. This finding indicates that oridonin is a potential therapeutic agent for RA.

Antimicrobial peptides have been attracting increasing attention for their multiple beneficial effects. In present study, a novel AMP with a molecular weight of 1875.5 Da, was identified from the genome of Lactobacillus casei HZ1. The peptide, which was named as LHH1 was comprised of 16 amino acid residues, and its α-helix content was 95.34% when dissolved in 30 mM SDS. LHH1 exhibited a broad range of antimicrobial activities against Gram-positive bacteria and fungus. It could effectively inhibit Staphylococcus aureus with a minimum inhibitory concentration of 3.5 μM and showed a low hemolytic activity. The scanning electron microscope, confocal laser scanning microscope and flow cytometry results showed that LHH1 exerted its antibacterial activity by damaging the cell membrane of Staphylococcus aureus. Meanwhile, LHH1 also exhibited anti-cancer cell activities against several cancer cells via breaking the cell membrane of MGC803, HCT116 and C666-1 cancer cells.

As a natural radionuclide, uranium (U) has obvious phytotoxicity, the purpose of this study is to unravel the response mechanism of U on photosynthetic and respiratory metabolism in plants. Therefore, 14-day-old Vicia faba seedlings were exposed to 0-25 μM U during 72 h. U effects on growth parameters, physiological parameters of plants, and potential phytotoxicity mechanism were investigated by physiological analysis, and metabolome and transcriptome data. U significantly inhibited photosynthesis and respiration of plants. In metabolome analysis, 53 metabolites related to carbohydrate metabolism were identified (13 up-regulated, 12 down-regulated). In transcriptome analysis, U significantly inhibited the expression of photoreactive electron transport chain (up: 0; down: 31), Calvin cycle (up: 0; down: 12) and photorespiration pathway genes (up: 0; down: 8). U significantly inhibited the expression of cellular energy metabolic pathways genes (e.g., glycolysis, TCA cycle, and oxidative phosphorylation pathways) (up 8, down 18). We concluded that U inhibited the expression of genes involved in the photosynthetic metabolic pathway, which caused the decrease of photosynthetic rate. Meanwhile, U inhibited the expression of the electron transport chain genes in the mitochondrial oxidative phosphorylation pathway, which leads to the abnormal energy supply of cells and the inhibition of root respiration rate., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The roles of RNA m6A modification in carcinogenesis have attracted much interest recently. However, the dysregulation of RNA m6A regulators (writers, readers, and erasers) in nasopharyngeal carcinoma (NPC) has never been reported. In this study, we showed that METTL3, one of the writers, was upregulated in NPC. Functional studies revealed that METTL3 promoted the migration and invasion of NPC cells. However, METTL3 knockdown reversed this effect and inhibited the migration, invasion and metastasis of NPC cells. METTL3 activated the luciferase activity of TOPflash (a reporter for beta-catenin/TCF signaling), and downregulation of METTL3 inhibited the expression of beta-catenin/TCF target genes vimentin and N-cadherin, which are two regulators of epithelial-mesenchymal transition. Moreover, dominant negative beta-catenin blocked the migration and invasion of NPC cells. Further mechanistic studies showed that METTL3 silencing decreased the m6A methylation and total mRNA levels of Tankyrase, a negative regulator of axin. Moreover, Tankyrase overexpression abrogated the repressive effects of METTL3 silencing on the migration of NPC cells. Collectively, our study demonstrates the oncogenic roles of METTL3 in NPC, and suggests that METTL3 might be a therapeutic target for NPC., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Palladium has attracted a growing number of attention due to its widely application and environmental toxicity. Consequently, a novel colorimetric and fluorescent turn-on probe (NT-Pd) was designed for sensing of palladium. This probe was capable of detecting palladium in aqueous solution (DMSO was less than 1%, v/v). Under this mild condition, NT-Pd displayed high selectivity and sensitivity for sensing of palladium in both colorimetric and fluorescent strategy, such as low detection limit (5.30 nM) and rapid response time (within 10 min). In addition, NT-Pd was successfully applied for imaging of exogenous palladium in living cells and zebrafishes with good biocompatibility and low toxicity, indicating this probe has satisfactory application potential to track palladium in the complicated biological 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 © 2020 Elsevier B.V. All rights reserved.)

A combined proteomic and metabonomic approach was used to investigate the metabolism of Lactococcus lactis ssp. lactis subjected to glucose stress treatment. A proteomic method was used to determine 1,427 altered proteins, including 278 proteins with increased expression and 255 proteins with decreased expression. A metabonomic approach was adopted to identify 98 altered metabolites, including 62 metabolites with increased expression and 26 metabolites with decreased expression. The integrated analysis indicated that the RNA and DNA mismatch repair process and energy metabolism were enhanced in response to high-glucose stress in L. lactis. Lactococcus lactis responded to glucose stress by up-regulating oxidoreductase activity, which acted on glycosyl bonds, hydrolase activity, and organic acid transmembrane transporter activity. This led to an improvement in the metabolic flux from glucose to pyruvate, lactate, acetate, and maltose. Down-regulation of amino acid transmembrane transporter, aminoacyl-transfer RNA ligase, hydroxymethyl-, formyl-, and related transferase activities resulted in a decrease in the nitrogen metabolism-associated metabolic pathway, which might be related to inhibition of the production of biogenic amines. Overall, we highlight the response of metabolism to glucose stress and provide potential possibilities for the reduced formation of biogenic amines in improved level of sugar in the dairy fermentation industry. Moreover, according to the demand for industrial production, sugar concentration in fermented foods should be higher, or lower, than a set value that is dependent on bacterial strain and biogenic amine yield., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor., Objectives: We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy., Methods: The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline-rich transmembrane protein 2 screening results were recorded using unified paroxysmal kinesigenic dyskinesia registration forms. Genotype-phenotype correlation analyses were conducted in patients with and without proline-rich transmembrane protein 2 mutations. High-knee exercises were applied in partial patients as a new diagnostic test to induce attacks., Results: Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of paroxysmal kinesigenic dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline-rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of paroxysmal kinesigenic dyskinesia, family history, and more forms of dyskinesia. The new high-knee-exercise test efficiently induced attacks and could assist in diagnosis., Conclusions: We propose recommendations regarding diagnostic criteria for paroxysmal kinesigenic dyskinesia based on this large clinical study of paroxysmal kinesigenic dyskinesia. The findings offered some new insights into the diagnosis and treatment of paroxysmal kinesigenic dyskinesia and might help in building standardized paroxysmal kinesigenic dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Background: Osteonecrosis of the femoral head (ONFH) is a destructive condition most commonly affecting young and middle-aged patients. The leading consequence of ONFH is often a significant articular disability. Effective joint-preserving surgical treatments are urgently needed for patients with early stage ONFH when outcomes of treatment are in general better than the advanced stage disease., Aim: To introduce a new surgery procedure called percutaneous expanded core decompression and mixed bone graft technique, which is a new way of joint-preserving surgical treatments., Methods: The clinical data of 6 patients with ONFH diagnosed and treated with the procedure called percutaneous expanded core decompression and mixed bone graft technique at The First Hospital of Qiqihar from March 2013 to August 2019 were retrospectively analyzed; the follow-up ended in December 2019., Results: There were 6 male patients with an average age of 43 years in our study. Gratifying results have been obtained from the comparison of Harris hip score, visual analogue scale, and imaging examination before and after operation., Conclusion: This new modified technique is simple, safe, and reliable. No serious perioperative complications were observed in our cases. Advantages of the single blade expandable reamer are obvious. The adjuvant substance is inexpensive and easy to obtain. Thus, this technique is an effective joint-preserving surgical treatment for patients with early stage of ONFH., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)