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Biochar application to soil has proven to be an excellent approach for decreasing the concentration of auto-toxic compounds and promoting plant growth in continuous-cropping fields. However, the mechanisms underlying the action pathway among biochars, auto-toxic compounds and tobacco remain unknown. In this study, we conducted an experiment tracking the incidence rate of black rot and auto-toxic compounds for a 3-year continuous-cropping tobacco pot trial in response to biochar treatment intensity compared with that of non-biochar treatment. Biochar inhibited the incidence of black rot. Using ultra-high-performance liquid chromatography–mass spectrometry (UPLC‒MS/MS), we revealed that biochar can effectively decrease the concentration of p-hydroxybenzoic acid (PHA), which is associated with the incidence rate of black rot (R2 = 0.890, p

Woojun Kim,1 Hyunjo Lee,2 Kyung Won Lee,3 Eunjin Yang,3 Seonghoon Kim3 1Department of Neurology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Department of Neurology, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of Korea; 3Department of Neurology, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Seonghoon Kim, Department of Neurology, The Catholic University of Korea, College of Medicine, Uijeongbu St. Mary’s Hospital, 271 Cheonbo-ro, Uijeongbu-si, Gyeonggi-do, Seoul, Republic of Korea, Tel +82-31-820-3114, Fax +82-31-821-3661, Email antilefty4@gmail.comPurpose: Patients with epilepsy frequently experience autonomic dysfunction, closely related to sudden unexplained death in epilepsy (SUDEP). SUDEP occurs most often at night or during sleep, and frequent nocturnal seizures are an established risk factor. This study investigated the influence of nocturnal seizures on autonomic dysfunction in epilepsy.Patients and Methods: This retrospective study enrolled frontal lobe epilepsy (FLE) patients who performed 24-hour EEG monitoring. All participants were divided into nocturnal FLE (NFLE, > 90% of seizures occurring during sleep) or diurnal FLE (DFLE) groups. EEG and ECG signals were simultaneously obtained during waking and sleep stages. EEG current density source and connectivity analysis of the autonomic network were performed. ECG was analyzed across time and frequency domains heart rate variability (HRV) analysis method was used. The obtained parameters were compared between the NFLE and DFLE groups.Results: Fifteen NFLE and 16 DFLE patients were enrolled with no significant difference in age, sex, disease duration, seizure frequency, or the number of anti-seizure medications between the two groups. During sleep, a decrease in HRV parameters and an increase of the beta-1 (13– 22 Hz) current source density power in the bilateral paracentral lobule (BA4,5,6), precuneus (BA7), and cingulate (BA31) were observed in the NFLE group compared to DFLE group. The NFLE group also showed hyperconnectivity in the central autonomic (12 edges distributed over 10 nodes), sympathetic (2 edges distributed over 3 nodes), and parasympathetic (4 edges distributed over 6 nodes) beta-1 frequency band networks during sleep. During wakefulness, central and cardiac autonomic variables were not significantly different between the NFLE and DFLE groups.Conclusion: Interictal cardiac and central autonomic dysfunction occurred simultaneously and can be attributed to the brain-heart autonomic axis. Our findings suggest that nocturnal seizures may contribute to interictal autonomic dysfunction during sleep in people with epilepsy.Keywords: nocturnal seizure, heart rate variability, central autonomic network, sleep, autonomic dysfunction

Abstract Biochar has been considered an effective approach as soil amendment for decreasing incidences of disease and regulating microbial populations in continuous-cropping soil. Although researches have extensively focused on changes of soil microbes and unbalance of nutrition in continuous-cropping soil, the relationship between soil properties and pathogens by biochar application remains poorly understood. In this study, we applied ITS ribosomal RNA gene profiling to analyze tobacco root microbiota of biochar and non-biochar treatment in a 3-year continuous-cropping tobacco field, comparing firstly planting tobacco as control. We found that biochar application decreased the relative abundance of the soil fungal pathogens (Ceratobasidium and Monosporascus), which are the prime pathogens of tobacco root rot in continuous-cropping soil. Using RDA, co-occurrence and PLS-PM approaches, we provided evidence that there was a negative correlation between fungal genera (especially for Ceratobasidium and Monosporascus) and soil polyphenol oxidase (PPO) activity (R2 incidence rate = − 0.930, R2 disease index = − 0.905, both p

Xin Jing,&ast; Yuhui Yun,&ast; Xiang Ji, Ende Yang, Pei Li Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pei Li; Ende Yang, Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China, Email yanglinglipei@163.com; endeyangfmmu@163.comBackground: Cancer development and tumor immune microenvironment remodeling are closely linked to pyroptosis and inflammasome activation. However, little information is available in single nucleotide polymorphisms (SNPs) in pyroptosis and inflammasome-related genes in patients with lung cancer. This study aims to evaluate the associations between pyroptosis-related gene (NLRP3, NLRC4, and NLRP7) polymorphisms and the risk of lung cancer.Methods: The MassARRAY platform was used to genotype six SNPs of the NLRP3, NLRC4, and NLRP7 genes in 660 lung cancer cases and 660 controls.Results: Individuals with rs35829419-A, rs385076-C, and rs775882-T alleles exhibited a higher risk of lung cancer (p < 0.01), while rs212704-T appears protective (p = 0.006). The rs35829419-AA, rs385076-TC/CC, and rs775882-CT/TT genotypes were associated with various degrees of elevated risk of lung cancer (p< 0.02), whereas rs212704-TT was associated with a reduced risk of the disease (p=0.014). Genetic models analysis showed that rs35829419, rs385076, and rs775882 was associated with an increased risk of lung cancer, while rs212704 was related to a reduced risk in all three models (p < 0.05). The four SNPs remained significant in smoker and nonsmoker subgroups (p < 0.05). However, rs35829419 was correlated with risk of adenocarcinoma and small cell lung cancer, and rs212704 was only protective for squamous cell carcinoma. The rs385076 and rs775882 were associated with all three pathological types (p < 0.01).Conclusion: Besides providing candidate markers for identification of high-risk populations and early prevention of the disease, our research also provided new insight into anti-tumor strategies targeting inflammasomes and pyroptosis.Keywords: lung cancer, single nucleotide polymorphisms, pyroptosis, inflammasome, case–control study

We provide an overview of the status of Monte-Carlo event generators for high-energy particle physics. Guided by the experimental needs and requirements, we highlight areas of active development, and opportunities for future improvements. Particular emphasis is given to physics models and algorithms that are employed across a variety of experiments. These common themes in event generator development lead to a more comprehensive understanding of physics at the highest energies and intensities, and allow models to be tested against a wealth of data that have been accumulated over the past decades. A cohesive approach to event generator development will allow these models to be further improved and systematic uncertainties to be reduced, directly contributing to future experimental success. Event generators are part of a much larger ecosystem of computational tools. They typically involve a number of unknown model parameters that must be tuned to experimental data, while maintaining the integrity of the underlying physics models. Making both these data, and the analyses with which they have been obtained accessible to future users is an essential aspect of open science and data preservation. It ensures the consistency of physics models across a variety of experiments.

Biochar and sulfur are considered useful amendments for soil cadmium (Cd) contamination remediation. However, there is still a gap in the understanding of how combined biochar and sulfur application affects Cd resistance in rice, and the role of the accumulation of iron plaque and the expression of Cd efflux transporter-related genes are still unclear in this type of treatment. In this study, we screened an effective combination of biochar and sulfur (0.75 % biochar, 60 mg/kg sulfur) that significantly reduced the Cd content of rice roots (32.9 %) and shoots (12.3 %); significantly reduced the accumulation of amino acids and their derivatives, organic acids and their derivatives and flavonoids in rice roots; and altered secondary metabolite production and release. This combined biochar and sulfur application alleviated the toxicity of Cd to rice, in which the enhancement of iron plaque (24.8 %) formation and upregulated expression of heavy metal effector genes (NRAMP3, MTP3, ZIP1) were important factors. These findings show that iron plaque and heavy metal transport genes are involved in the detoxification of rice under the combined application of biochar and sulfur, which provides useful information for the combined treatment of soil Cd pollution.

Hyun Chul Kim,1,2 Eunsol Yang,1,3 Mu Seong Ban,1 Yu Kyong Kim,4 Sung Hee Hong,5 Jina Jung,5 In-Jin Jang,1 SeungHwan Lee1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea; 3Kidney Research Institute, Seoul National University Medical Research Center, Seoul, Republic of Korea; 4Department of Clinical Pharmacology and Therapeutics, Chungbuk National University College of Medicine and Hospital, Cheongju, Republic of Korea; 5Hanmi Pharmaceutical Co., Ltd., Seoul, Republic of KoreaCorrespondence: SeungHwan Lee, Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea, Tel +82-2-2072-2343, Fax +82-2-742-9252, Email leejh413@snu.ac.krBackground: Esomeprazole, a proton pump inhibitor (PPI), is widely used to treat acid-related disorders, but it has short plasma half-life which can cause insufficient gastric acid suppression, such as nocturnal acid breakthrough. A new dual delayed-release (DR) formulation of esomeprazole (Esomezol DR), was developed to extend the duration of gastric acid suppression.Purpose: This study aimed to evaluate the pharmacokinetics (PKs) and pharmacodynamics (PDs) of esomeprazole for the DR formulation compared to a conventional enteric-coated (EC) formulation (Nexium) in healthy male subjects.Methods: Two randomized, open-label, multiple-dose, two-way crossover studies with esomeprazole 20 mg and 40 mg were conducted. Subjects received the DR formulation or the EC formulation once daily for 7 days in each period with a 7-day washout. Serial blood samples were collected up to 24 hours after the 1st dose, and 24-hour intragastric pH was continuously monitored before the 1st dose as baseline and after the 1st and the 7th dose.Results: In 20 mg and 40 mg dose groups, 38 and 44 subjects completed the study, respectively. The DR formulation exhibited the dual-release pattern of esomeprazole, resulting in more sustained plasma concentration–time profiles compared to the EC formulation. The systemic exposure of esomeprazole for the DR formulation was comparable to that for the EC formulation, showing the similar area under the plasma concentration–time curve. The 24-hour gastric acid suppression was also similar between the two formulations, while the inhibition during night-time (22:00– 06:00) showed a better tendency in the DR formulation.Conclusion: The sustained exposure of esomeprazole in the DR formulation led to well-maintained and higher acid inhibition compared to the EC formulation, especially during the night-time. These results suggest that the DR formulation can be an alternative formulation to the conventional EC formulation, expecting the potential of relieving nocturnal acid-related symptoms.Keywords: proton pump inhibitors, esomeprazole, dual delayed-release formulation, gastro-esophageal reflux disease, GERD, nocturnal acid breakthrough

IntroductionBiochar has been shown to be an effective soil amendment for promoting plant growth and improving nitrogen (N) utilization. However, the physiological and molecular mechanisms behind such stimulation remain unclear.MethodsIn this study, we investigated whether biochar-extracted liquor including 21 organic molecules enhance the nitrogen use efficiency (NUE) of rice plants using two N forms (NH4+-N and NO3--N). A hydroponic experiment was conducted, and biochar-extracted liquor (between 1 and 3% by weight) was applied to rice seedlings.ResultsThe results showed that biochar-extracted liquor significantly improved phenotypic and physiological traits of rice seedlings. Biochar-extracted liquor dramatically upregulated the expression of rice N metabolism-related genes such as OsAMT1.1, OsGS1.1, and OsGS2. Rice seedlings preferentially absorbed NH4+-N than NO3--N (p < 0.05), and the uptake of NH4+-N by rice seedlings was significantly increased by 33.60% under the treatment of biochar-extracted liquor. The results from molecular docking showed that OsAMT1.1protein can theoretically interact with 2-Acetyl-5-methylfuran, trans-2,4-Dimethylthiane, S, S-dioxide, 2,2-Diethylacetamide, and 1,2-Dimethylaziridine in the biochar-extracted liquor. These four organic compounds have similar biological function as the OsAMT1.1 protein ligand in driving NH4+-N uptakes by rice plants.DiscussionThis study highlights the importance of biochar-extracted liquor in promoting plant growth and NUE. The use of low doses of biochar-extracted liquor could be an important way to reduce N input in order to achieve the purpose of reducing fertilizer use and increasing efficiency in agricultural production.

Yuhui Yun,1,&ast; Yun Wang,2,&ast; Ende Yang,1 Xin Jing1 1Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China; 2Department of Medical Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Jing; Ende Yang, Email jingxintd2014@163.com; endeyangfmmu@163.comBackground: Cuproptosis is a novel copper-dependent cell death, and the copper level was increased in lung cancer patients. However, few studies evaluated the association between single-nucleotide polymorphisms (SNPs) in cuproptosis-related genes and lung cancer risk.Methods: Six SNPs of the SLC31A1, FDX1 and ATP7B genes were genotyped in a case–control cohort including 650 lung cancer cases and 650 controls using the MassARRAY platform.Results: The minor alleles of SLC31A1-rs10981694 and FDX1-rs10488764 were associated with an increased risk of lung cancer (rs10981694: OR=1.455, 95% CI: 1.201– 1.763, p< 0.001; rs10488764: OR=1.483, 95% CI: 1.244– 1.768, p< 0.001). In contrast, the minor alleles of rs9535826 and rs9535828 in ATP7B were related to a decreased risk of the disease (rs9535826: OR=0.714, 95% CI: 0.608– 0.838 p< 0.001; rs9535828: OR=0.679, 95% CI: 0.579– 0.796, p< 0.001). The frequencies of rs10981694-TG/GG and rs10488764-GA/AA genotypes were significantly higher in lung cancer cases than that in controls, making them risk genotypes for the disease (p < 0.001); while the rs9535826-TG/GG and rs9535828-GA/AA genotypes were protective genotypes and associated with a reduced risk of the disease (p< 0.001). Genetic model evaluation revealed that SLC31A1-rs10981694 and FDX1-rs10488764 were associated with a growing risk of lung cancer in dominant, recessive and log-additive models (p< 0.001). Moreover, rs9535826 and rs9535828 in ATP7B were related to a declining risk of the disease in three genetic models (p< 0.001). In addition, stratification analysis showed that FDX1-rs10488764 was risk variant for lung cancer in both smokers and nonsmokers, and was associated with risk of each pathological type of lung cancer (p< 0.008).Conclusion: The results shed new light on the correlation between cuproptosis-related genes and risk of lung cancer.Keywords: lung cancer, single-nucleotide polymorphisms, SNPs, solute carrier family 31 member 1, SLC31A1, ferredoxin 1, FDX1, ATPase copper transporting beta, ATP7B

Objective: To investigate the effect of retaining the vessels around the orbicularis oculi muscle on reducing local swelling after blepharoplasty. Methods: A total of 309 patients undergoing blepharoplasty (total incision) were observed and randomly assigned to three groups; (A) conventional operation; (B) preservation of deep vessels; (C) preservation of anterior vessels of orbicularis oculi muscle. The groups were compared based on intraoperative blood loss, operation time, swelling, satisfaction, and complications. Results: Among the 309 patients, 39 were lost to follow‐up. c Additionally, A had the shortest operation time, followed by C with slightly longer duration. On the 7th day, 15th day, and 1 month after surgery, both B and C demonstrated significantly lower levels of swelling compared to A. Moreover, patient satisfaction was higher in B and C than in A. Conclusion: Retaining either superficial or deep veins of the orbicularis oculi muscle can effectively reduce short‐term postoperative swelling. However, when retaining the superficial central group of this muscle during surgery, it is crucial to strictly control the amount of surrounding tissue around vessels. [ABSTRACT FROM AUTHOR]

Biochar is a potential amendment for the remediation of Cd-contaminated soils. Although the immobilization effect of biochar on soil Cd has been studied under indoor laboratory conditions, the effect of biochar on rice Cd uptake and soil Cd fractions under field conditions is still poorly understood. Here, the Cd content of the different organs of rice and the Cd fractions in soil were characterized for three years after the application of different amounts of biochar (0, 7.5, 15, 30 t ha−1, and 3 t ha−1 year−1). The Cd content of brown rice, husk, leaf, stem and sheath, and root under biochar treatment could be maximally reduced by up to 26.25%, 20.16%, 20.74%, 33.2%, and 26.89%, respectively. Biochar altered the Cd fractions in soil, including the decrease in exchangeable Cd content and the increase in Fe-Mn oxide bound Cd and organic bound Cd. The concentration factor of Cd uptake by rice was reduced by 32% under biochar application, while biochar had little influence on the transfer factor and distribution factor. The immobilization effect of biochar on soil Cd lasted for at least three years, but the trend of Cd immobilization efficiency over time for different amounts of biochar treatment was different. The Risk Assessment Code (RAC) of Cd in soil with biochar amendment could be reduced to a medium risk level from a high risk level. Redundancy analysis (RDA) revealed that changes in soil pH and Fe-Mn oxide bound Cd content caused by biochar application contributed most to the reduction in the Cd content of rice organs. These findings would enhance our understanding of the immobilization effect of biochar on Cd in paddy soil under field conditions.

Eunsol Yang, Hyounggyoon Yoo, In-Jin Jang, Kyung-Sang Yu, SeungHwan Lee Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of KoreaCorrespondence: SeungHwan LeeDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of KoreaTel +82-2-2072-2343Fax +82-2-742-9252Email leejh413@snu.ac.krPurpose: A fixed-dose combination (FDC) of gemigliptin/rosuvastatin 50/20 mg as a monolayer tablet has been used to treat patients with both type 2 diabetes mellitus and dyslipidemia. To improve the stability of the FDC, a new FDC formulation as a bilayer tablet was developed. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of the FDC of gemigliptin/rosuvastatin 50/20 mg between the newly developed bilayer tablet and the approved monolayer tablet in healthy subjects.Materials and Methods: A randomized, open-label, single-dose, two-treatment, two-way crossover study was conducted. Subjects received a single dose of the FDC of gemigliptin/rosuvastatin 50/20 mg as the bilayer tablet or the monolayer tablet in each period with a 7-day washout. For PK and PD analyses, serial blood samples were collected up to 72 hours after dosing to determine plasma concentrations of gemigliptin, its active metabolite LC15-0636 and rosuvastatin, and plasma dipeptidyl peptidase-4 (DPP-4) activity. PK and PD parameters were calculated using non-compartmental methods and compared between the two formulations.Results: A total of 48 healthy subjects were randomized, and 45 subjects completed the study. The concentration–time profiles of gemigliptin, LC15-0636 and rosuvastatin were comparable between the two formulations. All geometric mean ratios (90% confidence intervals) of the bilayer tablet to the monolayer tablet for maximum plasma concentration and area under concentration–time curve from 0 to last measurable time point of the three compounds fulfilled the bioequivalence criteria of 0.80– 1.25. Likewise, area under plasma DPP-4 activity inhibition from baseline-time curve from 0 to last measurable time point and maximum inhibition of plasma DPP-4 activity were similar between the two formulations.Conclusion: The FDC of gemigliptin/rosuvastatin 50/20 mg as the bilayer tablet showed equivalent PK and PD properties with the FDC of gemigliptin/rosuvastatin 50/20 mg as the monolayer tablet in healthy subjects. These results suggest that the newly developed bilayer tablet can become an alternative formulation to the commercially available monolayer tablet.Keywords: DPP-4 inhibitor, statin, type 2 diabetes, dyslipidemia, bioequivalence

The integrity of the plasma membrane is critical to cell function and survival. Cells have developed multiple mechanisms to repair damaged plasma membranes. A key process during plasma membrane repair is to limit the size of the damage, which is facilitated by the presence of tetraspanin-enriched rings surrounding damage sites. Here, we identify phosphatidylserineenriched rings surrounding damaged sites of the plasma membrane, resembling tetraspanin-enriched rings. Importantly, the formation of both the phosphatidylserine- and tetraspanin-enriched rings requires phosphatidylserine and its transfer proteins ORP5 and ORP9. Interestingly, ORP9, but not ORP5, is recruited to the damage sites, suggesting cells acquire phosphatidylserine from multiple sources upon plasma membrane damage. We further demonstrate that ORP9 contributes to efficient plasma membrane repair. Our results thus unveil a role for phosphatidylserine and its transfer proteins in facilitating the formation of tetraspanin-enriched macrodomains and plasma membrane repair. [ABSTRACT FROM AUTHOR]

Micanorm-based logics with a weak form of associativity are introduced and their completeness results are addressed. More concretely, first the basic wat-uninorm logic WAtBUL and its axiomatic extensions are introduced as [0, t]- continuous wat-uninorm analogues of the logics based the [0, 1)-continuous uninorms. Next algebraic structures characterizing the logics are introduced along with algebraic completeness results. Third, wat-uninorms are introduced as uninorms with weak t-associativity instead of associativity and associated properties are discussed. Finally, by virtue of Yang–style construction, it is verified that the logics based on wat-uninorms are complete on unit real interval [0, 1], i.e., so called standard complete. [ABSTRACT FROM AUTHOR]