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Panax ginseng, a perennial medicinal plant, utilizes its dried roots and rhizomes for medicinal purposes. Currently, in China, ginseng cultivation employs two methods: under-forest and farmland planting. These methods create distinct habitats, significantly influencing the ginseng’s rhizome morphology and, consequently, its economic value. In this study, two-year-old ginsengs were transplanted into farmland (TCG), a larch forest (TLCG) and a Quercus mongolica forest (TQCG) to analyze the differences in rhizome phenotypes caused by habitat changes. The results showed that there were significant differences in light intensity and the soil’s available phosphorus and potassium contents between farmland and forest environments. The differences in habitats led to different adaptability of the ginseng’s rhizome morphology. Compared with TCG, the rhizomes of TLCG and TQCG were significantly elongated by 48.36% and 67.34%, respectively. After the rhizomes’ elongation in TLCG and TQCG, there was an increase in indole-3-acetic acid (IAA) contents and a decrease in lignin contents. By analyzing the expression of key genes, we found that, compared with TCG, the expression of key enzymes of lignin biosynthesis genes such as PgCOMT and PgCCR4 were down-regulated. The difference in ginseng’s rhizome length is related to the signal transduction pathway of auxin and gibberellin. In addition, we preliminarily screened out transcription factors PgWRKY75, PgDIV, and PgbHLH93.1, which can actively respond to habitat changes and play important roles in the elongation of ginseng rhizomes. In summary, this study elucidates the phenotypic plasticity strategy of ginseng rhizomes in response to habitat changes and delineates the regulatory mechanism behind phenotypic adaptation, offering novel insights into ginseng’s morphogenesis.

Abstract The acidification of coastal waters is distinguished from the open ocean because of much stronger synergistic effects between anthropogenic forcing and local biogeochemical processes. However, ocean acidification research is still rather limited in polar coastal oceans. Here, we present a 16 year (2002–2018) observational dataset in the Chukchi Sea during the rapid sea‐ice melting season to determine the long‐term changes in pH and aragonite saturation state (Ωarag). We found that pH and Ωarag significantly declined in the water column with average rates of −0.0095 ± 0.0027 years−1 and −0.0333 ± 0.0098 years−1, respectively, and are 4–6 times faster than those solely due to increasing atmospheric CO2. We attributed the rapid acidification to the increased dissolved inorganic carbon owing to a combination of ice melt‐induced increased atmospheric CO2 invasion and subsurface remineralization induced by a stronger surface biological production as a result of the increased inflow of the nutrient‐rich Pacific water.

Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to 2019. The treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble status. Relative to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice with low stubble height under mechanized harvesting, the timely application of nitrogen fertilizer is fundamental, coupled with moderate field drying for root-vigor preservation and tiller promotion before and after the mechanical harvesting of the main crop.

Nitrogen (N) is the primary essential nutrient for ginseng growth, and a reasonable nitrogen application strategy is vital for maintaining the stability of soil microbial functional communities. However, how microbial-mediated functional genes involved in nitrogen cycling in the ginseng rhizosphere respond to nitrogen addition is largely unknown. In this study, metagenomic technology was used to study the effects of different nitrogen additions (N0: 0, N1: 20, N2: 40 N g/m2) on the microbial community and functional nitrogen cycling genes in the rhizosphere soil of ginseng, and soil properties related to the observed changes were evaluated. The results showed that N1 significantly increased the soil nutrient content compared to N0, and the N1 ginseng yield was the highest (29.90% and 38.05% higher than of N0 and N2, respectively). N2 significantly decreased the soil NO3–N content (17.18 mg/kg lower than N0) and pH. This resulted in a decrease in the diversity of soil microorganisms, a decrease in beneficial bacteria, an increase in the number of pathogenic microorganisms, and an significant increase in the total abundance of denitrification, assimilatory nitrogen reduction, and dissimilatory nitrogen reduction genes, as well as the abundance of nxrA and napA genes (17.70% and 65.25% higher than N0, respectively), which are functional genes involved in nitrification that promote the soil nitrogen cycling process, and reduce the yield of ginseng. The results of the correlation analysis showed that pH was correlated with changes in the soil microbial community, and the contents of soil total nitrogen (TN), ammonium nitrogen (NH4+-N), and alkaline-hydrolyzed nitrogen (AHN) were the main driving factors affecting the changes in nitrogen cycling functional genes in the rhizosphere soil of ginseng. In summary, nitrogen addition affects ginseng yield through changes in soil chemistry, nitrogen cycling processes, and functional microorganisms.

Abstract Background In paddy fields, the noxious weed barnyard grass secretes 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) to interfere with rice growth. Rice is unable to synthesize DIMBOA. Rice cultivars with high or low levels of allelopathy may respond differently to DIMBOA. Results In this study, we found that low concentrations of DIMBOA (≤ 0.06 mM) promoted seedling growth in allelopathic rice PI312777, while DIMBOA (≤ 0.08 mM) had no significant influence on the nonallelopathic rice Lemont. DIMBOA treatment caused changes in the expression of a large number of glutathione S-transferase (GST) proteins, which resulting in enrichment of the glutathione metabolic pathway. This pathway facilitates plant detoxification of heterologous substances. The basal levels of GST activity in Lemont were significantly higher than those in PI312777, while GST activity in PI312777 was slightly induced by increasing DIMBOA concentrations. Overexpression of GST genes (Os09g0367700 and Os01g0949800) in these two cultivars enhanced rice resistance to DIMBOA. Conclusions Taken together, our results indicated that different rice accessions with different levels of allelopathy have variable tolerance to DIMBOA. Lemont had higher GST activity, which helped it tolerate DIMBOA, while PI312777 had lower GST activity that was more inducible. The enhancement of GST expression facilitates rice tolerance to DIMBOA toxins from barnyard grass root exudates.

Abstract Background Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. Methods This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. Results Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug–related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. Conclusions FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. Trial registration ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

Panax ginseng taproot serves as a crucial storage organ and constitutes a significant component of Chinese herbal medicine. In China, ginseng is cultivated using two primary methods: under-forest planting and farmland planting. These methods create distinct habitats that notably influence the morphology of ginseng taproots. However, the precise regulatory mechanisms governing ginseng taproot expansion remain to be fully elucidated. This study aimed to delineate the patterns of ginseng taproot expansion by examining taproots transplanted into farmland (TCG) and forest environments (TLCG and TQCG). Our findings indicate that light intensity and soil available potassium levels in TCG plots significantly exceed those in TLCG and TQCG plots. Compared with TLCG and TQCG, the taproot diameter of TCG increased by 11.54% and 27.73%, respectively. At the same time, combined with the microstructure of the transverse section of the taproot, it showed that the expansion of the TCG taproot was closely related to cell expansion. During TCG taproot expansion, there was an increase in indole-3-acetic acid (IAA) content, significant starch accumulation, and a decrease in lignin content. By analyzing the expression of key genes, we found that compared with TLCG and TQCG, the expression of genes PgTPS1 and PgALDH1 was upregulated, and the expression of genes PgHCT1, PgPAL3, PgPER3, and PgPER51 were downregulated in TCG taproot. Additionally, the transcription factors PgARF18.1 and PgbHLH42 were identified as responsive to habitat changes, playing pivotal roles in taproot expansion. In conclusion, this study provides foundational insights into the regulatory mechanisms of ginseng taproot expansion, offering significant implications for enhancing the quality and value of ginseng.

The strong CO2 sink in Arctic Ocean plays a significant role in the global carbon budget. As a high-latitude oceanic ecosystem, the features of sea surface pCO2 and air-sea CO2 flux are significantly influenced by sea ice melt; however, our understanding of pCO2 evolution during sea ice melt remains limited. In this study, we investigate the dynamics of pCO2 during the progression of sea ice melt in the western Arctic Ocean based on data from two cruises conducted in 2010 and 2012. Our findings reveal substantial spatiotemporal variability in surface pCO2 on the Chukchi Sea shelf and Canada Basin, with a boundary along the shelf breaks at depths of 250-500 m isobaths. On the Chukchi Sea shelf, strong biological consumption dominates pCO2 variability. Moreover, in Canada Basin, the pCO2 dynamics are modulated by various processes. During the active sea ice melt stage before sea ice concentration decreases to 15%, biological production through photosynthetic processes and dilution of ice melt water lead to a reduction in DIC concentration and subsequent decline in pCO2. Further, these effects are counteracted by the air-sea CO2 exchange at the sea surface which tends to increase seawater DIC and subsequently elevate surface pCO2. Compared to the pCO2 reduction resulting from biological production and dilution effects, the contribution of air-sea CO2 exchange is significantly lower. The combined effects of these factors have a significant impact on reducing pCO2 during this stage. Conversely, during the post sea ice melt stage, an increase in pCO2 resulting from high temperatures and air-sea CO2 exchange outweighs its decrease caused by biological production. Their combined effects result in a prevailing increase in sea surface pCO2. We argue that enhanced air-sea CO2 uptake under high wind speeds also contributes to the high sea surface pCO2 observed in 2012, during both active sea ice melt stage and post sea ice melt stage. The present study reports, for the first time, the carbonate dynamics and pCO2 controlling processes during the active sea ice melt stage. These findings have implications for accurate estimation of air-sea CO2 fluxes and improved modeling simulations within the Arctic Ocean.

BackgroundExamining mental health among nurses in the later stages of the COVID-19 pandemic could offer valuable information for addressing these symptoms in the long term. Therefore, the current study aimed to assess the mental health and well-being of Chinese nurses, as well as investigate the impact of psychological flexibility and night shifts on this relationship.MethodIn cross-sectional, hospital-based, multicenter study, 422 Chinese nurses were selected by multistage stratified cluster random sampling. The mental health status, psychological flexibility, and wellbeing were assessed via 12-item General Health Questionnaire (GHQ-12), Chinese version of Personalized Psychological Flexibility Index, and Chinese version of the 5-item WHO Well-Being Index, respectively. To examine the proposed theoretical model, we conducted structural equation modeling using SPSS Amos 26 version. The age, gender, night shift, psychological flexibility, mental health, and well-being data were entered into the model. Pearson correlation and chi-square were used to explore the correlation between variables.ResultsThe high night shifts, being young and low psychological flexibility significantly had a direct effect on worse mental health (night shifts: ES, 95% CI: 0.619, 0.328-0.725; age: ES, 95% CI: 0.542, 0.226-0.993; psychological flexibility: ES, 95% CI: 0.675, 0.369-1.466). The low psychological flexibility and worse mental health were able to directly effect on worse wellbeing (psychological flexibility: ES, 95% CI: 0.419, 0.757-1.519; mental health: ES, 95% CI: 0.719, 1.109-2.607). In addition, psychological flexibility through the mediation of mental health also had an indirect effect on wellbeing (ES, 95% CI: 0.269, 0.957-2.165).ConclusionsBeing young, having more night shifts and having less psychological flexibility can be related to the deterioration of mental health and well-being in nurses. Therefore, it is recommended that nurses use the shift routine program with the least focus on the night shifts. Also, interventions to teach younger nurses how to face work stress and interventions to improve the psychological flexibility of all nurses are needed.

Oceanic uptake of anthropogenic CO2 causes a decrease in seawater pH and aragonite saturation state (Ωarag), a process known as ocean acidification (OA). The western North Pacific is a hotspot for anthropogenic CO2 sinks; however, the spatiotemporal variability of pH and Ωarag and their controlling mechanisms remain unexplored. In this study, we provide high-frequency and high-precision underway measurements of sea surface pCO2 and pH to investigate the distribution and drivers of OA metrics across different hydrochemical gradients in the western North Pacific in late spring 2018, a season with the highest primary production in the year. Our results show that the surface pH reached near air-sea equilibrium in the subtropical zone but gradually increased northward across the Kuroshio Recirculation (KR) zone and peaked in the Kuroshio Extension (KE) zone. We found that sea surface temperature played the most prominent role in regulating pH, which was also counteracted by the effects of air–sea gas exchange and vertical mixing. In contrast, the distribution of Ωarag largely mirrored the pH and was governed by air–sea gas exchange and vertical mixing, the effects of which on Ωarag were enhanced by temperature. Biological activity thrived in the KE zone to increase both pH and Ωarag, which further reinforced the latitudinal pattern of pH, but weakened that of Ωarag. These findings are based on direct in situ measurements of pH and improve our understanding of the spatiotemporal variability of OA metrics in the western North Pacific region.

Abstract With the expansion of the epidemic, online multimedia teaching has become a common trend. The reasoning model of multimedia teaching evaluation is a useful tool to infer the result of teaching effects and predict the tendency. However, the ambiguity in the linguistic-valued evaluation leads to reasoning problems always in the context with uncertainty. To make the reasoning model better deal with multiple and multidimensional reasoning problems in uncertainty environment, while considering both positive evidence and negative evidence at the same time, this paper mainly focuses on a linguistic truth-valued intuitionistic fuzzy layered aggregation (LTV-IFLA) reasoning method. First, based on the layered linguistic truth-valued intuitionistic fuzzy lattice (LTV-IFL), we realize aggregating the linguistic truth-valued information through the layered average aggregation (LAA) operator presented by this paper. Furthermore, a layered weighted average aggregation (LWAA) operator is proposed to consider setting different weights to achieve personalization of the reasoning results. Finally, a multiple multidimensional reasoning model which simulates the reasoning of human language is presented to illustrate the method’s rationality and validity.

The study of marine microbial communities is crucial for comprehending the distribution patterns, adaptations to the environment, and the functioning of marine microorganisms. Despite being one of the largest biomes on Earth, the bacterioplankton communities in the Northwest Pacific Ocean (NWPO) remain understudied. In this research, we aimed to investigate the structure of the surface bacterioplankton communities in different water masses of the NWPO. We utilized metagenomic sequencing techniques and cited previous 16S rRNA data to explore the distribution patterns of bacterioplankton in different seasons. Our results revealed that Cyanobacteria, Proteobacteria, Bacteroidetes, and Actinobacteria dominated the microbial communities, accounting for over 95% of the total. During spring, we observed significant differentiation in community structure between the different water masses. For instance, Prochlorococcus and Pseudoalteromonas were primarily distributed in the nutrient-deficient subtropical countercurrent zone, while Flavobacteriaceae and Rhodobacteraceae were found in the Kuroshio-Oyashio mixing zone. During summer, the surface planktonic bacteria communities became homogenized across regions, with Cyanobacteria becoming the dominant group (68.6% to 84.9% relative abundance). The metabolic processes of the microorganisms were dominated by carbohydrate metabolism, followed by amino acid transport and metabolism. However, there was a low relative abundance of functional genes involved in carbohydrate metabolism in the Kuroshio-Oyashio mixing zone. The metagenomic data had assembled 37 metagenomic-assembled genomes (MAGs), which belong to Proteobacteria, Bacteroidetes, and Euryarchaeota. In conclusion, our findings highlight the diversity of the surface bacterioplankton community composition in the NWPO, and its distinct geographic distribution characteristics and seasonal variations.

The effects of surface defects at the sidewall of absorption and multiplication layers on the sidewall leakage current in separate-absorption-charge-multiplication Ge/Si avalanche photodiodes with a mesa structure are investigated. It is found that high-density surface defects and a strong electric field at the sidewall are the reasons for the large sidewall leakage current. In addition, the influence of the width of the guard ring on the sidewall leakage current is also studied. It is found that increasing the width of the guard ring is beneficial to the reduction of the sidewall leakage current by reducing the sidewall electric field and the reduction is not significant when the guard-ring width is greater than 2 µm.

Objective In this randomized controlled study, we aimed to determine whether non-contact infrared thermometers (NCITs) are more time-efficient and create less patient distress than mercury axillary thermometers (MATs) and infrared tympanic thermometers (ITTs). Methods Forty-five rehabilitation inpatients were randomly assigned to one of three groups (NCIT, MAT, and ITT). Time required to measure body temperature with an NCIT, MAT, and ITT was recorded. We examined associations between time required to take patients’ temperature and measuring device used. Patient distress experienced during temperature measurement using the three thermometers was recorded. Results A significantly longer average time was required to measure temperatures using the MAT (mean 43.17, standard deviation [SD] 8.39) than the ITT (mean 13.74, SD 1.63) and NCIT (mean 12.13, SD 1.18). The thermometer used influenced the time required to measure body temperature (t = 33.99). There were significant differences among groups (NCIT vs. ITT, NCIT vs. MAT, and ITT vs. MAT) regarding patient distress among the different thermometers. Most distress arose owing to needing help from others, sleep disruption, and boredom. Conclusion The NCIT has clinically relevant advantages over the ITT and MAT in measuring body temperature among rehabilitation patients, including saving nurses’ time and avoiding unnecessary patient distress. Clinical trial registration number ( http://www.chictr.org.cn ): ChiCTR1800019756.

Objective. To investigate the treatment effect of a vascular-disrupting agent, M410, using diffusion-weighted imaging in a rabbit model of hepatic VX2 tumor. Methods. 28 New Zealand white rabbit models with VX2 liver tumors were established and were randomly divided into M410 (intravenous injection of M410 at a dose of 25 mg/kg every three days) and control (intravenous injection of saline every three days) groups. Conventional and diffusion-weighted imaging (DWI) were acquired on a 3.0 T MR unit at baseline, 4 h, d 1, d 4, d 7, and d 14 posttreatment. B-value with 700 (s/mm2) was chosen during DWI examinations. Tumor volume and apparent diffusion coefficient (ADC) values of the entire tumor and solid component of the tumor at every time point were measured. Two randomly chosen rabbits from each group were sacrificed for H&E staining and CD34 immunohistochemical assessments at each time point. An independent sample t-test was used to assess differences in tumor sizes and ADC values of the entire tumor and solid component of tumors between two groups, with P

Objective: Pretreatment of biological samples is the most critical step in pharmacokinetic studies, especially pre-treatment of plasma samples. The pretreatment of biological samples in pharmacokinetic study of Traditional Chinese Medicines (TCM) is difficult due to the complexity of the ingredients. An organic solvent system ethyl acetate: acetone (10: 1) solution used for liquid-liquid extraction has been developed in this study and compared with the commonly used protein precipitation method. Methods: Rats, Beagle dogs and humans plasma samples were adopted in this study in order to demonstrate the universality of the pretreatment method. Feasibility of this pretreatment method was also verified through its application to the pharmacokinetics of rhubarb in rats. Results: According to the results of extraction recovery matrix effect, it was indicated that the liquid-liquid extraction methods with new organic solvent might be suitable for variety of structures of compounds and various types of plasma samples. The pharmacokinetic study result showed that the developed pretreatment method could successfully be used for simultaneous determination of three active compounds modin, emodin-8-O-β-D-glucopyranoside (EDG) and rhein in rat plasma with high sensitivity, accuracy, and recovery by liquid chromatography tandem mass spectrometry (LC-MS/MS). Conclusion: The pretreatment method of liquid-liquid extraction methods with new organic solvent could be successfully applied for multi-component pharmacokinetics of TCM. Keywords: Pretreatment method, Liquid-liquid extraction, Protein precipitation, LC-MS/MS, Rhubarb

The upper part of the 4th member of Paleogene Shahejie Formation in Bonan sag, Bohai Bay Basin, East China was taken as the study object. Conventional core analysis, casting and conventional thin section inspection, scanning electron microscope observation, particle size analysis and fluid inclusion analysis were carried out on cores, and the data from these analyses and tests was used to find out the evolution of diagenetic environment of the saline lacustrine basin and the main factors controlling the deep formation of high quality reservoirs. The diagenetic environment of the saline lacustrine basin experienced alkali and acid alternation. In the early alkali diagenetic environment, large amounts of carbonate cement filled the primary pores, making the reservoir porosity reduce sharply from 37.3% to 18.77%, meanwhile, keeping the primary pores from compaction, and retaining the dissolution space. In the middle-late stage of acid diagenetic environment, early carbonate cement was dissolved, resulting in rise of reservoir porosity by 10.59%, and thus the formation of the deep high quality reservoirs. The distribution of high quality deep reservoirs is controlled by the development of gypsum salt rock, source rock, fracture system and sedimentary body distribution jointly. Deeply buried high quality reservoirs in the upper part of the 4th member of the Shahejie Formation in Bonan sag are nearshore subaqueous fan-end sandstone and some fan-medium fine conglomerate buried at 3 400−4 400 m in the north steep slope. Key words: Bohai Bay Basin, Bonan sag, 4th member of Paleogene Shahejie Formation, saline lacustrine basin, high quality reservoir, formation mechanism

Background/Aims: Clinical reports on adverse reactions that result from Polygonum multiflorum (PM) and its preparations, especially regarding liver injury, have recently received widespread attention. This study aimed to investigate the mechanism of hepatotoxicity induced by different PM extracts through iTRAQ quantitative proteomics. Methods: The different PM extracts were orally administrated for 90 days to rats, and the hepatotoxicity effect was evaluated through measurement of biochemical indexes, oxidative damage indexes and hematoxylin-eosin (HE) staining. Then, the hepatotoxicity mechanism was investigated by iTRAQ quantitative proteomics. Results: The results of biochemical and histopathological analyses showed that liver injury occurred in all groups of rats given by various PM extracts, which proved all of the PM extracts could induce hepatotoxicity. The hepatotoxicity mechanism may differ between the total extract group and the other groups through the results of biochemical indicators. The iTRAQ proteomics study showed that hepatotoxicity resulting from PM was mainly related to the abnormal activity of mitochondrion function-related oxidative phosphorylation pathways. Conclusion: This iTRAQ proteomics study revealed that the hepatotoxicity induced by PM is primarily related to the oxidative phosphorylation pathways. NADH dehydrogenase family proteins and Slc16a2 could be potential biomarkers of hepatotoxicity resulting from PM.

Objective: To investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim. (Z. bungeanum oil) on active components in externally-applied traditional Chinese medicines. Methods: Five model drugs, geniposide, puerarin, ferulic acid, tetramethylpyrazine, and osthole, were chosen based on their lipophilicity and tested using in vitro transdermal permeation studies consisting of Franz diffusion cells and full thickness rat abdominal skin. Scanning electron microscopy was employed to observe the morphological changes of rat skin tissue after treatment with Z. bungeanum oil. The molecular interactions between the oil and the polar head groups in stratum corneum (SC) lipids were monitored using molecular dynamic simulation, and the SC/vehicle partition coefficients and saturation solubilities of the selected model drugs treated with and without the oil were also determined to ascertain its mechanisms of action. Results: As oil concentration increased, the log ERflow trended toward a negative linear relationship with the lipophilicity of drugs. After treatment with Z. bungeanum oil, a mild lifting up and wrinkle on the SC surface were observed, and appeared to become more pronounced as oil concentration increased. There was no significant difference between the control and the Z. bungeanum oil at different concentrations in terms of saturation solubility of GP, while saturation solubilities of the 4 other drugs gradually increased as oil concentration increased. The oxygen-containing constituents in Z. bungeanum oil, such as terpinen-4-ol and 1,8-cineole, which accounted for 57.95% of total oil, could form stable hydrogen bonds with the polar head group of ceramide 3. Conclusion: Z. bungeanum oil facilitated transdermal permeation of drugs with different lipophilicity, including the extremely hydrophilic and lipophilic drugs, whereas it exhibited greater enhancement activity for strongly hydrophilic drugs. The mechanisms of transdermal permeation enhancement by the oil could be explained with SC/vehicle partition coefficient, saturation solubility, and the interactions with SC lipids.

The liver injury induced by Polygonum multiflorum (PM) used for clinical treatment has recently received widespread attention. This study aimed to determine the hepatotoxicity of PM through pharmacokinetics studies. The extract of PM was separated to isolate the anthraquinone fraction, the tannin and polysaccharide fraction, the hydroxystilbene fraction, and the combined anthraquinone fraction. A rapid LC-MS/MS method was developed and validated to simultaneously analyze 2,3,5,4′-tetrahydroxystilbene-2-O-β-glucoside (TSG), emodin-8-O-β-D-glucopyranoside (EDG), and emodin in rat plasma, and was applied to the pharmacokinetics (PK) studies. The hepatotoxicity of different extracted parts of PM was evaluated through the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBil), direct bilirubin (DBil), and indirect bilirubin (IBil) in rat serum. The results showed that liver injury occurred in all the treated groups and that the hepatotoxicity performance of the total extract was different from other groups. The pharmacokinetic studies showed that the Cmax, Tmax, AUC, t1/2, and MRT of the major compounds of different extracted parts were significantly different in rat plasma at same dosage. Emodin-O-hex-sulfate, tetrahydroxystilbene-O-(galloyl)-hex, emodin (original and generated through EDG deglycosylation), and other free anthraquinones might be responsible for the hepatotoxicity of PM in vivo. PM extracts produced inhibitory effects on drug metabolic enzymes, include CYP3A4, CYP2C19, CYP2E1, UGT1A1, etc. And these effects may be related to its hepatotoxicity and pharmacokinetic behavior different. This information on hepatotoxicity and the pharmacokinetic comparison may be useful to understand the toxicological effects of PM.

Herbal medicine has been widely used in the treatment of various diseases; however, the adverse reactions cannot be ignored. Most previous studies have ignored the relationship between the factors of geographical areas/batches and toxicity. This study used Polygonum multiflorum (PM) as an example to analyze the relationship between the geographical areas/batches and toxicity and speculated on the hepatotoxicity-inducing components in PM based on high content screening, UHPLC-Q-TOF/MS and Progenesis QI software analysis. The results of the study show that the toxicity of PM was obviously different among the different geographical areas, and the most toxic PM was from the Sichuan province. To obtain more accurate results and to reduce the false-positive rate, two methods were used to evaluate the speculative results. It was noteworthy that emodin was not the main hepatocyte toxicity constituent of PM. The analysis methods suggested that PM toxicity may be associated with tetrahydroxystilbene-O-(galloyl)-hex and emodin-O-hex-sulfate. The toxicity of these two components requires further study.

Objective: To establish a basis for Angelica Sinensis Radix (ASR) as a dietary supplement for colorectal cancer chemoprevention, the effect of co-existent components in supercritical fluid extract (SFE) of ASR on the pharmacokinetics of Z-ligustilide after oral administration was investigated in vitro and in vivo. Methods: Incubation in gastrointestinal contents and incubation in rat liver tissue homogenates post-mitochondrial supernatant (PMS) experiments were used to study changes in the levels of Z-ligustilide in vitro. Results: Within 4 hours, the level of Z-ligustilide in SFE declined at a slower rate than in its pure form. Clearance of Z-ligustilide after administration in its pure form was significantly slower than that of SFE of ASR (CL, 0.96 ± 0.16 mL·min/kg versus 1.24 ± 0.21 mL·min/kg P

Introduction: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC), but is associated with poor chest tumor control. Here we report results of a randomized phase 3 study comparing two CCRT regimens in improving chest tumor control by low-dose paclitaxel chemoradiation for LA-NSCLC. Methods: Due to the logistics of local referral pattern, the study was designed to enroll patients with stage III LA-NSCLC who had completed 2-4 cycles of full-dose chemotherapy. One hundred thirty four were randomized to either Arm 1 (paclitaxel at 15 mg/m2, three times/wk [M, W, F] for 6 weeks, n=74), or Arm 2 (weekly paclitaxel at 45 mg/m2 for 6 weeks, n=60). Chest RT was 60-70 Gy in standard fractionation. Response rate was the primary endpoint, with recurrence-free survival (RFS) as the secondary endpoint. Results: From March 2006 to February 2013, seventy-one patients completed Arm 1 treatment, and 59 completed Arm 2 treatment. The response rate for Arm 1 was significantly higher (83.1%) than Arm 2 (54.2%) (p＝0.001). RFS was superior in Arm 1: median 14.6 months vs. 9.4 months, p=0.005, Hazard ratio (HR) 1.868 (95% CI 1.203, 2.901). Overall survival was not significantly different: median 32.6 months in Arm 1 vs. 31.3 months in Arm 2, p = 0.91, HR 0.969 (95% CI 0.552, 1.703). Toxicity was significantly lower in Arm 1 for grade 3 and 4 leucopenia/neutropenia (p

The strong CO2 sink in Arctic Ocean plays a significant role in the global carbon budget. As a high-latitude oceanic ecosystem, the features of sea surface pCO2 and air-sea CO2 flux are significantly influenced by sea ice melt; however, our understanding of pCO2 evolution during sea ice melt remains limited. In this study, we investigate the dynamics of pCO2 during the progression of sea ice melt in the western Arctic Ocean based on data from two cruises conducted in 2010 and 2012. Our findings reveal substantial spatiotemporal variability in surface pCO2 on the Chukchi Sea shelf and Canada Basin, with a boundary along the shelf breaks at depths of 250-500 m isobaths. On the Chukchi Sea shelf, strong biological consumption dominates pCO2 variability. Moreover, in Canada Basin, the pCO2 dynamics are modulated by various processes. During the active sea ice melt stage before sea ice concentration decreases to 15%, biological production through photosynthetic processes and dilution of icemeltwater lead to a reduction in DIC concentration and subsequent decline in pCO2. Further, these effects are counteracted by the air-sea CO2 exchange at the sea surface which tends to increase seawater DIC and subsequently elevate surface pCO2. Compared to the pCO2 reduction resulting from biological production and dilution effects, the contribution of air-sea CO2 exchange is significantly lower. The combined effects of these factors have a significant impact on reducing pCO2 during this stage. Conversely, during the post sea ice melt stage, an increase in pCO2 resulting from high temperatures and air-sea CO2 exchange outweighs its decrease caused by biological production. Their combined effects result in a prevailing increase in sea surface pCO2. We argue that enhanced air-sea CO2 uptake under high wind speeds also contributes to the high sea surface pCO2 observed in 2012, during both active sea ice melt stage and post sea ice melt stage. The present study reports, for the first time, the carbonate dynamics and pCO2 controlling processes during the active sea ice melt stage. These findings have implications for accurate estimation of air-sea CO2 fluxes and improved modeling simulations within the Arctic Ocean. [ABSTRACT FROM AUTHOR]