Genome-wide identification and expression analysis of the PP2C gene family in Apocynum venetum and Apocynum hendersonii.

BACKGROUND: Protein phosphatase class 2 C (PP2C) is the largest protein phosphatase family in plants. Members of the PP2C gene family are involved in a variety of physiological pathways in plants, including the abscisic acid signalling pathway, the regulation of plant growth and development, etc., and are capable of responding to a wide range of biotic and abiotic stresses, and play an important role in plant growth, development, and response to stress. Apocynum is a perennial persistent herb, divided into Apocynum venetum and Apocynum hendersonii. It mainly grows in saline soil, deserts and other harsh environments, and is widely used in saline soil improvement, ecological restoration, textiles and medicine. A. hendersonii was found to be more tolerant to adverse conditions. The main purpose of this study was to investigate the PP2C gene family and its expression pattern under salt stress and to identify important candidate genes related to salt tolerance. RESULTS: In this study, 68 AvPP2C genes and 68 AhPP2C genes were identified from the genomes of A. venetum and A. hendersonii, respectively. They were classified into 13 subgroups based on their phylogenetic relationships and were further analyzed for their subcellular locations, gene structures, conserved structural domains, and cis-acting elements. The results of qRT-PCR analyses of seven AvPP2C genes and seven AhPP2C genes proved that they differed significantly in gene expression under salt stress. It has been observed that the PP2C genes in A. venetum and A. hendersonii exhibit different expression patterns. Specifically, AvPP2C2, 6, 24, 27, 41 and AhPP2C2, 6, 24, 27, 42 have shown significant differences in expression under salt stress. This indicates that these genes may play a crucial role in the salt tolerance mechanism of A. venetum and A. hendersonii. CONCLUSIONS: In this study, we conducted a genome-wide analysis of the AvPP2C and AhPP2C gene families in Apocynum, which provided a reference for further understanding the functional characteristics of these genes.

Effectiveness of APG and Honey Gauze in Pressure Injury of Elderly: A Randomized Control Trial.

This study was designed to evaluate the efficiency of the combination of autologous platelet-rich plasma gel (APG) and Manuka honey gauze in the treatment of Stages 3-4 pressure injury of older adults. Patients were divided into four groups: Manuka honey gauze and APG (M + A), Manuka honey gauze (M), APG (A), and a control group (C). Different treatments were given, then wound bed coverage with granulation tissue, wound size reduction, and Pressure Ulcer Scale for Healing (PUSH) score were examined. Paraffin-embedded sections of wound tissues were analyzed and wound swab cultures were assessed. Kruskal-Wallis test and Mann-Whitney U test were performed in statistical analysis at a 5% significance level. A total of 42 patients were accepted. Significant increase of wound bed coverage with granulation tissue (51.24%, P = .004, Kruskal-Wallis test) and decrease of PUSH score (-5) were observed in the M + A group at the end of the observation (P = .032, Mann-Whitney U test). The hematoxylin-eosin staining of wound tissues showed that typical squamous epithelium was seen in wound bed of patient in M + A group. Manuka honey gauze and APG were proved to be superior treatments for pressure injury of old patient. Increase of granulation tissue coverage, reduction of PUSH score, and improved growth of epithelium were observed in M + A group. There was no side-effect, and the treatment would not cause infection.

Transcriptome analysis unveils the mechanisms of lipid metabolism response to grayanotoxin I stress in Spodoptera litura.

Background: Spodoptera litura (tobacco caterpillar, S. litura) is a pest of great economic importance due to being a polyphagous and world-distributed agricultural pest. However, agricultural practices involving chemical pesticides have caused resistance, resurgence, and residue problems, highlighting the need for new, environmentally friendly methods to control the spread of S. litura. Aim: This study aimed to investigate the gut poisoning of grayanotoxin I, an active compound found in Pieris japonica, on S. litura, and to explore the underlying mechanisms of these effects. Methods: S. litura was cultivated in a laboratory setting, and their survival rate, growth and development, and pupation time were recorded after grayanotoxin I treatment. RNA-Seq was utilized to screen for differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to determine the functions of these DEGs. ELISA was employed to analyze the levels of lipase, 3-hydroxyacyl-CoA dehydrogenase (HOAD), and acetyl-CoA carboxylase (ACC). Hematoxylin and Eosin (H & E) staining was used to detect the development of the fat body. Results: Grayanotoxin I treatment significantly suppressed the survival rate, growth and development, and pupation of S. litura. RNA-Seq analysis revealed 285 DEGs after grayanotoxin I exposure, with over 16 genes related to lipid metabolism. These 285 DEGs were enriched in the categories of cuticle development, larvae longevity, fat digestion and absorption. Grayanotoxin I treatment also inhibited the levels of FFA, lipase, and HOAD in the hemolymph of S. litura. Conclusion: The results of this study demonstrated that grayanotoxin I inhibited the growth and development of S. litura. The mechanisms might, at least partly, be related to the interference of lipid synthesis, lipolysis, and fat body development. These findings provide valuable insights into a new, environmentally-friendly plant-derived insecticide, grayanotoxin I, to control the spread of S. litura.

Comprehensive Analysis of WUSCEL-Related Homeobox Gene Family in Ramie (Boehmeria nivea) Indicates Its Potential Role in Adventitious Root Development.

A WUSCHEL-related homeobox (WOX) gene family has been implicated in promoting vegetative organs to embryonic transition and maintaining plant embryonic stem cell identity. Using genome-wide analysis, we identified 17 candidates, WOX genes in ramie (Boehmeria nivea). The genes (BnWOX) showed highly conserved homeodomain regions typical of WOX. Based on phylogenetic analysis, they were classified into three distinct groups: modern, intermediate, and ancient clades. The genes displayed 65% and 35% collinearities with their Arabidopsis thaliana and Oryza sativa ortholog, respectively, and exhibited similar motifs, suggesting similar functions. Furthermore, four segmental duplications (BnWOX10/14, BnWOX13A/13B, BnWOX9A/9B, and BnWOX6A/Maker00021031) and a tandem-duplicated pair (BnWOX5/7) among the putative ramie WOX genes were obtained, suggesting that whole-genome duplication (WGD) played a role in WOX gene expansion. Expression profiling analysis of the genes in the bud, leaf, stem, and root of the stem cuttings revealed higher expression levels of BnWOX10 and BnWOX14 in the stem and root and lower in the leaf consistent with the qRT-PCR analysis, suggesting their direct roles in ramie root formation. Analysis of the rooting characteristics and expression in the stem cuttings of sixty-seven different ramie genetic resources showed a possible involvement of BnWOX14 in the adventitious rooting of ramie. Thus, this study provides valuable information on ramie WOX genes and lays the foundation for further research.

The chain mediating roles of anxiety and depression in the relationship between the effects of the COVID-19 pandemic and procrastination in adolescents: a longitudinal study.

BACKGROUND: The relationship between the Coronavirus Disease 2019 (COVID-19) pandemic, which is a traumatic event for adolescents, and procrastination is not clear. Mental health may play an important role in this relationship; however, the underlying mechanisms remain unknown. This study aimed to construct chain mediation models to examine whether anxiety and depression symptoms mediate the effects of the COVID-19 pandemic on procrastination in adolescents. METHODS: A convenience sample of 12 middle and high schools in Harbin, China, with four follow-up online surveys was conducted during the COVID-19 pandemic. A total of 4,156 Chinese adolescents were enrolled in this study, of whom ages 11-18 (Mean = 13.55; SD = 1.18), 50.75% were male, and 93.24% were middle school students. Descriptive demographic analysis and Pearson's correlation analysis of the effects of the COVID-19 pandemic (T1), anxiety(T2), depression (T3), and procrastination (T4) were performed in SPSS 22.0. Chain mediation analysis performed with Mplus 8.3. RESULTS: The effects of the COVID-19 pandemic, anxiety symptoms, depression symptoms, and procrastination were positively correlated (P < 0.01). The effects of the COVID-19 pandemic have a direct link on adolescent procrastination (effect = 0.156; SE = 0.031; 95%CI: 0.092, 0.214), and have three indirect paths on procrastination: the independent mediating role of anxiety symptoms was 29.01% (effect = 0.047; SE = 0.012; 95%CI: 0.024, 0.072), the independent mediating role of depression symptoms was 29.01% (effect = 0.047; SE = 0.010; 95%CI: 0.030, 0.068), as well as the completely chain mediating role of anxiety and depression symptoms was 15.43% (effect = 0.025; SE = 0.005; 95%CI: 0.017, 0.036). CONCLUSIONS: Our results suggest that anxiety and depressive symptoms are part of a causal chain between the effects of the COVID-19 pandemic and procrastination among Chinese adolescents. To effectively reduce their procrastination, attention should be paid to the emotional distress caused to adolescents by major events such as the COVID-19 epidemic. All data were taken from self-reported measures and one city in China, which may bias the results and limit their generalizability.

Trajectories and influencing factors in adolescent procrastination behavior throughout the COVID-19 pandemic: a four-wave prospective longitudinal study.

Background: Despite the growing attention given to adolescent behavior problems, little is known about the trajectories and factors that have influenced adolescent procrastination during the COVID-19 pandemic. This study monitors changes in procrastination behavior among Chinese adolescents during the pandemic and identifies vulnerable groups. Methods: A four-wave study using a representative sample of 11-to 18-year-olds in China was conducted, with baseline data collected in June 2020 (n = 4,156; 49% girls) and follow-ups in December 2020 (n = 3,392; 50% girls), August 2021 (n = 2,380; 48% girls), and October 2021 (n = 1,485; 49% girls). Procrastination behavior was assessed using the General Procrastination Scale. Latent growth curve models, latent growth mixture modes, and multivariate logistic regression models were used to describe the trajectory of procrastination and identify predictors of deterioration. Results: The proportion and overall trends of adolescent procrastination increased with the pandemic. Higher parental over-protection was a contributing factor to the higher baseline levels leading to the faster growth of adolescent procrastination. The model identified three distinct trajectories of low-increasing [including 2,057 participants (49.5%)], moderate-stable [including 1,879 participants (45.2%)], and high-decreasing procrastination [including 220 participants (5.3%)]. More daily leisure screen-time, lower frequency of exercise weekly, and dissatisfaction with distance learning were the top three risk factors for moderate-stable and high-decreasing procrastination compared to low-increasing procrastination. Adolescents with mothers with a higher level of education were more liable to be high-decreasing procrastination than moderate-stable procrastination. Conclusion: The proportion and overall trends of adolescent procrastination increased with the pandemic. The categories of procrastination among adolescents during that time period were probed. Also, the study further clarified the risk factors for severe and moderate procrastination relative to no procrastination. Thus, effective procrastination prevention and intervention strategies need to be implemented to support adolescents, particularly those at risk.

YF343, A Novel Histone Deacetylase Inhibitor, Combined with CQ to Inhibit- Autophagy, Contributes to Increased Apoptosis in Triple- Negative Breast Cancer.

BACKGROUND: Compounds that target tumor epigenetic events are likely to constitute a prominent strategy for anticancer treatment. Histone deacetylase inhibitors (HDACis) have been developed as prospective candidates in anticancer drug development, and currently, many of them are under clinical investigation. We assessed the anticancer efficacy of a now hydroxamate-based HDACi, YF-343, in triple-negative breast cancer development and studied its potential mechanisms. METHODS: YF-343 was estimated as a novel HDACi by the HDACi drug screening kit. The biological effects of YF-343 in a panel of breast cancer cell lines were analyzed by Western blot and flow cytometry. YF-343 exhibited notable cytotoxicity, promoted apoptosis, and induced cell cycle arrest. Furthermore, it also induced autophagy, which plays a pro-survival role in breast cancer cells. RESULTS: The combination of YF-343 with an autophagy inhibitor chloroquine (CQ) significantly suppressed breast tumor progression as compared to the YF-343 treatment alone both in vitro and in vivo. Mechanistically, the molecular mechanism of YF-343 on autophagy was elucidated by gene chip expression profiles, qPCR analysis, luciferase reporter gene assay, chromatin immunoprecipitation assays, immunohistochemical analysis, and other methods. E2F7, a transcription factor, promoted the expression of ATG2A via binding to the ATG2A promoter region and then induced autophagy in triple-negative breast cancer cells treated with YF-343. CONCLUSION: Our studies have illustrated the mechanisms for potential action of YF-343 on tumor growth in breast cancer models with pro-survival autophagy. The combination therapy of YF-343 and CQ maybe a promising strategy for breast cancer therapy.

Effects of Modified Baizhu Shaoyao San on Postoperative Diarrhea in Colorectal Cancer Patients: A Single-Blind, Randomized Controlled Trial.

INTRODUCTION: Postoperative gastrointestinal tract dysfunction is considered a common complication affecting patients undergoing intestinal surgery. This research aims to provide evidence to assess the efficacy and safety of Baizhu Shaoyao San (BSS) or modified BSS in treating postoperative diarrhea of colorectal cancer patients. METHODS: Eighty patients with colorectal cancer were randomized within 2 weeks after surgery to receive either modified BSS or Loperamide combined with the respective dummy. The curative effect was evaluated with the traditional Chinese medicine (TCM) syndrome score. Determination of motilin and gastrin in plasma was conducted utilizing ELISA. RESULTS: Compared with Loperamide therapy, the efficacy of modified BSS was statistically significant, the TCM syndrome score decreased, and the total effective rate increased. Levels of motilin and gastrin in plasma decreased. CONCLUSION: The curative effect and safety of modified BSS were statistically significant.

A Nitrite Excipient Database: A Useful Tool to Support N-Nitrosamine Risk Assessments for Drug Products.

N-Nitrosamine risk assessment and control have become an integral part of pharmaceutical drug product development and quality evaluation. Initial reports of nitrosamine contamination were linked with the drug substance and its manufacturing process. Subsequently, the drug product and aspects of the formulation process have shown to be relevant. Regarding specific formulation contributions to nitrosamine content in a product, one risk lies in possible interactions between nitrosating agents, derived from nitrite in excipients, and vulnerable amines, either present as moieties of the active molecule or as impurities / degradants. However, the limited validated information on nitrite levels in excipients available until now, has been an obstacle for scientists to assess the risk of nitrosamine formation in pharmaceutical products. This has driven the creation of a database to store and share such validated information. The database, maintained by Lhasa Limited, constitutes a central platform to hold the data donated by the pharmaceutical company members on the nitrite concentrations in common excipients measured with validated analytical procedures. The goal of this data sharing initiative is to provide a common framework to contextualize and estimate the risk posed by presence of nitrites to contribute to the formation of nitrosamines in drug products. The major findings from the database analyses are: (1) average nitrite content and batch to batch variance differ among excipients, (2) for solid dosage forms, the nitrite contribution is dominated by the highest formula % excipients, e.g., the fillers (diluents), which are typically used in larger proportion, and are characterized by low nitrite levels and low variability, leading to an average value of 1 µg/g nitrite in a typical formulation, (3) substantial differences in average nitrite content in batches from different excipient vendors potentially reflecting differences in source materials or processing methods for excipient manufacturing. That final point suggests that future selection of raw materials or processing by excipient manufacturers may help reduce nitrite levels in finished drug product formulations, and thus the overall risk of nitrosamine formation in cases where the product contains vulnerable amines.

Effect of Ramie on the Production Performance of Laying Hens, and the Quality, Nutrient Composition, Antioxidation of the Eggs.

Ramie (Boehmeria nivea), which is rich in protein, fatty acid, vitamins and minerals, has become a potential alternative feed resource for poultry, and has attracted more and more attentions in nutrition research. The objective of this study is to evaluate the effect of dietary ramie at different concentrations on the production performance of the hens, and the quality, nutrient composition, and antioxidation of the eggs. A total of 432 34-week-old Lohmann commercial laying hens were divided into four groups, that were fed with corn-soybean meal-based control diet, control mixed with ramie at concentrations of 3, 6, or 9% separately for 8 weeks. Results showed that dietary ramie did not affect production performance. And egg yolk color gradually deepened as the inclusion levels of ramie increased. Ramie at tested concentration could significantly reduce the content of malondialdehyde (MDA) (p = 0.002) and 3% ramie supplementation significantly increased total antioxidative capacity (T-AOC) concentrations in egg yolk compared to the control group (p = 0.033). In addition, dietary supplementation with 6% ramie significantly reduced total cholesterol (T-CHO) content (p < 0.05) compared with controls. For egg nutrient composition, compared with the control group, the addition of 6% ramie significantly increased (p < 0.05) total omega-3 polyunsaturated fatty acids (n-3PUFA) and phenylalanine (Phe) in yolk. In conclusion, dietary inclusion of 6% ramie was most effective in improving the color, antioxidative capability, and reducing T-CHO contents of the egg yolks without any negative impacts on the production performance of the hens.

Association of the Combined Effects between Insulin-Like Growth Factor-1 Gene Polymorphisms and Negative Life Events with Major Depressive Disorder among Chinese population in the Context of Oxidative Stress.

Background: Oxidative stress may be increased in a number of psychiatric disorders, including major depressive disorder (MDD). MDD has been shown to be related to insulin-like growth factor-1 (IGF-1) as well as to negative life events; exploring the interaction of IGF-1 polymorphisms and negative life events on the risk of MDD is needed. The aim of this study was to analyze the single and combined effects of IGF-1 polymorphisms (rs972936 and rs978458) and negative life events with MDD among Chinese population. Methods: 420 MDD patients (according to DSM-V) and 420 age- and gender-matched control subjects were recruited in a case-control study. Negative life events were assessed using standard rating scales. IGF-1 rs972936 and rs978458 were identified by sequencing. The chi-square (χ 2) tests were performed to explore the association of negative life events and IGF-1 polymorphisms with MDD. Results: Our results found that the negative life events were associated with the risk of MDD (P < 0.001; OR = 3.28, 95% CI: 2.19-4.85). The genotypes of IGF-1 were associated with the risk of MDD (P < 0.001); carrying the IGF-1 rs972936 C allele (OR = 1.53, 95% CI: 1.26-1.85) and rs978458 T allele (OR = 1.92, 95% CI: 1.58-2.34) had a higher risk of MDD. The combined effects between IGF-1 rs978458 and negative life events were associated with the risk of MDD (P < 0.05; OR = 2.94, 95% CI: 1.23-7.03), but IGF-1 rs972936 was not associated (P > 0.05). Conclusions: Based on the oxidative stress hypothesis, we confirm that carrying IGF-1 rs972936 C allele and rs978458 T allele have a higher risk of MDD and the combined effects between IGF-1 rs978458 and negative life events were associated with the risk of MDD among Chinese population.

An Intercompany Perspective on Compatibility and In-use Stability Studies to Enable Administration Of Biopharmaceutical Drug Products.

In-use stability and compatibility studies are often used in biotherapeutic development to assess stability and compatibility of biologic drugs with diluents and/or administration components at relevant conditions for the target route of administration (commonly intravenous, subcutaneous or intramuscular), to assure that patient safety and product efficacy are maintained during clinical use. To gain an understanding of current industry approaches for in-use stability and compatibility studies, the Formulation Workstream of the BioPhorum Development Group (BPDG), an industry-wide consortium, conducted an inter-company collaboration exercise, which included five bench-marking surveys around in-use stability and compatibility studies of biologic drugs. The results of this industry collaboration provide insights into the practicalities of these studies and how they are being used to support administration of biologics from early clinical programs to marketed products. The surveys queried topics including regulatory strategies and feedback; clinical in-use formulation, patient and site considerations; clinical blinding, masking and placebo approaches; study setup, execution and reporting; and clinical in-use stability and compatibility testing to provide a comprehensive picture of the range of common industry practices. This paper discusses the survey results and presents various approaches which can be used to guide the strategy and design of an in-use stability and compatibility program based on clinical and biomolecule needs.

Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/reperfusion-induced acute kidney injury via mitochondrial dysfunction.

Kidney tubular epithelial cells are high energy-consuming epithelial cells that depend mainly on fatty acid oxidation for an energy supply. AMP-activated protein kinase (AMPK) is a key regulator of energy production in most cells, but the function of AMPK in tubular epithelial cells in acute kidney disease is unclear. Here, we found a rapid decrease in Thr172-AMPKα phosphorylation after ischemia/reperfusion in both in vivo and in vitro models. Mice with kidney tubular epithelial cell-specific AMPKα deletion exhibited exacerbated kidney impairment and apoptosis of tubular epithelial cells after ischemia/reperfusion. AMPKα deficiency was accompanied by the accumulation of lipid droplets in the kidney tubules and the elevation of ceramides and free fatty acid levels following ischemia/reperfusion injury. Mechanistically, ischemia/reperfusion triggered ceramide production and activated protein phosphatase PP2A, which dephosphorylated Thr172-AMPKα. Decreased AMPK activity repressed serine/threonine kinase ULK1-mediated autophagy and impeded clearance of the dysfunctional mitochondria. Targeting the PP2A-AMPK axis by the allosteric AMPK activator C24 restored fatty acid oxidation and reduced tubular cell apoptosis during ischemia/reperfusion-induced injury, by antagonizing PP2A dephosphorylation and promoting the mitophagy process. Thus, our study reveals that AMPKα plays an important role in protecting against tubular epithelial cell injury in ischemia/reperfusion-induced acute kidney injury. Hence, activation of AMPK could be a potential therapeutic strategy for acute kidney injury treatment.

Application of silanized melamine sponges in matrix purification for rapid multi-residue analysis of veterinary drugs in eggs by UPLC-MS/MS.

Fast and convenient matrix purification is an important prerequisite for high-throughput analysis of drug multiresidues in food. In this study, a silanized melamine sponge was prepared and first applied in the rapid determination of multiclass veterinary drugs in eggs by ultrahigh-performance liquid chromatography-tandem mass spectrometry. Within five seconds, fast, convenient and efficient matrix separation could be achieved through simple soaking and squeezing. Compared to other matrix adsorbents, the developed material demonstrated equivalent or better purification performance. Good validation results were obtained in terms of drug recoveries (61.5%~97.0%, relative standard deviation (RSD) ≤ 10.8%), and linearities (R2 ≥ 0.999), as well as low limits of quantitation (0.3 ~ 10.9 µg·kg-1) and detection (0.1 ~ 3.8 µg·kg-1). By analyzing 52 egg samples, high concentrations of ofloxacin, trimethoprim, metronidazole, and dimetridazole were found at 542.9, 121.2, 66.1 and 58.0 µg·kg-1, respectively. The silanized melamine sponge has shown its great potential for rapid analysis of multiclass residues in food safety.

Rhodomeroterpene alleviates macrophage infiltration and the inflammatory response in renal tissue to improve acute kidney injury.

Inflammation is broadly recognized as an important factor in the pathogenesis of acute kidney injury (AKI), but pharmacological approaches to alleviate inflammation in AKI have not been proved successful in clinical trials. Macrophage infiltration into renal tissue promotes inflammatory responses that contribute to the pathogenesis of AKI. Suppression of renal tissue inflammatory responses is postulated to improve renal injury of patients and animals. Rhodomeroterpene (RMT) is a novel meroterpenoid isolated from the Rhododendron genus that was shown to exert anti-inflammatory action in vivo or in vitro in this study. We investigated the treatment effects of RMT on LPS-induced sepsis and two different AKI models. The results showed that pretreatment with RMT (30 mg kg-1  d-1 , ip, for 3 days) significantly inhibited acute inflammatory responses in LPS-induced septic mice. In both renal ischemia-reperfusion injury (I/R) and sepsis-induced AKI models, RMT (30 mg kg-1  d-1 , ip, for 3 days) ameliorated renal function and injury and alleviated inflammation by reducing the infiltration of immune cells, including macrophages and neutrophils. Furthermore, our study demonstrated that RMT inhibits inflammatory responses in macrophages. The anti-inflammatory effects of RMT may be due to the inactivation of the IKK/NF-κB and PI3K/PDK1/Akt inflammatory signaling pathways in macrophages. Collectively, our findings indicate that RMT ameliorates renal injury and alleviates the renal inflammatory state in different AKI models, suggesting that RMT may be a potential agent for the treatment of AKI.

Evidence of the moderating role of hair cortisol and hair cortisone in the relationship between work stress and depression symptoms among Chinese fishermen.

BACKGROUND: Stress plays an important role in the pathogenesis of depression through functional changes to the hypothalamic-pituitary-adrenal (HPA) axis, a key output of which is the stress hormone cortisol. But the precise relationship between HPA axis activity and depression remains unclear, in part because mostly cortisol measurement only provides reflect acute or short-term fluctuations. In this study, hair cortisol and its metabolite cortisone were measured in a prospective, pre and post follow-up study of working stress and depressive symptoms in Chinese fishermen. We evaluated HPA activity, work stress, and depression symptoms before and after fishing to determine whether cortisol and cortisone in hair can moderate the work stress and depression symptoms of Chinese fishermen. METHODS: Hair cortisol, hair cortisone, work stress, and depression were measured in Chinese fishermen (n=229; age 16-65) before and after 1-3 months at sea. A week after the fishermen returned, they provided 2-4 cm hair segments closest to the scalp. We measured hair cortisol and hair cortisone using high-performance liquid chromatography-tandem mass spectrometry. RESULTS: The work stress and hair cortisol of fishermen before fishing were significantly higher than those after fishing, while hair cortisone was lower. There was no significant difference in depressive symptoms. Fishermen with low hair cortisol or high hair cortisone were more likely to show depressive symptoms after experiencing stress, and were less likely to show depressive symptoms when faced with lower levels of work stress, consistent with the differential susceptibility model. LIMITATIONS: The assumption of an average hair growth of 1 cm/month may cause time overlap between pre- and post-fishing, and time error between the hormone data and questionnaire collection. The present study evaluated only two observation points. The use of self-report scales may affect interpretability of the results. Finally, the study used a limited sample of marine fishermen working out of a single location in Hainan province, China. CONCLUSIONS: Hair cortisol and hair cortisone appear to have a moderating role in the relationship between work stress and depressive symptoms among fishermen, which fits with the differential susceptibility model of depression. However, their mechanisms of moderation are not the same, which may reflect the complexity of physiological indicators.

Zebrafish Minichromosome Maintenance Protein 5 Gene Regulates the Development and Migration of Facial Motor Neurons via Fibroblast Growth Factor Signaling.

Minichromosome maintenance protein 5 (MCM5), a member of the microchromosomal maintenance protein family, plays an important role in the initiation and extension of DNA replication. However, its role in neural development in zebrafish remains unclear. Here, we used morpholino (MO) and CRISPR/Cas9 to knock down mcm5 and investigated the developmental features of facial motor neurons (FMNs) in the hindbrain of zebrafish. We found that knockdown of mcm5 using mcm5 MO resulted in a small head, small eyes, and a blurred midbrain-hindbrain boundary, while MO injection of mcm5 led to decrease in FMNs and their migration disorder. However, the mutant of mcm5 only resulted in the migration defect of FMNs rather than quantity change. We further investigated the underlying mechanism of mcm5 in the development of hindbrain using in situ hybridization (ISH) and fgfr1a mRNA co-injected with mcm5 MO. Results from ISH showed that the fibroblast growth factor (FGF) signaling pathway was changed when the MCM5 function was lost, with the decrease in fgfr1a and the increase in fgf8, while that of pea3 had opposite trend. FMN development defects were rescued by fgfr1a mRNA co-injected with mcm5 MO. Our results demonstrated that FGF signaling pathway is required for FMN development in zebrafish. Specifically, mcm5 regulates FMN development during zebrafish growing.

Analysis of biopharmaceutical formulations by Time Domain Nuclear Magnetic Resonance (TD-NMR) spectroscopy: A potential method for detection of counterfeit biologic pharmaceuticals.

1H Time-Domain Nuclear Magnetic Resonance (TD-NMR) is used to characterize solutions of antibodies that simulate biologic pharmaceutical formulations. The results from these measurements are compared with those from solutions in which the concentration or identity of the antibody has been altered. TD-NMR is shown to be very sensitive to differences in the amount of antibody in solution, with the ability to detect variations in as low as 2 mg/mL. It is therefore capable, by comparison with data from known formulations, of determining whether a particular sample is likely to be of an authentic biologic formulation. This method expands on the previous use of HPLC, UV/VIS, Near-IR and High-Resolution NMR to detect adulterated pharmaceutical materials. While the sensitivity of the method is high, it is a fingerprinting methodology, illustrating differences but not elucidating their origin. The extracted relaxation times reflect the combined effect of all solutes (antibody, buffer components, etc.) on the solvent (water).

Effects of Dietary Ramie Powder at Various Levels on the Production Performance, Serum Biochemical Indices, Antioxidative Capacity, and Intestinal Development of Laying Hens.

The purpose of this study was to investigate the effects of ramie (0, 3, 6, and 9%) included in diets on production performance, antioxidative capacity, serum biochemical indices, and intestinal development of laying hens. A total of 432 Lohmann commercial laying hens were randomly allotted to one of four dietary treatments and fed for 6 weeks. The results showed that the inclusion of ramie had no negative effects on laying performance, and increased (quadratic, P < 0.05) the laying rate with the highest value in the 6% ramie group. However, ramie content in the diet up to 9% reduced the apparent metabolic energy, dry matter, and organic matter apparent digestibility of laying hens compared with those in the 3% ramie group. The content of high-density lipoprotein (HDL-C) in serum was increased (P < 0.05), but the activity of aspartate aminotransferase (AST) was decreased (P < 0.05) by dietary ramie supplementation. As the dietary ramie level increased, the activity of serum glutathione peroxidase (GSH-Px) was increased quadratically (P < 0.05). Compared with control, 3% ramie group significantly increased (P < 0.01) liver total superoxide dismutase (SOD) activity. Meanwhile, the addition of 3∼6% ramie powder increased (P < 0.05) villus height of jejunum and villus height/crypt depth (V/C) of ileum, which reflected the intestinal promotional effect of ramie powder. In conclusion, ramie in a diet of less than 9% might protect the liver and improve the antioxidative capacity with no detrimental impacts on the laying hens. Moreover, it could promote the intestinal mucosal structure and have a positive impact on the intestine health of the laying hens.

Meroterpenoids with diverse structures and anti-inflammatory activities from Rhododendron anthopogonoides.

Eight pairs of meroterpenoid enantiomers and four achiral meroterpenoids were isolated from Rhododendron anthopogonoides Maxim. Seventeen of them, named (+)-/(-)-anthoponoids A-G, (+)-daurichromene D, and anthoponoids H and I, are undescribed compounds with structural diversity. Their structures were characterized herein by a combined application of spectroscopic techniques, X-ray crystallographic analysis, ECD calculation, and the modified Mosher's method. (+)-/(-)-Anthoponoid A and anthoponoid I are the first Rhododendron meroterpenoids found to possess a hexahydroxanthene motif and a diterpene unit, respectively. Some isolates were identified as NF-κB pathway inhibitors, and (+)-anthoponoid E, (-)-anthoponoid G, and anthoponoid H showed suppressive effects on LPS-induced inflammatory responses in RAW 264.7 macrophages.