Physiological Effects of Oxidative Stress Caused by Saxitoxin in the Nematode Caenorhabditis elegans.

Saxitoxin (STX) causes high toxicity by blocking voltage-gated sodium channels, and it poses a major threat to marine ecosystems and human health worldwide. Our work evaluated the neurotoxicity and chronic toxicology of STX to Caenorhabditis elegans by an analysis of lifespan, brood size, growth ability, reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels, and the overexpression of green fluorescent protein (GFP). After exposure to a series of concentrations of STX for 24 h, worms showed paralysis symptoms and fully recovered within 6 h; less than 5% of worms died at the highest concentration of 1000 ng/mL for first larval stage (L1) worms and 10,000 ng/mL for fourth larval stage (L4) worms. Declines in lifespan, productivity, and body size of C. elegans were observed under the stress of 1, 10, and 100 ng/mL STX, and the lifespan was shorter than that in controls. With STX exposure, the productivity declined by 32-49%; the body size, including body length and body area, declined by 13-18% and 25-27%, respectively. The levels of ROS exhibited a gradual increase over time, accompanied by a positive concentration effect of STX resulting in 1.14-1.86 times higher levels compared to the control group in L4 worms. Conversely, no statistically significant differences were observed between L1 worms. Finally, after exposure to STX for 48 h, ATP levels and GFP expression in C. elegans showed a significant dose-dependent increase. Our study reports the first evidence that STX is not lethal but imposes substantial oxidative stress on C. elegans, with a dose-responsive relationship. Our results indicated that C. elegans is an ideal model to further study the mechanisms underlying the fitness of organisms under the stress caused by paralytic shellfish toxins including STX.

The role of mitogen-activated protein kinase signaling pathway in endometriosis.

AIM: Endometriosis is an estrogen-dependent chronic inflammatory condition which causes pain, infertility, and predisposition for ovarian cancer. Endometriosis generates a unique microenvironment for survivability of endometriotic lesions which includes cell proliferation, differentiation, migration, and apoptosis. For these cellular activities, cascading activations of intracellular kinases are needed. Many kinase signaling pathways, IKKß/NK-κB pathway, PI3K/AKT/mTOR, and the mitogen-activated protein kinase (MAPK) pathways (ERK1/2, p38, and JNK), are activated in endometriosis. In this review, we focus on the role of MAPK pathways in endometriosis. METHODS: To identify the role of MAP Kinase signaling pathway in endometriosis we searched the Pubmed database using the search terms in various combinations "endometriosis," "endometrium," "ovary," "MAPK pathway," "ERK pathway," "p38 pathway," "JNK pathway," "estrogen," and "progesterone." RESULTS: According to the current literature, MAPK signaling pathway has various roles in generating microenvironment and survival of endometriosis. Abnormal MAPK activation in migration, implantation, growth, invasion into the pelvic structures, proliferation, and apoptosis leads to the form of endometriosis and to worsen the condition in patients with endometriosis. CONCLUSION: To further investigations on the effective and long-term endometriosis treatment, MAPK signaling pathways may be targeted. Molecular mechanism of MAPK signaling pathway in endometriosis should be more deeply understood and clinical trials should be more commonly performed for possible new endometriosis treatments to improve fertility and rescue endometriosis irreversibly.

NaCl improves reproduction by enhancing starch accumulation in the ovules of the euhalophyte Suaeda salsa.

BACKGROUND: Halophytes show optimal reproduction under high-salinity conditions. However, the role of NaCl in reproduction and its possible mechanisms in the euhalophyte Suaeda salsa remain to be elucidated. RESULTS: We performed transcript profiling of S. salsa flowers and measured starch accumulation in ovules, sugar contents in flowers, and photosynthetic parameters in the leaves of plants supplied with 0 and 200 mM NaCl. Starch accumulation in ovules, sugar contents in flowers and ovules, and net photosynthetic rate and photochemical efficiency in leaves were significantly higher in NaCl-treated plants vs. the control. We identified 14,348 differentially expressed genes in flowers of NaCl-treated vs. control plants. Many of these genes were predicted to be associated with photosynthesis, carbon utilization, and sugar and starch metabolism. These genes are crucial for maintaining photosystem structure, regulating electron transport, and improving photosynthetic efficiency in NaCl-treated plants. In addition, genes encoding fructokinase and sucrose phosphate synthase were upregulated in flowers of NaCl-treated plants. CONCLUSIONS: The higher starch and sugar contents in the ovules and flowers of S. salsa in response to NaCl treatment are likely due to the upregulation of genes involved in photosynthesis and carbohydrate metabolism, which increase photosynthetic efficiency and accumulation of photosynthetic products under these conditions.

A novel mathematics model of covid-19 with fractional derivative. Stability and numerical analysis.

a mathematical model depicting the spread of covid-19 epidemic and implementation of population covid-19 intervention in Italy. The model has 8 components leading to system of 8 ordinary differential equations. In this paper, we investigate the model using the concept of fractional differential operator. A numerical method based on the Lagrange polynomial was used to solve the system equations depicting the spread of COVID-19. A detailed investigation of stability including reproductive number using the next generation matrix, and the Lyapunov were presented in detail. Numerical simulations are depicted for various fractional orders.

[Toxicological characteristics of plant growth regulators and their impact on male reproductive health].

Plant growth regulators (PGRs) have similar physiological and biological effects to those of plant hormones, and therefore are used widely in agroforestry. The residues of PGRs in agricultural products are seriously detrimental to human health because they have been found with hepatotoxicity, nephrotoxicity, genotoxicity, neurotoxicity, even carcinogenicity and teratogenicity. Furthermore, PGRs are suspected to disrupt the function of human and animal reproductive systems. This paper presents an overview on various toxicities of PGRs on human and animal reproductive health and their underlying mechanisms, aiming to arouse people's attention to PGR residues in food and environment and reduce PGR-induced damage to the male reproductive system and to human health as well.

Effects of a New Benzimidazole Derivative on Generative Function of Female Rats.

The effects of a new thietanylbenzimidazole derivative (K-134) on estrous cycles, conception processes, and sexual behavior of female rats were studied. Two-week oral treatment with K-134 in doses of 5 and 50 mg/kg shortened the estrus phase and prolonged proestrus. Changes in sexual behavior were presented by activation of receptive sexual motivations without affecting proceptive motivations. The pregnancy and fertility indexes in experimental females after mating with intact males increased and pre- and postimplantation embryonic death decreased.

Effect of Myrtus communis L. Plant Extract as a Milk Supplement on the Performance, Selected Blood Parameters and Immune Response of Holstein Calves.

This research aimed to understand the effects of adding myrtle plant extract obtained from its leaves (MPEL) and roots (MPER) to the milk fed to suckling female Holstein calves, focusing on performance, reproduction, selected blood parameters and immune response. The 50 Holstein female calves, one week of age, were divided into five groups: one group received no plant extract (Control), while the others were supplemented with myrtle plant extracts at doses of 25 mL/day leaf extract (MPEL-25), 25 mL/day root extract (MPER-25), 50 mL/day leaf extract (MPEL-50) and 50 mL/day root extract (MPER-50) for each calf in each treatment group. The extracts were given along with the milk to the experimental groups for 60 days, and for an additional 12 days post-weaning. The results reveal that the feed consumption and live weights increased significantly. Significantly higher leukocyte counts were observed in the 50 mL/head × day myrtle groups, and a higher IgG concentration was also noted in the MPER-50 group compared to the other groups. The serum non-esterified fatty acid (NEFA) concentration significantly decreased in the MPEL-50 and MPER-50 groups, whereas the betahyrdoxy butyric acid (BHBA) concentration increased and the serum glucose concentration significantly decreased with myrtle supplementation. In conclusion, it was determined that the performance, immune system and negative energy balance compensation of female Holstein calves were positively affected by administering extracts obtained from the leaves and roots of the Myrtus communis L. plant at dose levels of 25 and 50 mL/head × day for 72 days, without causing any side effects.

Rapid determination of germanium in lignite coal and coal-related solid byproducts by graphite furnace digestion inductively coupled plasma emission spectroscopy.

This study developed a rapid and efficient graphite furnace digestion combined with inductively coupled plasma emission spectrometry (ICP-OES) method, enabling precise quantification of germanium (Ge) in coal and various coal-derived metallurgical byproducts across a broad concentration level (∼ppm-n%). The graphite furnace digestion conditions were examined intensively as a function of the acid amounts of HNO3 and HF (5-10 mL), temperature (80-180 °C), time (1-5 h), and acid drive methods (H3BO3 neutralization versus heating). Coal references including SARM 19, SARM 20, NIST SRM 1632e, and fly ash standard NIST SRM 2689 were tested. The optimum recovery of germanium was obtained when the HNO3 dosage, HF dosage, solid sample mass, temperature, and duration time were 10 mL, 5 mL, 0.1 g, 80 °C and 1 h. Agreement of 95.15-96.54 % between the measured and certified value was obtained under the optimum conditions. The spiked recovery was 103.23-103.54 %, indicating the matrix-analytes interactions were negligible. Boric acid neutralization reduced the recovery rates to 47.2-49.3 % and was not be appropriate for driving HF. The optimal spectral line for determining Ge is at a wavelength of 265.117 nm, at which the limit of detect and the limit of quantification were 0.46 µg L-1 and 1.53 µg L-1, respectively. The applicability of the method was validated by quantifying Ge in Ge-rich lignite, fly ashes (FA), and chlorinated distillation residue (CR) samples. The concentration of Ge in coals was 44.75-225.41 µg g-1, the content in FA was 0.68%-2.3 %, and the content in CR was 0.18 %, with the uncertainty of the method obtained being less than 0.5 %. X-ray fluorescence spectrometer (XRF) was used to verify the results. The difference between XRF data and ICP-OES data was less than 5 %, confirming the accuracy and reproductivity of the analytical method.

Iron reproductive toxicity of marine rotifer sibling species: Adaptation to temperate and tropical habitats.

Iron (Fe), a trace metal in coastal waters has increased significantly due to anthropogenic activities, however, few studies have examined its toxicity to marine organism reproduction and associated mechanisms. We employed two marine rotifers, the temperate Brachionus plicatilis, and tropical B. rotundiformis to investigate the toxicity of iron (FeSO4•7H2O) and its deleterious effects on reproductive features in females (sexual fecundity, abnormal resting eggs, and swimming speed) and males (lifespan, swimming speed, and spermatozoa quality) under lethal and sub-lethal exposure. The 24 h median lethal concentration (LC50) of iron was determined as 0.9 and 1.7 µg/mL per ng of dry weight for B. plicatilis and B. rotundiformis, respectively. During sub-lethal iron (20-75 µg/mL) exposure, higher iron (≥ 20 µg/mL for B. plicatilis and ≥ 45 µg/mL for B. rotundiformis) induced rotifer sexual toxicity especially in normal resting egg development and production. These were supported by the data of male shorter lifespan, poor sperm vitality, and rotifer behavioral changes as the iron concentration increased. Iron effects on swimming behavior, slower males and faster females, should reduce male/female encounter rates associated with inactive fertilized egg (resting egg) production. Two rotifer species exhibited different iron-response patterns in genetic and enzymatic activities including iron homeostasis-maintaining related Fe-S protein, and oxidative/antioxidant related lipid peroxidation product (MDA), superoxidase dismutase/SOD, catalase/CAT, and cytochrome P450 under acute iron exposure. Antioxidant activities were vulnerable in B. plicatilis but kept activities in B. rotundiformis, which may attribute to their temperate and tropical habitat adaptations.

Healthy Long-Lived Human Beings-Working on Life Stages to Break the Limitation of Human Lifespans.

The human lifespan has been increasing but will soon reach a plateau. A new direction based on the principal law of lifespan (PLOSP) may enable the human lifespan to be extremely healthy and long by the proper manipulation of the well-defined growing stages of the lifespan. The lifespan of creatures on earth from a single cell to animals can be elongated at different life stages including prenatal development, body growth, reproductivity, and aging. Each life stage has its own specific physiological and metabolic characteristics. Each life stage can be lengthened by either slowing its processes or continuously maintaining the activities of its function. Unfortunately, the current biomedical research on the extension of lifespans has mainly focused on the aging stage. Recognizing and clearly defining the periods of transition and the boundaries of life stages are essential for achieving the goal of long-lived healthy humans based on the PLOSP. The biomedical measures and pharmacological treatments for the extension of lifespans is life-stage-specific. The PLOSP can be tested with modified studies on longevity with a variety of technologies such as castration and ovariectomy. Sex differences in biological functions and the sequential order of the life stages requires different approaches for females and males.

Epigenetic Effect of Maternal Methyl-Group Donor Intake on Offspring's Health and Disease.

Maternal exposure to some dietary and environmental factors during embryonic development can affect offspring's phenotype and, furthermore, the risk of developing diseases later in life. One potential mechanism responsible for this early programming may be the modification of the epigenome, such as DNA methylation. Methyl-group donors are essential for DNA methylation and are shown to have an important role in fetal development and later health. The main goal of the present review is to summarize the available literature data on the epigenetic effect (DNA methylation) of maternal methyl-group donor availability on reproductivity, perinatal outcome, and later health of the offspring. In our literature search, we found evidence for the association between alterations in DNA methylation patterns caused by different maternal methyl-group donor (folate, choline, methionine, betaine) intake and reproductivity, birth weight, neural tube defect, congenital heart defect, cleft lip and palate, brain development, and the development of obesity and associated non-communicable diseases in later life. We can conclude that maternal methyl-group donor availability could affect offspring's health via alterations in DNA methylation and may be a major link between early environmental exposure and the development of diseases in the offspring. However, still, further studies are necessary to confirm the associations and causal relationships.

Comparison of three TaqMan real-time reverse transcription-PCR assays in detecting SARS-CoV-2.

Quick and accurate detection of SARS-CoV-2 is critical for COVID-19 control. Dozens of real-time reverse transcription PCR (qRT-PCR) assays have been developed to meet the urgent need of COVID-19 control. However, methodological comparisons among the developed qRT-PCR assays are limited. In the present study, we evaluated the sensitivity, specificity, amplification efficiency, and linear detection ranges of three qRT-PCR assays, including the assays developed by our group (IPBCAMS), and the assays recommended by WHO and China CDC (CCDC). The three qRT-PCR assays exhibited similar sensitivities, with the limit of detection (LoD) at about 10 copies per reaction (except the ORF 1b gene assay in CCDC assays with a LoD at about 100 copies per reaction). No cross reaction with other respiratory viruses were observed in all of the three qRT-PCR assays. Wide linear detection ranges from 106 to 101 copies per reaction and acceptable reproducibility were obtained. By using 25 clinical specimens, the N gene assay of IPBCAMS assays and CCDC assays performed better (with detection rates of 92 % and 100 %, respectively) than that of the WHO assays (with a detection rate of 60 %), and the ORF 1b gene assay in IPBCAMS assays performed better (with a detection rate of 64 %) than those of the WHO assays and the CCDC assays (with detection rates of 48 % and 20 %, respectively). In conclusion, the N gene assays of CCDC assays and IPBCAMS assays and the ORF 1b gene assay of IPBCAMS assays were recommended for qRT-PCR screening of SARS-CoV-2.

Casein kinase 1G2 suppresses necroptosis-promoted testis aging by inhibiting receptor-interacting kinase 3.

Casein kinases are a large family of intracellular serine/threonine kinases that control a variety of cellular signaling functions. Here we report that a member of casein kinase 1 family, casein kinase 1G2, CSNK1G2, binds and inhibits the activation of receptor-interacting kinase 3, RIPK3, thereby attenuating RIPK3-mediated necroptosis. The binding of CSNK1G2 to RIPK3 is triggered by auto-phosphorylation at serine 211/threonine 215 sites in its C-terminal domain. CSNK1G2-knockout mice showed significantly enhanced necroptosis response and premature aging of their testis, a phenotype that was rescued by either double knockout of the Ripk3 gene or feeding the animal with a RIPK1 kinase inhibitor-containing diet. Moreover, CSNK1G2 is also co-expressed with RIPK3 in human testis, and the necroptosis activation marker phospho-MLKL was observed in the testis of old (>80) but not young men, indicating that the testis-aging program carried out by the RIPK3-mediated and CSNK1G2-attenuated necroptosis is evolutionarily conserved between mice and men.

Effects of pesticide exposure on reproductivity of male groundnut farmers in Kyauk Kan village, Nyaung-U, Mandalay region, Myanmar.

INTRODUCTION: Kyauk Kan village of Nyaung-U, Mandalay region, Myanmar is one of the most famous groundnut-growing zones and has been exposed to pesticides. METHODS: This study design provided evaluation of within-person changes in the season across growing and nongrowing periods. A cross-sectional study was performed to identify health problems related to organophosphate pesticide (OP) exposure, to explore the protected use of this pesticide among 400 participants in the community by face-to-face interviews, and to determine the reproductive effects of OP exposure by using biomarkers of 100 male groundnut farmers aged 18-49 years. RESULTS: The mean age of the participants was 37.5±9.45 years. Analysis revealed statistically significant differences in seminal parameters (P<0.05 for pH, viscosity, motility, morphology, and sperm count) and in a reproductive hormonal assay (P<0.05 in follicle-stimulating hormone and testosterone) between the growing and nongrowing periods. Blood-cholinesterase levels of plasma cholinesterase in the growing period were significantly higher than those in the nongrowing period (P<0.05). CONCLUSION: Our results suggest that chronic exposure related to OP dose may reduce potential male reproductivity.

Ovarian stem cells: From basic to clinical applications.

The field of reproductive biology has undergone significant developments in the last decade. The notion that there is a fixed reserve pool of oocytes before birth was established by Zuckerman in 1951. However, in 2004, an article published in nature challenged this central dogma of mammalian reproductive biology. Tilly's group reported the existence of ovarian germline stem cells (GSCs) in postnatal ovaries of mice and suggested that the bone marrow could be an extragonadal source of ovarian GSCs. These findings were strongly criticized; however, several independent groups have since successfully isolated and characterized ovarian GSCs in postnatal mice. The ovarian GSCs are located in the ovarian surface epithelium and express markers of undifferentiated GSCs. When transplanted into mouse ovaries, mouse ovarian GSCs could differentiate and produce embryos and offspring. Similarly, in a recent study, ovarian GSCs were found to be present in the ovaries of women of reproductive age. Conversely, there is increasing evidence that stem cells responsible for maintaining a healthy state in normal tissue may be a source of some cancers, including ovarian cancer. Cancer stem cells (CSCs) have been found in many tissues, including ovaries. Some researchers have suggested that ovarian cancer may be a result of the transformation and dysfunction of ovarian GSCs with self-renewal properties. Drug resistant and metastasis-generating CSCs are responsible for many important problems affecting ovarian cancer patients. Therefore, the identification of CSCs will provide opportunities for the development of new therapeutic strategies for treatments for infertility and ovarian cancer. In this article, we summarize the current understanding of ovarian GSCs in adult mammals, and we also discuss whether there is a relationship between GSCs and CSCs.

Anhydrobiosis in Pratylenchus penetrans.

Anhydrobiotic survival of Pratylenchus penetrans was compared in several soil moisture regimes. Bodies of anhydrobiotic nematodes were coiled. In slow-dried soils, Vineland silt loam (VSL) and Fox loamy sand (FLS), 70 and 58% of the total P. penetrans populations were anhydrobiotic when soil moistures reached ca. 3% and water potential 15 kPa or greater. Coiling began at a much lower water potential in FLS than in VSL. In fast-dried soils, only 31 and 22% of the P. penetrans populations in the same two soil types had entered the anhydrobiotic state at comparable moistures. In the above soils, 76-96% of the P. penetrans were alive immediately after entering the anhydrobiotic state. In slow-dried VSL, some nematodes (1%) survived 770 days. In the other soils, all anhydrobiotic nematodes were dead after 438 days. Anhydrobiosis increased the ability of nematodes to survive subzero temperatures, but it did not increase their ability to survive temperatures above 40 C. Infectivity and reproductivity of rehydrated P. penetrans were not affected by anhydrobiosis.