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Di-(2-ethylhexyl) phthalate (DEHP) is a male reproductive toxicant. This research is aimed at investigating the effect of pubertal DEHP exposure on testicular endoplasmic reticulum (ER) stress and germ cell apoptosis. Five-week-old male mice were orally administered with DEHP (0, 0.5, 50, or 500 mg/kg/day) for 35 days. Testis weight and sperm count were reduced in mice exposed to 500 mg/kg/day DEHP. The number of seminiferous tubules in stages VII-VIII, mature seminiferous tubules, was reduced and the number of seminiferous tubules in stages IX-XII, immature seminiferous tubules, was elevated in mice treated with 500 mg/kg/day DEHP. Numerous apoptotic germ cells were observed in mouse seminiferous tubules exposed to 50 and 500 mg/kg/day DEHP. Moreover, cleaved caspase-3 was elevated in mouse testes exposed to 500 mg/kg/day DEHP. In addition, Bcl-2 was reduced and Bax/Bcl-2 was elevated in mouse testes exposed to 500 mg/kg/day DEHP. Additional experiment showed that GRP78, an ER molecular chaperone, was downregulated in mouse testes exposed to 500 mg/kg/day DEHP. Testicular p-IRE-1α, p-JNK, and CHOP, three markers of ER stress, were upregulated in mice exposed to 500 mg/kg/day DEHP. These results suggest that pubertal exposure to high doses of DEHP induces germ cell apoptosis partially through initiating ER stress in testes.

Persistent tapetal cell1 (PTC1) plays a curial role in pollen development, and is thought to function as a transcriptional activator in rice. However, the molecular mechanism of PTC1 in regulating pollen development and its cis-elements are not well understood. We identified a novel weak male sterility mutant (ms92) which exhibited expanded tapetum and shrink pollen grains. Map-based cloning and allelic analysis suggested that the male sterility of ms92 was caused by a DNA fragment substitution in the promoter of PTC1. The decreased expression of MS92/PTC1 in ms92 and cis-element analysis indicated that the substituted sequence contained several potential binding cis-element of negative feedback. MS92/PTC1 was specifically expressed in tapetum and microspores at the young microspore stage, and its protein was localized in nucleus. We further found that MS92/PTC1 functions as a transcription activator by recognizing H3K4me3. Transcriptomic analysis revealed that a number of genes involved in tapetum degeneration and pollen wall formation were down-regulated in ms92, which are the potential targets of MS92/PTC1. The substitution fragment in MS92/PTC1 promoter was essential for pollen development, and we provided a novel mutant for further identifying the cis-elements in promoter and the molecular network of MS92/PTC1.

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case‐control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53‐2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04‐1.85) (heterogeneity‐P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2‐deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.

The larvae of hymenopteran Symphyta are eruciform, with several pairs of abdominal prolegs in addition to three pairs of thoracic legs. However, it is still controversial whether these abdominal prolegs are serially homologous with the thoracic legs. Here we studied the embryonic development of the larval appendages of the large rose sawfly Arge pagana (Panzer, 1798) to investigate the origin and homologous relationship of the abdominal prolegs of Argidae. The results show that paired swellings (proleg primordia) on the embryonic abdomen are not aligned with the thoracic legs, but are slightly closer to the midventral line. During the embryonic development, the thoracic leg primordia are differentiated into six segments, while the abdominal appendage primordia remain unsegmented and eventually develop into conical prolegs. The abdominal prolegs of larval A. pagana are likely developed from the endites of the primary embryonic appendages, and the paired anal prolegs arise from the eleventh abdominal segment. Therefore, the abdominal prolegs of sawfly larvae are very likely to have an appendicular nature but not the main axes of appendages.

This study aimed to extract polysaccharides from pumpkin, characterize the structures of four of them, and evaluate their in vitro antioxidant and hypoglycemic activities. Additionally, an animal model of type 2 diabetes mellitus (T2DM) was established and used to determine their hypoglycemic and hypolipidemic effects in vivo, and the underlying mechanisms related to the regulation of gut microbiota. Water-extracted crude pumpkin polysaccharides (W-CPPs), water extraction and alcohol precipitation crude pumpkin polysaccharides (WA-CPPs), deproteinized pumpkin polysaccharides (DPPs), and refined pumpkin polysaccharides (RPPs) were sequentially extracted and purified from pumpkin powder by hot water extraction, water extraction, and alcohol precipitation, deproteinization and DEAE-52 cellulose gel column, respectively. The extraction and purification methods had significant influence on the extraction yield, physicochemical properties, and in vitro antioxidant and hypoglycemic activities. W-CCP and RPPs had a significant positive free radical-scavenging capacities and inhibitory activities on α-glucosidase and α-amylase. RPP-3 not only inhibited the uptake of glucose in Caco-2 monolayer but also promoted the excretion of glucose, while RPP-2 had no inhibitory effect. Animal experiment results showed that W-CPP treatment significantly improved the T2DM symptoms in mice, which included lowering of fasting blood glucose (FBG), reducing insulin resistance (IR), and lowering of blood lipid levels. It increased the diversity of intestinal flora and reduced the harmful flora of model mice, which included Clostridium, Thermoanaerobe, Symbiotic bacteria, Deinococcus, Vibrio haematococcus, Proteus gamma, and Corio. At the family level, W-CPP (1,200 mg/kg) treatment significantly reduced the abundance of Erysipelotrichaceae, and the Akkermanaceae of Verrucobacterium became a biomarker. Pumpkin polysaccharides reshaped the intestinal flora by reducing Erysipelotrichaceae and increasing Akkermansia abundance, thereby improving blood glucose and lipid metabolism in the T2DM mice. Our results suggest that W-CCP and RPP-3 possess strong antioxidant and hypoglycemic activities, and are potential candidates for food additives or natural medicines.

Jun-Ting Huang,1,2 Jian-Ning Chen,1 Yuan-Hua Bi,1 Li-Ping Gong,1 Jing-Yue Zhang,1 Yu DU,1 Chun-Kui Shao1 1Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Chun-Kui ShaoDepartment of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 500 Tian He Road, Guangzhou, 510000, People’s Republic of ChinaEmail shaochk@mail.sysu.edu.cnPurpose: Epstein–Barr virus (EBV) is widely recognised to cause various tumours, and EBV-associated gastric carcinoma (EBVaGC) is a special type of GC. It has obviously different clinical features and pathological manifestations from EBV-negative gastric carcinoma, but its progression remains elusive. The underlying cancer progression of viral infection detected by genome-wide transcriptome analysis has been demonstrated in numerous diseases.Methods: We performed comparative RNA sequencing to identify gene expression signatures between GC and EBVaGC cell lines. The differentially expressed (DE) genes were analysed using gene ontology and pathway enrichment.Results: A total of 4438 DE mRNAs, 3650 DE long non-coding RNAs (lncRNAs), and 248 DE circular RNAs (circRNAs) were detected in GC cells after EBV infection, most of which were highly related to oncogenesis. Likewise, EBV-coding RNA and non-coding RNA were also well-supplemented in EBVaGC. According to bioinformatics, DE mRNAs may contribute to the completion of EBV-infected host cells and modulate mitosis. Binding to actin and participating in adherens junctions to promote contact between the virus and cells are a potential function of DE lncRNAs. The roles of DE circRNAs were enriched in DNA repair and protein modification, and a typical example of this is acting as an miRNA sponge. The establishment of a circRNA-miRNA-mRNA network helps to determine the key elements in the progression of EBVaGC.Conclusion: This study is the first to systematically reveal the transcriptome landscape of EBVaGC, which will provide an essential resource for genomic, genetic, and molecular mechanisms in the future.Keywords: transcriptome, RNA-sequencing, bioinformatics, regulatory network, EBV-associated gastric cancer

An E3 ubiquitin ligase gene (Genbank accession no.: MD01G1010900) was cloned from the Royal Gala apple genome ( Malus x domestica Borkh.). Sequence analysis showed that the length of the MdPUB29 gene was 1 275 bp, encoding 424 amino acids. Phylogenetic tree analysis indicated that the apple E3 ubiquitin ligase exhibited the greatest sequence similarity to Pyrus × bretschneideri. The predicted protein structural domain of MdPUB29 showed that it contained a U-box domain. qRT-PCR analysis showed that MdPUB29 was expressed widely in different tissues of the Royal Gala apple species, and was highly expressed in the root, while the expression of MdPUB29 was significantly inhibited by exogenous NaCl. Immunoblotting assays revealed that MdPUB29 protein abundance in tissue cultures of the Royal Gala apple accumulated under NaCl stress conditions. Three-dimensional protein structure prediction indicated that MdPUB29 was highly homologous with AtPUB29. The growing potential of MdPUB29-expressing apple calli and Arabidopsis were much stronger than that of the control under salt stress conditions, suggesting that MdPUB29 may positively regulate salt tolerance.

High salt restricts the growth and development of plants. A diverse range of genes are involved in the response to salt stress. Here we report that MdCAIP1 (C2-domain ABA Insensitive Protein1), a single C2-domain containing protein, has a conserved structure consisting of an eight-stranded anti-parallel β-sandwich. MdCAIP1 was able to bind to phospholipids in a Ca2+-dependent manner and localized to the plasma membrane. qRT-PCR analysis showed that MdCAIP1 was induced by abiotic stresses including salt, osmotic, and drought stress, as well as the hormone JA. Transgenic apple calli and Arabidopsis over-expressing MdCAIP1 were more tolerant to salt and osmotic stress, and had higher proline content and lower MDA content under these stressful conditions. Furthermore, MdCAIP1 could homodimerize. These results indicate that MdCAIP1 is a Ca2+-dependent phospholipid-binding protein, and implicate it in tolerance to salt and osmotic stress. MdCAIP1, a Ca2+-dependent phospholipid-binding protein, could homodimerize and positively regulated salt and osmotic tolerance in plants.

Circular RNAs (circRNAs) are a novel class of non-coding RNA molecules in eukaryotic organisms that have potentially important roles in gene regulation. Nevertheless, whether viruses can encode circRNA is still uncertain. To examine whether large genome DNA viruses can generate circRNA during the infection of human cells, we performed RNA sequencing of ribosomal RNA-depleted total RNA from Epstein-Barr virus (EBV)-infected cell lines, including SNU-719, AGS-EBV, C666-1 and Akata. We identified an EBV-encoded circRNA, ebv_circ_RPMS1, that consists of the head-to-tail splicing of exons 2–4 from the RPMS1 gene. Furthermore, we demonstrated that ebv_circ_RPMS1 was localized in both cytoplasm and nuclei. Given that circRNAs shape gene expression by titrating microRNAs, regulating transcription and/or interfering with splicing, we identified a novel viral regulator of host and/or viral gene expression.

Human papillomavirus (HPV) is recognized as a major cause of oropharyngeal cancer (OPC) in Western countries. Less is known regarding its contribution to the OPC occurring in Asia. The current study aimed to investigate the association between antibody responses to HPV16 E7 and head and neck cancer (HNC) risk in a hospital‐based case–control study conducted in Taiwan with 693 HNC cases and 1,035 controls. A positive association was observed between seropositivity to HPV16 E7 and OPC risk, whereas no significant association was found in the non‐OPC cases. The increased OPC risk associated with seropositivity to HPV16 E7 was more significant among nonbetel quid or noncigarette users. Seropositivity to HPV16 E7 showed moderate agreement with P16 expression in OPC. OPC patients that were seropositive to HPV16 E7 or p16 positive were more highly educated and less likely to use alcohol, betel quids, and cigarettes compared to HPV16 E7 seronegative or p16 negative OPC patients. Furthermore, patients with p16 positive OPC were more likely to be women compared to patients with p16 negative OPC, likely owing to the low prevalence of alcohol, betel quid, and cigarette users among women. Overall, this study suggested that similar to Western countries, HPV may also be an important risk factor of OPC in Taiwan. With the declining consumption of betel quids and cigarettes in Taiwan, a higher percentage of OPC cases in Taiwan will be attributed to HPV in the future. Public health measures, including HPV vaccination, need to be implemented to prevent the occurrence of HPV‐positive OPC., The current study found a a positive association between seropositivity to HPV16 E7 and oropharyngeal cancer risk. This study suggested that similar to Western countries, HPV may also be an important risk factor of OPC in Taiwan.

Sea buckthorn（Hippophae rhamnoides L.） is a flowering shrub native to cold-temperate regions of Eurasia, which is also valuable for its berries and leaves containing various vitamins and flavonoids (Pundir et al. 2021). In late June 2020, high mortality (more than 70%) was observed in sea buckthorn in a 1.6-ha seedling nursery in Chaoyang City, Liaoning province, China, where 16 Chinese and Russian cultivars (cv.) had been planted since 2014 (cv. Shenqiuhong, eshi01 through eshi15). The mortality of two introduced sea buckthorn varieties (eshi02, eshi04) was 100% (125 trees died in total). The symptoms include massive drooping leaves and dried-up stems on 6-year-old infected trees. Pieces of tree roots and stems with brown discoloration in the xylem vessels were selected. Small tissue fragments (0.2-0.5 cm) were surface disinfested (3 min in 75% ethanol, rinsed with sterile distilled water), air-dried, and placed on potato dextrose agar (PDA) medium for 5 days at 25°C in the dark. A fungus was consistently isolated from both diseased roots and stems tissues, and a representative isolate (LC-1) was harvested. Genomic DNA was extracted for amplification and sequencing of the partial translation elongation factor-1α (EF1 and EF2 primers, accession Nos. MZ669853) (O'Donnell et al. 1998) and RNA polymerase II second largest subunit (RPB2) (7cf/11aR primers, accession Nos. MZ669854) (O'Donnell et al. 2007). The sequences were further analyzed at the Fusarium MLST (https://fusarium.mycobank.org/) for identity confirmation, and showed 99.8% (over 95.2% query coverage) and 96.4% (over 88.4% query coverage) similarity to Fusarium proliferatum (NRRL 13584, 13591). Isolates on Spezieller Nahrstoffarmer agar (SNA) produced abundant aerial white mycelia and yellow pigmentation. The 30 macroconidia measured ranged from 28.5 - 62.5 × 3.2 - 5.4 μm, were thin, slender, with 3-5 septa. The aseptate microconidia ranged from 4.7 - 13.6 × 2.2 - 4.3 μm (n = 30). Pathogenicity tests were performed on healthy, potted 1-year-old sea buckthorn seedlings (cv. eshi05) using two isolates in a greenhouse at 25 °C, 80% relative humidity, and 12-hour light/dark photoperiod. Ten potted seedlings were inoculated on the stems by placing a 5-mm-diameter mycelial plug (5-day-old PDA cultures for each isolate) into the surface of a wound created with a needle, and the inoculation sites were covered with Parafilm to maintain moisture. Ten seedlings were inoculated with PDA plugs as controls. Six to ten days after inoculation, color of the leaves in the middle of the stems was variegated, and then dark necrotic lesions on leaf margins were observed. Three weeks after inoculation, 80% of inoculated stems were wilted, while control plants remained asymptomatic. The pathogen was consistently re-isolated and the recovered isolates were identified as F. proliferatum by amplifying the EF-1α gene. The typical symptoms on inoculated plants were dark to brown necrotic lesions on chlorotic leaves initially, and black withered stems in the terminal stage, similar to those observed on sea buckthorn trees infected with Fusarium sporotrichioides in Gansu and Heilongjiang provinces (Song et al. 2010; Xia et al. 2021). To our knowledge, this is the first report of sea buckthorn stem wilt caused by F. proliferatum in Liaoning province, China, which will be beneficial for expanding knowledge of Fusarium disease in sea buckthorn and provide more information for sustainable disease management in sea buckthorn.

Background: Recent investigations have suggested that long noncoding RNA (lncRNA) MIR22HG is commonly dysregulated in multiple types of malignancies. Nevertheless, the roles of MIR22HG in human col...

Silver nanoparticles pose a potential risk to ecosystems and living organisms due to their widespread use in various fields and subsequent gradual release into the environment. Only a few studies have investigated the effects of silver nanoparticles (AgNPs) toxicity on immunological functions. Furthermore, these toxic effects have not been fully explored. Recent studies have indicated that zebrafish are considered a good alternative model for testing toxicity and for evaluating immunological toxicity. Therefore, the purpose of this study was to investigate the toxicity effects of AgNPs on innate immunity using a zebrafish model and to investigate whether the natural compound pterostilbene (PTE) could provide protection against AgNPs-induced immunotoxicity. Wild type and neutrophil- and macrophage-transgenic zebrafish lines were used in the experiments. The results indicated that the exposure to AgNPs induced toxic effects including death, malformation and the innate immune toxicity of zebrafish. In addition, AgNPs affect the number and function of neutrophils and macrophages. The expression of immune-related cytokines and chemokines was also affected. Notably, the addition of PTE could activate immune cells and promote their accumulation in injured areas in zebrafish, thereby reducing the damage caused by AgNPs. In conclusion, AgNPs may induce innate immune toxicity and PTE could ameliorate this toxicity.

Microcystin-leucine arginine (MC-LR) has reproductive and developmental toxicities. Previous studies indicated that gestational exposure to MC-LR induced fetal growth restriction in mice. The aim of this study was to further evaluate the effect of paternal MC-LR exposure before mating on fetal development. Male mice were intraperitoneally injected with either normal saline or MC-LR (10 μg/kg) daily for 35 days. Male mouse was then mated with female mice with 1:1 ratio. There was no significant difference on the rates of mating and pregnancy between MC-LR-exposed male mice and controls. Body weight and crown-rump length were reduced in fetuses whose fathers were exposed to MC-LR. Despite no difference on relative thickness of labyrinthine layer, cell proliferation, as measured by Ki67 immunostaining, was reduced in labyrinth layer of MC-LR-exposed mice. Moreover, blood sinusoid area in labyrinth layer was decreased in the fetus whose father was exposed to MC-LR before mating. Correspondingly, cross-sectional area of CD34-positive blood vessel in labyrinth layer was lower in fetuses whose fathers were exposed to MC-LR than in controls. These results provide evidence that paternal MC-LR exposure before mating induces fetal growth restriction partially through inhibiting cell proliferation and vascular development in labyrinth layer.

Acute lung injury (ALI) is a common disease that may result in acute respiratory failure and death. However, there are still no effective treatments for ALI. Several studies have shown that farnesoid X receptor (FXR) has an anti-inflammatory effect. We investigated the effects of obeticholic acid (OCA), an agonist of FXR, on Lipopolysaccharide (LPS)-induced ALI in mice. Sixty male mice were randomly divided into six groups, and orally administered with or without OCA once daily for 3 consecutive days before LPS (1.0 mg/kg). Animals were sacrificed at 0 h, 2 h or 6 h after LPS. As expected, OCA enhanced pulmonary FXR activity. OCA prevented LPS-induced ALI. Additional experiment showed that OCA alleviated LPS-induced up-regulation of pulmonary pro-inflammatory and chemokine genes. Moreover, OCA also repressed LPS-induced the release of TNF-α and KC in serum and bronchoalveolar lavage fluid. In contrast, OCA further up-regulated LPS-induced the expression of Il-10, an anti-inflammatory cytokine. Further study showed that OCA inhibited LPS-evoked NF-κB signaling in the lungs. OCA attenuated LPS-induced ERK1/2, JNK, p38 and Akt phosphorylation in the lungs. Overall, these results suggest that OCA prevent LPS-induced ALI may be through enhancing pulmonary FXR activity and then blockading several inflammatory signaling pathways.

Background: Mitochondrial genomes play a significant role in reconstructing phylogenetic relationships and revealing molecular evolution in insects. However, only two species of Panorpidae have been documented for mitochondrial genomes in Mecoptera to date.Results: We obtained complete mitochondrial genomes of 17 species of Panorpidae. The results show that the complete mitogenome sequences of Panorpidae all contain 37 genes (13 protein-coding genes (PCGs), two rRNAs, 22 tRNAs) and one control region. The mitogenomes exhibit a strong AT bias. The AT-skew can either be slightly positive or slightly negative, while the GC-skew is usually negative. The 22 tRNA genes can fold into a common cloverleaf secondary structure except trnS1. The sliding window and genetic distance analyses demonstrate highly variable nucleotide diversity among the 13 protein-coding genes, with comparatively low evolutionary rate of cox1, cox2 and nad1, and high variability of nad2 and nad6. The phylogeny of Panorpidae can be presented as (Neopanorpa + Furcatopanorpa) + (Dicerapanorpa + (Panorpa debilis + (Sinopanorpa + (Cerapanorpa + Panorpa)))).Conclusions: Our analyses indicate that the genes nad2 and nad6 can be regarded as potential markers for population genetics and species delimitation in Panorpidae. Panorpa is reconfirmed a paraphyletic group.

Nanotechnology has rapidly promoted the development of a new generation of industrial and commercial products; however, it has also raised some concerns about human health and safety. To evaluate the toxicity of the great diversity of nanomaterials (NMs) in the traditional manner, a tremendous number of safety assessments and a very large number of animals would be required. For this reason, it is necessary to consider the use of alternative testing strategies or methods that reduce, refine, or replace (3Rs) the use of animals for assessing the toxicity of NMs. Autophagy is considered an early indicator of NM interactions with cells and has been recently recognized as an important form of cell death in nanoparticle-induced toxicity. Impairment of autophagy is related to the accelerated pathogenesis of diseases. By using mechanism-based high-throughput screening in vitro, we can predict the NMs that may lead to the generation of disease outcomes in vivo. Thus, a tiered testing strategy is suggested that includes a set of standardized assays in relevant human cell lines followed by critical validation studies carried out in animals or whole organism models such as C. elegans (Caenorhabditis elegans), zebrafish (Danio rerio), and Drosophila (Drosophila melanogaster)for improved screening of NM safety. A thorough understanding of the mechanisms by which NMs perturb biological systems, including autophagy induction, is critical for a more comprehensive elucidation of nanotoxicity. A more profound understanding of toxicity mechanisms will also facilitate the development of prevention and intervention policies against adverse outcomes induced by NMs. The development of a tiered testing strategy for NM hazard assessment not only promotes a more widespread adoption of non-rodent or 3R principles but also makes nanotoxicology testing more ethical, relevant, and cost- and time-efficient.

Purpose Nanoencapsulated triterpenoids from petri dish-cultured Antrodia cinnamomea (PAC) and its amelioration effects on reproductive function in diabetic rats were investigated. Materials and methods PAC encapsulated in silica-chitosan nanoparticles (Nano-PAC) was prepared by the biosilicification method. The diabetic condition in male Sprague Dawley rats was induced by high-fat diet and streptozotocin (STZ). Three different doses of Nano-PAC (4, 8, and 20 mg/kg) were administered for 6 weeks. Metformin and control of nanoparticles (Nano-con) were taken as positive and negative controls, respectively. Results The average particle size was ~79.46±1.63 nm, and encapsulation efficiency was ~73.35%±0.09%. Nano-PAC administration improved hyperglycemia and insulin resistance. In addition, Nano-PAC ameliorated the morphology of testicular seminiferous tubules, sperm morphology, motility, ROS production, and mitochondrial membrane potential. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) antioxidant, as well as testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were increased, whereas proinflammatory cytokines TNF-α, IL-6, and IFN-γ were decreased. Conclusion In the present study, we successfully nanoencapsulated PAC and found that a very low dosage of Nano-PAC exhibited amelioration effects on the reproductive function of diabetic rats.

The aim of the present study was to investigate the potential mechanism underlying the anti-obesity-asthmatic effects of resveratrol (RSV) in a rat model of obese-asthma. Rat models of obesity and asthma were established using a high-fat diet and the administration of ovalbumin, respectively. Rats were divided into 7 different groups: A normal control, a normal obese, a normal asthma, a normal obese + asthma, a RSV obese, a RSV asthma and a RSV obese + asthma group. Body weight, Lee index, body fat and lung histopathological changes were evaluated. Serum lipid levels were evaluated using calorimetric methods. Levels of reactive oxygen species (ROS) were examined using enzyme-linked immunosorbent assays. Cellular antioxidant enzyme activities were measured using commercial kits. Levels of kelch-like ECH associated protein 1 (Keap-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) was examined using western blot analysis. The results indicated that obese and asthma rat models were successfully established. It was also demonstrated that RSV decreased fasting blood glucose in obese, asthmatic and obese-asthmatic rats. RSV altered serum lipid levels; it significantly increased high density lipoprotein cholesterol levels and significantly decreased serum triglyceride, serum total cholesterol and very low density lipoprotein levels, compared with untreated obese, asthmatic and obese-asthmatic rats (P

A new species of Panorpidae,Panorpabashanicolasp. n., is described and illustrated from the Bashan Mountains in central China. The new species is characterized by the following characters: vertex black, with two pale longitudinal stripes and four pale rounded spots; vein 1A ending before the origin of Rs; meso- and metanotum pale, and the pale color extending to tergum III in V-shape; male epandrium emarginate distally in deep U-shape; hypovalves without basal stalk, completely represented by a pair of short hypovalves, extending to distal third of gonocoxite, with five black stout setae in distal portion; paramere simple, S-shaped; a bundle of long hairs between dorsal and ventral valves of aedeagus; dorsal valves of aedeagus much longer than ventral valves and curved ventrally, with distal portion foot-shaped; female medigynium twice as long as wide, with stout axis extending over one-third its length beyond main plate.

Acute pulmonary embolism is a common disease, which is associated with high mortality and morbidity. There is significant relationship between haptoglobin and pulmonary embolism, however, the usefulness of haptoglobin as a biomarker for the diagnosis of pulmonary embolism remains poorly defined. The aim of the present study was to investigate the change and clinical diagnostic value of haptoglobin in pulmonary embolism. A comparative proteomic analysis was used for clinical screening of serum proteins in 18 patients (9 patients with pulmonary embolism and 9 controls). ELISA was used to validate the dysregulated proteins in 48 patients (24 patients with pulmonary embolism and 24 controls). Immunohistochemical staining was performed to detect the expression of haptoglobin in pulmonary artery of both groups. The diagnostic value of the differential protein and its association with the severity of pulmonary embolism were evaluated. Eight proteins showed significant changes in serum of pulmonary embolism patients. Haptoglobin, as one of the eight differential proteins, was significantly overexpressed in the serum of pulmonary embolism patients. In accordance, the expression of haptoglobin was increased in pulmonary artery of pulmonary embolism patients. The ROC curve showed that serum haptoglobin was a specific parameter in the diagnosis of pulmonary embolism with an area under the curve of 0.764 (95% confidence interval, 0.622-0.906; P < 0.01); in particular, the haptoglobin level at least 256.74 mg/l was the most useful cut-off value, with the sensitivity of 62% and specificity of 83%. Increased haptoglobin level may be an acceptable diagnostic parameter for pulmonary embolism.

Ergothioneine is an effective antioxidant and is abundant in species of genus Pleurotus. This research focused on developing an ergothioneine extract from P. eryngii and P. citrinopileatus under optimal extraction conditions. The hot-water and 70% ethanol extractions yielded more ergothioneine than microwave, ultrasonic, and autoclaving extractions. Hot-water extraction with optimal conditions-125 rpm at 75°C for 5 minutes-produced P. eryngii and P. citrinopileatus extracts with 0.86 and 3.73 mg ergothioneine/g dry weight, respectively. In addition to 50% of added maltodextrin, spray-dried products from mushrooms contained 23.07-16.58% carbohydrates and 18.32-21.40% protein. The microstructure of spray-dried products showed shrunken spheres with mean particle diameters of 15.82-19.94 μm. After in vitro simulated gastric and intestinal digestion, the spray-dried P. eryngii and P. citrinopileatus products contained 88% and 91% residual ergothioneine, respectively. Overall, the spray-dried products could be used as antioxidative supplements.

Triple-negative breast cancer (TNBC) treatment offers only limited benefits, and it is very relevant given the significant number of deaths that it causes. DNA repair pathways can enable tumor cells to survive DNA damage that is induced by chemotherapeutic or radiation treatments. Histone deacetylase inhibitors (HDACi) inhibited DNA repair proteins. However, the detailed mechanisms for this inhibition remain unclear. In the present study, we investigated whether a newly developed HDACi, TMU-35435, could enhance etoposide cytotoxicity by inhibiting DNA repair proteins in triple-negative breast cancer. We found synergistic cytotoxicity following treatment of 4T1 cells with etoposide and TMU-35435. Furthermore, TMU-35435 enhances etoposide-induced DNA damage by inhibiting the DNA repair pathway (non-homologous end joining, NHEJ). TMU-35435 suppresses the NHEJ pathway through the ubiquitination of DNA-dependent protein kinase catalytic subunit (DNA-PKcs). In addition, TMU-35435 ubiquitinated DNA-PKcs by inducing the interaction between RNF144A (an E3 ligase) and DNA-PKcs. The combined treatment induced apoptosis and autophagic cell death in 4T1 cells. In an orthotopic breast cancer model, combined treatment with TMU-35435 and etoposide showed anti-tumor growth through the increase of DNA damage and cell death. Taken together, our data suggest that TMU-35435 enhances etoposide cytotoxicity by regulating ubiquitin-proteasome system and inhibiting the DNA repair pathway in TNBC.

Irreversible electroporation (IRE) is a physical, non-thermal cancer therapy, which leads to cell death via permanent membrane permeability. This differs from reversible electroporation (RE), which is used to transfer macromolecules into target cells via transient membrane permeability. Given the electrical impedance of the electric field, RE co-exists outside the central zone of IRE ablation. In the present study, the feasibility of using IRE at a therapeutic dose to mediate short hairpin RNA (shRNA) knockdown of human papillomavirus (HPV)18 E6 in HeLa cervical cancer cells in vitro and in vivo was investigated. Experimental results indicated that the HeLa cells survived the combined treatment with IRE and shRNA plasmid transfection. Additionally, residual tumor tissue in a nude mouse model demonstrated green fluorescence. Subsequent studies showed that the combined treatment inhibited the growth of HeLa cells and tumors. Western blotting analysis showed marked changes in the growth-associated proteins between the combined treatment group and the control. It was concluded that a therapeutic dose of IRE was able to mediate the transfection of HPV18 E6 shRNA into HeLa cervical cancer cells in vitro and in vivo. This combined treatment strategy has promising implications in cancer treatment for the ablation of tumors, and in eliminating microscopic residual tumor tissue.

Vitamin D deficiency has been associated with increased risks of prostate cancer. Nevertheless, the mechanisms remain unclear. The aim of this study was to analyze the association among prostate cancer, vitamin D status and inflammation. Sixty patients with newly diagnosed prostate cancer and 120 age-matched controls were recruited for this study. Vitamin D status was evaluated and serum inflammatory molecules were measured. Serum 25-(OH)D was lower in patients with prostate cancer. Moreover, serum 25(OH)D was lower in patients with severe prostate cancer than patients with mild and moderate prostate cancer. By contrast, serum C-reactive protein (CRP) and interleukin (IL)-8, two inflammatory molecules, were elevated in patients with prostate cancer. Serum 25-(OH)D was negatively correlated with serum CRP and IL-8 in patients with prostate cancer. Additional analysis showed that the percentage of vitamin D receptor positive nucleus in the prostate was reduced in patients with prostate cancer. By contrast, the percentage of nuclear factor kappa B p65-positive nucleus was elevated in patients with prostate cancer. Our results provide evidence that there is an association among prostate cancer, vitamin D deficiency and inflammatory signaling. Inflammation may be an important mediator for prostate cancer progression in patients with low vitamin D status.

The male reproductive system may provide significant evidence for the taxonomic and phylogenetic analyses of insects. However, current knowledge of the male reproductive system in Mecoptera is mainly concentrated on the external genitalia, and is rarely involved in the internal reproductive system. Here, we investigated the morphology and the fine structure of the vasa deferentia and associated structures of the male reproductive system of Panorpodes kuandianensis Zhong et al., 2011 (Panorpodidae) using light, scanning, and transmission electron microscopy. The male reproductive system of P. kuandianensis consists of a pair of symmetrical testes with three tubular testicular follicles, two epididymides, two distinctly partitioned vasa deferentia, a pair of mesadenia, one ejaculatory sac, and the external genitalia. A pair of expanded seminal vesicles are modified from the median part of the vasa deferentia, and evolve into secretory organs. The seminal vesicles have elongated cylindrical epithelial cells, which contain abundant secretory materials in the cytoplasm and form a small central lumen, likely serving a secretory function rather than provisionally storing sperm as in most other insects. Alternatively, the sperm are stored temporarily in the epididymis, the greatly coiled portion of the vasa deferentia. The morphology of the male reproductive system supports the close relationships of Panorpidae and Panorpodidae.

Cancer stem cells (CSCs) are cancer‐initiating cells that are not only a source of tumorigenesis but also the cause of tumour progression, metastasis and therapy resistance. EBV‐associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer with unique clinicopathological and molecular features. However, whether CSCs exist in EBVaGC, and the tumorigenic mechanism of EBV, remains unclear. Here, NOD/SCID mice were injected subcutaneously with the EBVaGC cell line SNU719 and treated with 5‐fluorouracil weekly. Successive generations of xenografts yielded a highly malignant EBVaGC cell line, SNU‐4th, which displays properties of CSCs and mainly consists of CD44(+) CD24(−) cells. In SNU‐4th cells, an EBV‐encoded circRNA, ebv‐circLMP2A, expression increased and plays crucial roles in inducing and maintaining stemness phenotypes through targeting miR‐3908/TRIM59/p53 axis. Additionally, high expression of ebv‐circLMP2A is significantly associated with metastasis and poor prognosis in patients with EBVaGC. These findings not only provide evidence for the existence of CSCs in EBVaGC and elucidate the pathogenic mechanism of ebv‐circLMP2A in EBVaGC, but also provide a promising therapeutic target for EBVaGC.

Gestational vitamin D deficiency is associated with pulmonary diseases. This study aimed to investigate the effect of gestational vitamin D deficiency on fetal lung development in mice. Absolute and relative weights of fetal lungs were reduced in vitamin D deficient (VDD) group. Incrassate mesenchyme, measured by septal wall thickness, accompanied by lessened saccular space, was shown in VDD group. Numerous immature type II pneumocytes, as determined by PAS staining, were observed in VDD group. Moreover, increased Ki67-positive cells, a marker of cell proliferation, was detected in VDD group. The additional experiments showed that Sftpa, Sftpb, Sftpc and Sftpd, four surfactant genes, were downregulated and pro-surfactant protein B was reduced in VDD group. FoxA1, FoxA2 and TTF-1, three transcription factors that regulate surfactant genes, and VEGF, a key regulator for pulmonary maturation, were downregulated in VDD group. These results suggest that gestational vitamin D deficiency impairs fetal lung development partially through suppressing type II pneumocyte differentiation.

Insects are the most diverse group of organisms in the world, but how this diversity was achieved is still a disputable and unsatisfactorily resolved issue. In this paper, we investigated the correlations of habitat preferences and morphological traits in larval Panorpidae in the phylogenetic context to unravel the driving forces underlying the evolution of morphological traits. The results show that most anatomical features are shared by monophyletic groups and are synapomorphies. However, the phenotypes of body colorations are shared by paraphyletic assemblages, implying that they are adaptive characters. The larvae of Dicerapanorpa and Cerapanorpa are epedaphic and are darkish dorsally as camouflage, and possess well-developed locomotory appendages as adaptations likely to avoid potential predators. On the contrary, the larvae of Neopanorpa are euedaphic and are pale on their trunks, with shallow furrows, reduced antennae, shortened setae, flattened compound eyes on the head capsules, and short dorsal processes on the trunk. All these characters appear to be adaptations for the larvae to inhabit the soil. We suggest that habitat divergence has driven the morphological diversity between the epedaphic and euedaphic larvae, and may be partly responsible for the divergence of major clades within the Panorpidae.

Cadmium (Cd) is a major environmental pollutant. Maternal Cd exposure throughout pregnancy caused fetal growth restriction (FGR). However, the pivotal time window of Cd-evoked FGR and its mechanism are unknown. Here, we will establish a murine model to explore the effects of maternal Cd exposure at different stages of gestation on fetal growth and placental progesterone biosynthesis. Pregnant mice were randomly divided into four groups. For Cd groups, mice were given with CdCl2 (150 mg/L) through drinking water at early (GD0-GD6), middle (GD7-GD12) and late (GD13-GD17) gestation, respectively. The controls received reverses osmosis (RO) water. Results showed that maternal cadmium exposure only in late gestation lowered fetal weight and length. Correspondingly, placental Cd level in late gestational Cd exposure is the highest among three different gestational stages. Although gestational Cd exposure had few adverse effects in the weight and diameter of mouse placenta, placental vascular development, as determined by H&E staining and cluster of differentiation-34 (CD-34) immunostaining, was impaired in mice exposed to Cd during late pregnancy. Additionally, late gestational exposure to cadmium markedly reduced progesterone level in maternal serum and placenta. In line, the expression of key progesterone synthetases, including steroidogenic acute regulatory protein (StAR) and 3β-hydroxyl steroid dehydrogenase (3β-HSD), was obviously downregulated in placenta from mice was exposed Cd during late pregnancy. These data suggest that maternal Cd exposure during late pregnancy, but not early and middle pregnancy, induces fetal growth restriction partially via inhibiting placental progesterone synthesis.

Cadmium (Cd), a ubiquitous environmental pollutant, is known to impair placental development. However, the underlying mechanisms remain unclear. The present study used in vivo and in vitro models to investigate the effects of Cd on apoptosis and autophagy in placental trophoblasts and its mechanism. Pregnant mice were exposed to CdCl2 (4.5 mg/kg) on gestational day (GD) 9. Human JEG-3 cells were exposed to CdCl2 (0–40 μM) for different time points. Gestational Cd exposure obviously lowered the weight and diameter of mouse placentas. Number of TUNEL-positive cells was markedly elevated in Cd-administered mouse placentas and JEG-3 cells. Correspondingly, Cd significantly up-regulated cleaved caspase-3 protein level, a key indicator of apoptosis, in murine placentas and JEG-3 cells. Simultaneously, Cd also triggered autophagy, as determined by an elevation of LC3B-II and p62 protein, and accumulation of LC3-positive puncta, in placental trophoblasts. Chloroquine an autophagy inhibitor, obviously aggravated Cd-induced apoptosis in JEG-3 cells. By contrast, rapamycin, a specific autophagy inducer, significantly alleviated Cd-triggered apoptosis in JEG-3 cells. Mechanistically, autophagy inhibited Cd-induced apoptosis mainly via degrading caspase-9. Co-localizations of p62, a classical autophagic receptor, and caspase-9 were observed in Cd-stimulated human JEG-3 cells. Moreover, p62 siRNAs pretreatment markedly blocked the degradation of caspase 9 proteins via Cd-activated autophagy in JEG-3 cells. Collectively, our data suggest that activation of autophagy inhibits Cd-induced apoptosis via p62-mediated caspase-9 degradation in placental trophoblasts. These findings provide a new mechanistic insight into Cd-induced impairments of placental and fetal development.

Apple ring rot is a severe disease that affects the yield and quality of apple fruits worldwide. However, the underlying molecular mechanism that involved in this process still remains largely unexplored. Here, we report that apple POZ/BTB CONTAINING-PROTEIN 1 (MdPOB1), a BTB-BACK domain E3 ligase protein, functions to suppress apple pathogen defense against Botryosphaeria dothidea (B. dothidea). Both in vitro and in vivo assays indicated that MdPOB1 interacted directly with and degraded apple U-box E3 ligase MdPUB29, a well-established positive regulator of plant innate immunity, through the ubiquitin/26S proteasome pathway. A series of transgenic analyses in apple fruits demonstrated that MdPOB1 affected apple pathogen defense against B. dothidea at least partially, if not completely, via regulating MdPUB29. Additionally, it was found that the apple pathogen defense against B. dothidea was correlated with the H2O2 contents and the relative expression of salicylic acid (SA) synthesis- and SA signaling-related genes, which might be regulated via degradation of MdPUB29 by MdPOB1. Overall, our findings provide new insights into the mechanism of the MdPOB1 modulation of apple ring rot resistance, which occur by directly regulating potential downstream target protein MdPUB29 for proteasomal degradation in apple.

Farnesoid X receptor (FXR) is expressed in human and rodent placentas. Nevertheless, its function remains obscure. This study investigated the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, on LPS-induced fetal death and intrauterine growth restriction. All pregnant mice except controls were i.p. injected with LPS (100 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were orally administered with OCA (5 mg/kg) daily from GD13 to GD17. As expected, placental FXR signaling was activated by OCA. OCA pretreatment protected against LPS-induced fetal death. In addition, OCA pretreatment alleviated LPS-induced reduction of fetal weight and crown-rump length. Additional experiments showed that OCA inhibited LPS-evoked TNF-α in maternal serum and amniotic fluid. Moreover, OCA significantly attenuated LPS-induced upregulation of placental proinflammatory genes including Tnf-α, Il-1β, IL-6, Il-12, Mip-2, Kc, and Mcp-1. By contrast, OCA elevated anti-inflammatory cytokine IL-10 in maternal serum, amniotic fluid, and placenta. Further analysis showed that OCA blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth zone. These results provide a mechanistic explanation for placental FXR-mediated anti-inflammatory activity. Overall, this study provides evidence for roles of FXR as an important regulator of placental inflammation.

Cadmium (Cd) is linked with increased risk of fetal growth restriction (FGR). Nevertheless, the mechanism remains unknown. This study established a mouse model of Cd-induced FGR through two exposure methods. Pregnant mice were either administered with CdCl2 (5, 50 and 250ppm) throughout pregnancy through drinking water or intraperitoneally injected with CdCl2 (4.5mg/kg) on GD9. As expected, fetal weight and crown-rump length were reduced in a gender-independent manner. Interestingly, Mt1 and Mt2, two metallothionein genes, were up-regulated in maternal liver. Correspondingly, Cd accumulated mainly in maternal liver and kidney, and only trace amounts of Cd could pass from dam to placentas and fetuses. Further analysis showed that placental Zn concentration was elevated. Conversely, embryonic Zn concentration was reduced. Moreover, placental Znt1 and Znt2, two zinc transporters, were down-regulated in Cd-exposed mice. These results suggest that maternal Cd exposure during pregnancy reduces placental Zn transport and induces fetal growth restriction.

To identify effective and low toxicity synergistic antifungal compounds, 24 derivatives of chalcone were synthesized to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant Candida albicans. This was done via methods established by the clinical and laboratory standards institute (CLSI). Of the synthesized compounds, 2'-hydroxy-4'-methoxychalcone (8) exhibited the most potent in vitro (FICI=0.007) effects. The structure activity relationship of the compounds are then discussed.

Society of Toxicologic Pathology has recommended mDF to fix testes since 2002. However, subsequent studies showed that false TUNEL-positive cells were observed in mDF-fixed testes. This study compared the effects of different fixation methods on histology and TUNEL staining in mouse testes. Results showed that fixation for 24 or 36h in mDF provided better morphologic details in untreated testes, but markedly enhanced false TUNEL-positive staining. To optimize the fixation, testes were fixed using mDF for 6h and then PFA for 18h. Interestingly, fixation using mDF/PFA manifested better morphologic details, and rarely caused false TUNEL-positive cells in testes. Finally, we examined germ cell apoptosis in testes using mDF/PFA fixation in cadmium-treated mice. As expected, cadmium triggered germ cell apoptosis which was well visualized in the mDF/PFA fixed testes. Taken together, mDF plus PFA fixation not only minimizes false TUNEL-positive cells, but also provides integrated morphologic details in testes.

Peroxisome proliferator-activated receptor (PPAR)-γ is highly expressed in human and rodent placentas. Nevertheless, its function remains obscure. The present study investigated the effects of rosiglitazone, a PPAR-γ agonist, on LPS-induced fetal death. All pregnant mice except controls were intraperitoneally injected with LPS (150 μg/kg) daily from gestational day (GD)15 to GD17. As expected, maternal LPS injection caused placental inflammation and resulted in 63.6% fetal death in dams that completed the pregnancy. Interestingly, LPS-induced fetal mortality was reduced to 16.0% when pregnant mice were pretreated with RSG. Additional experiment showed that rosiglitazone pretreatment inhibited LPS-induced expressions of tumor necrosis factor (Tnf)-α, interleukin (Il)-1β, Il-6, macrophage inflammatory protein (Mip)-2 and keratinocyte-derived chemokine (Kc) in mouse placenta. Although rosiglitazone had little effect on LPS-evoked elevation of IL-10 in amniotic fluid, it alleviated LPS-evoked release of TNF-α and MIP-2 in amniotic fluid. Further analysis showed that pretreatment with rosiglitazone, which activated placental PPAR-γ signaling, simultaneously suppressed LPS-evoked nuclear factor kappa B (NF-κB) activation and blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth layer. These results provide a mechanistic explanation for PPAR-γ-mediated anti-inflammatory activity in the placentas. Overall, the present study provides additional evidence for roles of PPAR-γ as an important regulator of placental inflammation.

Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL.

MicroRNA-10a (miRNA-10a) promotes lung cancer; however, to the best of our knowledge, its involvement in other cancer types is unknown. The present study aimed to investigate the role of miRNA-10a in oral cancer. Expression levels of miRNA-10a and glucose transporter 1 (GLUT1) in tumor tissues and adjacent healthy tissues obtained from patients with oral squamous cell carcinoma (OSCC) were detected by reverse transcription-quantitative polymerase chain reaction. Correlation analysis between the expression levels of miRNA-10a and GLUT1 was performed using Pearson's correlation coefficient. It was identified that miRNA-10a and GLUT1 were upregulated in tumor tissues compared with adjacent healthy tissues of patients with OSCC. Expression levels of miRNA-10a and GLUT1 were positively correlated in tumor tissues but not in adjacent healthy tissues. In addition, miRNA-10a overexpression promoted glucose uptake and upregulated GLUT1 in OSCC cells. Furthermore, GLUT1 overexpression promoted glucose uptake; however, no significant increase in the expression level of miRNA-10a in OSCC cells was detected. Overexpression of miRNA-10a and GLUT1 promoted OSCC cell proliferation, while GLUT1-knockdown inhibited OSCC cell proliferation. GLUT1-knockdown also attenuated the enhancing effect of miRNA-10a overexpression on cancer cell proliferation. Therefore, miRNA-10a may promote cancer cell proliferation in OSCC by upregulating GLUT1 and promoting glucose metabolism.

Aims The aim of the study was to investigate the effects of high-fat diets before pregnancy and/or during pregnancy on fetal development. Main methods Female mice were fed with standard diets (SD) or high-fat diets (HFD). After 12 weeks, females were mated. In the SD + SD and HFD + SD groups, pregnant mice were fed with standard diets. In the SD + HFD and HFD + HFD groups, pregnant mice were fed with high-fat diets. All pregnant mice were sacrificed on gestational day (GD) 16. Key findings Fetal weight and crown-rump length were increased in SD + HFD-fed mice, whereas were decreased in HFD + SD-fed mice. The levels of CRP and TNF-α in maternal serum and amniotic fluid were elevated in all HFD-fed mice. Placenta weight was elevated in SD + HFD-fed but not in HFD + SD-fed mice. Blood sinusoid areas, and the number of Ki67-positive cells, a marker of cell proliferation, were elevated in placental labyrinth layer of SD + HFD-fed mice, but decreased in HFD + SD-fed mice. Finally, placental Fatp1, a fatty acid transporter gene, was up-regulated in SD + HFD-fed mice. By contrary, placental Fatp1, and Snat2, an amino acid transporter, were down-regulated in HFD + SD-fed mice. Moreover, the levels of placental FATP4 and SNAT2 were up-regulated in SD + HFD-fed mice. Significance HFD before pregnancy and HFD during pregnancy differentially disturb fetal growth development. HFD before pregnancy-induced fetal SGA might be partially attributed to inflammatory cytokines and mediators derived from maternal adipose tissue. By contrary, HFD during pregnancy-induced fetal overweight may be partially attributed to the increase of placental nutrient transport capacity.

Background Dysbiosis (alterations in microbiota composition) is associated with autoimmune diseases, including lupus. Factors that are thought to influence gut microbiota include diet, age and more recently, sex. Like humans, female NZBxNZWF1 (BWF1) mice spontaneously develop lupus-like disease, and exhibit much greater incidence of disease than males. Castration of male BWF1 mice increases disease onset/incidence and decreases survival suggesting that male sex steroids, androgens, play an important role in protection of males from disease. Methods Intact female and male, or castrated and sham-castrated male BWF1 mice were used in this study. Cecal contents (microbiota) from different groups were transferred into female BWF1 mice shortly after weaning (∼26 days) and either disease or in vitro cell function (cell culture, flow cytometry) was evaluated. Feces were collected from adult mice and analyzed for either microbiota composition (deep sequencing of 16S gene) or metabolomic profiles (mass spectrometry). Results We have found that the composition of gut microbiota and metabolomic/lipidomic profiles differ between mature female and male BWF1 mice. Transfer of male microbiota to female BWF1 mice suppresses disease and increases survival. Further, we found that male microbiota may protect, in part, via an effect on tolerogenic CD103+ dendritic cells (CD103DC) that induce peripheral Tregs (pTregs) through TGFβ and retinoic acid (RA) production. Female BWF1 CD103DC have a decreased ability to induce pTregs and express retinaldehyde dehydrogenase, (RALDH2), an enzyme involved in RA synthesis. Transfer of male microbiota to female BWF1 mice reconstitutes both RALDH2 expression and the ability of the CD103DC to induce pTregs. Interestingly, castration of male mice significantly alters gut microbiota composition and metabolomic/lipidomic profiles by comparison to males, diminishes CD103DC function and decreases the ability of the microbiota to protect female mice from disease. The mechanisms underlying male microbiota-mediated protection from disease are unknown, but may be mediated through the production of metabolites. We have identified several metabolites that are increased in male compared to both female and castrated male feces that function as retinoid X receptor agonists and enhance RALDH2 activity and increase pTregs in vivo. Conclusions Our data suggest that androgens alter the composition and function of the gut microbiota in males, and the metabolites produced by the male microbiota may have potential for development into therapeutic strategies for the treatment of disease. Acknowledgements Funded by Lupus Research Institute, Alliance for Lupus Research and National Institutes of Health.

This study aims to determine the protective effects of red seaweed Eucheuma cottonii (EC) ethanol extract on acute colitis disease in mice. Male BALB/c mice used for acute colitis disease model by induced 2.5% (w/v) of dextran sulfate sodium (DSS) for 7 days for all groups, except control group. The DSS-induced mice then treated by three different doses of EC extracts (0.35, 0.70, 1.75 g/kg body weight), curcumin (as a positive control, 0.10 g/kg), and a group was orally only by water. In 8th day, the mice sacrificed and collected the blood, then measured the body weight, colon weight, and colon length. Disease activity index (DAI), pro-inflammatory such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, as well as IL-10 as anti-inflammatory were measured. The results showed that after treatment for 7 days, EC extract protected the weight loss and decreased the colon weight per length ratio. In addition, EC extract also decreased the pro-inflammatory cytokines expression in serum and increased the IL-10. Moreover, EC extract protected the colonic tissue damage. According to this results, the EC ethanol extract might be can used for the treatment of colitis disease.

Ethanol is a widely used beverage and abused drug. Alcoholism causes severe damage to human health and creates serious social problems. Understanding the mechanisms underlying ethanol actions is important for the development of effective therapies. Alcohol has a wide spectrum of effects on physiological activities and behaviours, from sensitization to sedation and even intoxication with increasing concentrations. Animals develop tolerance to ethanol. However, the underlying mechanisms are not well understood. In Caenorhabditis elegans, NPR-1 negatively regulates the development of acute tolerance to ethanol. Here, using in vivo Ca2+ imaging, behavioural tests and chemogenetic manipulation, we show that the soluble guanylate cyclase complex GCY-35/GCY-36—TAX-2/TAX-4 signalling pathway in O2 sensory neurons positively regulates acute functional tolerance in npr-1 worms.

This research shows the phenolic composition and anti-inflammation properties of fruiting bodies and mycelia of 15 strains of 12 species of higher Basidiomycetes medicinal mushrooms. In this research, 15 extracts were prepared and their effects on inflammation-related mediators in RAW 264.7 cells were evaluated. In the extracts, amounts of total phenols ranged from 8.47 to 70.32 gallic acid equivalents mg/g and amounts of flavonoids ranged from 0.13 to 15.21 rutin equivalents mg/g. The production of nitric oxide, tumor necrosis factor-α, and interleukin-6 was decreased at different levels by these extracts, whereas the production of interleukin-10 was increased by 6 of the extracts. Overall, Cordyceps militaris fruiting bodies, Grifola frondosa fruiting bodies, and Ophiocordyceps sinensis mycelia might be used to ameliorate inflammatory responses.

Increasing evidence demonstrates that reactive oxygen species plays important roles in sepsis-induced acute kidney injury. This study investigated the effects of VitD3 pretreatment on renal oxidative stress in sepsis-induced acute kidney injury. Mice were intraperitoneally injected with lipopolysaccharide (LPS, 2.0mg/kg) to establish an animal model of sepsis-induced acute kidney injury. In VitD3+LPS group, mice were orally pretreated with three doses of VitD3 (25 μg/kg) at 1, 24 and 48 h before LPS injection. As expected, oral pretreatment with three daily recommended doses of VitD3 markedly elevated serum 25(OH)D concentration and efficiently activated renal VDR signaling. Interestingly, LPS-induced renal GSH depletion and lipid peroxidation were markedly alleviated in VitD3-pretreated mice. LPS-induced serum and renal nitric oxide (NO) production was obviously suppressed by VitD3 pretreatment. In addition, LPS-induced renal protein nitration, as determined by 3-nitrotyrosine residue, was obviously attenuated by VitD3 pretreatment. Further analysis showed that LPS-induced up-regulation of renal inducible nitric oxide synthase (inos) was repressed in VitD3-pretreated mice. LPS-induced up-regulation of renal p47phox and gp91phox, two NADPH oxidase subunits, were normalized by VitD3 pretreatment. In addition, LPS-induced down-regulation of renal superoxide dismutase (sod) 1 and sod2, two antioxidant enzyme genes, was reversed in VitD3-pretreated mice. Finally, LPS-induced tubular epithelial cell apoptosis, as determined by TUNEL, was alleviated by VitD3 pretreatment. Taken together, these results suggest that VitD3 pretreatment alleviates LPS-induced renal oxidative stress through regulating oxidant and antioxidant enzyme genes.