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In vitro fertilization (IVF) has wide application in human infertility and animal breeding. It is also used for research on reproduction, fertility and development. However, IVF embryos are still inferior to their in vivo counterparts. Some substances in seminal plasma appear to have important roles in embryo development, and during the traditional IVF procedure, the seminal plasma is washed away. In this study, extracellular vesicles (EVs) were concentrated from seminal plasma by ultracentrifugation, visualized using transmission electron microscopy, and particle size distributions and concentrations were determined with a NanoSight particle analyzer. We found particles of various sizes in the seminal plasma, the majority having diameters ranging from 100 to 200 nm and concentrations of 6.07 × 1010 ± 2.91 × 109 particles/ml. Addition of seminal plasma EVs (SP-EVs) to the IVF medium with mouse oocytes and sperm significantly increased the rate of blastocyst formation and the inner cell mass (ICM)/trophectoderm (TE) cell ratio, and reduced the apoptosis of blastocysts. Our findings provide new insights into the role of seminal plasma EVs in mediating embryo development and it suggests that SP-EVs may be used to improve the developmental competence of IVF embryos, which has important significance for assisted reproduction in animals and humans.
This study is performed to figure out how the presence of diabetes affects the infection, progression and prognosis of 2019 novel coronavirus disease (COVID-19), and the effective therapy that can treat the diabetes-complicated patients with COVID-19. A multicentre study was performed in four hospitals. COVID-19 patients with diabetes mellitus (DM) or hyperglycaemia were compared with those without these conditions and matched by propensity score matching for their clinical progress and outcome. Totally, 2444 confirmed COVID-19 patients were recruited, from whom 336 had DM. Compared to 1344 non-DM patients with age and sex matched, DM-COVID-19 patients had significantly higher rates of intensive care unit entrance (12.43% vs. 6.58%, P = 0.014), kidney failure (9.20% vs. 4.05%, P = 0.027) and mortality (25.00% vs. 18.15%, P < 0.001). Age and sex-stratified comparison revealed increased susceptibility to COVID-19 only from females with DM. For either non-DM or DM group, hyperglycaemia was associated with adverse outcomes, featured by higher rates of severe pneumonia and mortality, in comparison with non-hyperglycaemia. This was accompanied by significantly altered laboratory indicators including lymphocyte and neutrophil percentage, C-reactive protein and urea nitrogen level, all with correlation coefficients >0.35. Both diabetes and hyperglycaemia were independently associated with adverse prognosis of COVID-19, with hazard ratios of 10.41 and 3.58, respectively.
The parasite Fasciola hepatica is an important zoonotic parasite. The development of an animal model of F. hepatica's life cycle is critical for studying the biological characteristics of the parasite in snails and mammals. Eggs of F. hepatica of bovine origin were cultured, and metacercariae were obtained after infection of Galba pervia snails. The life cycle system of F. hepatica was initiated in 2 different animals by orally infecting rabbits, SD rats and Kunming mice with the metacercariae. The animals' survival after infection, parasite migration in the animals and pathological damage to the liver were observed. We discovered that rabbits died due to acute suppurative hepatitis 60–69 days after infection, and eggs were found in the feces on day 63 of infection. The liver of SD rats showed punctate lesions on day 3 of infection, and further changes occurred as the infection progressed. However, liver repair was observed at week 9. SD rats survived for more than a year after infection and continued the F. hepatica life cycle. The liver lesions in Kunming mice after infection were similar but more severe than those in SD rats. Death was observed on the 31st post-infection day. We discovered that while rabbits, SD rats and Kunming mice can all be used as animal models of F. hepatica, SD rats are more suitable experimental animals in terms of tolerance and pathological response.
It is generally accepted that high-oleic crops have at least 70% oleate. As compared to their normal-oleic counterparts, oil and food products made from high-oleic peanut have better keeping quality and are much healthier. Therefore, high-oleic peanut is well recognized by processors and consumers. However, owing to the limited availability of high-oleic donors, most present-day high-oleic peanut varietal releases merely have F435 type FAD2 mutations. Through screening of a mutagenized peanut population of 15L46, a high-yielding peanut line with desirable elliptical oblong large seeds, using near infrared model for predicting oleate content in individual single seeds, high-oleic peanut mutants were identified. Sequencing FAD2A and FAD2B of the mutants along with the wild type revealed that these mutants possessed G448A FAD2A (F435 type FAD2A mutation) and G558A FAD2B (non-F435 type FAD2B mutation). Expression of the wild and mutated type FAD2B in yeast verified that the functional mutation contributed to the high-oleic phenotype in these mutants. The mutants provided additional high-oleic donors to peanut quality improvement.
Rheumatoid arthritis (RA) is a heterogeneous autoimmune disorder that leads to severe joint deformities, negatively affecting the patient's quality of life. Extracellular vesicles (EVs), which include exosomes and ectosomes, act as intercellular communication mediators in several physiological and pathological processes in various diseases including RA. In contrast, EVs secreted by mesenchymal stem cells perform an immunomodulatory function and stimulate cartilage repair, showing promising therapeutic results in animal models of RA. EVs from other sources, including dendritic cells, neutrophils and myeloid-derived suppressor cells, also influence the biological function of immune and joint cells. This review describes the role of EVs in the pathogenesis of RA and presents evidence supporting future studies on the therapeutic potential of EVs from different sources. This information will contribute to a better understanding of RA development, as well as a starting point for exploring cell-free-based therapies for RA.
Maternal overnutrition-induced fetal programming predisposes offspring to cardiovascular health issues throughout life. Understanding how these adverse cardiovascular effects are regulated at the maternal–fetal crosstalk will provide insight into the mechanisms of these cardiovascular diseases, which will help in further identifying potential targets for intervention. Here, we uncover a role of oxidative stress caused by prenatal overnutrition in governing cardiac damage. Mice exposed to maternal obesity showed remarkable pathological cardiomyocyte hypertrophy (pmale < 0.001, Cohen’s dmale = 1.77; pfemale < 0.001, Cohen’s dfemale = 1.94), increased collagen content (pmale < 0.001, Cohen’s dmale = 2.13; pfemale < 0.001, Cohen’s dfemale = 2.71), and increased levels of transforming growth factor β (TGF-β) (pmale < 0.001, Cohen’s dmale = 3.02; pfemale < 0.001, Cohen’s dfemale = 4.52), as well as left ventricular dysfunction in adulthood. To cope with increased oxidative stress in the myocardial tissue of offspring from obese mothers, we sought to decrease the effect of oxidative stress and prevent the development of these cardiovascular conditions with use of the antioxidant N-acetylcysteine during pregnancy. As predicted, after treatment with the antioxidant, there was greatly mitigated cardiomyocyte hypertrophy (pmale < 0.001, Cohen’s dmale = 1.31; pfemale < 0.001, Cohen’s dfemale = 0.82) and cardiac fibrosis, including decreased composition of collagen fibers (pmale < 0.01, Cohen’s dmale = 1.45; pfemale < 0.05, Cohen’s dfemale = 1.23) and reduced levels of TGF-β (pmale < 0.05, Cohen’s dmale = 1.83; pfemale < 0.01, Cohen’s dfemale = 3.81). We also observed improved left ventricle contractile function together with the alleviation of enhanced oxidative stress in the myocardial tissue of offspring. Collectively, these results established a crucial role of oxidative stress in prenatal overnutrition-associated ventricular remodeling and cardiac dysfunction. Our findings provided an important target for intervention of cardiovascular disease in overnutrition-related fetal programming.
Viruses completely rely on the energy and metabolic systems of host cells for life activities. Viral infections usually lead to cytopathic effects and host diseases. To date, there are still no specific clinical vaccines or drugs against most viral infections. Therefore, understanding the molecular and cellular mechanisms of viral infections is of great significance to prevent and treat viral diseases. A variety of viral infections are related to the p38 MAPK signalling pathway, and p38 is an important host factor in virus-infected cells. Here, we introduce the different signalling pathways of p38 activation and then summarise how different viruses induce p38 phosphorylation. Finally, we provide a general summary of the effect of p38 activation on virus replication. Our review provides integrated data on p38 activation and viral infections and describes the potential application of targeting p38 as an antiviral strategy.
Migratory insects display diverse behavioral strategies in response to external environmental shifts, via energy allocation of migration-reproduction trade-offs. However, how migratory insects distribute energy between migration and reproduction as an adaptive strategy to confront temporary low temperatures remains unclear. Here, we used Mythimna separata, a migratory cereal crop pest, to explore the effects of low temperature on reproductive performance, behavior, and energy allocation. We found that the influence of low temperatures on reproduction was not absolutely negative, but instead depended on the intensity, duration, and age of exposure to low temperature. Exposure to 6°C for 24 h significantly accelerated the onset of oviposition and ovarian development, and increased the synchrony of egg-laying and lifetime fecundity in 1-day-old adults compared to the control, while female's flight capacity decreased significantly on the first and second day after moths were exposed to 6°C. Furthermore, the abdominal and total triglycerides levels of females decreased significantly from exposure to low temperature, but their thoracic triglyceride content was significantly higher than the control on the third and fourth day. These results indicated that low temperatures induced M. separata to reduce energy investment for the development of flight system. This resulted in the shifting of moths from being migrants to residents during the environmental sensitive period (first day post-emergence). This expands our understanding of the adaptive strategy employed by migratory insects to deal with low temperatures and aids in the management of this pest species in China.
Application of biochar to rice has shown to elicit positive environmental and agricultural impacts due to its physicochemical properties. However, the relationship between greenhouse gas (GHG) emissions, rice yield, and soil nutrient status under biochar amendment remains unclear. In this study, rice yield and methane (CH4) and nitrous oxide (N2O) emissions were quantified in response to biochar application rate (0, 10, 20, and 40 t ha−1) to early and late subtropical rice cropping systems. We found that application of 10 t of biochar ha−1 to early rice reduced average CH4 emission fluxes, while all biochar application rates diminished average emissions in late rice paddy. Total global warming potential (GWP) and GHG intensity (GHGI) were inherently greater in late rice than early rice cropping. In early rice, GWP and GHGI were found to be similar between soil control, 10 and 20 t of biochar ha−1 treatments, although the largest occurred in the 40 t of biochar ha−1 treatment, whereas in late rice cropping, they were not affected by biochar application rates. Compared to the nil-biochar application, biochar application at varied rates did not affect rice yield. However, compared to 10 t biochar ha−1, increasing biochar application rate to 40 t ha−1 significantly decreased total rice yield (sum of early and late cropping). Generally, application of biochar increased soil salinity and total Fe and Fe2+ content while reducing soil bulk density. Temporal effects of biochar application were noted on CH4 emission flux, soil temperature, and soil Fe2+ and Fe3+ in early rice; and soil temperature, salinity, NH4+-N, NO3−-N, and soil Fe2+ and Fe3+ in late rice. This study confirms that the application of biochar at the lower rate of 10 t ha−1 is optimal for maintaining rice yield while reducing GHG emissions. Moreover, the study demonstrates the potential benefit of biochar in sustainable subtropical rice production.
Cancer remains the leading cause of death worldwide, and metastasis is still the major cause of treatment failure for cancer patients. Epithelial–mesenchymal transition (EMT) has been shown to play a critical role in the metastasis cascade of epithelium-derived carcinoma. Tumour microenvironment (TME) refers to the local tissue environment in which tumour cells produce and live, including not only tumour cells themselves, but also fibroblasts, immune and inflammatory cells, glial cells and other cells around them, as well as intercellular stroma, micro vessels and infiltrated biomolecules from the nearby areas, which has been proved to widely participate in the occurrence and progress of cancer. Emerging and accumulating studies indicate that, on one hand, mesenchymal cells in TME can establish ‘crosstalk’ with tumour cells to regulate their EMT programme; on the other, EMT-tumour cells can create a favourable environment for their own growth via educating stromal cells. Recently, our group has conducted a series of studies on the interaction between tumour-associated macrophages (TAMs) and colorectal cancer (CRC) cells in TME, confirming that the interaction between TAMs and CRC cells mediated by cytokines or exosomes can jointly promote the metastasis of CRC by regulating the EMT process of tumour cells and the M2-type polarisation process of TAMs. Herein, we present an overview to describe the current knowledge about EMT in cancer, summarise the important role of TME in EMT, and provide an update on the mechanisms of TME-induced EMT in CRC, aiming to provide new ideas for understanding and resisting tumour metastasis.
During the late Palaeozoic Era, a series of related marine strata dominated by multi-layer limestones were deposited in the southern North China Craton. In order to gain new insights into the systematic geochemistry of the carbonate succession of the representative formation (Taiyuan Formation), we examined 59 limestone samples collected from the Huaibei Coal Basin (HCB), with a view towards quantitatively determining the major and trace elements and stable isotope compositions. The data obtained can provide essential evidence for reconstruction of the depositional palaeo-environment and tectonic setting of the Taiyuan Formation. Both X-ray diffraction analyses and palaeoredox proxies (e.g. V/Cr, V/(V + Ni) and authigenic U) indicated that the limestone layers were deposited in an oxic–dysoxic zone, with calcite as the main component. Moreover, palaeomagnetic evidence provided support for the conclusion that these limestones were laid down within an epicontinental sea depositional environment under a warm or hot palaeoclimate during the transition between late Carboniferous and early Permian time. Additionally, evidence obtained from our analyses of trace and rare earth elements revealed that the tectonic setting of the Taiyuan Formation (L1–L5) in the HCB transited from an open ocean to a passive continental margin, thereby indicating that this transformation stemmed from the subduction closure of the northeastern Palaeotethys Ocean. The findings of this study would be of interest to those working on the upper Palaeozoic marine strata in the southern North China Craton.
Understanding factors associated with post-discharge sleep quality among COVID-19 survivors is important for intervention development.
This study investigated sleep quality and its correlates among COVID-19 patients 6 months after their most recent hospital discharge.
Healthcare providers at hospitals located in five different Chinese cities contacted adult COVID-19 patients discharged between 1 February and 30 March 2020. A total of 199 eligible patients provided verbal informed consent and completed the interview. Using score on the single-item Sleep Quality Scale as the dependent variable, multiple linear regression models were fitted.
Among all participants, 10.1% reported terrible or poor sleep quality, and 26.6% reported fair sleep quality, 26.1% reported worse sleep quality when comparing their current status with the time before COVID-19, and 33.7% were bothered by a sleeping disorder in the past 2 weeks. After adjusting for significant background characteristics, factors associated with sleep quality included witnessing the suffering (adjusted B = −1.15, 95% CI = −1.70, −0.33) or death (adjusted B = −1.55, 95% CI = −2.62, −0.49) of other COVID-19 patients during hospital stay, depressive symptoms (adjusted B = −0.26, 95% CI = −0.31, −0.20), anxiety symptoms (adjusted B = −0.25, 95% CI = −0.33, −0.17), post-traumatic stress disorders (adjusted B = −0.16, 95% CI = −0.22, −0.10) and social support (adjusted B = 0.07, 95% CI = 0.04, 0.10).
COVID-19 survivors reported poor sleep quality. Interventions and support services to improve sleep quality should be provided to COVID-19 survivors during their hospital stay and after hospital discharge.
To explore and develop effective treatments is crucial for patients with Alzheimer’s dementia (AD). In pathology, the amyloid deposits of AD result in disruption of the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. Although an increasing number of studies have been concluded a positive therapeutic effect on cognition in AD, tDCS studies to date are limited on exploring the duration of its efficacy. In this pilot study, we investigate the effects of tDCS in AD and verify its extending beneficial effects for 3 months follow-up period after the end of stimulation.
34 AD participants aged 55-90 years (mean age 75.9 (66-86)) were included in a double-blind, randomized, sham-controlled crossover study. All participants were randomly assigned to receive 10 consecutive daily sessions of active tDCS (or sham) and switched groups 3 months later. The anodal electrode was on the left dorsal lateral prefrontal cortex and the cathodal electrode was on the right supraorbital area. In each active session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in the active group. All subjects received a series of neuropsychological assessments including CDR, MMSE, CASI and WCST at baseline and in 2 weeks, 4 weeks, and 12 weeks post-tDCS (or sham) 10 sessions. Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess the differences in participant demographic characteristics and to compare the differences of test scores between groups.
The active tDCS group showed significant improvements on CASI total scores from baseline to 2-weeks, 1-month and 3-months after active stimulations, though the improvement declined over time. There are also different presentations in total correct items, conceptual level responses, failure to maintain sets of WCST between active tDCS and sham groups. There is no difference in MMSE, CASI and WCST scores in the sham groups.
These results suggest a long term-beneficial effects of tDCS in AD.
Dementia with Lewy Bodies (DLB), this second most common form of degenerative dementia, presents more functional disability, more potentially fatal complication, more impaired quality of life than Alzheimer’s dementia. There is no FDA-proved medication can slow, stop or improve the progression of cognitive declines in DLB. Identifying effective treatments is a critical issue for DLB. In neuropathology, extracelluar α-syn oligomers interfere with the expression of long-term potentiation, and influence memory and learning. Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. So far, only two researches assess the effect of tDCS in DLB. In this pilot study, we investigate the effects of tDCS in DLB.
Using a double-blind, randomized, sham- controlled and crossover trial design, 11 DLB aged 55-90 years (mean age 77.8) were included in the study. DLB diagnostics is according to DSM-5 criteria. The CDR ratings of DLB participants ranged from 0.5 to 2. The active tDCS (or sham) process includes consecutive daily sessions of active tDCS (or sham) for 10 days. The anodal electrode was over the left dorsal lateral prefrontal cortex (DLPFC) and the cathodal electrode on the right supraorbital area. In each session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in the active group. All subjects received a series of neuropsychological tests, which included CDR, MMSE, CASI, NPI and WCST, before and after these treatment sessions. Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess the differences in participant demographic characteristics and to compare the differences among groups.
On CASI, MMSE, NPI and WCST, there were no statistically significant differences between pre- and post the 10-session course for the active and the sham groups. No side effects reported during or immediately after active tDCS stimulation.
These results suggest that left DLPFC anodal, and right deltoid cathodal tDCS, do not improve cognition, behavioral and psychological symptoms in DLB. Larger-scale trials are needed to confirm the effect of tDCS in DLB.
Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.
Long non-coding RNAs (lncRNAs) exert vital functions in the occurrence and development of various tumours. The aim of this study was to examine the regulatory effect and underlying molecular mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) on the proliferation, invasion and migration of thyroid tumour cells. The expression of SNHG14 in thyroid tumour cell lines was determined using qRT-PCR. CCK-8 and western blot were used to detect the effects of SNHG14 on proliferation and apoptosis of thyroid tumour cells. The effect of SNHG14 on the migration and invasion of thyroid tumour cells was analyzed using immunofluorescence, wound-healing and transwell assays. A targeting relationship between SNHG14 and miR-93-5p was determined using bioinformatics software and luciferase reporter assays. In addition, CCK-8, immunofluorescence, wound-healing and transwell assays were applied to demonstrate that SNHG14 promoted the proliferation, migration and invasion of thyroid tumour cells by targeting miR-93-5p. The biological function of SNHG14 in vivo was explored through a xenograft model and immunohistochemistry. SNHG14 was upregulated in thyroid tumour cells compared with normal cells. Downregulation of SNHG14 effectively reduced the proliferation, migration and invasion of TPC-1 cells, and induced cell apoptosis. Moreover, SNHG14 directly targeted miR-93-5p and there was a negative correlation between them. Further functional experiments illustrated that miR-93-5p overexpression dramatically reversed the promoting role of SNHG14 in proliferation, migration and invasion of TPC-1 cells. Our results demonstrated that SNHG14 promotes the proliferation, invasion and migration of thyroid tumour cells by downregulating miR-93-5p.
Inflammation is a central mechanism in metabolic disorders associated with morbidity and mortality and dietary factors can modulate inflammation. We aimed to prospectively investigate the association between an empirically developed, food-based dietary inflammatory pattern (EDIP) score and the risk of overall and cause-specific mortality, using data from the US National Health and Nutrition Examination Survey from 1999 to 2014. EDIP score was derived by entering thirty-nine predefined commonly consumed food groups into the reduced rank regression models followed by stepwise linear regression, which was most predictive of two plasma inflammation biomarkers including C-reactive protein and leucocyte count among 25 500 US adults. This score was further validated in a testing set of 9466 adults. Deaths from baseline until 31 December 2015 were identified through record linkage to the National Death Index. During a median follow-up of 7·8 years among 40 074 participants, we documented 4904 deaths. Compared with participants in the lowest quintile of EDIP score, those in the highest quintile had a higher risk of overall death (hazard ratio (HR) = 1·19, 95 % CI 1·08, 1·32, Ptrend = 0·002), and deaths from cancer (HR = 1·41, 95 % CI 1·14, 1·74, Ptrend = 0·017) and CVD (HR = 1·22, 95 % CI 0·98, 1·53, Ptrend = 0·211). When stratified by age, the association of EDIP with overall mortality was stronger among individuals under 65 years of age (Pinteraction = 0·001). Diets with a higher inflammatory potential were associated with increased risk of overall and cancer-specific mortality. Interventions to reduce the adverse effect of pro-inflammatory diets may potentially promote health and longevity.
This study analyzed the effects of the day of trophectoderm (TE) biopsy and blastocyst grade on clinical and neonatal outcomes. The results showed that the implantation and live birth rates of day 5 (D5) TE biopsy were significantly higher compared with those of D6 TE biopsy. The miscarriage rate of the former was lower than that of the latter, but there was no statistically significant difference. Higher quality blastocysts can achieve better implantation and live birth rates. Among good quality blastocysts, the implantation and live birth rates of D5 and D6 TE biopsy were not significantly different. Among fair quality and poor quality blastocysts, the implantation and live birth rates of D5 TE biopsy were significantly higher compared with those of D6 TE biopsy. Neither blastocyst grade nor the day of TE biopsy significantly affected the miscarriage rate. Neonatal outcomes, including newborn sex, gestational age, preterm birth, birth weight and low birth weight in the D5 and D6 TE biopsies were not significantly different. Both blastocyst grade and the day of TE biopsy must be considered at the same time when performing preimplantation genetic testing–frozen embryo transfer.