Recurrent implantation failure (RIF) refers to repeated failure to become pregnant after transferring embryos with normal morphology. However, the pathogenesis of RIF remains unrevealed, especially ...for those without any pathological features. In this study, we characterized the vaginal microbiota and metabolomes of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first frozen embryo transfer (FET) cycle were used as controls. Based on 16S rRNA gene sequencing of the vaginal microbiota, the vaginal
showed a significant positive correlation with the pregnancy rate, and the RIF group presented higher microbial α-diversity than the control group (
value = 0.016). The metabolomic profile identified 2,507 metabolites, of which 37 were significantly different between the two groups (
value < 0.05, variable importance for the projection VIP > 1). Among them, 2',3-cyclic UMP and inositol phosphate were the top two metabolites that were higher in the RIF group, while glycerophospholipids and benzopyran were important metabolites that were lower in the RIF group. A lack of lysobisphosphatidic acid and prostaglandin metabolized from glycerophospholipids will lead to deferred implantation and embryo crowding. Benzopyran, as a selective estrogen receptor modulator, may affect the outcome of pregnancy. All of the changes in metabolite profiles may result in or from the differential microbiota compositions in RIF patients. In conclusion, significant differences were presented in the vaginal microbiota and metabolomes between patients with unexplained RIF and women who became pregnant in the first FET cycle. For the first time, this study elaborates the possible pathogenesis of RIF by investigating the vaginal microbiota and metabolites in RIF patients.
fertilization-embryo transfer (IVF-ET) is now widely applied for treating infertility, and unexplained recurrent implantation failure (RIF) has become a substantial challenge. We hypothesize that vaginal microbial dysbiosis is associated with RIF, as it is linked to many female reproductive diseases. In this study, we characterized the vaginal microbiota and metabolomes of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first IVF cycle were set as controls. In general, significant differences were discovered in the vaginal microbiota and metabolomes between the two groups. This study is the first detailed elaboration of the vaginal microbiota and metabolites associated with RIF. We believe that our findings will inspire researchers to consider the dynamics of microbiomes related to the microenvironment as a critical feature for future studies of nosogenesis not only for RIF but also for other reproductive diseases.
Nitrated phenols in particulate matters are among the major components of brown carbon, harm plant growth and human health. To understand the size distributions of nitrated phenols in the polluted ...coastal region and the factors influencing these distributions, size-resolved particulate matters were collected from a rural site in the coastal city of Qingdao, China, in January 2019, and analyzed for the presence of 11 nitrated phenols. The average concentrations of total nitrated phenols in fine- and coarse-mode particles were 123.6 and 37.2 ng m−3, respectively. 4-Nitrophenol was found to be the dominant nitrated phenol, followed by 3-methyl-6-nitrocatechol, 3-methyl-4-nitrophenol, and 4-nitrocatechol. On average, maximum concentrations of nitrated phenols were in condensation-mode particles, whereas a minor concentration peak of nitro-salicylic acids was present in droplet-mode particles. In addition, a minor concentration peak of 4-methyl-2,6-dinitrophenol was noticed in coarse-mode particles. Comparisons of the size distributions under different situations confirmed that both primary emissions and secondary formation had significant effects on the abundances and particle-sizes of nitrated phenols. Coal combustion in residential villages and firework burning during a festival led to a sharp increase of nitrated phenols in condensation-mode particles, whereas dust promoted their heterogeneous formation in coarse-mode particles, and high humidity in the coastal area facilitated their aqueous formation in droplet-mode particles.
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•Concentrations and size distributions of 11 nitrated phenols (NPs) were presented.•Primary sources and secondary formation had impacts on size distributions of NPs.•Coal combustion and fireworks promoted the increases of NPs in condensation mode.•Dust in the atmosphere caused the heterogeneous formation of NPs in coarse particles.•High humidity obviously facilitated the aqueous formation of NPs in droplet mode.
Low energy availability (LEA) is a medical condition observed in athletes, with a higher prevalence in aesthetic sports. For the first time, this study evaluated the relative prevalence of LEA in ...female elite athletes (ELA) and recreational athletes (REA) in aesthetic sports in China.
Female athletes from 6 sports (trampolining, rhythmic gymnastics, aerobics, dance sport, cheerleading and dance) were recruited, including ELA (n = 52; age = 20 ± 3) on Chinese national teams and REA (n = 114; Age = 20 ± 2) from Beijing Sport University. Participants completed 2 online questionnaires to assess LEA and eating disorder risk. These included the Low Energy Availability in Females Questionnaire (LEAF-Q), which provided information on injury history, gastrointestinal function and menstrual history, and the Eating Disorder Inventory-3 Referral Form (EDI-3 RF). For a sub-group of elite athletes (n = 14), body composition, bone mineral density, and blood serum were also quantified.
A total of 41.6% of participants (n = 69) were at increased risk of LEA, and 57.2% of participants (n = 95) were classified as high in eating disorder risk. For ELA vs. REA, there was a significantly higher prevalence of LEA risk (55.8% vs. 35.1%; p = 0.012) and amenorrhea (53.8% vs. 13.3%; p < 0.001). Elite athletes at increased risk of LEA had significantly lower estradiol (p = 0.021) and whole-body BMD (p = 0.028). Pearson correlations indicated that the whole-body BMD (r = - 0.667, p = 0.009) correlated negatively with LEAF-Q score.
Results of this study indicate that there is a risk of LEA in female Chinese athletes within aesthetic sports, and significantly higher prevalence of increased LEA risk observed in ELA than in REA. Chinese coaches and sports medicine staff working elite female athletes in aesthetic sports should develop strategies to reduce the prevalence of LEA.
Amines in fine particles constitute a significant fraction of secondary organic aerosols and have adverse effects on air quality and human health. To understand the chemical composition, variation ...characteristics, and potential sources of fine particulate amines in the coastal area in northern China, field sampling and chemical analysis were conducted in coastal Qingdao in the winter of 2018 and 2019. A total of 15 major amines were identified and quantified by using an ultra-high-performance liquid chromatography coupled with mass spectrometry. The average concentration of total amines in PM2.5 samples was approximately 130 ng m−3. Dimethylamine was the most abundant species with average fractions of 44.8% and 65.0% in the quantified amines during the two field campaigns, followed by triethylamine (22.9% and 8.7%) and methylamine (8.3% and 4.4%). The amines in PM2.5 usually exhibited elevated concentrations in the presence of high levels of SO2 and NOx or in the condition of high relative humidity. A receptor model of positive matrix factorization was employed and seven major sources were identified, including coal combustion, industrial production, vehicle exhaust, biomass burning, agricultural activities, secondary formation, and marine emission. Surprisingly, most of 15 amines in fine particles primarily originated from the primary emissions of anthropogenic activities particularly related to coal combustion and industrial productions, which should be given close concern to address the amine pollution.
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•Fifteen amines in ambient fine particles were identified and quantified by UHPLC-MS.•DMA and TMA were the most abundant amines in PM2.5 in winter in coastal Qingdao.•Elevated concentrations of amines were associated with coal combustion activities.•Particulate amines were apt to increase in the condition of high humidity.•Anthropogenic sources were the major sources of most particulate amines.
Accurate identification Candida is important for successful therapy and epidemiology study. The aim of research is to study API 20C yeast identification system identification rate by using molecular ...identification as gold standard and tested the antifungal susceptibility of Candida from patients with vulvovaginal candidiasis (VVC).
In total, 3574 yeast isolates were obtained from patients with VVC. API 20C yeast identification, molecular identification and in vitro antifungal susceptibility were performed.
C. albicans was the predominant Candida species 2748 isolates, 76.9% in VVC. The isolates from vaginal samples represented 22 species based on molecular identification. The API 20C system identifies only 11 of the species encountered during the study period. Based on the API 20C system, 3273 (91.78%) isolates were correctly identified to the species level. The correct identification rate of the API 20C system for rare yeast was 15.29% (26/170 isolates). Antifungal susceptibility was tested in a total of 1844 isolates of Candida from patients with VVC. C. albicans was susceptible to most of the tested antifungals. The MICs of azoles for C. glabrata were higher than those for C. albicans. The MICs of echinocandins for C. parapsilosis were higher than those for C. albicans.
The API 20C yeast identification system can be used to reliably identify the most common Candida species while molecular methods are necessary for the identification of closely related, emerging, and rare yeast species. The results from this study suggest that much of the previous studies on the epidemiology of VVC should be re-thought. C. albicans was susceptible to most of the tested antifungals.
Anti-tumor activity of
polysaccharides (TFPS) has been widely reported, but its mechanism remains poorly understood. In this study, we established an in vitro co-culture system (B16 melanoma cells ...and RAW 264.7 macrophage-like cells) to explore the potential anti-tumor mechanism of TFPS. Based on our results, TFPS exhibited no inhibition on the cell viability of B16 cells. However, significant apoptosis was observed when B16 cells were co-cultured with TFPS-treated RAW 264.7 cells. We further found that mRNA levels of M1 macrophage markers including iNOS and CD80 were significantly upregulated in TFPS-treated RAW 264.7 cells, while M2 macrophage markers such as Arg-1 and CD 206 remained unchanged. Besides, the migration, phagocytosis, production of inflammatory mediators (NO, IL-6 and TNF-α), and protein expression of iNOS and COX-2 were markedly enhanced in TFPS-treated RAW 264.7 cells. Network pharmacology analysis indicated that MAPK and NF-κB signaling pathways may be involved in M1 polarization of macrophages, and this hypothesis was verified by Western blot. In conclusion, our research demonstrated that TFPS induced apoptosis of melanoma cells by promoting M1 polarization of macrophages, and suggested TFPS may be applied as an immunomodulatory for cancer therapy.
Atopic dermatitis (AD), characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, has a high incidence worldwide. Recent evidence has shown that the modulation of gut ...microbiota is crucial for alleviating clinical symptoms of AD. Tremella fuciformis polysaccharides (TFPS) have been demonstrated to have a variety of biological activities such as immunomodulatory, anti-tumor, antioxidant, anti-inflammatory, neuroprotective, hypoglycemic and hypolipidemic effects. However, their effects on AD treatment have never been investigated. In this study, we compared the therapeutic effects of topical or oral administration of TFPS on AD in dinitrofluorobenzene (DNFB)-induced AD mice. Both topical application and oral administration of TFPS led to improvement on transdermal water loss, epidermal thickening, and ear edema in AD mice, but the oral administration showed significantly better efficacy than the topical application. The TFPS treatment increased the proportion of CD4 (+) CD25 (+) Foxp3 (+) regulatory T cells in mesenteric lymph nodes. Additionally, the non-targeted metabolomics and sequencing of 16S rDNA amplicons were performed, revealing metabolite modulation in feces and changed composition of gut microbiota in mice, which were induced for AD-like disorder and treated by oral administration of TFPS. Collectively, these data suggest that the oral administration of TFPS may constitute a novel effective therapy for AD, with underlying mechanisms associated with the regulation of immune response, and improvement of both metabolism and the composition of intestinal microbiota.
Preeclampsia is a multi-system disease that is unique to human pregnancy. Impaired extravillous trophoblast migration and invasion accompanied by poor spiral vascular remodeling is thought to be the ...initial reason. This study investigated cAMP-dependent protein kinase inhibitor-b(PKIB) expression in placentas and its involvement in the pathogenesis of PE. We used immunohistochemistry and western blotting to calculate PKIB levels in the placentas. Then we knocked down PKIB by siRNA and used real-time cell analysis to assess the invasion and migration ability of trophoblasts. Tube formation assay and spheroid sprouting assay were utilized to identify the ability to form vessels of trophoblasts. At last, western blotting was used to demonstrate the level of phosphorylated Akt, as well as downstream-related genes of Akt signaling pathway in trophoblasts. We first found that PKIB expression level was lower in the PE placentas than in the normal placentas. In addition, we found that downregulation of PKIB can inhibit the migration, invasion, and the ability to form vessels of HTR8/SVneo cells. Downregulation of PKIB leaded to a decrease in phosphorylated Akt, as well as downstream proteins such as matrix metalloproteinase 2, matrix metalloproteinase 9, and glycogen synthase kinase 3β, which are related to migration and invasion. Our study revealed that the downregulation of PKIB expression resulted in decreased migration, invasion, and vessel formation ability by regulating Akt signaling pathway in placental trophoblasts in PE.
Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation ...with live
may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin
with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral
TM13 and
LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that
TM13 and
LG55 mainly acted through the intestine. A higher abundance of
at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up,
TM13 and
LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV.
https://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.
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