After a failed in vitro fertilization (IVF) procedure in which no transferable embryo was obtained, the possibility of a subsequent pregnancy for the patient is unknown. We conducted a cohort ...retrospective study evaluating the live birth rate in the subsequent cycles of the patients with no embryo for transfer in their first IVF attempt between 2017and 2020. The first cycle variables of patients who conceived in subsequent cycles were compared to those who did not. Additionally, for patients who conceived at last, variables related to ovarian stimulation were compared between the first cycle and the conceiving cycle. In accordance with the inclusion criteria, 529 were enrolled during the study period, of which 230 had successful pregnancies and 192 gave birth to a live infant. Cumulative live birth rates (CLBR) per cycle and patient were 26% and 36% respectively. Moreover, 99% of the live births were obtained within the first three attempts, beyond six cycles, there was no pregnancy. Stimulating variables in the first cycle were not effective in predicting the likelihood of a patient's subsequent pregnancy. Overall, patients who did not have embryos available for transfer in the first cycle had a 36% chance of getting a live birth in subsequent attempts, and the cause of failure should be considered.
An 8-week feeding trial was conducted to investigate the influence of partial replacement of fishmeal (FM) by black soldier fly (BSF) (Hermetia illucens) on the growth, distal intestine morphology, ...intestinal flora, and intestinal immune response of pearl gentian grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂). Four diets were formulated, 0% (0 g kg−1), 10% (50 g kg−1), 20% (100 g kg−1) and 30% (150 g kg−1) fishmeal were replaced with BSF, named as FM, BSF10, BSF20, BSF30, severally. The study found that, with the increasing dietary BSF levels, growth and feed conversion ratio of fish decreased significantly (P < 0.05). Chitinase and trypsin activities were significantly increased with increasing dietary BSF levels (P < 0.05). With the increasing dietary BSF levels, distal intestinal muscularis thickness and mucosal fold length decreased significantly (P < 0.05), as well as total abundance of intestinal flora. The relative abundance of four phyla and six genera among the top 20 genera were significantly affected by dietary BSF levels (P < 0.05). With the increasing dietary BSF levels, the mRNA levels of nf-κbem1, r-cel and il-10 up-regulated significantly (P < 0.05). For fish fed BSF30 diet, the mRNA levels of myd88 and tlr22 were significantly higher than fish fed FM diet (P < 0.05). In conclusion, replacement fishmeal with BSF increased activity of digestive enzymes, but negatively affected growth performance and intestinal health of pearl gentian grouper.
•The feasibility of replacing fishmeal with black soldier fly in pearl gentian grouper diet were investigated.•Dietary replacement of 10% fishmeal with BSF can negatively affected growth performance and intestinal health.•Dietary replacement of fishmeal with BSF increased feed intake and digestive enzymes activities.
Geraniin has been reported to possess potent anti-inflammatory properties and to modulate the macrophage polarization. This study sought to evaluate the protective effects and underlying mechanisms ...of geraniin on lipopolysaccharide (LPS)-induced neuroinflammation and neurobiological alternations as well as cognitive impairment. Daily intragastrical administration with geraniin (20 mg kg–1 day–1) for 14 days significantly prolonged the duration in the target quadrant (26.53 ± 2.03 versus 37.09 ± 3.27%; p < 0.05) and increased crossing-target number (1.93 ± 0.22 versus 3.08 ± 0.17; p < 0.01) in the probe test of LPS-treated mice. Geraniin also ameliorated LPS-elicited neural/synaptic impairments and decreased levels of LPS-induced Aβ generation (p < 0.05), amyloid precursor protein (APP) (p < 0.05) and β-site amyloid precursor protein cleavage enzyme 1 (BACE1) (p < 0.05). Furthermore, geraniin suppressed the production of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) (9.85 ± 0.58 versus 5.20 ± 0.52 pg/mg of protein; p < 0.01), interleukin (IL)-1β (16.31 ± 0.67 versus 8.62 ± 0.46 pg/mg of protein; p < 0.01), and IL-6 (12.12 ± 0.45 versus 7.43 ± 0.32 pg/mg of protein; p < 0.05), and inhibited glial cell activation. Moreover, geraniin effectively polarized the microglia toward an anti-inflammatory M2 phenotype. Further study revealed that geraniin targeted toll-like receptor 4 (TLR4)-mediated signaling and decreased the production of pro-inflammatory cytokines in BV-2 microglial cells. These results indicate that geraniin mitigates LPS-elicited neural/synaptic neurodegeneration, amyloidogenesis, neuroinflammation, and cognitive impairment and suggest geraniin as a therapeutic option for neuroinflammation-associated neurological disorders, such as Alzheimer’s disease.
We investigated the effects of low and high doses of β-conglycinin and the ameliorative effects of sodium butyrate (based on high-dose β-conglycinin) on the growth performance, serum immunity, distal ...intestinal histopathology, and gene, protein expression related to intestinal health in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂). The results revealed that the instantaneous growth rate (IGR) of grouper significantly increased, decreased, and increased in the low-dose β-conglycinin (bL), high-level β-conglycinin (bH) and high-level β-conglycinin plus sodium butyrate (bH-NaB), respectively. The feed coefficient ratio (FCR) was significantly increased in the bH and bH-NaB, serum levels of IFN-γ, IL-1β, and TNF-α were upregulated in the bH. The intestinal diameter/fold height ratio was significantly increased in the bH. Furthermore, there were increases in nitric oxide (NO), total nitric oxide synthase (total NOS), and peroxynitrite anion (ONOO
) in the bH, and decreases in total NOS and ONOO
in the bH-NaB. In the distal intestine, IL-1β and TGF-β1 mRNA levels were downregulated and upregulated, respective in the bL. The mRNA levels of TNF-α and IL-6 were upregulated in the bH, and downregulated in the bH-NaB, respectively. Occludin, claudin3 and ZO-3 mRNA levels were upregulated in the bL, downregulated in the bH and then upregulated in the bH-NaB. No significant differences were observed in the mRNA levels of IFN-γ and jam4. And the p-PI3K p85
/total PI3K p85 value was significantly increased in the bH and then decreased in the bH-NaB, and the total Akt value was significantly increased in the bH. These indicate β-conglycinin has a regulatory effect on serum immunity and affect distal intestinal development by modulating distal intestinal injury-related parameters. Within the distal intestinal tract, low- and high-dose β-conglycinin differentially affect immune responses and tight junctions in the distal intestine, which eventually manifests as a reduction in growth performance. Supplementing feed with sodium butyrate might represent an effective approach for enhancing serum immunity, and protects the intestines from damage caused by high-dose β-conglycinin.
Efficient delivery of specific cargos in vivo poses a major challenge to the secretory pathway, which shuttles products encoded by ∼30% of the genome. Newly synthesized protein and lipid cargos ...embark on the secretory pathway via COPII-coated vesicles, assembled by the GTPase SAR1 on the endoplasmic reticulum (ER), but how lipid-carrying lipoproteins are distinguished from the general protein cargos in the ER and selectively secreted has not been clear. Here, we show that this process is quantitatively governed by the GTPase SAR1B and SURF4, a high-efficiency cargo receptor. While both genes are implicated in lipid regulation in humans, hepatic inactivation of either mouse Sar1b or Surf4 selectively depletes plasma lipids to near-zero and protects the mice from atherosclerosis. These findings show that the pairing between SURF4 and SAR1B synergistically operates a specialized, dosage-sensitive transport program for circulating lipids, while further suggesting a potential translation to treat atherosclerosis and related cardio-metabolic diseases.
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•Lipoprotein transport is segregated from general secretion upon ER exiting•The cargo receptor SURF4 selectively transports lipoproteins from the ER•Lipid-associated non-coding SNP in humans regulates SURF4 expression•Dose-dependent SURF4 loss in mice prevents hyperlipidemia and atherosclerosis
Xiao-Wei Chen and colleagues report that synergistic pairing between the cargo receptor SURF4 and the GTPase SAR1B defines a selective transport program for circulating lipoproteins from the ER. They also show that genetic depletion of Surf4 in mice strongly protects from atherosclerosis development.
Predicting the next most likely interactive item based on the current session is the goal of session-based recommendation (SBR). In order to model the adjacent item transition information from ...previous session sequences and the current session sequences, the most advanced techniques in SBR use graph neural networks and attention mechanisms. Position-aware attention is used to incorporate the reversed position information in an item in order to learn the importance of each item in the session when generating the session representation. However, these methods have certain drawbacks. First, using data from previous sessions always introduces uncorrelated items (noise). Second, learning the sequence transition relations between items in the session sequence is challenging due to reverse position coding. This study presents a novel SBR technique called TGIE4Rec. Specifically, TGIE4Rec learns two levels of session embedding, global information enhanced session embedding and transition information enhanced session embedding. The global information enhanced session representation learning layer employs the information of other sessions and the current session to learn global-level session embedding, and the transition information enhanced session representation learning layer employs the items of the current session to learn new session embedding and integrates the time information into the item representation in the session sequence for neighbor embedding learning, so as to further enhance the sequential transition relations in the session sequence. Experiments on three benchmark datasets have demonstrated that TGIE4Rec is superior to other advanced methods.
Introduction: Type 2 diabetes mellitus (T2DM) is commonly accompanied by obesity and non-alcoholic fatty liver disease (NAFLD), yet the mechanism underlying diabetes-related NAFLD is not fully ...understood. It has been reported that melatonin can regulate glucose and lipid metabolism. This study aims to investigate the actions and mechanisms of melatonin toward the development of diabetes-related NAFLD. Methods: Melatonin (bid, 30 mg/kg/day, i.p.) was administrated to db/db mice for 8 weeks, while saline was administrated to db/m mice. The metabolic parameters of mice were measured using an automatic biochemistry analyzer. The oxidative stress indexes and mitochondrial membrane potential (MMP) were determined with kits. Pathological assessment in liver tissues was used to analyze the effects of melatonin on hepatic steatosis. The levels of IL-1β and IL-18 were detected with ELISA kits. The mRNA levels of NLRP3 inflammasome were detected using quantitative real-time PCR assay, and protein expressions were estimated using Western blotting assay. Immunofluorescence staining was used to evaluate the caspase-1 expression in the liver. Results: Melatonin treatment significantly reduced blood glucose, serum insulin, body weight, related liver weight, serum lipids, and hepatic enzymes in db/db mice. Melatonin markedly corrected the NAFLD phenotypes, including lipid accumulation, steatohepatitis, fibrosis, and oxidative stress levels. Melatonin significantly improved the MMP level and decreased the serum IL-1β and IL-18 concentrations. The mRNA levels of the NLRP3 inflammasome could also be remarkably reversed by melatonin in the liver tissues. The activation of the NLRP3 inflammasome was also suppressed, evidenced by the downregulated proteins of NLRP3, caspase-1, IL-1β, and IL-18. The enhanced fluorescence intensity of caspase-1 in the liver tissues was also obviously weakened by the melatonin treatment. Conclusion: Our study concluded that melatonin could safeguard against NAFLD by improving hepatic steatosis in db/db mice, and this action could be associated with the regulation of the NLRP3 inflammasome activation.
The purpose of subject was to explore the optimum protein requirement of juvenile grouper (Epinephelus coioides). In the test, 450 juveniles with an average weight (10.02 ± 0.22) g were randomly ...divided into six groups with triplicate, and were fed with 350, 400, 450, 500, 550 and 600 g/kg iso-lipid test diet twice 1 day for 8 weeks, respectively. The results showed that: (1) With the increase of protein level, the body weight gain rate and specific growth rate first increased and then reduced, while the feed coefficient rate first decreased and then increased, while the protein efficiency significantly decreased (P < 0.05). (2) With the increase of protein level, the condition factor, hepaticsomatic index and visceralsomatic index significantly reduced (P < 0.05). (3) With the increase of protein level, the crude protein content of whole fish and muscle gradually increased, while the crude lipid content gradually decreased. (4) High-protein diet (550-600 g/kg) significantly increased the plasma total protein content and decreased the triglyceride content of orange-spotted grouper (P < 0.05). (5) Compared with the 350 g/kg group, 500, 550, 600 g/kg groups significantly increased the activities of glutamic-pyruvic transaminase and glutamic oxaloacetic transaminase in liver (P < 0.05). (6) With the increase of protein level, the protease activity of intestine first increased and then decreased, and reached the maximum at the protein level of 500 g/kg, while lipase and amylase decreased significantly (P < 0.05). (7) The activities of acid phosphatase, superoxide dismutase and lysozyme in liver increased first and then decreased with the increase of protein level, and reached the maximum in the 400 g/kg protein group. According to the analysis specific growth rate, the optimum protein level of juvenile orange-spotted grouper is 521.84 g/kg.
Soy glycinin (11S) is involved in immune regulation. As an additive, sodium butyrate (SB) can relieve inflammation caused by 11S. To further delve into the mechanisms. A diet containing 50% fishmeal ...was the control group (FM group), and the experimental groups consisted of the FM group baseline plus 2% glycinin (GL group), 8% glycinin (GH group), and 8% glycinin + 0.13% sodium butyrate (GH-SB group). The specific growth ratio (SGR), feed utilization, and density of distal intestinal (DI) type II mucous cells were increased in the GL group. In the serum, IFN-γ was significantly upregulated in the GL group, and IgG and IL-1β were upregulated in the GH group. IgG, IL-1β, and TNF-α in the GH-SB group were significantly downregulated compared to those in the GH group. The mRNA levels of mTOR C1, mTOR C2, and Deptor were upregulated in the GL, GH, and GH-SB groups in the DI compared with those in the FM group, while the mRNA levels of mTOR C1 and Deptor in the GH group were higher than those in the GL and GH-SB groups. 4E-BP1, RICTOR, PRR5, MHC II, and CD4 were upregulated in the GH group. TSC1, mLST8, and NFY mRNA levels in the GL and GH-SB groups were upregulated compared with those in the FM and GH groups. Western blotting showed P-PI
3
K
Ser294
/T-PI
3
K, P-Akt
Ser473
/T-Akt, and P-mTOR
Ser2448
/T-mTOR were upregulated in the GH group. Collectively, our results demonstrate that low-dose 11S could improve serum immune by secreting IFN-γ. The overexpression of IgG and IL-1β is the reason that high-dose 11S reduces serum immune function, and supplementing SB can suppress this overexpression. Low-dose 11S can block the relationship between PI
3
K and mTOR C2. It can also inhibit the expression of 4E-BP1 through mTOR C1. High-dose 11S upregulates 4E-BP2 through mTOR C1, aggravating intestinal inflammation. SB could relieve inflammation by blocking PI
3
K/mTOR C2 and inhibiting 4E-BP2. Generally speaking, the hybrid grouper obtained different serum and DI immune responses under different doses of 11S, and these responses were ultimately manifested in growth performance. SB can effectively enhance serum immunity and relieve intestinal inflammation caused by high dose 11S.
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