Construction of an Angular Tricyclic Benzofuran Skeleton Using the C-H Activation Strategy.

A protocol for the construction of an angular tricyclic benzofuran skeleton based on the C-H activation strategy has been established. Different phthalide lactones on this skeleton can be easily assembled with various side chains by using C-H activation with aldehydes and subsequent reduction. This skeleton provides a versatile and crucial motif for the total synthesis of naturally occurring angular tricyclic benzofurans and their derivatives. Based on this protocol, the improved total syntheses of daldinin A and annullatin D were achieved in yields of 17.3 and 7.6%, respectively.

Photocatalyst-free visible-light-induced highly selective acylation of purine nucleosides at the C6 position.

A protocol for visible-light-induced C-H acylation selectively at the C6 position of purine nucleosides with aldehydes under photocatalyst-free conditions was established herein. This protocol allows the green, mild, and efficient functionalization of various purine nucleosides with a broad range of alkyl and aryl aldehydes.

Electrochemical Synthesis of Nb-Doped BaTiO3 Nanoparticles with Titanium-Niobium Alloy as Electrode.

In this paper, Nb-doped BaTiO3 nanoparticles (BaNb0.47Ti0.53O3) were prepared using an electrochemical method in an alkaline solution, with titanium-niobium alloy as the electrode. The results indicated that under relatively mild conditions (normal temperature and pressure, V < 60 V, I < 5 A), cubic perovskite phase Nb-doped BaTiO3 nanoparticles with high crystallinity and uniform distribution can be synthesized. With this increase in alkalinity, the crystallinity of the sample increases, the crystal grain size decreases, and the particles become more equally dispersed. Furthermore, in our study, the average grain size of the nanoparticles was 5−20 nm, and the particles with good crystallinity were obtained at a concentration of 3 mol/L of NaOH. This provides a new idea and method for introducing foreign ions under high alkalinity conditions.

MicroRNA-126 engineered muscle-derived stem cells attenuates cavernosa injury-induced erectile dysfunction in rats.

BACKGROUND: Cavernosa injury is a common cause of organic erectile dysfunction (ED), which requires safe and effective treatments. In the present study, the therapeutic efficiency of muscle-derived stem cells (MDSCs) modified with microRNA-126 (miR-126) was determined in rats with cavernosa injury. METHODS: MDSCs were transfected with miR-126 and then were transplanted into rats with cavernosa injury. Erectile function, vascular function (western blot and immunofluorescence), extraction, and detection of exosomes were then undertaken. RESULTS: On the 28th day after transplantation, the highest value of intra-cavernous pressure (ICP)/mean arterial pressure (MAP) in rats of miRNA-126 group (0.84 ± 0.14) was observed (Control: 0.38 ± 0.07; MDSC: 0.54 ± 0.11, Vector: 0.60 ± 0.02; respectively). Treatment of miRNA-126-modified-MDSCs remarkably strengthened vascular structure, supported by hematoxylin-eosin staining. The expression of CD31, von Willebrand Factor and vascular endothelial factors were higher than those in other groups, indicating improved vascular function. In vitro mechanism studies showed that exosomes containing miR-126 isolated from MDSCs promoted angiogenesis and attenuated apoptosis of human umbilical venous endothelial cells. Finally, insulin receptor substrate 1 and Krüppel-like factor 10 were determined as the direct target genes of miR-126. CONCLUSIONS: MiR-126 engineered MDSCs notably repaired cavernosa injury in rats via vascular reconstruction by directly targeting IRS1 and KLF10, in which the exosomes secreted by MDSCs played a critical role.

Role of treatment with human chorionic gonadotropin and clinical parameters on testicular sperm recovery with microdissection testicular sperm extraction and intracytoplasmic sperm injection outcomes in 184 Klinefelter syndrome patients.

OBJECTIVE: To investigate whether preoperative human chorionic gonadotropin (hCG) treatment can help predict the outcomes of microdissection testicular sperm extraction (micro-TESE) and affect fertility outcomes in non-mosaic Klinefelter syndrome (KS) patients. DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility center. PATIENT(S): A total of 184 non-mosaic KS patients who underwent micro-TESE with or without preoperative hCG treatment from January 2016 to July 2019. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm retrieval rate (SRR) with and without hCG treatment, logistic models analysis. RESULT(S): Eighty KS patients (43.5%) had successful sperm retrievals after micro-TESE. There was no statistically significant difference in the SRR between the group who received hCG treatment and the group that did not (44.0% vs. 43.3%). Logistic regression analyses demonstrated that the hCG treatment had no statistically significant effect on successful sperm retrieval. However, higher preoperative testosterone (T) levels seemed to be associated with a higher probability of successful sperm retrieval (multivariate adjusted odds ratio 1.09; 95% confidence interval [CI], 1.04-1.16). The prediction model for SRR on KS patients had an area under the curve of 67.3% (95% CI, 59.3-75.3%). In the hCG treatment group, the data indicated that the three parameters of testicular volume, pretreatment T level, and alterations of T were associated with the probability of successful sperm retrieval. Moreover, hCG therapy did not affect intracytoplasmic sperm injection (ICSI) outcomes. No differences in the pregnancy rate or live-birth rate were observed between the two groups. CONCLUSION(S): Therapy with hCG does not affect SRR or ICSI outcomes of non-mosaic KS patients. However, preoperative T levels, whether treated with hCG or not, can predict the chance of sperm retrieval with micro-TESE.

Functional reconstruction of injured corpus cavernosa using 3D-printed hydrogel scaffolds seeded with HIF-1α-expressing stem cells.

Injury of corpus cavernosa results in erectile dysfunction, but its treatment has been very difficult. Here we construct heparin-coated 3D-printed hydrogel scaffolds seeded with hypoxia inducible factor-1α (HIF-1α)-mutated muscle-derived stem cells (MDSCs) to develop bioengineered vascularized corpora. HIF-1α-mutated MDSCs significantly secrete various angiogenic factors in MDSCs regardless of hypoxia or normoxia. The biodegradable scaffolds, along with MDSCs, are implanted into corpus cavernosa defects in a rabbit model to show good histocompatibility with no immunological rejection, support vascularized tissue ingrowth, and promote neovascularisation to repair the defects. Evaluation of morphology, intracavernosal pressure, elasticity and shrinkage of repaired cavernous tissue prove that the bioengineered corpora scaffolds repair the defects and recover penile erectile and ejaculation function successfully. The function recovery restores the reproductive capability of the injured male rabbits. Our work demonstrates that the 3D-printed hydrogels with angiogenic cells hold great promise for penile reconstruction to restore reproductive capability of males.

Circular RNA-0001283 Suppresses Breast Cancer Proliferation and Invasion via MiR-187/HIPK3 Axis.

BACKGROUND Circular RNAs (circRNAs) are key regulators that take part in the carcinogenesis and development of breast cancer. The current study aimed to identify the expression of and explored the function of circRNA-0001283 in breast cancer. MATERIAL AND METHODS Breast cancer tissue samples were tested using high-throughput sequencing to identify the levels of relative genes; and proteins were addressed by using quantitative real-time polymerase chain reaction (qRT-PCR) and western-blot. Cell ability and cell apoptosis were investigated by Cell Counting Kit-8 (CCK-8) and flow cytometry. Invasion was detected by Transwell invasion assay. The identification of target genes was analyzed by dual-luciferase reporter assay. RESULTS Downregulation of circRNA-0001283 expression was observed in breast cancer tissue samples. Ectopic expression of circRNA-0001283 remarkably suppressed cell viability and invasion, and induced apoptosis in breast cancer cells. Furthermore, circRNA-0001283 bound to miR-187 and decreased the expression of miR-187, which resulted in inhibition in cell growth and invasion. Finally, we showed that circRNA-0001283 positively regulated HIPK3 expression by sponging miR-187. CONCLUSIONS The results reveal a new functional circRNA-0001283 in breast cancer and may provide targets for developing novel therapeutic strategies for breast cancer.

Effects of Single Probiotic- and Combined Probiotic-Fermented Milk on Lipid Metabolism in Hyperlipidemic Rats.

Previous studies have shown that probiotics have positive effects on hyperlipidemia by lowering the serum lipid concentration and improving the lipid profile. To explore the mechanism by which probiotic-fermented milk improves lipid metabolism, the transcription of genes regulated by liver X receptors (LXRs), 5'-AMP-activated protein kinase, and the farnesoid X receptor (FXR), which play integral roles in lipid metabolism, was investigated in hyperlipidemic rats. Compared with rats fed a high-fat diet, the administration of probiotic-fermented milk significantly lowered the levels of total cholesterol (TC) and total triglycerides (TG) in rat serum and viscera (P < 0.05) and significantly increased the level of total bile acid in the rat liver and small intestine (P < 0.05). The quantitative PCR results showed that the probiotics ameliorated the TC levels in the rats by activating the transcription of genes involved in the LXR axis, which promoted TC reverse transport and increased the conversion of TC to bile acids. The level of TG in the hyperlipidemic rats was ameliorated by the inhibition of the transcription of carbohydrate reaction element binding protein genes and activation of the transcription of PPARα genes. The regulation of lipid metabolism-related gene transcription by the single probiotic (Lactobacillus rhamnosus LV108)-fermented milk was more effective than that by the combined probiotic (L. rhamnosus LV108, Lactobacillus casei grx12, and Lactobacillus fermentum grx08)-fermented milk (P < 0.05).

Outcome of Oocyte Vitrification Combined with Microdissection Testicular Sperm Extraction and Aspiration for Assisted Reproduction in Men.

BACKGROUND As a safety and efficacy protocol, oocyte vitrification has been widely used in IVF treatment. The aim of this study was to evaluate the outcome of ICSI-ET utilizing vitrified oocytes with sperm obtained from non-obstructive azoospermia (NOA) patients via micro-TESE. MATERIAL AND METHODS A total of 150 NOA patients underwent micro-TESE. Ten patients were unable to ejaculate and refused to accept TESA at the time of oocyte retrieval; later, these patients underwent TESA. A total of 174 obstructive azoospermia (OA) patients underwent TESA. Vitrified oocytes were used with micro-TESE in 35 cycles (group 1), and TESA in 10 cycles (group 2). Fresh oocytes were used with micro-TESE in 38 cycles (group 3) and TESA in 174 cycles (group 4). RESULTS The overall sperm retrieval rate of the 150 NOA patients was 48.7% (73/150). A total of 257 cycles of ICSI-ET were conducted with testicular spermatozoa; 212 cycles utilized fresh oocytes and 45 cycles utilized vitrified oocytes. No differences were observed with fertilization (73.8%, 77.2%,72.8%, 73.6%), implantation (33.3%, 34.7%, 33.8%, 37.5%), or clinical pregnancy rates (51.4%, 60%, 52.6%, 51.7%) for groups 1 through 4, respectively (P>0.05). Developmental competence was greatest among couples using sperm obtained via TESA rather than micro-TESE, not dependent on whether vitrified or fresh oocytes were utilized. Fertilization, implantation, and clinical pregnancy rates did not differ between using fresh vs. vitrified oocytes, nor did they differ between using testicular sperm derived from men with NOA vs. men with OA. CONCLUSIONS Vitrified oocytes combined with micro-TESE showed similar clinical efficacy when compared with fresh oocytes.

Effect of Lactobacillus rhamnosus hsryfm 1301 on the Gut Microbiota and Lipid Metabolism in Rats Fed a High-Fat Diet.

Accumulating evidence indicates that lactic acid bacteria could improve host physiology and lipid metabolism. To investigate the effect of the gut microbiota on host lipid metabolism, a hyperlipidemic rat model was established by feeding rats a high-fat diet for 28 days, and the gut microbiota of the rats was analyzed using real-time PCR before and after administration of Lactobacillus rhamnosus hsryfm 1301 and its fermented milk for 28 days. The findings showed that the Lactobacillus spp., Bifidobacterium spp., Bacteroides spp., and Enterococcus spp. content in the hyperlipidemic rats gut was increased significantly (p < 0.05), while the Clostridium leptum and Enterobacter spp. content was decreased significantly after intervening with L. rhamnosus hrsyfm 1301 and its fermented milk for 28 days (p < 0.05). Furthermore, the lipid levels of the serum and the liver were decreased significantly (p < 0.05) and the fecal water content was increased significantly (p < 0.05) in the hyperlipidemic rats after the intervention, and hepatocyte fatty degeneration of liver tissues was also prevented. A positive correlation was observed between the Clostridium leptum content and the level of serum cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein, and a negative correlation was observed between the Enterobacter spp. content and the Lactobacillus spp. and Bifidobacterium spp. content in the hyperlipidemic rats gut. These results suggest that the gut microbiota and lipid metabolism of hyperlipidemic rats could be improved by supplementation with L. rhamnosus hsryfm 1301 and its fermented milk.

The effect of Lactobacillus rhamnosus hsryfm 1301 on the intestinal microbiota of a hyperlipidemic rat model.

BACKGROUND: Growing evidence indicates that intestinal microbiota regulate our metabolism. Probiotics confer health benefits that may depend on their ability to affect the gut microbiota. The objective of this study was to examine the effect of supplementation with the probiotic strain, Lactobacillus rhamnosus hsryfm 1301, on the gut microbiota in a hyperlipidemic rat model, and to explore the associations between the gut microbiota and the serum lipids. METHODS: The hyperlipidemic rat model was established by feeding rats a high-fat diet for 28 d. The rats' gut microbiota were analyzed using high-throughput sequencing before and after L. rhamnosus hsryfm 1301 supplementation or its fermented milk for 28 d. The serum lipids level was also tested. RESULTS: The rats' primary gut microbiota were composed of Bacteroidetes, Firmicutes, Proteobacteria, Spirochaetes and Verrucomicrobia. The abundance and diversity of the gut microbiota generally decreased after feeding with a high-fat diet, with a significant decrease in the relative abundance of Bacteroidetes, but with an increase in that of Firmicutes (P < 0.05). Administration of L. rhamnosus hsryfm 1301 or its fermented milk for 28 d, could recover the Bacteroidetes and Verrucomicrobia abundance and could decrease the Firmicutes abundance, which was associated with a significant reduction in the serum lipids' level in the hyperlipidemic rats with high-fat diet induced. The abundance of 22 genera of gut bacteria was changed significantly after probiotic intervention for 28 d (P < 0.05). A positive correlation was observed between Ruminococcus spp. and serum triglycerides, Dorea spp. and serum cholesterol (TC) and low-density lipoprotein (LDL-C), and Enterococcus spp. and high-density lipoprotein. The Butyrivibrio spp. negatively correlated with TC and LDL-C. CONCLUSIONS: Our results suggest that the lipid metabolism of hyperlipidemic rats was improved by regulating the gut microbiota with supplementation of L.rhamnosus hsryfm 1301 or its fermented milk for 28 d.